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[0001] This application claims priority to U.S. Provisional Application Ser. No. 61/021,404, filed Jan. 16, 2008.
BACKGROUND
[0002] The present invention relates generally to large containers, in particular dumpsters that can be lifted and dumped by forks of a refuse or recycling truck. Traditionally, these dumpsters were constructed of metal with metal pockets welded to side walls for receiving the forks of the truck. A more recent dumpster is constructed entirely of plastic. The pockets on the side walls are integrally molded with the walls of the dumpster in a rotomolding process.
SUMMARY
[0003] The present invention provides several embodiments of plastic dumpsters with improved strength and durability.
[0004] In one embodiment, gussets connect pockets to bevel walls, connecting the side walls to front and rear walls of the dumpster. The bevel walls are stronger than the side walls of the dumpster. Other embodiments disclose gussets integral with front and rear walls of the dumpster for improved strength. Other embodiments disclose removable, separately formed sleeves that are secured to the sides of the dumpster to form pockets for receiving the forks of a truck.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] FIG. 1 is a perspective view of a dumpster according to a first embodiment.
[0006] FIG. 2 is a front view of the dumpster of FIG. 1 .
[0007] FIG. 3 is a side view of the dumpster of FIG. 1 .
[0008] FIG. 4 is a section view of the dumpster of FIG. 1 .
[0009] FIG. 5 is a section view through one of the pockets of the dumpster of FIG. 1 .
[0010] FIG. 6 is a front view of the dumpster of FIG. 1 .
[0011] FIG. 7 is a rear view of the dumpster of FIG. 1 .
[0012] FIG. 8 is a top view of the dumpster of FIG. 1 .
[0013] FIG. 9 is a bottom view of the dumpster of FIG. 1 .
[0014] FIG. 10 is a perspective view of a dumpster according to a second embodiment.
[0015] FIG. 11 is a section view through one of the pockets of the dumpster of FIG. 10 .
[0016] FIG. 12 is a perspective view of a dumpster according to a third embodiment.
[0017] FIG. 13 is a side view of the dumpster of FIG. 12 .
[0018] FIG. 14 is a section view through one of the pockets of the dumpster of FIG. 12 .
[0019] FIG. 15 is a perspective view of a dumpster according to a fourth embodiment.
[0020] FIG. 16 is a section view through one of the pockets of the dumpster of FIG. 15 .
[0021] FIG. 17 is a perspective view of a dumpster according to a fifth embodiment.
[0022] FIG. 18 shows the dumpster of FIG. 17 with the lids removed.
[0023] FIG. 19 is a bottom perspective view of the dumpster of FIG. 18
[0024] FIG. 20 shows the dumpster of FIG. 18 with the sleeves removed.
[0025] FIG. 21 is a top view of the dumpster of FIG. 20 .
[0026] FIG. 22 is a section view taken along line 22 - 22 of FIG. 21 .
[0027] FIG. 23 is a section view taken along line 23 - 23 of FIG. 21 .
[0028] FIG. 24 is a perspective view of one of the sleeves of the dumpster of FIG. 17 .
[0029] FIG. 25 is a rear view of the sleeve of FIG. 24 .
[0030] FIG. 26 is a horizontal section view through the sleeve of FIG. 24 .
[0031] FIG. 27 is a vertical section view through the sleeve of FIG. 24 .
[0032] FIG. 28 is a section view through one set of supports and one sleeve of the dumpster of FIG. 17 .
[0033] FIG. 29 is a side view of the dumpster of FIG. 17 with a similar dumpster nested therein.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0034] A dumpster 10 according to a first embodiment of the present invention is shown in FIG. 1 . The dumpster 10 includes a base wall 12 , front wall 14 , side walls 16 and a rear wall 46 ( FIGS. 3 and 4 ) defining an interior of the dumpster 10 . Between the front wall 14 and side walls 16 are front bevel walls 18 . Between the rear wall 46 and side walls 16 are rear bevel walls 19 .
[0035] The dumpster 10 includes pockets 20 adjacent each side wall 16 . An upper gusset 22 above the pocket and a lower gusset 24 below the pocket 20 are integral with the rear bevel wall 19 . An upper gusset 28 above the pocket and a lower gusset 30 below the pocket 20 are integral with the front bevel wall 18 . The gussets 22 , 24 , 28 , 30 support and reinforce the pockets 20 . The pockets 20 include openings 32 for receiving the fork of a truck for lifting and dumping the dumpster 10 .
[0036] By virtue of the connected perpendicular walls, the joints between the side walls and the front or rear wall of a container (usually the “corners,” and here including the bevel walls) are inherently stronger and more rigid than the walls themselves. By positioning the gussets 22 , 24 , 28 , 30 in the corners (i.e. the bevel walls 18 , 19 ) in the dumpster 10 , the connection of the pockets 20 to the dumpster 20 is stronger and more rigid.
[0037] The dumpster 10 may include optional casters 36 on the base 12 .
[0038] As shown, the upper edges of the side walls 16 are angled downwardly toward the front wall 14 . The upper edges of the walls 14 , 16 , 46 include a lip 38 that reinforces the walls and accommodates a hinge 42 connecting a pair of lids 40 to the rear wall 46 .
[0039] FIG. 2 is a front view of the dumpster 10 . FIG. 3 is a side view of the dumpster 10 , showing the gussets 22 , 24 , 28 , 30 connected only to the bevel walls 18 , 19 .
[0040] FIG. 4 is a perspective interior view of the dumpster 10 , partially broken away. The base 12 may include convex portions 13 for reinforcement. The lip 38 is hollow, as shown. A center wall 48 extends outwardly from the rear bevel wall 19 to the pocket 20 . The gussets 22 , 24 on the rear bevel wall 19 are open to the interior of the dumpster 10 . The upper gusset 22 includes a first wall 50 extending from the rear bevel wall 19 to the center wall 48 , a second wall 52 adjacent the first wall 50 and extending from the rear bevel wall 19 to an area proximate the outer edge of the pocket 20 and a third wall 54 adjacent the second wall 52 and extending from the bevel wall 19 across a portion of the pocket 20 .
[0041] Similarly, the lower gusset 24 includes a first wall 56 extending upwardly from the rear bevel wall 19 to the center wall 48 , a second wall 58 adjacent the first wall 56 and extending from the rear bevel wall 19 to an area proximate the outer edge of the pocket 20 and a third wall 60 adjacent the second wall 58 and extending from the bevel wall 19 across a portion of the pocket 20 .
[0042] As can be seen in FIG. 4 , apertures 73 are formed through the side wall 16 above and below the pocket 20 .
[0043] The apertures 73 are also shown in FIG. 5 , which illustrates a portion of the pocket 20 , sectioned laterally and longitudinally. The pocket 20 includes an upper wall 68 , a lower wall 64 and an outer wall 66 . The upper wall 68 includes alternating single wall sections 76 and box beam sections 80 , thereby defining alternating channels 78 above the single wall sections 76 between the box beam sections 80 . The box beam sections 80 define apertures 73 that open to the interior of the dumpster 10 ( FIG. 3 ). The lower wall 64 includes alternating single wall sections 70 and box beam sections 72 , thereby defining alternating channels 74 above the single wall sections 70 between the box beam sections 72 . The box beam sections 72 define apertures 73 that open to the interior of the dumpster 10 ( FIG. 3 ).
[0044] FIGS. 6-9 are front, rear, top and bottom views of the dumpster 10 , without the lids 40 or casters 36 .
[0045] FIG. 10 is a perspective view of a dumpster 110 according to a second embodiment. The dumpster 110 includes a base wall 112 , front wall 114 , side walls 116 and a rear wall 146 defining an interior of the dumpster 110 . The dumpster 110 includes pockets 120 adjacent each side wall 116 . The pockets 120 define openings 132 for receiving a fork of a truck. A lip 138 is defined around the upper edges of the walls. Lids 140 may be connected via a hinge 142 .
[0046] Each pocket 120 is supported by the front wall 114 and rear wall 146 which extends outward continuously to circumscribe the opening 132 of the pocket 120 .
[0047] FIG. 11 illustrates one of the pockets 120 in more detail in section. The pocket 120 includes a lower wall 164 , outer wall 166 , inner wall 167 and upper wall 168 that define the opening 132 through the pocket 120 . The lower wall 164 is formed similarly to that of the embodiment of FIGS. 1-9 , having box beam sections 172 having openings 173 into the interior of the dumpster 110 . Over the side walls 116 , the lip 138 includes an upper wall 180 having a inner flange 182 extending downward from an inner edge thereof. A corrugated wall 184 extends downward from the outer edge of the upper wall 180 down to the upper wall 168 of the pocket 120 . The corrugations increase the rigidity and strength of the corrugated wall 184 to further support the pocket 120 , although most of the support for the pocket 120 comes from the front wall 114 and rear wall 146 . When the dumpster 110 is lifted by the fork, most of the weight of the dumpster 110 and its contents is transferred directly to the front wall 114 and rear wall 146 .
[0048] FIGS. 12-14 illustrate a dumpster 210 according to a third embodiment. The dumpster 210 includes a base wall 212 , front wall 214 , side walls 216 and rear wall 246 . Pockets 220 are adjacent side walls 214 and are reinforced by rear gussets 222 , 224 and front gussets 228 , 230 .
[0049] Referring to FIG. 13 , the upper rear gusset 222 includes a first wall 250 , second wall 252 and third wall 254 all supporting the pocket 220 . The third wall 254 is generally parallel to the rear wall 246 of the dumpster 210 so that weight is transferred directly to the side wall 216 , while the first wall 250 is generally a continuous extension of the outer wall of the lip 238 . Similarly, the lower rear gusset 224 includes a first wall 256 , second wall 258 and third wall 260 , with the third wall 260 being generally parallel to the rear wall 246 of the dumpster 210 and connected to the side wall 216 .
[0050] The front gussets 228 , 230 each have three walls extending to the pocket 220 in a similar manner, such that the innermost walls of the gussets 228 , 230 are generally continuous extensions of the front wall 214 . Additionally, the outermost wall of the upper gusset 228 is generally a continuous extension of the outer wall of the lip 238 .
[0051] Referring to FIG. 14 , the pocket 220 has walls that are generally formed with alternating single wall sections and box beam sections, as described above with respect to the embodiment of FIGS. 1-9 .
[0052] FIGS. 15 and 16 illustrate a dumpster 310 according to a fourth embodiment. The dumpster 310 includes a base wall 312 , front wall 314 , side walls 316 and rear wall 346 . The pockets 320 are each formed by a sleeve 390 inserted (or, alternatively, insert-molded) into a front support 392 and a rear support 394 .
[0053] The supports 392 , 394 are reinforced by gussets 328 , 322 . Additional gussets below the supports 392 , 394 could optionally be used. Referring to FIG. 16 , the upper front gusset 328 includes a wall 329 extending perpendicularly to the side wall 316 and to the pocket 320 .
[0054] The sleeves 390 could be formed of a material different from that of the rest of the dumpster 310 . For example, the sleeves 390 could be metal, or the sleeves 390 could be a higher-density polymer. If plastic, the sleeves 390 could be injection molded or extruded. The sleeves 390 could be removable, such that damaged sleeves 390 could be replaced.
[0055] A dumpster 410 according to a fifth embodiment is shown in FIGS. 17-21 . Referring to FIG. 17 , the dumpster 410 includes a base wall 412 , front wall 414 , side walls 416 and rear wall 446 ( FIG. 18 ). A hollow lip 438 extends around the upper edge of the periphery of the dumpster 410 . Lids 440 are hingeably mounted on the dumpster 410 . Pockets 420 are each formed by a sleeve 490 inserted (or, alternatively, insert-molded) into a front support 492 and a rear support 494 .
[0056] The supports 492 , 494 are reinforced by upper gussets 428 , 422 . Stacking posts 506 are formed below the supports 492 , 494 . The sleeves 490 could be formed of a material different from that of the rest of the dumpster 410 . For example, the sleeves 490 could be metal, or the sleeves 490 could be a higher-density polymer. The sleeves 490 could be removable, such that damaged sleeves 490 could be replaced. The sleeves 490 each include a front flange 496 , including a large inner flange portion 498 .
[0057] FIG. 18 shows the dumpster 410 with the lids removed to show the interior. The upper gusset 422 includes an outer wall 422 a extending at an angle from the lip 438 to an inner wall 494 a of the support 494 . The upper gusset 422 also includes generally triangular side walls 422 b extending between the side walls 416 of the dumpster 410 to the inner wall 494 a of the support 494 . The upper edge of the lip 438 includes stacking recesses 508 aligned with the stacking posts 506 .
[0058] FIG. 19 is a bottom perspective view of the dumpster 410 of FIG. 18 . The base wall 412 includes a plurality of recesses 510 for receiving plates of casters (e.g. casters 36 of FIG. 1 ).
[0059] FIG. 20 shows the dumpster 410 without the lids 440 or sleeves 490 . In the illustrated embodiment, what is shown in FIG. 20 is rotomolded as a single piece. The lids 440 and sleeves 490 are subsequently attached.
[0060] FIG. 21 is a top view of the dumpster 410 of FIG. 20 . FIG. 22 is a section view taken along line 22 - 22 of FIG. 21 . FIG. 23 is a section view taken along line 23 - 23 of FIG. 21 . As shown, each pocket support 494 includes an inner wall 494 a spaced inwardly of the pocket support 494 .
[0061] The sleeve 490 is shown in more detail in FIGS. 24-27 . The sleeve 490 includes the front flange 496 around the periphery of the front opening of the sleeve 490 . The inner flange portion 498 is larger than the remainder of the front flange 496 and includes a convex outer surface 500 protruding outwardly. The convex outer surface 500 protects the outer surface of the front wall 414 of the dumpster 410 from the fork and helps redirect the fork into the sleeve 490 . The sleeve 490 further includes an elongated hollow body portion 502 , which in the example shown is tapered toward the rear of the sleeve 490 . At least one, and optionally several, protruding retainers 504 are integrally formed in the body portion 502 of the sleeve 490 . One is shown formed in the front surface of the sleeve 490 , and a second retainer 504 is formed one the rear surface of the example sleeve 490 (as can be seen in FIG. 25 ), but the upper and lower surfaces could also be used. The retainers 504 are sized and positioned to snap-fit past the front supports 492 to retain the sleeves 490 in the supports 492 , 494 , as shown in FIG. 28 . Alternatively, recesses could be formed in the sleeves 490 , with corresponding protrusions formed in the supports 492 , 494 . Additional, or alternate, fasteners (e.g. screws, rivets, etc) could also fasten the sleeves 490 to the dumpster 410 .
[0062] Referring to FIG. 28 , the retainers 504 and the sleeve 490 deform as the sleeve 490 is inserted through the front support 492 and then the retainers 504 snap behind the support 492 to prevent the unintended removal of the sleeve 490 forwardly from the support 492 . Meanwhile, the front flange 496 and the taper of the body portion 502 prevent the sleeve 490 from sliding rearwardly in the supports 492 , 494 .
[0063] During use, the sleeves 490 will be subject to impact from the forks of the truck, but can be replaced by releasing the sleeve 490 by depressing the retainers 504 and sliding the sleeve 490 forwardly.
[0064] FIG. 29 illustrates the dumpster 410 (without lids 440 ) with a similar dumpster 410 ′ nested therein, such as for shipping or for storage. The stacking posts 506 ′ of the upper dumpster 410 ′ are received in the stacking recesses 508 of the lower dumpster 410 for more stable stacking and better transfer of the weight of the upper dumpster 410 ′ to the lower dumpster 410 .
[0065] The dumpsters 10 , 110 , 210 , 310 , 410 disclosed herein can be rotomolded plastic dumpsters; however, other manufacturing techniques could conceivably be used instead or in addition to rotomolding. The dumpsters 10 , 110 , 210 are disclosed as having integrally molded pockets, but alternatively the pockets could be formed separately and subsequently attached.
[0066] In accordance with the provisions of the patent statutes and jurisprudence, exemplary configurations described above are considered to represent a preferred embodiment of the invention. However, it should be noted that the invention can be practiced otherwise than as specifically illustrated and described without departing from its spirit or scope. Alphanumeric identifiers on method steps are for convenient reference in dependent claims and do not signify a required sequence of performance unless otherwise indicated in the claims.
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Several embodiments of plastic dumpsters with improved strength and durability are disclosed. In one embodiment, gussets connect pockets to bevel walls, connecting the side walls to front and rear walls of the dumpster. The bevel walls are stronger than the side walls of the dumpster. Other embodiments disclose gussets integral with front and rear walls of the dumpster for improved strength. Other embodiments disclose removable, separately formed sleeves that are secured to the sides of the dumpster to form pockets for receiving the forks of a truck.
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BACKGROUND OF THE INVENTION
The present invention relates to a multi-layer dressing for wounds which provides for an initial period of wound hypoxia followed by oxygen availability to the wound, without disturbing the covering immediately in contact with the wound.
As understanding of the healing process has progressed, various theories have been advanced on the most advantageous way to treat wounds to promote healing. For many years, it was generally believed the wounds required atmospheric oxygen to aid epithelial resurfacing and so oxygen permeable wound dressings were used. Subsequently, however, it has been reported that oxygen-free or hypoxic conditions are either as good as, or preferable to aerobic conditions for the promotion of healing.
Alvarez et al. compared the effects of oxygen permeable and oxygen impermeable occlusive dressings on collagen synthesis and re-epithelialization. Infections in Surgery, March, 1984, pages 173-181. They found that occlusive dressings, and not the presence or absence of oxygen, led to improvement in both collagen synthesis and re-epithelialization.
Knighton et al. have reported that macrophage mediated angiogenesis is promoted by hypoxic conditions, and that, at least to the extent that new capillary growth is required, hypoxia is preferably maintained throughout most of the healing process. Allowing oxygen to contact the wound was found to slow angiogenesis unless capillary regeneration had proceeded to a point where more than 80% of the wound space had been filed. In that case, angiogenesis proceeded at the same rate, regardless of the atmospheric oxygen tension within the wound.
SUMMARY OF THE INVENTION
It has now been found that for wounds, particularly wounds requiring debridement, optimum healing results if a wound is first covered with an oxygen impermeable dressing to promote hypoxia, and subsequently allowed contact with atmospheric oxygen. Depending on the nature and extent of the wound, periods of hypoxia from about 3 to about 72 hours are indicated.
Such treatment is provided according to this invention by the application of a multi-layer wound dressing. The dressing is made of
(a) an outer layer of a material having low-oxygen permeability;
(b) an inner layer of a highly oxygen permeable material, affixed on one side to the outer layer; and
(c) an adhesive applied to at least a part of the other side of the inner layer. The adhesion between the inner layer and the skin is greater than the adhesion between the inner and outer layers
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a cross-sectional view of a multi-layer wound dressing.
FIG. 2 shows a three-dimensional projection of a multi-layer wound dressing.
DETAILED DESCRIPTION OF THE INVENTION
When wounding occurs, disruption in blood flow to the wound site leads to an initial decrease in the oxygen supply to cells at the wound surface. Inadequate blood supply and oxygen consumption leads to a state of localized hypoxia and cells in the hypoxic region shift from an aerobic to an anaerobic metabolism. As a part of this shift, enzymes which are not ordinarily present or active in aerobic tissue are synthesized and activated. It now appears that one of these enzymes plays a significant role in triggering the healing Lactate dehydrogenase (LDH) is produced in response to hypoxia to catalyze the conversion of pyruvic acid to lactic acid, providing energy to cells existing in an anerobic environment. Lactic acid accumulates until the anaerobic condition is terminated and then is reconverted to pyruvic acid by LDH. I believe that LDH acts as a triggering mechanism for the healing process. Induction of increase amounts of LDH should, therefore, lead to more rapid triggering. Prolonged hypoxia would not be required, however, since LDH does not immediately disappear following the return of oxygenation.
Consistent with this theory, it has been found that wounds which are initially covered with an oxygen impermeable dressing which enhances and prolongs hypoxia, and then subsequently covered with an oxygen permeable dressing exhibit improved rates of epidermal resurfacing as compared to wounds treated with either oxygen permeable or oxygen impermeable dressings alone. Furthermore, it has been found that epidermal cells grown in culture exhibit maximum adherence at 13 mm Hg. of oxygen, but undergo maximum regeneration at 37 mm of Hg. Fibroblasts exhibit maximum growth at about 16 mm Hg.
Superficial partial thickness wounds (epidermal and inclusive of papillary dermis) can be effectively treated with as little as 6 hours of hypoxia, while wounds requiring substantial debridement should be treated for up to 72 hours. In general, however, the preferred duration for the hypoxic phase of the treatment is about 24 hours. Maintaining hypoxia for periods in excess of 72 hours may not lead to an enhancement of healing, and may result in detrimental effects such as anaerobic organism overgrowth or shifts in microbial flora. Although not a direct effect of hypoxia, prolonged use of the dressing according to this inventions can also lead to tissue maceration due to poor transmission of moisture vapor when both films are intact.
Advantageous treatment of wounds to promote healing can be achieved utilizing a multi-layer wound dressing. As shown in FIG. 1, the multi-layer dressing comprises an oxygen impermeable outer layer (10) affixed to one side of an oxygen permeable inner layer (12). Inner layer (12) has a coating of adhesive (14) applied to all or part of the other side of inner layer (12). Prior to application, adhesive (14) is protected by a layer of a release sheet (16) which is removed to expose the adhesive for application of the dressing to the wound area.
The outer layer of the dressing may be made of any material with low-oxygen permeability which can be formed into a continuous film of sufficient flexibility for use as a wound dressing. Preferably, the outer layer should have an oxygen permeability of less than about 200 cm 3 /100 in 2 /mil/24 hrs. In particular, films of polyvinyl alcohol, polyviriylidene chloride, polyvinyl chloride, high density polyethylene and high density polypropylene are suitable for use as the outer layer of the multi-layer dressing.
The inner layer of the dressing may be made of any oxygen permeable material which can be formed into a continuous film of sufficient flexibility for use as a wound dressing. Suitable materials include films made of polyurethane, co-polyester, mixtures of polyester and urethanes, foams, and silicone materials.
If desired, either or both of the layers can be opacified and colored to blend in with skin coloration.
In the assembled dressing, the inner and outer layers are affixed together. This can be achieved using an attraction based on static charge. As an alternative, a low-tack adhesive may be used. The use of a low-tack adhesive permits the low-oxygen permeability outer layer to be re-affixed to the inner layer if it is removed prematurely.
The adhesive applied to the inner side of the oxygen permeable layer is used to attach the dressing to the patient's skin. It will be understood that any suitable nontoxic adhesive for use in bandages or dressings can be used for this purpose. Preferably, the adhesive will be a pressure sensitive adhesive. Suitable adhesives include ether based or water based adhesives, acrylates, polyisobutylene, starch based adhesives, pectin, and other hydrocolloids or gums. Adhesive preparations having antimicrobial effects, or those containing medications are also suitable for use in this invention.
The adhesive is applied to all or part of the surface of the inner layer. This means that the adhesive can be applied in a continuous fashion. The adhesive can also be restricted to the margins of the dressing so that an adhesive-free window remains in the central portion of the dressing which will be in actual contact with the wound.
As is conventionally known, a layer of release material may be used to cover the adhesive until the time of application of the dressing.
A preferred embodiment of the multi-layer wound dressing according to this invention is shown in FIG. 2. The dressing is made of outer layer (10), inner layer (12), and adhesive (14) and a release sheet (16). In addition, a tab (18) is attached along one edge of outer layer (10). The tab (18) does not adhere to inner layer (12), and serves to allow easy removal of the outer layer. Preferably, tab (18) is made of a material which is readily marked with conventional writing implements. This will allow the treating professional to write instructions for the removal of outer layer (10) directly on the dressing.
Optionally, a second tab may be included along the opposite edge of the dressing. This tab would be brightly colored, e.g. red, or obviously numbered to alert the patient that the dressing still needs attention.
As a further refinement, the dressings according to the claimed invention may include a removable coding strip which can be used for billing and inventory control purposes, and to monitor the occurrence of treatments in hospital. Advantageously, the coding strip is an adhesive backed perforated extension of the wound dressing which is separated from the dressing and adhered to the patient's chart at the time of application of the dressing. The coding strip preferably has printed upon it the type and inventory control numbers of the dressing in both conventional and machine readable formats, and may advantageously be made of a material which is readily marked with conventional writing implements to allow for noting the date or time of application on the coding strip.
It will be understood by one skilled in the art that the low-oxygen permeability outer layer of a multi-layer wound dressing according to this invention may be smaller in area than the oxygen permeable inner layer. If this is the case, the low-oxygen permeability layer should be centered over the wound, and sized such that it completely covers the wound area.
EXAMPLE
The effect of oxygen impermeable (low permeability) and oxygen permeable films and of multi-layer dressings according to this invention on epidermal resurfacing of partial thickness wounds was studied. Pigs were wounded to a depth of 0.3 mm, and the wounds treated according to one of the following regimens: (1) untreated; (2) polyurethane film; (3) co-polyester film; (4) polyethylene film; (5) polyvinylidene film; (6) polypropylene film; (7) multi-layer dressing of polypropylene and co-polyester films; and (8) multi-layer dressing of polypropylene and polyurethane films. Each of the dressings was affixed with an adhesive applied only to the perimeter of the dressing such that the wound was not contacted with the adhesive.
From day 2 through day 6 after wounding, wounds from each treatment regimen were evaluated to determine the extent of epidermal resurfacing. From these results, HT 50 , the time required for 50% of the wounds to be 100% healed was determined for each treatment regimen. The values of HT 50 in Table 1 clearly show that treatment with multi-layer dressings according to this invention is superior to single dressings of either oxygen permeable or oxygen impermeable material.
TABLE 1__________________________________________________________________________ RELATIVE RATE OF HEALING.sup.b COMPAREDTREATMENT HT.sub.50 (DAYS).sup.a TO UNTREATED (%)__________________________________________________________________________UNTREATED 4.1 --POLYPROPYLENE/POLYURETHANE 2.8 +31POLYPROPYLENE FILM 3.2 +22POLYVINYLIDENE FILM 3.1 +22POLYETHYLENE FILM 3.1 +24CO-POLYESTER 3.4 +17POLYURETHANE FILM 3.4 +17POLYPROPYLENE/CO-POLYESTER 2.8 +31__________________________________________________________________________ .sup.a HT.sub.50 = Healing time 50, days needed for 50% of wounds to be 100% healed. .sup.b Relative rate of healing = (untreated HT.sub.50)/untreated HT.sub.50 × 100.
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A multi-layer wound dressing is provided which facilitates wound healing by creating hypoxia followed, after 3 to 72 hours, by an aerobic environment. The dressing is made of (a) a low-oxygen permeability outer layer; (b) an oxygen permeable inner layer, affixed on one side to the outer layer; and (c) an adhesive applied to the other side of the inner layer. The adhesive may be applied in a continuous or discontinuous manner, and may be applied only around the perimeter of the dressing, leaving an adhesive-free window. The entire dressing is applied to the wound and creates a hypoxic environment until the outer low oxygen permeability layer is removed after 3 to 72 hours. The oxygen permeable layer is left on to provide protection during a subsequent aerobic healing phase.
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BACKGROUND AND SUMMARY
The present disclosure generally relates to firearms, and more particularly to bolt handle assemblies for bolt action rifles.
Bolt action rifles generally include a barrel, a receiver onto which the barrel is mounted, and a bolt assembly including a cylindrical breech bolt that is axially movable in a receiver for opening and closing the breech. The bolt includes locking lugs at the front end which may be rotated into a locked position at the rear of the barrel. The bolt may be manually rotated between the locked and unlocked positions while in the closed breech position and also moved axially forward or rearward via a handle that protrudes approximately laterally outwards from the bolt for grasping by the user.
Many surplus military bolt action rifles are popular with civilian shooters and hunters because of their reliability and power. One of these firearms is the Mosin-Nagant rifle. This rifle was designed with open sights and a straight bolt handle that rotates to a vertical position when open. This design prohibits mounting a telescopic sight on the top of the rifle which limits the rifle's usefulness for long range hunting and shooting. Military sniper versions of the Mosin-Nagant have a modified bolt handle that allows a scope to be attached. Custom versions of the bolt handle are also available commercially. However, these modified bolt handles are generally welded onto the original bolt body in place of the original handle. This procedure requires a high level of skill to be done satisfactorily. A need therefore exists for a method to install a modified bolt handle that requires less specialized skill and equipment.
The present invention provides such a method of attachment of a new bolt handle to the bolt body of a bolt action rifle. This method requires only cutting and drilling. Unlike other existing methods, no welding is required. The new handle is designed to allow a low profile scope mount to be installed on the top of the rifle, which is not possible with the original straight bolt handle. The preferred embodiment is for a Mosin-Nagant rifle but could be applied to other rifles that have an action of similar configuration.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a perspective view of one embodiment of an original bolt action rifle bolt body with a straight bolt handle.
FIG. 2 shows an exploded perspective view of the modified body and new bolt handle.
FIG. 3 shows a perspective view of the modified body and new bolt handle.
REFERENCE NUMERALS IN DRAWINGS
The table below lists the reference numerals employed in the figures, and identifies the element designated by each numeral.
1 bolt body 1 2 original bolt handle 2 3 handle cut-off location 3 4 attachment hole 4 5 attachment nub 5 6 new bolt handle 6 7 tension pin hole 7 8 tension pin 8 9 proximate end 9 of new bolt handle 6 7 A tension pin hole 7 A
DETAILED DESCRIPTION
In one embodiment, a method for modifying a bolt handle comprises steps of: obtaining an original bolt body 1 has a bolt handle 2 attached thereto proximate a handle cutoff location 3 ; severing bolt handle 2 from original bolt body 1 proximate handle cutoff location 3 ; drilling an attachment hole 4 into original bolt body 1 proximate handle cutoff location 3 ; drilling a tension pin hole 7 into original bolt body 1 such that tension pin hole 7 is perpendicular and operatively connected to attachment hole 4 ; obtaining a new bolt handle 6 having an attachment nub 5 attached to a proximate end 9 thereof, attachment nub 5 having a tension pin hole 7 A; inserting attachment nub 5 into attachment hole 4 such that tension pin hole 7 A of attachment nub 5 coincides with tension pin hole 7 of original bolt body 1 ; and inserting a tension pin 8 through tension pin holes 7 , 7 A of original bolt body and attachment nub, respectively.
Tension pin 8 is adapted to frictionally fit within tension pin holes of original bolt body and attachment nub. Attachment nub 5 is substantially perpendicular to new bolt handle 6 ,
In one embodiment, a bolt handle modification system comprises: an original bolt body 1 having a bolt handle attachment hole 4 and a tension pin hole 7 ; a new bolt handle 6 having a bolt handle attachment nub 5 attached to a proximate end 9 thereof, bolt handle attachment nub having a tension pin hole 7 A; and a tension pin 8 adapted to frictionally fit within tension pin holes 7 , 7 A of original bolt body and new bolt handle, respectively.
Bolt handle attachment nub 5 is substantially perpendicular to new bolt handle 6 . As shown in FIGS. 2 & 3 , this structure allows new bolt handle 6 to be operated without interfering with an attached scope.
Attachment nub 5 fits within bolt handle attachment hole 4 such that tension pin holes 7 , 7 A coincide. Tension pin 8 is positioned through tension pin holes 7 , 7 A. Tension pin hole 7 of original bolt body 1 is perpendicular and operatively connected to attachment hole 4 of original bolt body 1 so that tension pin holes 7 , 7 A coincide when attachment nub 5 is fitted within bolt handle attachment hole 4 .
As shown in FIG. 2 , attachment hole 4 is drilled into original bolt body 1 at approximately the same location as original bolt handle 2 . Attachment hole 4 is sized to accommodate attachment nub 5 that extends from the end of the new bolt handle 6 . Attachment nub 5 is inserted into attachment hole 4 completely, and a tension pin hole 7 that is oriented perpendicular to attachment hole 4 is drilled through the bolt body 1 and attachment nub 5 . The new bolt handle 6 is secured into place with tension pin 8 that is driven into tension pin hole 7 .
In one embodiment, tension pin hole 7 extends entirely through original bolt body 1 , tension pin hole 7 A extends entirely through attachment nub 5 , and tension pin 8 is adapted to extend all the way through original bolt body 1 .
In another embodiment, tension pin hole 7 does not extend entirely through original bolt body 1 . Rather, it only extends into one side of original bolt body 1 , and tension pin 8 is adapted to extend into one side of original bolt body 1 , and extend entirely through attachment nub 5 . This variation is substantially functionally the same but may be more aesthetically appealing to some.
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A bolt action rifle bolt handle modification system and method replaces the original bolt handle with an assembly that allows use of a telescopic sight mounted on the top of the rifle. This system requires less skill and specialized equipment than existing handle modification methods.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to a hydraulic control system for an automatic gear change transmission. More particularly, the invention pertains to such a control system whose operation is controlled by an electronic control system which produces signals that cause selective pressurization of the gear change elements of the transmission.
2. Description of the Prior Art
Automatic transmissions for automotive use include planetary gearing in which the various gear elements are hydraulically braked in order to produce selected speed ratio ranged between the engine and drive wheels. Speed ratio changes result upon braking of a selected portion of the planetary gear drive.
Increasingly, automatic gear change transmissions are controlled by electronic means. Electronic control units operate reliably but it is possible that a cable may break or that the entire electronic control unit may fail. It is important, in the event of an electronic failure, that the various speed ratios of the transmission should be available to the operator in order to permit driving the vehicle to a service station for repair. It is known in the prior art that at least the first gear and the reverse gear of a transmission can operate in the event of an electronic system failure. U.S. Pat. No. 3,937,108 describes a system providing this function. U.S. Pat. No. 3,813,964 describes a control system wherein a valve prevents upshifting from the low speed range when the electronic control system fails and the transmission is set in the first speed ratio. It is preferable, however, that all the forward speed ratios and the reverse drive should be available to the vehicle operator if the electronic control system should fail. In this way, damage to the transmission can be avoided and the vehicle more easily driven to the service station.
SUMMARY OF THE INVENTION
The control unit of an electronic microprocessor will produce signals that operate to shift valves in the hydraulic control system of an automatic transmission. Generally, the electronic control systems operate such that if electric power is lost, the electronic control defaults to an OFF condition in which no control current is applied to operate the valves that are a part of hydraulic control system. When correctly operating, the electronic control produces an electronic signal for operating the hydraulic valves in response to the reading of the engine speed or the vehicle speed.
The first object of having all forward speed ratios and the reverse drive available to the vehicle operator in the event of an electronic failure is realized by allowing the hydraulic control system to pressurize the necessary elements of the transmission when a vehicle operator changes the position of a manual valve. The hydraulic control circuitry allows all of the gears of the transmission to be available when the electrically operated solenoid valves are in the OFF condition. The ON/OFF valves operating in combination with the manual valve permit manual control independently of the operation of the electrical control.
Another object of our invention is to provide a control system wherein line pressure regulation can occur either when a variable force solenoid is controlled by the control unit of a microprocessor or when the electronic signal to the solenoid is lost. This result occurs by biasing the line pressure regulator valve with a mechanical spring that produces a force in the direction of a force produced by the variable force solenoid. In this way if the electronic control signal is lost, the spring will modulate line pressure and produce a regulated line pressure determined by the force of the spring. The control system according to our invention includes a variable force solenoid for controlling the position of a line pressure regulator valve in response to an electronic signal from the microprocessor. First and second solenoids controls respectively the position of two solenoid valves which act as shift valves to produce the various speed ratios of the transmission.
First and second ON/OFF valves whose state is determined hydraulically act as pressure distributors that permit the manual valve to overrule the operation of the electronically controlled solenoid valves if there is an electronic malfunction. A manual valve is moveable between the usual park, reverse, neutral, drive 2 and 1 positions. The manual valve operates in the usual manner during normal operation to allow automatic shifting to the selected gear setting. However, the manual valve can be adjusted by the vehicle operator in the event of an electrical failure to produce shifting among the gear ratios of the transmission by adjusting the setting of the manual valve between any of the gear ratios available in the transmission.
Two hydraulically operated servos control friction brakes in the transmission and two clutches connect torque delivery elements in the transmission. The servos and the clutches are pressurized selectively in normal operation according to the electrical signals received from the microprocessor control unit. Alternatively, in the event of an electronic failure, the servos are pressurized according to the control exercised over the hydraulic circuitry by the vehicle operator upon setting the manual valve to any of the forward or reverse speed ratios.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows in schematic form the torque transmitting gear system for use with the control system of our invention.
FIG. 2 is a schematic diagram of the hydraulic circuit for controlling the gear system of FIG. 1 showing the several solenoids controlled by the control unit of a microprocessor.
FIG. 3 is a schedule of the ON and OFF status of the solenoids and ON-OFF valves that pressurize the various gear system components according to the setting of the manual valve and the operating mode of the transmission.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring first to FIG. 1, an internal combustion engine 10 in an automotive vehicle driveline includes a carburetor 12 which forms a part of the air fuel mixture intake manifold system. The engine crankshaft is driveably connected to the impeller drive shell 14 of a hydrokinetic torque converter unit 16. This unit includes a bladed impeller 18, a bladed turbine 20, and a bladed stator 22. The impeller, turbine and stator are disposed in the conventional torodial fluid flow relationship. A positive displacement pump 24 is driveably connected to the impeller 18.
An overrunning brake 30 for the stator 22 includes overrunning coupling elements between a shaft 26 and the stator 22 which permit free wheeling motion of the stator in the direction of rotation of the impeller, but rotation of the stator in the opposite direction is prevented.
The turbine 20 is connected driveably to a central turbine shaft 32. Shaft 32 is connected directly to a clutch element 34 which is common to a forward drive friction disc clutch 36 and to a reverse friction disc clutch 38. Clutch 36, which is actuated by means of a fluid pressure operated servo, functions to connect selectively the clutch element 34 to the ring 40 of a simple planetary gear unit 42. Clutch 38 is actuated by a fluid pressure operated servo as indicated. It functions to driveably connect element 34 to a drive shell 44 when it is engaged. The shell 44 is connected to a common sun gear 46 of the planetary gear unit 42 and to a second simple planetary gear unit 48.
An intermediate speed ratio friction brake band 50 surrounds the clutch drum 52 of the reverse and direct clutch 38. Drum 52 is connected to the drive shell 44. The brake band 50 is applied and released by means of a front intermediate brake servo 54, which includes a cylinder 56 and a cooperating piston 58. Cylinder 56 and piston 58 cooperate to define a brake release chamber 60 and a brake apply chamber 62. The piston 58 is connected to the brake band 50 by the linkage 64.
Planetary gear unit 42 includes a ring gear 66, planet pinions 68 and a carrier 70 on which the pinions 68 are journalled. Pinions 68 mesh with the ring gear 66 and with the sun gear 46. Carrier 70 is connected driveably to a power output shaft 72.
Planetary gear unit 48 includes a ring gear 74, planet pinions 76 and a carrier 78 on which the pinions 76 are journalled. Ring gear 74 and sun gear 46 are in mesh with the pinions 76. Power output shaft 72 is connected driveably to the ring gear 74.
Carrier 78 is connected to a brake drum 80, which has a reverse and low brake band 82 positioned adjacent its outer periphery. The brake band may be applied during reverse drive operation and during operation in the manual low drive range by means of fluid pressure applied to reverse-low servo 84. This servo includes a cylinder 86 and a piston 88, which cooperate to define a fluid pressure chamber 90. This chamber has pressurized fluid applied by means of the circuits illustrated in FIGS. 2 and 3.
The piston 88 is connected to the free end of the brake band 82 by the linkage 92. Brake drum 80 is connected to the inner race 94 of an overrunning reaction brake 96. The outer race of the brake 96 is connected to a portion of the transmission housing shown in 98. Brake 96 includes overrunning brake elements that anchor the carrier 78 against rotation in one direction to accommodate reaction torque, but allow freewheeling motion in the opposite direction. The brake 96 is effective during operation in the lowest speed ratio to accommodate driving torque reaction.
To condition the mechanism for operation at the lowest speed ratio in the drive range, it is necessary to apply the forward clutch 36. This clutch remains applied during operation in each forward drive speed ratio. In this condition, torque is delivered from a turbine 20 through the clutch 36 to the ring gear 40. Since the carrier 70 is connected to the power output shaft 72 and since it resists movement, sun gear 46 tends to be driven in a reverse direction. A positive driving torque, which is transmitted directly to the shaft 72 however, is applied to the carrier 70. The reverse motion of the sun gear 46 causes ring gear 74 to be driven in a forward drive direction because the carrier 78 acts as a reaction member. Carrier 78 is inhibited from rotation in the direction of rotation of the sun gear 46 by the overrunning brake 96, which acts as a reaction point for the gear system. The positive driving torque transmitted to the ring gear 74 is transmitted directly to the power output shaft 72. Therefore, a split torque delivery path is provided through the gearing during low speed ratio operation.
For intermediate underdrive operation in the drive range, the intermediate speed ratio brake band 50 is applied by pressurizing chamber 62 of the brake servo 54 and the clutch 36 is engaged. This action anchors the sun gear 46 so that it can function as a reaction member. Turbine torque is carried by the shaft 32 through the clutch 36 to the ring gear 40. Sun gear 46 accommodates reaction torque as the carrier 70 is driven in a forward driving direction. This drives the output shaft 72 at an increased speed ratio as the overrunning brake 95 overruns. Therefore a transition from the lowest speed ratio to the intermediate speed ratio in the drive range is accomplished by engaging only one friction torque establishing device, the brake band 50.
To establish a high speed ratio condition in the drive range, brake band 50 is released concurrently with the application of the reverse-high clutch 38. Friction clutch 36 remains applied. Thus the sun gear 46 becomes locked to the ring gear 40 and the elements of the gearing rotate in unison to establish a 1:1 speed ratio.
Continous operation at the low speed ratio of the 1 operating range results by engaging the brake band 82, which is accomplished by pressurizing the chamber 90 of the reverse-low servo 84. This anchors the carrier 78. The forward clutch 36 remains applied, as it is in all forward speed conditions. Turbine torque is carried, as previously described, to the ring gear 40 as a split torque delivery path is established in the gearing. The control system is conditioned so that upshifts to the higher speed ratios will be inhibited.
Continous operation at the intermediate speed ratio of the 1 operating range results upon application of the forward clutch 36 and the intermediate servo 54 upon pressurizing the apply chamber 62, as was previously described with respect to the intermediate speed ratio in the drive range. Continous intermediate speed ratio operation in the 2 range results from a similar application of the forward clutch 36 and the intermediate servo 54 upon pressurizing the apply cylinder 62.
Reverse drive operation is obtained by releasing the forward friction clutch 36 and applying the reverse-high clutch 38. Brake band 82 is applied by pressurizing the chamber 90 of the low-reverse servo 84 and the intermediate band 50 is released. Turbine torque is then distributed directly to the drive shell 44 through the reverse-high clutch 38. This drives the sun ear 46 in the direction of rotation of the turbine. Since carrier 78 is anchored, ring gear 48 and the output shaft 72 are driven in a reverse direction at a reduced speed ration.
During an upshift from a lower speed ratio to the intermediate speed ratio, fluid pressure is admitted to the brake servo chamber 62. Upon a subsequent upshift from the intermediate speed ratio to the high speed ratio, pressure is distributed simultaneously to chambers 62 and 60 of the intermediate servo 54 to relese the brake 50. Upon a subsequent downshift from the high speed ratio to the intermediate speed ratio, it is necessary to exhaust chamber 60 as the clutch 38 is released. The residual pressure in chamber 62 applies the servo 54.
The control system for obtaining automatic speed ratio changes in the torque transmitting structure of FIG. 1 is illustrated in FIG. 2. The pressure regulator solenoid 100 is connected by the electrical line 102 to the output port of an electronic microprocessor which supplies electrical current to the solenoid 100 in proportion to engine load. Look-up tables stored in RAM computer memory have a preferred schedule of the output current-engine load relationship for a particular engine-transmission combination. Actually any desired parameter, such as torque, engine speed, road speed, etc., could be the dependent variable from which the current magnitude can be determined from the tables or by calculation.
Solenoid 100 is a variable force solenoid which applies a force to the line pressure regulator valve that varies as the input current varies. The line pressure regulator valve 104 includes a multiple land valve spool 106 which has lands 108, 110 formed thereon. The valve spool 106 is slideably mounted within a valve chamber and is biased in one direction within the chamber by spring 112. Lands 108 and 110 are formed with different diameters and define an annular space between them at chamber 114, which communicates with the discharge side of the pump 24 by way of the passage 116. At one axial end of the valve spool 106, the chamber 118 is formed, which allows fluid pressure to be applied to the opposite face of the land 108 by way of the fluid passage 120.
The variable force solenoid 100 has an axially extending pin member 122 which contacts the valve spool 106. When the solenoid is activated, a force is applied to the spool 106 which varies with the amount of current supplied to the solenoid. The force applied to the valve spool by the solenoid acts in axial opposition to the net hydraulic force developed on the differential areas on the land 108 and 110. The effect of the solenoid 100 is to move the valve spool outwardly whereas the hydraulic force moves the valve spool toward the solenoid 100. An orifice 124 is formed within passage 116 and produces a pressure drop between the discharge side of the pump and the line pressure regulator valve 104.
A solenoid pressure regulator valve 130 has a valve spool 132 biased by a spring 134 in one direction within the valve chamber. The spool 132 has lands 136, 138 formed thereon. A hydraulic passage 140 communicating directly with the discharge side of the pump carries hydraulic fluid through the orifice 142 into the chamber 144. Chamber 146 communicates with chamber 144 when the valve spool 132 is positioned as shown in FIG. 2. Fluid passage 148 carries hydraulic fluid from a chamber 146 to the second ON/OFF valve 300. The pressure transmitted in the passage 148 differs from the pressure of passage 140 to the extent that the orifice produces a pressure drop. The spring 134 acts to bias the solenoid pressure regulator valve 130 to the open position where chambers 144 and 146 are in communication.
At the opposite end of valve 130 is a pressure modulator valve 150. A modulator valve spool 152 is positioned intermediate lands 154, 156 and the spool 152 is similarly biased by the mechanical spring 158. The fluid passage 160 communicates chamber 162 with a manual valve 350. Fluid line 164 connects the outlet side of chamber 162 with the second solenoid valve 224. The passage 166 communicates with the line 164 and carries hydraulic fluid through an orifice 168 into the chamber 170 behind the land 154. Chamber 172 is supplied with hydraulic fluid by the passage 174 which communicates the passage 172 with the manual valve 350.
A first solenoid 180 is connected by the electrical line 182 to the output port of a microprocessor. When solenoid 180 is ON and chamber 192 is pressurized, solenoid valve spool 184 is caused to move axially downwardly within the valve bore. This occurs because in the ON state solenoid 180 opens chamber 210 thereby causing the pressure force on the end face of land 186 to exceed the force of spring 208. In the OFF state, chamber 210 can be pressurized through passage 212. The spool is formed with lands 186, 188, 190, which have equal cross-sectional areas in registry with corresponding lands formed in the valve bore. Chamber 192 communicates via passage 194 with the corresponding chamber in solenoid valve 224. Chamber 196 is supplied with hydraulic fluid from the first ON/OFF valve 270 by passage 198. The outlet side of chamber 196 communicates with the apply chamber 62 of the intermediate servo 54 by way of the fluid passage 200. A third chamber 202 communicates with the first ON/OFF valve 270 by way of hydraulic line 204 and the outlet end of chamber 202 communicates with the brake release chamber 60 of the intermediate servo 54 by the hydraulic line 206. The spring 208 acts is axial opposition to the force applied to the valve spool 184 when the solenoid 180 is ON. A fourth chamber 210 has solenoid valve pressure applied through the hydraulic line 212 after passing through the orifice 214. The pressure area of land 216 is greater than that of lands 186, 188, 190; therefore, when chamber 210 is pressurized and solenoid 180 if OFF, the valve spool 184 is positioned as shown in FIG. 2.
A second solenoid 220 is connected by an electrical line 222 to the output port of a microprocessor. When solenoid 220 is ON and chamber 232 is pressurized, valve spool 224 slides axially downwardly within the valve bore. This occurs because in the ON state solenoid 220 depressurizes chamber 252 thereby causing the pressure force on the end face of land 226 to exceed the force of spring 250. In the OFF state, chamber 252 can be pressurized through passage 256.
Spool 224 has three equally sized lands 226, 228, 230 formed thereon which are in registry with lands formed in the valve bore. A first chamber 232 is in communication with an end chamber 192 of the first solenoid valve via line 194. Chamber 232 is supplied by a passage 234 communicating with the second ON/OFF valve 300. A second chamber 236 is pressurized by the hydraulic line 164 communicating with the pressure modulator 150. The outlet side of the chamber 236 communicates with the low-reverse servo 84 by way of the passages 238, 240. A third chamber 242 is supplied with hydraulic fluid by the line 244 which directs the fluid through an orifice 246 before its admittance to the chamber 242. The outlet side of the chamber 242 is in communication with the first ON/OFF valve by the passage 248. A spring 250 biases the valve spool 224 into the position shown in FIG. 2 where the valve spool is at rest at the top of chamber 232. A fourth chamber 252 is supplied with hydraulic fluid from the second ON/OFF valve by the passages 254, 234, and 256, which direct the fluid through an orifice 258 before entering the chamber 252. A fourth land 260 has a larger diameter than the lands 226, 228, 230 so that when chamber 252 receives solenoid valve pressure, spool 224 is biased by the spring 250 and the presure force acting on the land 260 toward the position shown in FIG. 2.
Solenoids 180 and 220 are energized by way of the microprocessor control according to programmed logic within the microprocessor to control automatic shifting among the several forward speed ratios. Information concerning various engine parameters and operating variables is received by the microprocessor from sensors such as transducers. The control produces a signal that switches the solenoid to the ON state; lack of a signal produces the OFF state. In case of loss of electronic control, the system default produces the OFF state in the solenoids.
A first ON/OFF valve 270 has a valve spool 272 slideable within a valve bore and biased by a spring 274 into the position shown in FIG. 2. The spool has three lands 276, 278, 280, which are in registry with corresponding lands formed in the valve bore. A first chamber 282 is supplied with hydraulic fluid from the second solenoid valve by way of passages 238, 284. When chamber 282 is pressurized, the hydraulic pressure produces a force on the land 276 acting in opposition to the spring biasing force. When this pressure force exceeds the spring force, the valve spool 272 is moved toward the left-hand end of the valve bore. This movement has the effect of opening and closing selectively the various passages of the ON/OFF valve 270. A second chamber 286 is in communication with the second solenoid valve by way of the passage 248 and with the first solenoid valve by way of the passage 288. Axial shifting movement of the ON/OFF valve spool 272 will selectively open and close communication between passages 288 and 248 depending on the position of the land 276. A third chamber 290 is supplied with hydraulic fluid from the second ON/OFF valve 300 through the passage 292. Depending upon the position of the lands 278, 280, the passage 198 will communicate chamber 290 with chamber 196 of the first solenoid valve.
The second ON/OFF valve 300 has a valve spool 302 slideably moveable within the valve chamber. The spool has four equal diameter lands 304, 306, 308, 310, which are in registry with lands formed in the valve bore. A first chamber 312 located at one end of the valve bore is supplied with hydraulic fluid from the pump 24 by way of the manual valve 350 through the hydraulic passages 314, 354. The valve spool 302 is biased by a spring 316, which acts in opposition to the pressure force developed on the outer pressure area of the land 304 when the chamber 312 is pressurized. When chamber 312 is pressurized the valve spool 302 is shifted in the right-hand direction against the force of the spring. The ON/OFF valve 300 has a second chamber 318, which is pressurized from the pump 24 by way of the manual valve 350 and the passages 320, 352. Passage 292 communicates chamber 318 with chamber 290 of ON/OFF valve 270. A third chamber 322 communicates with chamber 242 of the second solenoid valve by way of the passage 244. Axial shifting movement of spool 302 will selectively connect the discharge side of the pump by way of the manual valve to the chamber 322. The lands on the valve bore in registry with lands 306, 308 are supplied with hydraulic fluid from the manual valve by the passages 324, 326, respectively.
A fourth chamber 328 is pressurized with solenoid valve pressure by way of the passage 148 when the valve spool 302 is moved in the right-hand direction upon chamber 312 being pressurized. When this shifting motion occurs, solenoid valve pressure is transmitted axially in the bore of the valve 300 and applies pressure to chambers 232 and 192 at the axial ends of the first and second solenoid valves. A fifth chamber 330 communicates via passage 332 with the manual valve 350. When chamber 330 is pressurized, the pressure force acting on the inner end of the land 310 cooperates with the spring force to cause the valve spool 302 to move in the left-hand direction to the position shown in FIG. 2.
The manual valve 350 has one exit passage 352, which communicates with passages 320 and 332 for input to the second ON/OFF valve 300, and a second exit passage 354 which communicates with passage 314, 324, 326 to the several chambers of the second ON/OFF valve 300. Exit passage 354 directs hydraulic fluid through passage 356 to the forward clutch 36 after passing through an intermediate orifice 37. An inlet passage 358 communicates the manual valve 350 with the discharge side of the pump 24. A crossover passage 360 carries hydraulic fluid between internal chambers of the valve 350. An outlet passage 362 carries hydraulic fluid from the manual valve 352 to the valve bore of the first ON/OFF valve 270.
The manual valve includes a spool 364 whose axial position within the valve bore is determined by the setting of the gear shift selector by the vehicle operator. The shift selector allows the manual valve spool to be located at any of six axial settings marked P,R,N,D,2 and 1. These settings correspond respectively to the drive ranges at which the vehicle operator may set the transmission, namely park, reverse, neutral, drive and two low-speed ratios also available within the drive range. The manual valve spool 364 has five equal size lands 366, 367, 368, 369, 370 formed integrally therewith. The lands are in registry with the valve bore and operate selectively to open and close passages from the manual valve to the rest of the hydraulic control system. The valve spool is shown in FIG. 2 in the park condition.
Internal chambers 372 and 374 communicate the valve bore 376 with the outlet passage 362. Similarly, internal passages 378, 380 communicate the valve bore 376 with the passage 160 that carries hydraulic fluid to the pressure modulator 150. Internal passages 382, 384 communicate the exit passage 354 with the valve bore 376.
In operation, the low-reverse servo 84, the intermediate servo 54, the forward clutch 36 and the reverse-high clutch 38 are selectively supplied with pressurized hydraulic fluid in order for the gear arrangement of FIG. 1 to function in the operating mode selected by the vehicle operator by way of his control over the gear selector which directly controls the manual valve setting. The operation of the hydraulic control circuit shown in FIG. 2 will be described with respect to pressurizing the servos 54, 84 and the clutches 36 and 38 that are required to produce nine operating modes of the transmission, presented in FIG. 3. These modes can be derived from the six manual valve settings.
To condition the transmission for a neutral operation, the manual valve is set to either the park or neutral positions. When the manual valve is set at P, land 369 blocks supply passage 358, which otherwise would connect the discharge side of the pump 24 with the manual valve. When the manual valve is set at N, passage 358 communicates the pump 254 with the valve bore 376, but the lands 368 and 369 seal the valve bore and effectively close off communication of the pump with the control circuit by way of the manual valve. When the selector is set at P or N, line pressure is carried in passages 116 through the orifice 124 to the chamber 114 of the line pressure regulator valve 104. However, due to the force of the solenoid 100, the spool 106 of the regulator valve 104 is at the axial end of the valve bore; therefore chamber 114 is closed. Line pressure is supplied by passage 140 through the orifice 142 to the solenoid pressure regulator valve chamber 144. Solenoid valve pressure is applied by passage 148 to ON/OFF valve 300, but because valve 300 is OFF, as indicated by the schedule of FIG. 3, passage 148 is closed. Consequently, neither servo 54 or 84 nor clutches 36, 38 are pressurized when the manual valve is set at P or N. Line pressure was reduced, however, by way of the orifice 142 and solenoid valve pressure was reduced accordingly to a lesser value than line pressure.
When the manual valve is set for the R range, the transmission is disposed for reverse operation. When the reverse-high clutch 38, the low-reverse servo 84 and the release chamber 60 of the intermediate servo 54 are pressurized the hydraulic control system will pressurize passages 206, 240 and 386 by the procedure next to be described. According to the schedule of FIG. 3, the first ON/OFF valve 270 is in the ON position for reverse operation, which locates the valve spool 272 within the valve bore at the left-hand end. The first and second solenoids 180, 220 can be either in the ON or OFF condition. Whether solenoids 180 and 220 are ON or OFF, valve spools 184 and 224 move to the top of their valve bores as shown in FIG. 2. The electrical signal for actuating the solenoids to the ON condition would, of course, be supplied from output port of the microprocessor.
The discharge side of the pump 24 communicates with the bore 376 of the manual valve 350 and flow passes through the crossover passage 360 to the opposite side of land 369. Discharge pressure passes through the bore 376 through the internal chamber 372 and into the passage 362 through which it is carried to the first ON/OFF valve 270. However, this valve is ON and the valve spool 272, in moving toward the left, causes the land 278 to allow discharge fluid to enter chamber 286 and to exit the ON/OFF valve 270 by way of the passage 288, through which it is directed to the first solenoid valve. Land 276 prevents flow from chamber 386 into the passage 248.
With the first solenoid 180 positioned as shown in FIG. 2, chamber 202 of the first solenoid valve is pressurized by passage 204 and is exhausted through passage 206, which directly flows to the release chamber 60 of the intermediate servo 54.
The discharge side of the pump 24 is connected by passage 116 through the orifice 124 to chamber 114. The variable force solenoid 100 is always ON, absent an electrical failure. Since chamber 118 is not pressurized, the line pressure regulator valve 104 is positioned as shown in FIG. 2. This position causes chamber 114 to be closed off. Passage 140 carries fluid from the pump 24 through the orifice 122 and into chamber 144 of the solenoid pressure regulator valve 130. Hydraulic fluid at a reduced regulator valve pressure exits chamber 144 through the passage 148 through which it is carried to the second ON/OFF valve 300. This valve is in the OFF state; therefore, land 310 blocks the passage 148 and solenoid pressure is not applied to the hydraulic circuit. The pressure modulator valve 150 is, however, pressurized from the discharge side of the pump by way of the manual valve 350 through the passage 174 which directs flow into chamber 162. Similarly, passage 160 is pressurized by way of the internal passages 378 and 380 of the manual valve 350. Passage 160 directs flow into chamber 162. Flow from chamber 162 is carried in passage 164 to the chamber 236 of the second solenoid valve, which for purposes of this discussion is in the OFF state. Therefore, flow leaves chamber 236 through the passage 238 and is carried by passage 240 to the low-reverse servo 84. Passage 238, in addition to providing flow to 240, also directs flow to passage 284 and to chamber 282 of the first ON/OFF valve 270. The effect of pressurizing chamber 282 is to place valve 270 in the ON condition which, as previously described, causes the release chamber 60 to be pressurized. Similarly, the reverse-high clutch 38 is pressurized through passage 386, which intersects with passage 206.
In order to condition the gear arrangement for automatic shifting among the three forward speed ratios, the manual valve 350 is set in the D condition. To produce the lowest speed ratio drive condition, operation of the hydraulic control circuitry is directed to pressurizing the forward clutch 36. The first ON/OFF valve 270 is OFF and the second ON/OFF valve 300 is ON. The first and second solenoids 180, 220 are switched ON by the control unit of the microprocessor. The forward speed ratio drive operation will result when only the forward clutch 36 is pressurized.
When the manual valve 350 is at the D setting, land 368 has moved to the right side of the inlet passage 358, which communicates the discharge side of the pump 24 with the valve bore 376. Fluid flows in the valve bore through the internal passages 382, 384 and exits the manual valve through exit passage 354. Passage 352 is closed OFF by the land 367. The second ON/OFF valve 300 is switched to the ON position when chamber 312 is pressurized through passage 314. Valve spool 302 is moved to the right-hand end of the valve bore which opens communication between chambers 319 and 318. Passage 292, therefore communicates chamber 318 with chamber 290 of the first ON/OFF valve 270, which is OFF. Passage 198 communicates chamber 290 with chamber 196 of the first solenoid valve. However, solenoid 108 is ON; consequently, spool 184 is moved downwardly toward the solenoid 180 causing land 186 to close chamber 196. Chamber 323 of the second ON/OFF valve 300 is pressurized through the passage 326. Since valve 300 is ON, chambers 322 and 323 are in communication and passage 244 communicates ON/OFF valve 300 with chamber 242 of the second solenoid valve through the orifice 246. However, in the low speed ratio drive condition, the second solenoid 220 is ON; therefore land 228 is moved downwardly to close the chamber 242. Passage 358 communicates the discharge side of the pump 24 with the exit passage 354 of the manual valve 350.
Passage 140 connects the discharge side of pump 24 with chamber 144 of solenoid pressure valve 130 through the orifice 142. Consequently, hydraulic fluid at a reduced solenoid pressure exits chamber 144 through the passage 148, which carries it to chamber 331 of the second ON/OFF valve 300. With this valve in the ON condition, solenoid valve pressure exits chamber 328 through passage 254, which distributes the flow through passage 212 and orifice 214 to chamber 210 of the first solenoid valve. Because solenoid 180 is ON, chamber 210 is depressurized and the pressure force on the end of land 186 overcomes the force of spring 208. A second path from ON/OFF valve 300 carries fluid at solenoid valve pressure through passage 234 to chamber 232 and through passage 194 into chamber 192. A pressure force is developed on the spools 184, 224 in opposition to the force of the springs 208, 250.
With the manual valve 350 in the D range the transmission is disposed for intermediate speed ratio operation by pressurizing the forward clutch 36 and the apply chamber 62 of the intermediate servo 54. The hydraulic control circuit operates to produce this effect by first communicating the discharge side of pump 24 with the manual valve 350, which directs flow into passage 354. Intermediate speed ratio is produced when the second ON/OFF valve 300 is ON, the first solenoid 180 is OFF and the second solenoid 220 is ON.
When chamber 312 is pressurized through the passage 314, spool 302 is moved in the right-hand direction in the opposition to the force of the spring 316. Consequently, passage 324 is brought into communication with passage 292 when the chamber 319 is cleared by land 306. Passage 292 opens flow to chamber 290 of the first ON/OFF valve 270, which is in the OFF position shown in FIG. 2. Accordingly, passage 198 carries hydraulic fluid from chamber 290 to chamber 196 of the first solenoid valve. Solenoid 180 is OFF; hence flow is open to passage 200 and flow proceeds to the apply chamber 62 of the intermediate servo 54. The third passage 326 exiting the manual valve 350 carries the hydraulic fluid into chamber 323, which in this condition is in communication with chamber 322 since the land 308 is cleared. Flow then proceeds in passage 244 into chamber 242 of the second solenoid valve. In this case, solenoid 220 is ON and spool 224 moving downwardly causes land 228 to move into registry with chamber 242 and to close that chamber against further flow.
The fourth passage 356 exiting the manual valve carries hydraulic fluid at pump discharge pressure directly to the forward clutch 36 through the orifice 37. In addition, passage 120 carries hydraulic fluid into chamber 118 of the line pressure regulator valve 104. Passage 116 also directs flow from the discharge side of pump 24 into chamber 114 after passing through the orifice 124. Passages 116 and 140 communicate the pump 24 with the chamber 144 of the solenoid pressure regulator valve 130 by way of orifice 142. Fluid at a reduced solenoid pressure flows from the chamber 144 in passage 148 to the second ON/OFF valve 300 which, in the ON condition, permits flow to proceed through passage 254, 232, 194 into chamber 234 and 192 of the second and first solenoid valves, respectively. Passage 212 intersecting with passage 254 directs flow through the orifice 214 and into chamber 210 of the first solenoid valve. However, since the solenoid 180 is OFF, solenoid valve pressure flow is closed off by the land 216.
The gear arrangement is disposed for direct speed ratio drive when the manual valve is placed in the D condition. In this condition it is necessary that the reverse-high clutch 38, the forward clutch 36, and the apply chamber 62 and release chamber 60 of the intermediate servo 54 be pressurized. As FIG. 3 indicates, in this condition the second ON/OFF valve 300 is ON. The first ON/OFF valve 270 is OFF and both the first and second solenoids 180, 220 are OFF.
Again, the manual valve 350, when placed in the D condition, directs flow from the discharge side of pump 24 through passage 354 and through passages 314, 324, 326, 356. Passage 314 again pressurizes chamber 312 of the second ON/OFF valve 300 causing the valve spool 302 to compress the spring 316 when it moves in the right-hand direction. This sliding action opens communication between passage 324 and 292 and flow proceeds into chamber 290 of the first ON/OFF valve 270. Flow exits chamber 290 through passages 198, which communicates with chamber 196 of the first solenoid valve. Since solenoid 180 is OFF, spool 184 moves upward and communication is possible within chamber 196 between passage 198 and passage 200, which communicates directly with the apply chamber 62.
A third passage 326 connecting with passage 354 exits the manual valve and carries flow into chamber 323 of the second ON/OFF valve 300. Because land 308 has moved to the right, the net pressure forces on lands 228 and 260 add to the force of spring 250 whereby flow proceeds in passage 244 through orifice 246 and into chamber 242 of the second solenoid valve. Because solenoid 220 is OFF, communication between passages 244 and 248 is possible through the chamber 242. Passage 248 directs flow into chamber 286 of the first ON/OFF valve 270. Flow is unobstructed within the valve and exits the valve through passage 288 and 204, which communicate with chamber 202 of the first solenoid valve. Solenoid 180 is OFF, therefore, chamber 202 permits flow to exit the valve through passage 206 which communicates directly with the release chamber 60 of the intermediate servo 54. Passage 386 intersects with passage 206 and pressurizes the reverse-high clutch 38.
Passage 356 is supplied by passage 354 on the exit side of the manual valve and communicates the discharge side of pump 24 with the forward clutch 36 after passing through the orifice 37.
Passage 120 intersects with passage 356 and pressurizes chamber 118 of the line pressure regulator valve 104. This produces a pressure force on the face of land 108, which force acts in opposition to the force of the variable force solenoid 100. As has previously been described with respect to the other D-range conditions, passage 140 communicates the discharge side of pump 24 with chamber 144 of the solenoid pressure regulator valve 130. A pressure drop occurs across the orifice 142 and a reduced pressure flow exits chamber 144 through passage 148, which communicates with chamber 330 of the second ON/OFF valve 300. Because valve 300 is ON, flow exits valve 300 through passage 254, which communicates through passage 212 with chamber 210 of the first solenoid valve. Similarly, chamber 252 of the second solenoid valve is pressurized through the line 256. Because solenoids 180 and 220 are OFF, chambers 210 and 252 are closed by the lands 216 and 260, respectively.
The transmission will operate at intermediate speed ratio when the manual valve 350 is placed in the 2 range. In this case, the forward clutch 36 and the apply chamber 62 of the intermediate servo 54 are pressurized. The first and second ON/OFF valves 270, 300 are OFF and the first and second solenoids 180, 220 may be either ON or OFF.
Passage 358 communicates the discharge side of pump 24 with the bore 376 of the manual valve 350. Flow is conducted through internal passage 384 to the exit passage 354 which distributes the flow to passages 314, 324, 326 and 356. As in previously described conditions, passage 356 pressurizes directly the forward clutch 36 after passing through the orifice 37. Passage 120 pressurizes chamber 118 of pressure regulator valve 104. A force is produced on the face of land 108 in opposition to the force of the variable force solenoid 100.
Within the manual valve 350 flow passes through the internal passage 382 along the bore 376 to the exit passage 352, which dircts flow through passage 320 into the chamber 318 and through passage 332 into chamber 330 of the second ON/OFF valve 300. When chamber 330 is pressurized, valve 300 is turned OFF and spool 302 is moved in the left-hand direction for the position shown in FIG. 2. When this occurs, land 306 is brought into registry with the end of duct 324 and flow in that duct is closed. However, chamber 318 then communicates with chamber 290 of the first ON/OFF valve 270 by way of duct 292. Passage 198 communicates chamber 290 with chamber 196 of the first solenoid valve. Whether solenoid 180 is ON or OFF, spool 184 is moved by spring 208 to the position shown in FIG. 2 and chamber 196 is in communication with the apply chamber 62 of the intermediate servo 54 by way of passage 200. Since the second solenoid valve is not pressurized, solenoid 220 may be ON or OFF without altering the result.
Although chamber 312 is pressurized by duct 314, valve 300 is OFF because an equal but oppositely directed force is produced on the face of the land 310 to that of the land 304 and the force of the spring 316. Passage 326 is closed by land 308 of valve spool 302.
Passage 116 again communicates the discharge side of pump 24 through the orifice 142 with chamber 144 of the solenoid pressure regulator valve 130. A reduced solenoid pressure flow exits chamber 144 through the passage 148, which is closed by land 310.
With manual valve 350 set at the 1 position, the transmission will operate at the low speed ratio when the forward clutch 36 and the low-reverse servo 84 are pressurized. To produce this result, solenoids 180 and 220 are OFF and ON/OFF valves 270 and 300 are ON.
Passage 358 communicates the discharge side of pump 24 with bore 376 of the manual valve 350. Flow exits valve 350 through passage 354, but passage 352 is closed from communication with bore 376 by land 367. Chamber 312 of ON/OFF valve 300 is pressurized through passage 314 and a pressure force is produced on the face of land 304 acting in opposition to the force of the spring 316. The pressure force exceeds the spring force and the spool 302 is moved in the right-hand direction to the ON position. Accordingly, communication is open between passage 324 and passage 292. Chamber 323 of valve 300 is pressurized through passage 326 and communication is open between passages 326 and 244 because land 308 is displaced from its blocking position. Chamber 242 of the second solenoid valve allows communication between passage 242 and passage 248. Passage 248 is closed by land 276 when ON/OFF valve 270 is moved leftwardly.
The leftward shifting of valve spool 272 occurs when passage 160 is supplied from the discharge side of pump 24 through supply passage 358, crossover passage 360, bore 376 and internal passages 378, 380. Chamber 162 of the pressure modulator valve 150 is thereby pressurized and flow exits the valve through passage 164 by which chamber 236 of the second solenoid valve is pressurized. Because solenoid 220 is OFF, the net pressure forces on lands 226 and 260 add to the force of spring 250 whereby chamber 236 is in communication with chamber 282 of the first ON/OFF valve 270 through the passage 284. In this way, a pressure force is developed on the face of land 276 acting in opposition to the force of spring 274. The pressure force exceeds the force of the spring, hence ON/OFF valve 270 is biased to the ON condition. The exit passage 238 from chamber 236 intersects passage 240, through which hydraulic fluid pressure is applied to the low reverse servo 84.
A fourth passage supplied from exit passage 354 of manual valve 350 is passage 356, which pressurizes the forward clutch 36 through the orifice 37. As in other selector settings, passage 120 pressurizes chamber 118 at the end of the line pressure regulator valve 104 and produces a force on the face of land 108 acting in opposition to the variable force solenoid 100. Passages 116 and 140 direct hydraulic pressure from the discharge side of pump 24 through the orifice 142 and into the chamber 144 of the solenoid pressure valve 130. A pressure drop occurs across orifice 142 and fluid at reduced solenoid pressure exits chamber 144 through passage 148. ON/OFF valve 300 allows the solenoid pressure to flow from passage 148 into passage 254, which directs flow into chamber 210 of the first solenoid valve after passing through orifice 214. Similarly, passage 256 pressurizes chamber 252 of the second solenoid valve. However, because both solenoids 180 and 220 are OFF, lands 216, 260 close chambers 210 and 252, respectively.
With the manual valve placed at the 1 position, the transmission is disposed for intermediate speed ratio when the apply chamber 62 of the intermediate servo 54 and the forward clutch 36 are pressurized. The hydraulic control system will produce this effect when ON/OFF valve 270 is OFF, valve 300 is ON, solenoid 180 is OFF and solenoid 220 is ON.
Again, the discharge side of pump 24 communicates with the manual valve 350 through the passage 358. Flow exits the manual valve through passage 354, but passage 352 is closed by land 366. The forward clutch 36 is pressurized through passage 356 directly from passage 354. ON/OFF valve 300 is turned ON when chamber 312 is pressurized through passage 314. A pressure force is produced on a face of land 304 in opposition to the force of spring 316, which causes the spool 302 to move in the right-hand direction of FIG. 2. When this occurs, passage 324 is in communication with passage 292 through chamber 319 of the valve 300. Chamber 290 of the first ON/OFF valve 270 is pressurized by passage 292. Flow exits chamber 290 by way of passage 198, which pressurizes chamber 196 of the first solenoid valve. Because solenoid 180 is OFF, communication is open between passage 198 and passage 200, which pressurizes the apply chamber 62 of the intermediate servo 54.
Because of the ON position of valve 300, passage 326 is in communication with passage 244, which directs flow through the orifice 246 and into chamber 242 of the second solenoid valve. But because solenoid 220 is ON, land 228 closes off passage 242 and there is no exit flow.
A pressure force is produced on the face of land 108 when chamber 118 of the line pressure regulator valve 104 is pressurized through passage 120. The pressure force acts in opposition to the force of the variable force solenoid 100.
Passages 116 and 140 communicate the discharged side of pump 124 with chamber 144 through the orifice 142. Fluid at a reduced solenoid pressure exits chamber 144 through passage 148. ON/OFF valve 300 opens communication between passage 148 and passages 212, 234. Passage 212 directs flow through the orifice 214 into chamber 210 of the first solenoid valve, but land 216 closes off chamber 210. Similarly, chamber 252 of the second solenoid valve is pressurized through passage 256, but land 260 closes off chamber 252 from exiting flow. Fluid at solenoid pressure is supplied by passages 234 and 194 to chambers 232 and 192 at the ends of the second and first solenoid valves, respectively. Pressure forces are produced on the faces of lands 226 and 186, which forces act in opposition to the force of springs 250 and 208, respectively.
For operation with the manual valve in the 1 range, a pressure switch 390 connected to passage 386 or a potentiometer (not shown) mounted on the manual valve will produce a signal if pressure to the reverse-high clutch 38 is lost. The signal will cause the micropressure to turn ON solenoid 220. This will enable a more moderate shifting from the direct speed ratio if, for example, pressure is lost while driving down a hill and engine braking is required. In this case, the manual valve can be shifted from the D range directly to the 1 range. The transmission will shift from the third speed through the second speed ratio to first gear.
From the foregoing description and with reference to the schedule of FIG. 3, it can be seen that low speed ratio, intermediate speed ratio, direct speed ratio and reverse speed ratio can be produced by moving the manual valve to the desired setting, even if power and control from the control unit of the microprocessor is lost. Upon loss of electronic control, the microprocessor defaults to a zero current condition, which action effectively turns OFF solenoids 180, 220 and 100. In the event of loss of electronic control, in order to produce low speed ratio operation, the manual valve is placed at the 1 setting and the hydraulic control system will produce the low speed ratio as has been described. By shifting the manual valve to the 2 position, the intermediate speed ratio can be produced because solenoids 180 and 220 can be in the OFF condition and the transmission will operate at the intermediate speed ration. Upon loss of electronic control, the direct speed ratio is produced when the manual valve is placed at the D position. Similarly, to produce the reverse speed ratio, the manual valve is set at the R position. Reverse speed ratio is possible because solenoids 180 and 220 can be OFF for this mode of operation.
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A manual selector valve, whose setting is controlled by the vehicle operator, distributes flow from a fluid pump to an ON-OFF valve and to a hydraulic clutch which on being engaged disposes the transmission for forward drive. Two ON-OFF valves act as pressure distributors and enable the manual valve to overrule the operation of the automatic shift valves. The state of two solenoid-actuated valves is determined by an electrical signal received from a microprocessor that receives operational information and has stored within its memory logic that controls the signals. If the electronic control system should fail, the state of the solenoid valves is determined hydraulically and mechanically thus permitting complete functional response as the operator manually displaces the selector valve. A variable force solenoid actuates a line pressure regulator valve, which cooperates with a solenoid pressure regulator valve to reduce line pressure. A pressure modulator valve directs manual valve outlet flow to the solenoid valves, which function as shift valves.
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FIELD OF INVENTION
This invention relates to a method of laying floor tile and to the resulting assembly of floor tiles.
PRIOR ART
Witt et al U.S. Pat. No. 3,988,187 describes a method of applying floor tiles in which, throughout a central portion of the floor, there is not any conventional adherence of tiles to the subflooring and in which there is not any conventional adhesion of vertical walls of adjacent tiles to each other to bond together all of the tiles of the central portion for use as a flooring. The system works well and represents an outstanding commercial success. However, there have been some difficulties attributable to long term effects of fluctuations of humidity and/or temperature. In floors having uniform size tiles and laid in a staggered arrangement, it was discovered that if there was a malfunction, such malfunctioning usually occurred along a path of adhesion extending essentially as a straight line across the central portion of the floor of U.S. Pat. No. 3,988,187.
Heretofore there have been artistic designs for flooring utilizing a plurality of sizes of tiles. Such arrangements of the various sized tiles merely served aesthetic purposes as distinguished from efforts to solve engineering problems. Notwithstanding the great variety of suggestions of aesthetic patterns, the flooring industry continued to be faced with problems in meeting the desiderata of simplicity of application of the floor tiles and long term troublesome free maintenance of the thus laid flooring.
SUMMARY OF THE INVENTION
In accordance with the present invention, the paths of the boundary lines on both rectangular directions are staggered and offset so that there is no straight line portion longer than about one and one-half tile lengths. By thus having adequate staggering and offsetting in both directions, the adhesion of the tiles has greater durability and better withstands the fluctuations of humidity, temperature and other variables to decrease the likelihood of the opening of any gap between tiles. Such double staggering is achieved by the use of an equal number of large and small rectangular tiles, the two dimensions of the larger tiles being each twice that of the smaller tiles, i.e. the larger tile has an area which is four times that of the smaller tile. By using the combination of an equal number of smaller tiles and larger tiles so that approximately 20% of the area is covered by the smaller tiles and about 80% by the larger tiles, and by providing the combination of larger tile and smaller tile adjacent each edge of each large tile, the desired engineering effect of double staggering of the boundary lines is achieved. In the central zone of a floor (ignoring the exceptions inherent near the walls of a room) each larger tile on each of its four boundaries is bounded to be both a larger tile and a smaller tile.
The invention concerns a method of applying floor tiles to a subflooring for an area which includes the steps of
preparing a set of smaller rectangular floor tiles having a predetermined length and a predetermined width, each tile having overhanging-underfitting relationship of straight line boundary portions which in the unadhered conditions permit two adjacent tiles to be slideably adjustable with respect to each other;
preparing a set of larger rectangular floor tiles having a predetermined length substantially twice the length of said smaller tile and having a predetermined width substantially twice the width of said smaller tile, each tile having overhanging-underfitting relationship of straight line boundary portions which in the unadhered condition permits two adjacent tiles to be slideably adjustable with respect to each other;
applying floor tiles to a central portion of a subflooring, said tiles being adhered to each other only at the overhanging-underfitting zones, while retaining vent paths for the diffusion of moisture to permit the moisture content of the subflooring and the moisture content of the atmosphere to equilibrate readily in such central area because of not using conventional adhesive relationship of the floor tiles and subflooring throughout such central area, a gas permeation zone being maintained between the vertical walls of adjacent tiles, there being no adhesion between said vertical walls;
staggering the distribution of a substantially equal number of said smaller tiles and said larger tiles in said central area whereby any path of adhesion across the central portion in either of two rectangular directions has numerous offsets and staggers involving no continuous line longer than about one and one-half lengths of a larger tile, each larger tile on each of its four sides having the adhesive overhanging-underfitting bonding with a portion of at least one other larger tile and with at least a portion of a smaller tile, said staggering of the adhesion of the overlapping-underlying boundary portions without adhesion to the subflooring imparting greater resistence to buckling, separation of adjacent tiles and related long term malfunction stimulated by fluctuations of humidity and temperatutre than attained for the similar adhesion of the overlapping-underlying boundary portions of rectangular tiles of substantially uniform size when laid without adhesion to the subflooring.
The nature of the invention is further clarified by the description of some preferred embodiments.
DESCRIPTION OF DRAWINGS
FIG. 1 is a perspective view of an underfitting floor tile having overhanging-underfitting boundary portions.
FIG. 2 is a cross-sectional view of a portion of the tile of FIG. 1.
FIG. 3 is a perspective view of a room in which the tiles of a central portion are held together by the adhesion in the overlapping-underlying portions of the boundary portions of the adjacent tiles.
FIG. 4 is a schematic top view of a two-way staggering of small and large tiles.
FIGS. 5 and 6 are exploded views of the tile arrangements of FIG. 4 showing absence of straight line glue lines across layout.
DESCRIPTION OF PREFERRED EMBODIMENTS
Reference is made to Witt et al U.S. Pat. No. 3,988,187, all the disclosure of which is deemed here reiterated. Said Witt et al patent discloses a method of laying floor tile in the central portion of a subflooring by adhering marginal portions of adjacent tiles to each other at the overhanging-underfitting portions of such tiles. The equilibriation of moisture between the atmosphere and the subflooring is attained because of the venting paths between the subflooring and the atmosphere through the gaps existing where tiles abut. This advantageous bonding of adjacent tiles does not require any adhesion of the tile to the subflooring or any adhesive between abutting vertical walls of adjacent tiles.
Said system has been generally satisfactory and represents a significant commercial success. However, in some instances difficulties have been encountered by reason of the propensity of floor tiles to undergo dimensional changes when subjected to fluctuating humidity and fluctuating temperature. Under adverse conditions, some de-adhesion has occurred, thus stimulating efforts to minimize the possibility of de-adhesion.
As shown in FIG. 1, a floor tile 110 comprises a resilient layer 111 and a top attrition resistent layer 114. A wafer board layer comprising two strata 149 and 152 makes feasible tongue and groove fittings between adjacent tiles. The depth of groove 154 is less than the magnitude of the overhang 151 of an adjacent tile.
Only a tip of overhang 151 is inserted as a tongue 153 into groove 154, leaving a wide potential bonding zone 166 on the undersurface of overhang 151. Similarly underfitting boundary zone includes a potential gripping zone 165 which could be adhesively secured to a potential bonding zone 166 of an overhanging portion of an adjacent tile.
The use of a tongue 153 and groove 154, though desirable, is optional, inasmuch as the adhesion bonding between a bonding zone 166 and gripping zone 165 of adjacent tiles can glue the tiles together. A tile lacking the tongue and groove but having a potential gripping zone and a potential bonding zone can be comprehended as a modification of the tile shown in FIG. 2.
It is sometimes desirable to employ a film 156 of pressure sensitive adhesive along at least a portion of the three walls (top wall 161, rear wall 152, and bottom wall 163) of groove 154. Thus the tile can be shipped from the factory with the pressure sensitive adhesive at appropriate locations (e.g. top wall 161 and bottom wall 163 of groove 154) but without any protective paper thereover. It is only when the floor is being laid and tongue 153 is inserted in the groove 154 that the pressure sensitive adhesive encounters a surface to which it can bond. The remote location of the pressure sensitive adhesive permits convenient handling of the tiles prior to the laying of the floor. Using paper protection for a film or pressure sensitive adhesive, such adhesive can be on the gripping zone 165 for potential bonding with a bonding zone 166 of an adjacent tile, but no drawing of this comprehensible modification is necessary.
It is sometimes appropriate to employ a brushed on adhesive which can be applied to a potential gripping zone 165 on an underfitting boundary portion just prior to the positioning of a corresponding portion 166 of the overhanging boundary portion of an adjacent tile whereby a relatively wide band of adhesive can be effective in securing adjacent tiles together.
As shown in FIG. 3, a room 30 has walls 31 and 32, and a subflooring 33. A plurality of larger floor tiles 310 and smaller tiles 410, and intermediate sized tiles 510, corresponding generally to the floor tile described in connection with FIGS. 1 and 2, are laid so that the tiles are held together predominantly by reason of the adhesion at the overhanging-underfitting zone. The overlapping lip of a tile is pressed against boundary portions of an adjacent tile. The boundary portion is desirably coated with an adhesive to make such boundary portion a part of a path of adhesive. In this manner each tile is adhered to a plurality of adjacent tiles.
At the periphery of the room, where tile trimming is ordinarily required, the bottommost layer of the tile can be adhered to the subflooring, thus providing at least a partial anchoring of the entire floor system to subflooring while still permitting most of the floor tiles to retain a controlled amount of independent vertical resiliency of the type not readily achieved when each floor tile is adhered to the subflooring.
As shown in FIG. 4, a plurality of sizes of floor tiles must be employed. The length and width of a larger tile 310 are each essentially twice that of the smaller tile 410 so that the area of the attrition resistent top layer of the larger tile is four times that of the smaller tile. It should be noted that the marginal or boundary portions of the smaller tile have the same width as the boundary portions of the larger tile so that there can be interchangeability of interfitting.
Particular attention is directed to FIGS. 4, 5, and 6 in which an assortment of approximately an equal number of small tiles and large tiles are adhered to each other so that the boundary path across the zone is staggered in each of the two rectangular directions. Such double staggering of the paths of the adhesive bonding enhances the engineering strength of the flooring so that there is less propensity for any de-adhesion when subjected to the forces of contraction and expansion attributable to fluctuations of humidity and/or temperature. Moreover, settling of foundations and/or other modifications of the structure sometimes impose strains upon a flooring tending to urge the flooring to the bulging or opening along a gap. The double staggering of the tile arrangement of FIGS. 4, 5, and 6 significantly decreases the possibility of such strains leading to an actual de-adhesion of the adjacent tiles and helps maintain the bonded together structure of the pattern of floor tiles. At the periphery of the room, intermediate sized tiles 510 may be used, but two small tiles can be substituted for intermediate sized tiles.
Various aesthetically attractive patterns are feasible for the double staggering path of adhesion across the central portion of a flooring using the combination of larger tiles and smaller tiles of the present invention.
Various modifications of the invention are possible without departing from the scope of the appended claims.
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Changes in temperature and humidity over a long period of time lead to propensities for breaking the adhesive bond between adjacent tiles when the tiles are adhered together only at underfitting-overhanding boundary zones. Propensities for such malfunctioning are minimized by providing two sizes of tiles and laying the rectangular tiles so that in both rectangular directions, the adhesive paths across the floor area are not straight lines, but have offsets and staggers so that there is no straight line of adhesion longer than the length of one and one-half large tiles.
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This is a continuation of application Ser. No. 350,967, filed Apr. 13, 1973, and since abandoned.
BACKGROUND OF THE INVENTION
In all but rare instances, any industrial pneumatic system requires that the supply pressure be stepped-down and regulated at some lower working pressure. In addition, the air itself must be filtered to remove entrained moisture and other impurities while lubricants are often added to keep those pneumatic tools and other devices operated thereby properly oiled. The ordinary pneumatic system, therefore, requires not one, but several, lubricators, filters system pressure regulators located at various points downstream of the supply.
In the past, individual components have been serially connected into the supply line wherever needed. Each such component customarily required several fittings such as reducers, elbows, nipples, couplings and the like to integrate same into the existing air supply. Not only was such a procedure time-consuming and expensive, the individual components became difficult to service, repair or replace, oftentimes resulting in a complete shutdown of the system for protracted periods. Even mounting the components on the wall or other supporting surface was oftentimes done in a haphazard fashion thus resulting in an insecure as well as unsightly assemblage of uncoordinated parts.
It is the principal object of the present invention to provide a novel unitized filter-lubricator or filter-regulator-lubricator unit for use in pneumatic systems.
A second object is to provide a device of the type aforementioned that is reversible end-for-end to accommodate flow in either direction.
Another object of the invention is to provide a filter-lubricator unit with a partially-completed regulator section that can be either by-passed or rendered operative by finishing the incomplete passages and adding an adjustable control valve.
Still another objective of the invention is the provision of a combination unit wherein the manifold carries most, if not all, of the working parts of both the filter and lubricator while a detachable bowl carrying subassembly carries the gage and is reversible relative thereto.
An additional object is to provide an integrated multi-component combination air service unit for pneumatic systems that includes special wall mounts which enable it to integrate into any of the common sized air lines or to be removed therefrom by relatively unskilled persons using simple tools and with a minimal interruption in service.
Further objects are to provide a combination filter-regulator-lubricator unit for air lines that is simple, compact, easy to service, versatile, relatively inexpensive, rugged, dependable, efficient and decorative.
Other objects and advantages of the present invention will become apparent as the description of the present invention proceeds taken in conjunction with the description of the drawings that follows, and in which:
FIG. 1 is a perspective view looking down and to the right at the combination filter-regulator-lubricator unit of the present invention arranged such that flow is from lower left to upper right;
FIG. 2 is a top plan view to an enlarged scale with portions broken away to conserve space and other portions broken away and shown in section;
FIG. 3 is a longitudinal half section of the combination unit illustrated in FIG. 1 but to approximately the same scale as FIG. 2 and showing a different wall-mounting bracket than the latter;
FIG. 4 is a fragmentary transverse section taken along line 4--4 of FIG. 3 and with a portion broken away to more clearly reveal the interior construction;
FIG. 5 is a half section like FIG. 3 and to the same scale as the latter showing a modified version of the unit in which the regulator section has been eliminated and a cap substituted for the control valve;
FIG. 6 is a fragmentary transverse section similar to FIG. 4 but of the FIG. 5 modification taken along line 6--6 of the latter Figure; and,
FIG. 7 is an exploded half section similar to FIG. 3 and to the same scale differing therefrom only in that the manifold has been reversed end-for-end such that the flow is from right to left.
SUMMARY OF THE INVENTION
It has now been found in accordance with the teaching of the instant invention that these and other shortcomings of the prior art pneumatic systems can, in large measure, be overcome by the simple, but unobvious, expedient of combining at least a filter and lubricator, and preferably a regulator also, into a single unitized assembly. By specifying the proper set of wall-mounting brackets, the unit will integrate with all the common sizes of air lines with simple threaded connections being all that are required at its inlet and outlet ends. Not only do these brackets provide for a sturdy and decorative wall mounting, they also permit the entire unit to be quickly and easily detached therefrom with a minimum of down-time in case replacement or repair becomes necessary. Periodic servicing such as cleaning of the bowls can be accomplished even more quickly by merely detaching the bowl-carrying subassembly from the manifold.
The manifold can be reversed end-for-end to accommodate air flow in either of two opposite directions and the bowl-carrying subassembly is symmetrical about a transverse centerline thus making it reversible relative to the latter. While the bowls themselves are usually identical and will, therefore, accommodate either the filter or the lubricator, they are also removable and interchangeable so that they needn't necessarily be alike. For example, one could include an automatic drain of some type while the other has a manual one or none at all.
Finally, the manifold is designed with partially-completed porting which, upon completion, will integrate a regulator into the assembly. If the customer chooses to eliminate the regulator and purchase only the filter and lubricator, the partially-completed porting is left closed and the regulator subsection is by-passed while certain appurtenances necessary to the regulating function, like the control valve, are eliminated in favor of an inexpensive cap that produces a finished appearance. The pressure gage is left in the unit to monitor the air pressure.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The combination unit embodying the present invention has been broadly designated by reference numeral 10 and includes a manifold subassembly 12 and a bowl subassembly 14 detachably connected to one another in a manner which will be set forth in greater detail presently. The manifold subassembly is, in turn, subdivided into sections, the first being the filter section 16 and the last the lubricator section 18 with the regulator section 20 located therebetween when rendered operative, otherwise, the latter section is by-passed. Even when center section 20 does not include a pressure regulator 22, a pressure gage 24 is preferably connected to communicate with the air flowing therethrough in the manner indicated in FIG. 6. On the other hand, when pressure regulator 22 is included as a part of the combination unit as shown in FIGS. 1, 3, 4 and 7, this same gage 24 is connected to indicate the secondary pressure in the downstream side of the latter as seen in FIG. 4.
The bowl subassembly 14 comprises an open-tapped shell 26 or housing having a front wall 28, a rear wall 30 and right and left side walls 32R and 32L, respectively, all of which cooperate to produce a bowl guard. These walls are vertically-slotted to define windows 34 which open upon the bowls 36R and 36L located immediately therebehind. In addition, the front wall 28 has a centrally-located circular window 38 opening onto the dial of gage 24. Since this gage stays with the bowl subassembly 14 even though the manifold 12 is reversible end-for-end relative to the latter, the dial always faces the front.
Extending transversely of the bowl subassembly is a partial partition wall 40 in which is defined an integral preformed passage 42 which communicates between the pressure-responsive element (not shown) of a gage 24 with the main air passage 44 of the manifold 12. This partition wall 40 also supports a compression spring 46 of the regulator when one is included. The bowls 36R, 36L are retained in the shell 26 by means of integrally-formed upstanding posts 48 (FIGS. 3-7) which receive threaded screws 50, the heads 52 of which overhang the rims 54 of the bowls.
Generally cup-shaped integral webs bridge the gaps left between the partition wall, the front and rear walls, and the adjacent side walls to define a pair of partial bottom walls 56R and 56L in supporting relation to their respective bowls. These bottom walls each have an opening 58 therein sized to receive the petcock 60 or other element of similar nature provided in the bottom of the bowl for the purpose of draining fluid therefrom.
As can be seen with specific reference to the exploded view of FIG. 7, the entire bowl-carrying subassembly 14 is symmetrical about a transverse centerline such as that upon which the sections shown in FIGS. 4 and 6 are taken. As so constructed, the bowl subassembly will mate with the manifold subassembly 12 either with the filter on the left as shown in FIGS. 1 and 5 or on the right as shown in FIG. 7. Furthermore, the foregoing relationship can be achieved regardless of whether the combination unit includes regulator 22 or not, the only difference insofar as the bowl subassembly is concerned being whether the compression spring 46 is left out.
It will be noted, with reference to FIGS. 3, 5 and 7, that both bowls 36L and 36R are identical transparent plastic bowls ones with conventional screw-type petcocks 60 in the bottom. While such an arrangement is preferred in that it contributes to the versatility of the combination unit, it is by no means essential because the bowls are both removable and interchangeable in the shell 26. This means, of course, that other well known types and styles of bowls can be substituted for one or both of those shown and such is contemplated within the teaching found herein. Similarly, other types of drain valves including automatic valves can be substituted for the petcocks 60 shown.
The construction of the manifold subassembly 12 is shown in detail in FIGS. 3, 4, 5 and 6. The main body 62 of the manifold is a cast unit having an internally-threaded inlet 64 adjacent the filter section 16 and a similarly designed outlet 66 at the opposite end by the lubricator section 18. Both the inlet and outlet are preferably made one standard size say, for example, 1/2 inch while the mounting brackets 68 include a passage 70 therethrough that adapts same to whatever size of supply line piping is in use. By way of example, FIGS. 3, 5 and 7 show the mounting bracket 68 on the inlet end of the manifold as having a 3/8 inch upstream tap widening out to a full 1/2 inch at its downstream end. These same Figures show the bracket on the outlet end of the manifold as having a 1/2 inch upstream entryway reduced down to a 3/8 inch downstream end. Obviously, this has been done only for purposes of illustration and is not intended as being exemplary of the unit in actual use where, under all but rare circumstances, the supply piping will be the same size entering as leaving the unit. It should suffice to point out that a proper choice of mounting brackets enables the user to integrate the combination unit into his supply line without resorting to special fittings even though it is different than that of the manifold.
As shown in FIGS. 1 and 2, the mounting or wall brackets 68 are detachably secured to the inlet and outlet ends of the manifold by bolts 72. Each bracket has a pair of slotted ears 74 at its rear extremity that enable same to be fastened to the wall or other supporting surface in the usual manner. The faces 76 of the brackets that mate with the ends of the manifold 12 each include an O-ring groove encircling the adjacent end of passage 70 therethrough and in which is mounted a conventional O-ring seal 78. The brackets 68 are mounted on the supporting surface in position such that they can be drawn up tight against the ends of the manifold with bolts 72. In the event the unit needs to be replaced or serviced, these brackets will almost always yield enough play to permit the manifold to be slipped easily from its position therebetween, whereupon a standby manifold can be connected up and the system returned to service almost immediately.
The main body 62 of the manifold as shown in FIGS. 1, 2, 4 and 6, includes integrally-formed overhanging flanges both front and rear that have been designated by reference numerals 80 and 82, respectively, and which mate with the upper marginal edges of shell 26 to form a lid therefor. Also depending from the underside of the main body of spaced-apart the manifold are a pair of integrally-formed annular skirts 84L and 84R, both of which are shown centered with respect to the front and rear margins thereof as well as being spaced equidistant on opposite sides of its transverse centerline. Each of these skirts is bordered by an annular O-ring groove 86 containing the usual O-ring seal 88 that, upon entering one of the bowls 36, forms a fluid-tight seal therewith when the bowl-carrying subassembly 14 is in assembled relation on the manifold 12 as shown in FIGS. 3 and 5.
Interposed between these two annular skirts 84 in essentially tangential relation thereto is a third skirt 90 shown in each of the FIGS. 3-7, inclusive. The inside of this skirt is cylindrical and, as such, defines the cylinder within which piston 92 of the regulator 22 reciprocates as shown in FIGS. 3, 4 and 7. This piston is normally biased upwardly by compression spring 46 that is retained by an upstanding hollow vertically-slotted post 94 formed integral the horizontal portion 96 of the partition wall 40 in the shell 26.
Referring to FIGS. 3, 5 and 7, a filter component is broadly referred to by reference numeral 98 and a lubricator component is similarly referred to by reference numeral 100. The filter component of the combination is of a conventional construction and the particular form illustrated is but one version of several such air line filters that are commercially available. The same is true of the lubricator 100, although the particular lubricator 102 that has been shown incorporates a number of novel features not found in the prior art regulators. For present purposes, therefore, it should suffice to point out that filter 98 and lubricator 100 are intended as being merely representative of many such filters and lubricators that may be utilized in the filter and lubricator sections 16 and 18 of the combination unit. Air enters the manifold 12 through inlet 64 where it passes into annulus 104 before passing over the baffles 106 of the filter 98 and through filter cartridge 108 that cooperate in the usual manner to remove the water and entrained particulate matter therefrom, the fluid constituents dropping down into the bottom of the bowl 36L encasing the latter for subsequent removal. The filtered air then passes up into central cavity 110 of the manifold where it is discharged through port 112 of the main air passage 44 into the regulator section 20.
In the regulator section 20, the filtered air is either reduced in pressure to a preselected value or sent directly to the lubricator section 18 without having its pressure reduced. Ultimately, in either instance, the air emerges from port 114 in the regulator section 20 of the main air passage 44 and is discharged into the lubricator section 18 of the manifold 12.
In the particular lubricator 100 shown, the main flow of air is through section 116 of the main air passage 44 in the manifold, restricted orifice 118 of movable element 120, and outlet 66. In the event downstream demands exceed the volume of air that can pass through passage 118, movable element 120 will actuate to allow the necessary increment of additional air needed to satisfy the demand pass around the orifice without picking up any oil. Upstream of valve element 120 some air is bled off through bypass 122 where it passes through an ordinary tire valve housed underneath the fill plug and down into the bowl which will be partially filled with oil. Oil is forced up the syphon tube 124 by the positive air pressure in the bowl where it eventually emerges in dome 126 through drip tube 128 after having passed through passages in the manifold that have not been illustrated. Oil from the drip tube moves down into intersecting passage 130 where it enters the high velocity air stream passing through orifice 118 and is dispatched downstream in the form of a fine mist.
Once again, no particular novelty is ascribed to the lubricator shown as it is intended as being merely illustrative of one such lubricator that can be incorporated into the combination unit of the present invention, there being many others. In fact, under certain applications, air free of essentially all contaminants is needed such as, for example, in breathing apparatus and around food. Obviously, in circumstances such as these, oil vapor would not be added to the air stream, but instead, steps would be taken to remove any oil along with odors, bacteria and other airborne contaminants. Accordingly, in applications such as these, the lubricator can be eliminated and a second filter substituted therefor having the capability of removing submicron sized particulate matter. This secondary filter could easily be incorporated into the combination unit of the present invention in place of the lubricator shown by one of ordinary skill because all that is required by way of modification is to change the downstream section of the manifold beyond regulator section 20 to conform to the design of the head of a secondary filter that is used as a separate entity. A modified embodiment of the combination unit is shown in FIGS. 5 and 6. In this modification the regulator section 20 includes only pressure gage 24 and has no pressure regulator 22. The manifold includes an internally-threaded opening 132 connecting the main air passage 44 within the regulator section 20, which section is covered and sealed by means of a cap 134 and O-ring 136. Branch passages 138 are provided in the manifold (FIG. 6) extending from the main air passage 44 to the front and to the rear where they open through the lower ends of integrally-formed elements 140 that telescope into corresponding elements 142 and 144 formed as parts of the partition wall 40 of the shell 26 adjacent its front and rear walls. O-rings 146 encircle the elements 140 of the manifold and seal same within the corresponding elements of the shell as shown in FIG. 6. Front element 142 in the partition wall of the shell defines a blind passage 148, whereas, its counterpart 144 in the rear defines the previously-mentioned passage 42 that connects into the pressure gage. Obviously, whichever of the elements 140 of the manifold lies at the rear will connect into passage 42 of the shell and actuate the pressure gage while the other of said manifold elements 140 at the front thereof will be rendered inoperative.
Now, comparing FIGS. 4 and 6, it will be seen that branch passages 138 in the two-component version of the combination unit illustrated in FIGS. 5 and 6 differ from the corresponding passages 138M in the three-component version of the remaining Figures. Actually, the manifold is molded with only the lower portion of passages 138 or 138M completed. Then, if a customer orders the twocomponent version of FIGS. 5 and 6, passages 138 are completed by connecting them up to the main air passage 44 by drilling out passages 150 shown in FIG. 6. If, on the other hand, a customer orders a three-element unit, modified passages 138M are completed as shown in FIG. 4 by drilling passages 152 into them from a position beneath valve seat 154 and above piston 92.
The threecomponent version of the manifold 10 has been shown in FIGS. 1, 3, 4 and 7. In this form, the manifold 12 has been modified as described above to accommodate the regulator 22, in that it has the different arrangement of fluid passages 138m that have already been described and, in addition, a hole 156 is drilled in the bottom wall of the valve seat to receive valve stem 158 that bears against the top of the piston 92.
The pressure regulator 22 in the particular form disclosed herein has its stem 158 threaded through valve member 160. Control knob 162 is attached to coupling member 164 and it, in turn, is connected to the valve stem so as to rotate same. This same coupling member is attached to lock knob 166 by means of screw 168 such that if said lock knob is turned down tight, it will cooperate with the coupling 164 to force the control knob 162 down firmly against the valve body 170 so that the stem cannot be turned.
As the stem is moved up and down relative to the valve member 160, it acts through floating piston 92 to either further compress or release some of the compressive force acting on spring 46. As the spring bias on the piston increases, it will push upon the stem which telescopes into the coupling element and, at the same time, raises the valve member 160 off its seat thus permitting air to move past the latter and on through the main air passage 44. At such time as the pressure in the main air passage downstream of valve element 160 bleeds through orifice 172 and acts upon the top of piston 92 so as to depress same and overcome the spring bias exerted thereon, then it will drop down and allow spring 174 to close valve 160. If, on the other hand, the valve 160 is closed and the downstream pressure above piston 92 is sufficient to overcome the spring bias exerted thereon and drop it down further, it will immediately move out of contact with the valve stem thus permitting air to flow through orifice 176 in the center of the piston until an equilibrium condition is, once again, established.
An ordinary pressure regulator functions in a significantly different way, the main difference being that instead of changing the effective length of the valve stem, it remains the same and the position of the spring abutment opposite piston 92 is adjusted. Here again, the pressure regulator that has just been described is intended as being merely illustrative of one such regulator that can be used in the three-element combination unit of the present invention and, while it is considered novel, such novelty forms no part of the instant application.
The manner in which the bowl-carrying subassembly 14 is detachably connected to the manifold 12 is shown in FIGS. 1, 2 and 7. The manifold has tongue-forming portions 178 at its opposite ends which fit down into corresponding slots 180 in the sides of the bowl-carrying subassembly. Transversely-extending aligned openings 182 extend through both the manifold 12 and bowl-carrying subassembly 14 at opposite ends thereof when these elements are in assembled relation. Retractable pins 184 within these same openings releasably lock the manifold 12 and bowl subassembly together, yet enable the bowl subassembly to be removed from service and replaced with minimum disruption in service and without special tools. The portions of the pins lying within the confines of the front and rear walls of the shell contain annular grooves 186 and 188 while the opening 182 in the front wall is similarly grooved to receive spring 190. In the extended position shown in FIG. 2, spring 190 drops into the pin-encircling groove 186 nearest the head thereof and is thus releasably retained in latched position. Similarly, in the retracted position of the pin, spring 190 drops into the groove 188 in the end remote from the head to provide the same kind of releasable connection.
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This invention relates to a unitized air line filter and lubricator that includes provision for a pressure regulator therebetween that can either be by-passed or rendered operative by simply opening certain preformed passages in the manifold that connect same in series with the previously-mentioned components. The manifold houses nearly all of the working parts of both the filter and lubricator and their arrangement is such that the manifold can be reversed end-for-end to accommodate opposite directions of air flow. The subassembly that includes the bowls for the filter and lubricator along with the regulator spring therebetween in the three-component version will accommodate the manifold in either of its two positions and is, therefore, reversible relative thereto. Special sets of mounting brackets permit use of a single combination unit with air line piping of various sizes. These brackets also include a quick-disconnect feature wherein the entire combination unit can be detached therefrom and either serviced or replaced with another like unit in a very short time using only an allen wrench. The subassembly that carries the bowls includes a pair of quick-disconnect latches that are manually operated without any tools being required and which provide instant access to the bowls which are also removable.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional patent application Ser. No. 61/173,507 filed Apr. 28, 2009 and to U.S. provisional patent application Ser. No. 61/321,009 filed Apr. 5, 2010, and hereby incorporates the same provisional applications by reference herein in their entirety.
TECHNICAL FIELD
[0002] The present disclosure is related to the field of apparatuses, in particular, hand held pipe wipers and seals for wiping fluids and solids off pipe sections of a string used in the drilling of a well, or in the servicing of a well, as the pipe sections are removed from the well, and methods of using same.
BACKGROUND
[0003] As sections of pipe in a string used either on a drilling rig in the drilling of wells or on a service rig in the servicing of wells are removed from or “tripped out” of the well, they are often covered with solids and/or fluids. Before the pipe sections are put back into a storage rack or facility, it is desirable that the solids or fluids be removed or stripped off of the pipe. Known methods for removing solids or fluids from pipe sections being tripped out of a well are cumbersome and can be difficult, if not dangerous, for drilling personnel to use.
[0004] Known methods for removing solids or fluids from pipe sections being tripped out of a well include the manual use of rags and gunny sacks which require the hands of drilling personnel to be in close proximity to the drilling fluid. The drilling fluid is often at high temperatures and can burn the hands of drilling personnel. The known methods can result in the wiping device being dropped down into the drill hole.
[0005] It is, therefore, desirable to provide a pipe wiper and seal that can wipe or strip off solids from pipe sections being tripped out of a well that is easy to handle by personnel on the well.
SUMMARY
[0006] An apparatus and method for stripping solids and fluids from sections of pipe on a string used in the drilling of wells or used in the servicing of wells is disclosed. For purposes of this specification and the claims contained herein, the term “string” is defined to include a drill string comprised of multiple sections of drill pipe joined together and used on a drilling rig for the drilling of wells, a string of pipe comprised of multiple sections of pipe joined together and used on a service rig for the servicing of wells, and coil tubing that is used in the directional drilling of wells in addition to the servicing of wells. For purposes of this specification and the claims contained herein, the term “rig” is defined to include both well drilling rigs and well servicing rigs as well as snubbing units, push/pull rigs, coil tubing units, and other mechanical devices used to insert or remove string from a well.
[0007] In one embodiment, an apparatus is provided comprising a hand held pipe wiper. The pipe wiper can be used primarily to strip off solids and fluids from a string when it is being removed from a well. The pipe wiper can be provided with handles so it can be used manually by drilling personnel.
[0008] In one embodiment, the pipe wiper can comprise two or more portions that are hinged together so that the pipe wiper can be opened and placed around a string and then closed around the string to form a generally cylindrical body that encloses the string in a clamshell fashion. The pipe wiper can further comprise a releasable latch mechanism that can hold the pipe wiper body portions together. In this manner, the pipe wiper can easily and quickly be connected when installed on a string, and then easily and quickly disconnected and removed from the string when the string has been stripped of solids and fluids.
[0009] In another embodiment, the pipe wiper can further comprise a flexible toroidal seal disposed in the pipe wiper body. The seal can have multiple parts, one part for each portion of the hinged body. When the pipe wiper is enclosed around a string, the seal can form a toroidal sealing member having a central opening that can fit tightly around the string. In another embodiment, the seal can be configured to flex and stretch such that the central opening can expand in diameter so that the seal can pass over a connection between sections of pipe as the string is being raised out of a well, and then contract in diameter to the pipe's diameter after the pipe connection has passed through the pipe wiper. In operation, the pipe wiper can be placed and enclosed around a string and can be held in position by drilling personnel on the rig floor by gripping the handles to ensure stabilization of the pipe wiper as the string is being raised out of the well. As the string is raised, it passes through the pipe wiper and the sealing member in the pipe wiper strips off solids and fluids from the exterior surface of the string, the solids and fluids falling onto the rig floor.
[0010] In a further embodiment, the seal can be removably installed in the pipe wiper so as to provide a variety of seals having differently sized openings to accommodate strings of different diameters, or to be able to easily replace a damaged seal in the pipe wiper.
[0011] “Handle” as used herein can include anything know in the art or yet to be developed which will allow a worker to grip the apparatus. The handle can be integrally formed into the body of the apparatus or can be attached separately. The handle can allow for increasing the distance between the hands of drilling personnel and the drilling fluid.
[0012] Broadly stated, a hand held pipe wiper is provided for stripping off solids and fluids from a string in the drilling or servicing of a well, comprising: two or more arcuate body portions pivotally connected together and configured to form a cylindrical body when enclosed around the string; a latch mechanism disposed on one or more body portions, the latch mechanism configured to releasably connect the arcuate body portions together to form the cylindrical body; one or more handles disposed on the arcuate body portions; and a sealing member disposed in the cylindrical body, the sealing member configured to form a toroidal seal around the string when the cylindrical body is enclosed around the string whereby the sealing member strips solids and fluids off of the string when the string passes through the pipe wiper.
[0013] Broadly stated, a sealing member is provided which can be removably received by an apparatus having two or more arcuate body portions pivotally connected together and configured to form a cylindrical body when closed together for stripping off solids and fluids from a string used in the drilling or servicing of a well, the sealing member comprising: a plurality of seal portions having a top face and a bottom face, one seal portion for each arcuate body portion; and the seal portions configured to form an opening that forms a toroidal seal around the string when the cylindrical body is enclosed around the string whereby the sealing member strips solids and fluids off of the string when the string passes through the apparatus.
[0014] Broadly stated, a method is provided for stripping off solids and fluids from a string being removed from a well, the method comprising the steps of: providing a hand held pipe wiper, comprising: two or more arcuate body portions pivotally connected together and configured to form a cylindrical body when enclosed around the string, a latch mechanism disposed on one or more body portions, the latch mechanism configured to releasably connect the arcuate body portions together to form the cylindrical body, one or more handles disposed on the arcuate body portions, and a sealing member disposed in the cylindrical body, the sealing member configured to form a toroidal seal around the string when the cylindrical body is enclosed around the string whereby the sealing member strips solids and fluids off of the string when the string passes through the pipe wiper; enclosing the pipe wiper around the string whereby the sealing member has formed the toroidal seal around the string; and holding the pipe wiper in position while the string is being raised out of the well whereby the sealing element strips off solids and fluids from the string.
[0015] BRIEF DESCRIPTION OF THE DRAWINGS:
[0016] FIG. 1 is a top plan view depicting a pipe wiper;
[0017] FIG. 2 is a side elevation view depicting the pipe wiper of FIG. 1 ;
[0018] FIG. 3 is a side cross-section view depicting the pipe wiper of FIG. 2 along section lines A-A;
[0019] FIG. 4 is a perspective view depicting the pipe wiper of FIG. 1 installed on a string being raised;
[0020] FIG. 5 is a perspective view depicting a sealing member for a pipe wiper;
[0021] FIG. 6 is a side elevation view depicting the sealing member of FIG. 5 ;
[0022] FIG. 7 is a cross-section view depicting the sealing member of FIG. 5 along section lines B-B;
[0023] FIG. 8 is a perspective view depicting a female seal half of the sealing member of FIG. 5 ;
[0024] FIG. 9 is a side elevation view depicting the female seal half of FIG. 8 ;
[0025] FIG. 10 is a side cross-section view depicting the female seal half of FIG. 8 along section lines C-C;
[0026] FIG. 11 is a perspective view depicting a male seal half of the sealing member of FIG. 5 ;
[0027] FIG. 12 is a side elevation view depicting the male seal half of FIG. 11 ; and
[0028] FIG. 13 is a side cross-section view depicting the male seal half of FIG. 11 along section lines D-D.
DETAILED DESCRIPTION OF EMBODIMENTS
[0029] Referring to FIGS. 1 and 2 , an embodiment of pipe wiper 10 is shown. In this embodiment, pipe wiper 10 can comprise body 12 consisting of arcuate or semi-circular body halves 14 and 16 that are pivotally connected together with hinge 18 . When body halves 14 and 16 are closed together to meet at seam 19 , body 12 defines interior 11 through which a string can be placed and pass through. While this embodiment comprises two semi-circular body halves 14 and 16 to form cylindrical or tubular body 12 , it should be understood that three or more arcuate body portions pivotally connected together can be used to form body 12 . In other embodiments of pipe wiper 10 , body 12 can have a cross-sectional shape that is not circular, such shapes including: triangular, square, rectangular, oval and polygonal cross-sectional shapes. For the purposes of this specification and the claims contained herein, the terms “arcuate”, “semi-circular”, “cylindrical”, “tubular” and any other like terms are hereby defined to include both circular and non-circular cross-sectional shapes of body 12 and parts therefor, including a sealing member that is disposed in body 12 and discussed in further detail below.
[0030] Body 12 can further comprise handle 20 disposed on body half 14 and handle 22 disclosed on body half 16 so as to enable a person to grasp and hold onto pipe wiper 10 when a string is raised through it. Pipe wiper 10 can further comprise latch mechanism 24 to hold body halves 14 and 16 together when pipe wiper 10 is being used. In the illustrated embodiment, latch mechanism 24 can comprise fixed hinge member 28 disposed on body half 14 that can be pivotally connected to movable latch member 30 , which, in turn, can be pivotally connected to handle 26 . Handle 26 can be further configured to engage a keeper or stay member disposed on body half 16 (not shown) to hold body halves 14 and 16 together when handle 26 is rotated towards body 12 whereby latch mechanism 24 can operate as an “over center latch.” To open pipe wiper 10 , handle 26 can be pulled and rotated away from body half 16 to disengage the keeper disposed thereon whereby handle 26 and latch member 30 can be rotated further away from body half 16 so as to enable the removal of pipe wiper 10 from a pipe section. It should be apparent that any suitable latching mechanism can be used in substitution of the illustrated latch mechanism 24 to couple body halves 14 and 16 together.
[0031] Referring to FIG. 3 , a cross-sectional view of pipe wiper 10 is shown, namely, the interior view of body half 16 . As shown in this embodiment, the interior surface of body half 16 can comprise groove 32 disposed thereon where a sealing element can be removably placed. A corresponding groove 32 can also be disposed on the interior surface of body half 14 (not shown). Groove 32 enables the easy installation and removal of sealing elements in body halves 14 and 16 so that the sealing element can be replaced when it becomes damaged or when a sealing element for a different diameter pipe is required.
[0032] Referring to FIG. 4 , pipe wiper 10 is shown installed on pipe 36 as it is being raised through pipe wiper 10 . In this embodiment, pipe wiper 10 is shown comprised of semi-circular body halves 14 and 16 each having arcuate seal members 34 and 35 disposed therein, respectively. When pipe wiper 10 is installed around pipe 36 , as shown, seal members 34 and 35 meet at seam 40 to form opening 39 that, in turn, forms a toroidal seal around pipe 36 . Seal members 34 and 35 can be configured to be removably placed or installed in grooves 32 disposed in body halves 14 and 16 . Seal members 34 and 35 can be made of any suitable elastomeric material that enables seal members 34 and 35 to flex and stretch so as to maintain contact with the external surface of pipe 36 due to any irregularities to the cross-sectional shape of pipe 36 or to the contour of the pipe's external surface and, in addition, to allow opening 39 to expand in diameter so as to enable any joint connection between two sections of pipe to pass through seal members 34 and 35 as a joint connection can have a larger diameter than the diameter of the pipe itself. Suitable examples of the elastomeric material for seal members 34 and 35 can include natural rubber, neoprene rubber, foam rubber, silicone-based rubber, nitrile rubber and any other material that is suitable for use as a seal that can be used to strip petroleum-based substances from a string. The elastomeric material for seal members 34 and 35 can also be a low weight material which would allow seal members 34 and 35 to float on the drilling fluid if seal members 34 and 35 were dropped into well.
[0033] In another embodiment, seal members 34 and 35 can further comprise means for allowing opening 39 to expand and contract in diameter. In one embodiment, the means can comprise a plurality of relief cuts 38 disposed thereon to allow opening 39 to expand in diameter when a joint connection between two pipe sections are passed through pipe wiper 10 , and to contract in diameter when the joint connection has passed through pipe wiper 10 . In the illustrated embodiment, relief cuts 38 are shown as straight cuts in a radial configuration extending outwardly from opening 39 . The relief cuts 38 can be of any other suitable configuration on seal members 34 and 35 so as to allow opening 39 to expand and contract in diameter as a pipe joint connection passes through seal members 34 and 35 .
[0034] In a representative embodiment, body 12 , handles 20 and 22 , and latch mechanism 24 can be made of a polymer plastic material so as to minimize the weight of pipe wiper 10 and still maintain the necessary structural strength required for a tool of this nature. However, it should be understood that other materials can be used in the construction in pipe wiper 10 , such as metal, metal alloys or any other suitable construction material.
[0035] Referring now to FIGS. 5-13 , a further embodiment of a sealing member for use with pipe wiper 10 is shown as seal insert 42 . Seal insert 42 can include a female seal half 44 and a male seal half 46 . Outer edge 48 of seal insert 42 can be configured such that seal insert 42 can be removably placed or installed in body halves 14 and 16 . Seal insert 42 can include a top face 50 and bottom face 52 . Seal grooves 56 can be used to removably place seal insert 43 into groove 32 on the interior surface of body half 16 and the interior surface of body half 14 . Groove 32 can enable the easy installation and removal of seal halves 44 and 46 in body halves 14 and 16 so that the seal insert 42 can be replaced when it becomes damaged or when a seal insert 42 for a different diameter pipe 36 (as shown in FIG. 3 ) is required.
[0036] Female seal half 44 and a male seal half 46 can be made of any suitable elastomeric material that enables female seal half 44 and a male seal half 46 to flex and stretch so as to maintain contact with the external surface of pipe 36 due to any irregularities to the cross-sectional shape of pipe 36 or to the contour of the pipe's external surface and, in addition, to allow seal insert opening 54 to expand in diameter so as to enable any joint connection between two sections of pipe to pass through seal insert opening 54 as a joint connection can have a larger diameter than the diameter of the pipe 36 itself. Suitable examples of the elastomeric material for female seal half 44 and a male seal half 46 can include natural rubber, neoprene rubber, foam rubber, silicone-based rubber, nitrile rubber and combinations thereof or any other material suitable for use as a seal that can be used to strip petroleum-based produced substances from a string. The elastomeric material for female seal half 44 and a male seal half 46 can also be a low weight material which would allow female seal half 44 and a male seal half 46 to float on the drilling fluid if female seal half 44 and a male seal half 46 were dropped into well.
[0037] Referring to FIGS. 8 , 9 , and 10 , female seal half 44 can have notch 58 for receiving a tongue disposed on seal half 46 . Referring to FIGS. 11 , 12 , and 13 , male seal half 46 can have tongue 60 that can be inserted into notch 58 so that female seal half 44 and male seal half 46 can be brought together to form seal insert 42 which, in turn, can form a toroidal seal around pipe 36 (as shown in FIG. 3 ).
[0038] In another embodiment, seal insert 42 can also include channel 62 disposed between the top face 50 and bottom face 52 of seal insert 42 . Channel 62 can allow for a pipe joint or irregularity on pipe 36 to pass through seal insert opening 54 while allowing seal insert 42 to still strip pipe 36 of solids and fluids collected on the outside surface of pipe 36 .
[0039] Although a few embodiments have been shown and described, it will be appreciated by those skilled in the art that various changes and modifications might be made without departing from the scope of the invention. The terms and expressions used in the preceding specification have been used herein as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding equivalents of the features shown and described or portions thereof, it being recognized that the scope of the invention is defined and limited only by the claims that follow.
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An apparatus and method is provided for stripping solids and fluids from a string used in the drilling or servicing of a well when the string is removed from the well. The apparatus can comprise two or more pivotally connected arcuate body portions that can be enclosed around the string in a clamshell fashion. The apparatus can further comprise a seal disposed therein to provide a toroidal sealing member around the string when the apparatus encloses the string. A quick release latch mechanism is provided on the apparatus for easy and quick installation on, and removal from, the string. Handles on the apparatus allow personnel to hold the apparatus in a stationary position as the string passes through the apparatus when being raised from the well. In so doing, the sealing member strips solids and fluids from the string.
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DESCRIPTION
The invention relates to an optoelectronic measurement arrangement for determining the relative position of two bodies to each other.
An optoelectronic measurement arrangement is known from DE-PS 33 14 089 for determining the relative position of two bodies to each the other, with light emitters, from which light beams emanate, at the first body and position-sensitive, two-dimensionally measuring light receivers at the second body, on which the light beams impinge, wherein signal pairs, which represent the relative translation and/or rotation and from which the relative position of the two bodies to each other is derivable, are produced by the light receivers from the position of the points of incidence and the beam axes. This measurement arrangement, however, suffers from the disadvantage that it requires three two-dimensionally measuring light receivers. Since two-dimensionally measuring light receivers are expensive components, the entire measurement arrangement is thereby greatly impaired in its economy.
In printed specification FR-A 2 194 949 (Selcom) it is described how the images of several punctiform light sources on an areal diode are distinguishable by a different modulation of the individual light sources. As examples for the application of the modulated light sources, however, there are mentioned only examples which all have the object of observation of the time course of movement processes, such as, for example, a golf track, a jump or the beginning or a 100 meter run. However, no reference is to be found anywhere in the specification that the light points emitting modulated light together with the receiver shall serve for technical measurement determination of the relative position of two bodies.
Partial calculations for the relative position of two systems are carried out in specification GB-A-2 005 950 (HAY). Auxiliary computations are performed by a camera and further arrangement in order that, for example, a tunnel-drilling machine maintains its straight course. Measurement technique by way of a wide angle objective of a camera represents an imprecise measurement. A calculation of the relative position of two systems in six degrees of freedom is not described. The points in the target planes are defined by light-emitting diodes, which are operated in sequence by switches.
The invention is therefore based on the task of providing an optoelectronic measurement arrangement which enables the relative position of two bodies to be determined in their six degrees of freedom with the least possible number of light receivers.
According to the invention this task is solved as indicated in patent claim 1. Developments of the invention are described in dependent patent claims 2 to 7.
Embodiments of the invention are illustrated in the drawings, in which:
FIG. 1 shows a basic representation of light emitters and light receiver,
FIG. 2 shows a perpendicular section through a joystick, and
FIG. 3 shows a partial section through a manipulating device.
An optoelectronic measurement arrangement 1 is schematically illustrated in FIG. 1. The measurement arrangement 1 consists of, for example, three light emitters 11, 12 and 13, which are arranged at the first body and from which light beams 21, 22 and 23 emanate, and a position-sensitive, two-dimensionally measuring light receiver 3 at the second body. The light beams 21, 22 and 23 are concentrated by, for example, optical systems 24, 25 and 26 onto the light receiver 3. The light emitters 11, 12 and 13 arranged at the first body form the corner points of a first triangle.
The axes of the light beams 21, 22 and 23 represent in pairs, different direction vectors and respectively intersect the light receiver 3 at different angles, for example the three angles α1, α2 and α3. For graphical reasons, it is not possible in FIG. 1 to draw in the angle α2. The points of incidence 31, 32 and 33 of the light beams 21, 22 and 23 form a second triangle on the light receiver 3. Through the use of more than three light sources, respective polygons are present instead of the two triangles.
The measurement is now carried out with the afore-described basic measurement arrangement in such a manner that the light emitters 11, 12 and 13 emit light beam pulses which are modulated on-off in rotating sequence and do not overlap in their time lengths. Thereby, the respective coordinates x and y of the three points of incidence 31, 32 and 33 can be individually determined one after the other. The relative positional change of the two bodies to each other results unequivocally from the ratio of a zero or reference measurement to an actual measurement. If more than three light emitters are used, the afore-described measurements can then be performed with three of these light emitters each time and the results can be compared with each other and checked against one another. If it is evident in this case that a value significantly differs from the remaining results, which, for example, can be the case when two light points of a light point triangle 31, 32 and 33 lie too closely together or all three light points 31, 32 and 33 lie on a straight line, then this value is discarded. Thus, the security and the accuracy of the measurement can be appreciably increased.
For production of the light beams 21, 22 and 23, preferably lasers, laser diodes, light-emitting diodes or other light sources can be used, the light of which is guided through optical conductors, optical systems or the like.
A control handle 4 of a multi-dimensional joystick is illustrated in FIG. 2 as first example of application. The control handle 4 consists of the base body 5 and the handle member (handle) 6. The base body 5 is mounted on a pedestal 52 by way of a shank 51. The three light emitters 11, 12 and 13, which project their light beams 21 and 23 onto the light receiver 3, are disposed on the upper side of the base body 1. The line 92 leads through the hollow shank 51 from the electronic transmitting system 91 to the light emitters 11, 12 and 13 and the line 33 through the hollow shank 51 from the light receiver 3 to the electronic receiving system 94. The light emitters 11, 12 and 13 and the light receiver 3 are enveloped by an elastic element, preferably a spring bellows 61. At the same time, a mutual zero position is fixed by the spring bellows 61. The spring bellows 61 at the same time also forms a dustproof and watertight envelope.
The light receiver 3 can be a quadrant, matrix or lateral effect diode or a charge-coupled device receiver.
The afore-described control handle 4 permits a control with six degrees of freedom, as the handle member 6 is movable three-dimensionally relative to the base body 5 and thus has three degrees of freedom for translation and three degrees of freedom for rotation. These six dimensions are usable for the control of a manipulating device with six or fewer degrees of freedom. If, however, the degrees of freedom are used in only one plane, namely two degrees of freedom for the translation and one degree of freedom for the rotation, then a cursor on an image screen can be displaced or a cursor-like arrow can be displaced and/or rotated thereby. Its possibilities of use thus go beyond that of a "mouse", by which a cursor is merely displaceable on the image screen.
A simplified representation of a manipulating device 7 is illustrated in FIG. 3 as second example of application. In this case, a handle member 6 of fixed location is present, which is mounted in fixed location by a fastening carrier 62. The handle member 6 consists of an approximately hemispherical shell, in which the light receiver 3 is mounted. The circular base body 5 carries the light emitters 11, 12 and 13, which project light beams 21, 22 and 23 onto the light receiver 3. The base body 5 is elastically mounted on the handle member 6 by the spring bellows 61. A flange 53 is fastened to the base body 5. Disposed on an arm of the manipulating device 7 is the coupling 71 with grippers 72, which when coupled on encompass the flange 53 and thereby bring the system into measuring position.
The control of the light emitters 11, 12 and 13 as illustrated in FIG. 2 takes place through an electronic transmitting system 91, which is connected by a line 92 with the light emitters 11, 12 and 13 and modulates these on-off. According to FIG. 2 and FIG. 3, the reception signals of the light receiver 3 are conducted by the receiving line 93 to an electronic receiving system 94, which is connected by way of a line 95 to a computer interface with an evaluating computer 96.
In FIG. 3, a line 97 between the computer and the control unit then feeds the computed values to a control unit 98, which in its turn controls the manipulating device 7 by way of the line 99.
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An optoelectronic measurement arrangement (1) for determining the relative positioning of two bodies has light emitters (11, 12, 13) which emit light beams on the first body and a position-sensitive light receiver (3) which measures two dimensions on the second body. The light emitters (11, 12, 13) constitute the corners of a first polygon, for example a triangle, whose paired light beam axes represent different direction vectors which pass through a light receiver (3) and whose points of incidence (31, 32, 33) on the light receiver (3) constitute the corners of a second polygon located inside the light receiver (3). The light emitters (11, 12, 13) are modulated in cyclic on-off sequence and emit pulsed light beams which do not intersect as regards their duration.
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BACKGROUND OF THE DISCLOSURE
1. Field of the Invention
This invention relates to a quadrature amplitude modulation (QAM)-based communication system and, more particularly, to interference suppression in a digital QAM demodulator.
2. Description of the Background Art
Quadrature amplitude modulation (QAM) is a particularly advantageous technique for transmitting digital data because of its efficient utilization of bandwidth. As an example, high definition television (HDTV) signals are oftentimes broadcast as compressed digital data using QAM.
In essence, QAM transmits digital data as a sequence of two-dimensional complex symbols which may be expressed in terms of level and phase, or equivalently, in terms of in-phase and quadrature components. Each symbol, based upon the data represented by the symbol, takes on a specific pre-defined value from a set of values. The set of all values, when graphically plotted in two-dimensions, forms a so-called constellation. The size and shape of the constellation depends upon the number of discrete values in the set and their spatial location in the constellation. The constellation might contain, for example, 16 or 64 values, hence called 16 QAM or 64 QAM, respectively.
To broadcast QAM, the in-phase and quadrature digital components independently modulate in-phase and quadrature carrier signals, respectively, and the modulated carriers are propagated over the given channel or medium (e.g., cable or "over-the-air" broadcast).
To detect an incoming QAM signal, a QAM receiver demodulates the in-phase and quadrature incoming sampled signals using carrier signals derived from a carrier recovery circuitry, and the demodulated outputs are filtered, with the filtered signals serving as inputs to an appropriate decoder which typically utilizes slicer circuitry to produce detected symbols.
The incoming signals to the QAM receiver are provided, for example, over broadcast channels or cable systems. One deleterious type of interference which affects the desired incoming signal is a discrete, in-band radio-frequency (RF) tone. A low power RF tone is particularly troublesome for high-order constellations because of their compactness. Previously known techniques for interference cancellation, typically implemented at the front end of the receiver, are not particularly effective because these techniques rely upon substantial power in the interfering tone. The RF tone interference produces a significant error rate by causing perturbations of the constellation points. Such interference is not atypical and may arise on a cable system from sources such as crosstalk from co-channel NTSC broadcasts or beats from NTSC carriers on the same cable system.
Techniques which address interference suppression of co-channel NTSC interference signals into QAM signals are known for broadcast applications. Representative of these techniques are the disclosures of related U.S. Pat. Nos. 5,282,023; 5,325,188; 5,325,204; and 5,400,084. The underlying technique of these references utilizes a bank of narrow band IIR filters to isolate the interfering signal and subtract it from the desired signal. This technique is accomplished at the front end of the QAM demodulator, that is, ahead of any other processing. This technique is especially suitable for high power interference, but it is less effective at detecting and removing low power interference which may still be a problem for QAM signals having a relatively large number of symbol states, that is, high order constellations. Moreover, this technique requires complex circuitry for its implementation.
Other art, as set forth in U.S. Pat. Nos. 5,087,975 and 5,162,900, for canceling NTSC co-channel interference in a vestigial sideband pulse amplitude modulated system relies on special precoding at the transmitter and a fixed filter in the demodulator. Such a technique is not easily generalized to QAM and not applicable for solutions implemented only in the receiver.
Finally, other techniques for interference cancellation have been discussed in the literature; a survey of these techniques is covered in the article entitled "Adaptive Noise Cancelling: Principles and Applications," by Widrow et al, Proc. IEEE, Vol. 63, No. 12, pages 1692-1716, December 1975. These techniques generally rely on the availability of a correlated reference signal for the interference; such a reference signal is derived from a second receiver or generated from known properties of the signal, neither of which is known or available in a typical QAM application.
Thus, the prior art is devoid of teachings or suggestions for suppressing low-level discrete RF tone interference in a QAM system which is the focus of the present invention.
SUMMARY OF THE INVENTION
These shortcomings and other limitations and deficiencies are obviated in accordance with the present invention by circuitry and concomitant methodology which generates an estimate of the interference tone during the current processing interval, subtracts the estimate from the incoming signal during the current processing interval to produce the output signal, and modifies, if necessary, adaptive circuitry for use during the next processing interval.
Broadly, in accordance with one baseband method aspect of the present invention, an interference tone in an incoming, sampled baseband signal in a QAM system is suppressed to produce an output signal by, initially, generating a tone reference from a delayed version of the incoming signal and a delayed version of the output signal. Then the tone reference is weighted by an adaptive parameter to produce a tone estimate. The tone estimate is used to correct the incoming signal, and the corrected signal is threshold detected to produce the output signal. An error signal is derived from the corrected incoming signal and the output signal, and this error signal and the tone reference are used to adapt the parameter.
In another baseband method aspect of the present invention, an interference tone in an incoming, sampled baseband signal in a QAM system is suppressed to produce an output signal by, initially, generating an interference tone reference from a delayed version of the incoming signal and a delayed version of the output signal. Then the interference tone reference is further delayed to produce a delayed interference tone reference. The delayed interference tone reference is weighted by an initial adaptive parameter to produce an interference tone estimate. The tone estimate is used to correct the incoming signal, and the corrected signal is threshold detected to produce the output signal. An error signal is derived from the corrected incoming signal and the output signal, and this error signal and the tone reference are used to adapt the parameter.
In still another baseband method aspect of the present invention, an interference tone in an incoming, sampled baseband signal in a QAM system is suppressed to produce and output signal by, initially, generating a corrected incoming signal from the incoming signal and an interference tone estimate, wherein the interference tone estimate is obtained by weighting an interference tone reference by a present adaptive parameter. The interference tone reference is obtained from a delayed version of the interference tone estimate and a delayed version of the output signal. The corrected incoming signal is threshold detected to produce the output signal. An error signal is derived from the corrected incoming signal and the output signal, and this error signal and the tone reference are used to adapt the parameter.
In yet another baseband method aspect of the present invention, an interference tone in an incoming, sampled baseband signal in a QAM system is suppressed to produce an output signal by, initially, generating an interference tone reference from a delayed version of the incoming signal and a delayed version of the output signal. The delayed interference tone reference is weighted by an initial adaptive FIR filter to produce an interference tone estimate. The tone estimate is used to correct the incoming signal, and the corrected signal is threshold detected to produce the output signal. An error signal is derived from the corrected incoming signal and the output signal, and this error signal and the tone reference are used to adapt the FIR filter.
In fact, wherever an adaptive parameter is utilized in any embodiment, it is also readily contemplated that a FIR filter can be substituted, and the FIR filter is adapted rather than the single parameter.
Broadly, in accordance with one passband method aspect of the present invention, an interference tone in an incoming, sampled passband signal in a QAM system is suppressed to produce a baseband output signal by, initially, rerotating the baseband output signal to produce a rerotated output signal at passband. Then, an interference tone reference at passband is generated from a delayed version of the incoming signal and a delayed version of the rerotated output signal. The interference tone reference is weighted by an initial adaptive parameter to produce an interference tone estimate, which is then used to generate a corrected incoming signal from the incoming passband signal. The corrected incoming signal is mixed to produce a baseband corrected signal. The baseband corrected signal is threshold detected to produce the baseband output signal. A baseband error signal is generated from the baseband corrected signal and the baseband output signal. The baseband error signal is rerotated to passband to produce a rerotated error signal, and a new adaptive parameter is generated from the initial adaptive parameter, the interference tone reference, and the rerotated error signal.
In accordance with another passband method aspect of the present invention, the foregoing passband interference cancellation method utilizes pre-filtering to mitigate the effects of noise. The pre-filtering step produces a new interference tone reference from the original interference tone reference, and this new interference tone reference is then weighted by the initial adaptive parameter to produce the interference tone estimate.
In accordance with yet another passband method aspect of the present invention, an interference tone in an incoming, sampled passband signal in a QAM system is suppressed to produce a baseband output signal by, initially, generating a passband corrected incoming signal from the incoming passband signal and a passband interference tone estimate, wherein passband interference tone estimate is obtained by weighting a passband interference tone reference by a present adaptive parameter. The passband interference tone reference is generated from a delayed version of the interference tone estimate and a delayed version of a passband error signal. The passband corrected incoming signal is mixed to generate a baseband corrected signal, and the corrected baseband signal is threshold detected to produce the baseband output signal. A baseband error signal is generated from the corrected baseband signal and the baseband output signal, with the passband error signal being derived from the baseband error signal by rerotation. The next adaptive parameter is then generated from the initial adaptive parameter, the passband interference tone reference, and the passband error signal.
BRIEF DESCRIPTION OF THE DRAWINGS
The teachings of the present invention can be readily understood by considering the following detailed description in conjunction with the accompanying drawings, in which:
FIG. 1 illustrates a high-level block diagram of a prior art QAM demodulator;
FIG. 2 illustrates a high-level block diagram of a QAM demodulator depicting the electronic connectivity of the baseband tone canceller in accordance with the present invention;
FIG. 3 illustrates a high-level block diagram of a QAM demodulator depicting the electronic connectivity of the passband tone canceller in accordance with the present invention;
FIG. 4 depicts a spectral plot of an illustrative QAM signal showing the presence of an interference tone at baseband;
FIG. 5 depicts a spectral plot of an illustrative QAM signal showing the presence of an interference tone at passband;
FIG. 6 illustrates a block diagram of one illustrative baseband tone canceller;
FIG. 7 illustrates a block diagram of another illustrative baseband tone canceller;
FIG. 8 illustrates a block diagram of yet another illustrative baseband tone canceller;
FIG. 9 illustrates a block diagram of still another illustrative baseband tone canceller;
FIG. 10 illustrates a block diagram of one illustrative passband tone canceller;
FIG. 11 illustrates a block diagram of another illustrative passband tone canceller; and
FIG. 12 illustrates a block diagram of yet another illustrative passband tone canceller.
To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures.
DETAILED DESCRIPTION
To gain an appreciation for the meritorious advance provided by the present invention, it is helpful to first present in overview fashion the electronic context for the present invention. This approach has the added advantage of introducing terminology and notation useful in describing the detailed embodiments of the present invention, which then follow the overview exposition.
Overview
Generally a digital demodulator samples an incoming analog waveform and uses digital signal processing techniques to decode or extract the information carried in the analog waveform. In QAM, the information is a digital code which is encoded by a modulator as an analog level and phase, or equivalently, as analog in-phase and quadrature components; the in-phase and quadrature components are substantially independent of each other in a QAM system. (Without loss of generality, the following description will be couched in terms of in-phase and quadrature components.) The encoded analog signal is filtered to limit the bandwidth of the signal, and then mixed with a carrier frequency for transmission.
An illustrative QAM digital demodulator is depicted in FIG. 1, with the focus being on that portion of the QAM demodulator which processes the incoming analog signal after it has been mixed down to an intermediate frequency (IF) and passed through a channel selection filter by a front-end tuner (not shown). As is the notational convention when describing QAM systems, the signals which appear in FIG. 1 are complex in nature, that is, the signals have real and imaginary parts which are commensurate with the in-phase and quadrature components of the QAM signals.
The output of mixing and filtering operations is the signal appearing on lead 11 in FIG. 1. Analog-to-digital (A/D) converter 10 samples the analog signal on lead 11 to generate a series of digital samples appearing on lead 12. The sampling rate for A/D converter 10 is controlled by timing recovery circuitry 15. The sampled signal appearing on lead 12 is filtered by shaping filter 20, which is configured to match the spectral shape of the transmission pulse shaping filter in the modulator. The overall, combined frequency response of the transmitter and receiver filters is selected to minimize intersymbol interference as well as provide filtering to maximize the signal-to-noise ratio in the presence of gaussian white noise.
The output of filter 20 serves as the input to timing recovery circuitry 15. In addition, the output of filter 20 is connected to adaptive equalizer 25; equalizer 25 is used to correct for linear distortions in the transmission channel. For instance, these distortions may arise from multi-path reflections in the channel or from filter mismatches in the tuner.
The output of equalizer 25 is mixed by mixer 30 to baseband from IF by a reference carrier generated by carrier recovery circuitry 35. The baseband signal from mixer 30, which appears on lead 31, is an estimate of the in-phase and quadrature components of the particular digital code (the signal appearing on lead 31 is referred to as the "soft decision"). Slicer 40 is used to select the closest digital code representative of the soft decision, and slicer 40 outputs via lead 41 the exact in-phase and quadrature components for that digital code (the signal appearing on lead 41 is referred to as the "hard decision"). The difference between the soft decision and the hard decision, performed by subtractor 45, is an error signal on lead 46 which is used to control carrier recovery circuitry 35.
Now with reference to FIG. 2, there is shown, in accordance with the present invention, tone canceller 100 interposed between mixer 30 and slicer 40 and having the error signal on lead 46 and the output of slicer 40 on lead 41 as inputs. In this aspect of the present invention, tone canceller 100 is placed after mixer 30 and therefore operates on the baseband signal. Illustrative embodiments of tone canceller 100 are presented below.
Referring now to FIG. 3, there is shown, in accordance with the present invention, tone canceller 200 interposed between adaptive equalizer 25 and mixer 30 and having the signals on leads 53 and 54 as inputs. The signals on these leads are derived from mixers 51 and 52, respectively. Inputs to mixer 51 are provided by the error signal on lead 46 and carrier recovery circuitry 35; inputs to mixer 52 and provided by the output of slicer 40 and carrier recovery circuitry 35. The signal to mixer 51 from carrier recovery circuitry 35 is used to mix the error signal, which is at baseband, up to the passband for appropriate spectral alignment for processing in tone canceller 200--an operation referred to as "rerotation." Similarly, mixer 52 rerotates the output of slicer 40 to the passband. The signals provided by carrier recovery circuitry 35 to mixers 51 and 52 are the conjugate of the signal provided to mixer 30 by carrier recovery circuitry 35. In this aspect of the present invention, tone canceller 200 is placed before carrier recovery circuitry 35 and therefore operates on the passband signal. Illustrative embodiments of tone canceller 200 are presented below.
To visualize the desired cancellation property of the tone cancellers of the present invention, reference is now made to FIG. 4, wherein a baseband signal spectrum, identified by reference numeral 71, is depicted for an illustrative digital code. The interference tone is represented by spectral line 72. Tone canceller 100 is implemented to mitigate the effect of spectral line 72. Now with reference to FIG. 5, the passband version of the spectrum for the digital code is identified by reference numeral 81, and the interfering tone by spectral line 82. Tone canceller 200 is implemented to mitigate the effect of spectral line 82.
Baseband Tone Canceller
With reference to FIG. 6, there is shown one basic embodiment of tone canceller 100 of FIG. 2. Tone canceller 100 in FIG. 6 operates at baseband in that the signal appearing on lead 31 is representative of the output of carrier recovery mixer 30 of FIG. 1. Accordingly, lead 31 carries a sequence of sampled baseband symbol values each having an in-phase and quadrature component.
To describe the operation of tone canceller 100 of FIG. 6, it is presumed initially that a single interference tone at a fixed frequency within the transmitted spectrum of the QAM signal interferes with the desired signal, and that such a tone is detected by carrier recovery mixer 30 and passed along with the sequence of baseband symbols over lead 31 to tone canceller 100. The spectrum of an illustrative signal appearing on lead 31 is shown in FIG. 4, with the spectrum of the desired signal identified by reference numeral 71 and the interference tone identified by reference numeral 72. The interference tone is shown as having radian frequency f t in the baseband spectrum of the desired signal.
Broadly, tone canceller 100 of FIG. 6 is a discrete time processor which generates an estimate of the interference tone during the current processing interval, and subtracts the estimate from the incoming signal on lead 31 during the next processing interval to produce the output signal on lead 41. In mathematical terms, let the signal appearing on lead 31 be represented by s(i) (i.e., the soft decision):
s(i)=x(i)+t(i)+n(i), (1)
where x(i) is the exact or desired symbol value, t(i) is the interference tone, and n(i) is random noise, all evaluated at the i th sampling instant. Further, it is supposed for analysis purposes that the output of slicer 40, appearing on lead 41, is the desired symbol value x(i). A delayed version of the signal appearing on lead 41 is subtracted from a delayed version of the signal appearing on lead 31, via subtractor 115, to yield a tone reference r(i) indicative of the interference tone t(i) (which remains corrupted by n(i)), that is, the signal appearing on lead 116 is given by
r(i)=t(i-1)+n(i-1). (2)
The delays to signals on leads 31 and 41 are effected by delay elements 110 and 140, respectively.
The tone reference r(i) is then multiplied by an adaptive parameter A(i) in processing device 130 to yield a tone estimate A(i)r(i) appearing on lead 131; the parameter A(i) is a gain and phase adjustment to the tone reference r(i). The tone estimate is then subtracted from the incoming signal on lead 31 in subtractor 125. The output of subtractor 125, designated c(i) (i.e., the corrected incoming signal), may be expressed as
c(i)=s(i)-A(i)r(i). (3)
The adaption of A(i) is controlled by the product of a slice error and the conjugate of the tone reference. The slice error, designated e(i), is formed by subtracting the output of slicer 40 from the input of slicer 40 in subtractor 45; this subtraction may be expressed as
e(i)=c(i)-x(i). (4)
Processing device 130 then generates the next estimate A(i+1) in the following form:
A(i+1)=A(i)+μe(i)r(i)', (5)
where r(i)' is the conjugate of r(i), and μ is a pre-determined adaption gain (the manner of selecting μ is described below). In the preferred embodiment, processor 130 is arranged to: receive r(i) and e(i) as inputs; form the conjugate of r(i) to produce r(i)'; multiply μ (a stored quantity), e(i), and r(i)'; form the summation of A(i) and μe(i)r(i)'; and then store the sum as A(i+1) in, for example, a register for use during the next processing interval.
Qualitatively, whenever the adaptive parameter A(i+1) is misadjusted, tone canceller 100 allows a large component of the interference to pass through into the slice error e(i); thus, the cross-correlation between the slice error e(i) and the tone reference r(i) will be non-zero. As parameter A(i+1) approaches the correct value to cancel the interference tone t(i), the component of the interference tone in the slice error e(i) approaches zero and the cross-correlation approaches zero. Finally, when parameter A(i+1) is correctly adjusted and the interference tone has been reduced essentially to zero in the slice error e(i), the cross-correlation is zero.
In mathematical terms, analysis of the steady-state performance of A(i+1) leads to the following equation:
A(i+1)=A(i)[1-μ(Rtt(0)+Rnn(0)+Rtn(0)+Rnt(0)]+μ[Rtt(τ)+Rnn(τ)+Rtn(τ)+Rnt(τ)], (6)
where Rij represents the correlation between the two variables i and j, namely, Rtt is the auto-correlation of the interference tone, Rnn is the auto-correlation of the noise, and Rtn or Rnt is the cross-correlation of the interference tone and noise, A is the expected value of A(i), and τ is the delay effected by delay device 110. If the noise is assumed to be white noise with variance σ n .spsb.2, and the tone is uncorrelated with the noise and has power σ t .spsb.2, then, equation (6) simplifies to:
A(i+1)=A(i)[1-ν(σ.sub.t.spsb.2 +σ.sub.n.spsb.2)]+νRtt(τ). (7)
If it is presumed that Rtt(τ) is constant for a constant τ, for large i (i.e. i→∞), then
A(i→∞)→ρ.sub.τ /(1+σ.sub.n.spsb.2 /σ.sub.t.spsb.2), (8)
where ρ.sub.τ is the normalized correlation coefficient over the delay τ. For a single interfering tone, ρ.sub.τ is a phase delay e -j ω.sbsp.t t .
Thus, the parameter A(i→∞) of equation (8) represents the adjustment to the tone reference r(i) exactly correlated with the interference tone t(i) in the incoming signal s(i) so as to cancel t(i) to the level of the noise floor.
Note that in the absence of an interference tone, the tone reference r(i) and the slice error e(i) do not correlate and the expected value of the adaptive coefficient A(i+1) is zero. Thus, no correction is added to the incoming signal s(i) to yield the corrected signal c(i).
The difference relation expressed by equation (7) is used to determine the range on adaption gain μ. If the z-transform of equation (7) is taken, the following obtains:
zA(z)=A(z)[1-μ(σ.sub.t.spsb.2 +σ.sub.n.spsb.2)]+μRtt(z). (9)
In order to achieve and maintain a stable system expressed by equation (9), it is necessary to impose the following conditions on μ:
0<μ<2/(σ.sub.t.spsb.2 +σ.sub.n.spsb.2). (10)
There is generally a noise enhancement effect due to the cancellation process. Because the tone reference r(i) has a component of random noise n(i) as well as the interference tone t(i), when the adjusted reference is added to the soft decision s(i), the noise on the reference is also added, as noted above. The effective noise gain can be expressed as:
G=1+|a|.sup.2. (11)
In the exemplary case discussed above, where the adaptive parameter is expressed as a phase delay in steady-state, and the noise variance is much less than the tone power, there is approximately a 3 dB gain in the noise power. Later, an arrangement to reduce the noise power is discussed.
If there is a correlation between the tone reference and the slice error other than that due to the interference, the performance of tone canceller 100 can be somewhat degraded. This situation occurs if the noise in the system is not white but correlated. The parameter A(i) will then adapt to a value which is a compromise between the cancellation of the interference and the decorrelation of the noise. To mitigate the effect of the correlated noise, an alternative arrangement for tone canceller 100, depicted in FIG. 7, may be implemented. In this version of tone canceller 100, the tone reference t(i) is delayed by N symbols by delay device 160, where N is chosen sufficiently large to decorrelate the noise samples.
Since the tone reference r(i) is a function of the soft decision before cancellation and the hard decision, the tone reference may be shown to have the following form:
r(i)=e(i-1)+a(i-1)r(i-1). (12)
From the form of equation (12), another version of tone canceller 100 may be realized, as shown in FIG. 8. The only differences between FIG. 6 and FIG. 8 are that: (i) the input to delay device 110 is derived from lead 131 having the tone reference r(i) rather than input lead 31 having s(i); and (ii) the input to delay device 140 is provided by the slice error on lead 46.
To this point in the description, the realizations of tone canceller 100 have been based upon a single adaptive parameter A(i). Those with ordinary skill in the art will readily appreciated that an adaptive filter, such as an FIR filter having variable coefficients, can replace element 130. Such a realization of tone canceller 100 is shown in FIG. 9 wherein FIR filter 135 is shown in place of element 130. Filter 135 adapts to match the bandshape of the interference and thus reduces the noise enhancement discussed above. For example, an N-tap FIR filter 135 may be configured such that all the taps delay and sum the tone estimate coherently, thereby providing a power gain of N 2 . The corresponding noise power out of FIR filter 135 would then be 1/N, so the noise gain becomes
G=1+7/N. (13)
Thus, only 4 taps would yield a noise enhancement of only 1 dB.
It will also be readily appreciated that FIR filter 135 may also be arranged to cancel multiple tones, as each tap could independently adapt to a separate tone.
Finally, it is instructive to elucidate, as a prelude for the next section, what has been alluded to above but which remained essentially implicit in the foregoing description, namely, that the QAM signal appearing on lead 31 has both in-phase and quadrature components which, ideally, are independent. Thus, mixer 30 of FIG. 2 is presumed to have a complex demodulation signal of the form e -j ω.sbsp.c t supplied by carrier recovery circuitry 35, where ω c is the IF radian frequency. The in-phase component of the signal on lead 31 is mixed with the cosine part of the complex demodulation signal, whereas the quadrature component is mixed with the sine part of the complex demodulation signal, and the two components are then processed in two separately realizable branches of tone canceller 100. Moreover, since the baseband signal s(i) is presumed to appear on lead 31 in the foregoing discussion, then the signal on lead 26 is a passband signal which may be expressed as s(i)e j ω.sbsp.c t . It is clear then that any signal provided to or derived by a tone canceller operating at passband, such as tone canceller 200 in FIG. 3, will be expressed with the multiplicative factor e j ω.sbsp.c t , that is, be "rerotated", so as to locate the signal in the frequency domain in a manner consistent with the frequency spectrum of the signal incoming on lead 26.
Passband Tone Canceller
With reference to FIG. 10, there is shown passband tone canceller 200 in accordance with the present invention; tone canceller 200 is commensurate with and may be compared to the arrangement of tone canceller 100 of FIG. 6. In particular, a tone reference, which appears on lead 216, is formed in subtractor 215 as the difference between a delayed version of the input signal appearing on lead 26 and a delayed version of the rerotated output signal appearing on lead 54; the delays are effected by delay devices 210 and 240, respectively. If signal s(i) is on lead 31, h(i) is on lead 41, and e(i) is on lead 46 (commensurate with FIG. 6), and carrier recovery circuitry 35 provides the complex demodulation signal e -j ω.sbsp.c t to mixer 30 and its conjugate e j ω.sbsp.c t to mixers 51 and 52, then the signal on lead 216 may be expressed as r(i)e j ω.sbsp.c t , and the signal on lead 231 is A(i)r(i)e j ω.sbsp.c t . Moreover, processing circuitry computes the next coefficient A(i+1) as follows:
A(i+1)=A(i)+μe(i)e.sup.jω.sbsp.c.sup.t r(i)'e.sup.-jω.sbsp.c.sup.t =A(i)+μe(i)r(i)'. (14)
Thus, the computation of A(i+1) is the same at passband as at baseband. Moreover, the gain factor μ is selected in the same manner as in the baseband case, that is, equation (10) must be satisfied.
With reference to FIG. 11, there is shown passband tone canceller 2001 in accordance with the present invention. Canceller 2001 is a variation on canceller 200 in that the tone reference on lead 316 is derived from the rerotated slice error on lead 53 and the previous tone estimate appearing on lead 331. Otherwise, the operation of canceller 2001 is commensurate with the operation of canceller 200 of FIG. 10. With the circuit arrangement of FIG. 11, the hard decisions from slicer 41 need not be rerotated, thereby simplifying the architecture.
Pre-filtering to Reduce Noise Enhancement
The noise enhancement as expressed, for example, by equations (11) and (13) in the baseband discussion, can be mitigated by a pre-filter arrangement in certain situations. In the specific case of canceling a NTSC carrier, the interference tone is known relative to the QAM signal carrier. For instance, if the QAM signal is centered in the same 6 MHz channel as a NTSC signal, the interference tone from the co-channel picture carrier of NTSC will occur at -1.75 MHz with respect to the QAM carrier. Such knowledge about the location of the interference tone can be used to construct a pre-filter which reduces noise away from the expected interference tone frequency. The noise power in the tone estimate used to correct the incoming signal is then the ratio of the wideband filter gain over the gain of the filter at the interference frequency. Illustrative of such an improvement is the filter arrangement depicted by tone canceller 2002 in FIG. 12. Tone canceller 2002 is essentially the same arrangement as tone canceller 200 of FIG. 10 except that single pole, IIR fixed filter 400 is shown as being interposed between adder 215 and processing device 230. Filter 400 is composed of delay element 415, gain device 410 (having a gain factor β), and adder 416. Adder 416 receives as inputs both the original tone reference carried by lead 216 and the new tone reference carried by lead 417. The new tone reference on lead 417 also serves as the sole input to delay element 415 and, in turn, the output of delay element 415 serves as the sole input to gain device 410. The amplitude response of filter 400 is set to peak at the expected interference tone frequency, such as the frequency 1.75 MHz below the QAM carrier in the given example.
The characteristic equation of filter 400 may be expressed as
f(i)=βf(i-1)+r(i), (15)
where f(i) appears on lead 417, β=be j ω.sbsp.0, with 0<b<1 being a fixed gain and ##EQU1## wherein f s is the sampling frequency. The total noise enhancement may then be expressed as
G=2/(1-b). (16 )
As is evidenced by equation (16), the total noise enhancement is always less than 3 dB and approaches 0 dB as b approaches 1. The gain b is chosen as a trade-off between the narrowness of the filter characteristic (i.e., reduced noise enhancement) and the uncertainty as to the precise location of the interfering tone; a value of b=0.85 is typical.
Although various embodiments which incorporate the teachings of the present invention have been shown and described in detail herein, those skilled in the art can readily devise many other varied embodiments that still incorporate these teachings.
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Techniques in a QAM digital communication system for canceling one or more interference tones in an incoming signal to produce an output signal by generating an estimate of the interference tone during the current processing interval, subtracting the estimate to produce the output signal, and modifying, if necessary, adaptive circuitry for use during the next processing interval. Techniques which apply either at passband or at baseband, that is, before or after mixing the incoming signal with the recovered carrier, are disclosed. The adaptive circuitry includes a single weighting parameter or an adaptive filer. Passband techniques utilize rerotation of baseband signals to appropriately align the spectra of the processed signals.
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BACKGROUND OF THE INVENTION
[0001] This invention relates generally to an apparatus and method for reinforcing a tower monopole to which loads in excess of the design capacity will be added. More particularly, the invention relates to an apparatus and method that includes the use of vertical rods distributed around a monopole and fixed to the monopole at spaced intervals to increase monopole capacity and stability.
[0002] As wireless telecommunications traffic has increased, so has the need for transmission equipment mounted on poles. The transmission equipment needs to be mounted not only on new poles in new geographic areas by individual wireless service providers, but also by competing service providers who install equipment covering overlapping geographic areas. One solution includes purchasing additional land or easements, applying for the necessary government permits and zoning approvals, and constructing a new tower for the new transmission equipment.
[0003] Purchasing land or easements, however, can be an expensive undertaking, especially in urban areas where wireless telecommunications demand may be greatest. Zoning regulations often limit the construction of new towers to be in the vicinity of existing towers, or may prohibit the construction of new towers in a service provider's preferred location. The expense and delay associated with the zoning process may be so great that construction of a new tower is not feasible. Further, once zoning regulations are satisfied and permits are obtained, the service provider then incurs the expense associated with the construction and maintenance of a new tower.
[0004] The tower itself must be designed to support the weight of the telecommunications transmission equipment as well as the forces exerted on the pole by environmental factors such as wind and ice. The equipment and the environmental factors produce bending moment forces that may cause a single-pole tower, also referred to as a tower monopole, to overturn if not designed for adequate stability. Traditionally, tower monopoles have been designed to withstand only the forces expected from the equipment originally installed on the pole. Rarely are tower monopoles designed with sufficient stability to allow for the addition of new equipment.
[0005] Conventional reinforcing methods include the use of split sleeves that fully encircle the tower monopole, extending from an anchor in the foundation upward on the monopole. Such a system uses a significant amount of materials and is cumbersome to install. Other methods require welding of materials to the monopole, which is difficult given the heights at which the welding must be performed.
[0006] Thus, there is a need for a method and an apparatus for increasing the capacity and stability of a single-pole tower that will support the loads of additional equipment as well as the corresponding additional environmental forces exerted on the pole.
SUMMARY OF THE INVENTION
[0007] The present invention is directed to reinforcing apparatus for tower monopoles, as may be needed when additional loads are placed on an existing pole. The tower monopoles are made up of a metal pole, a concrete foundation, and usually a baseplate at the juncture of the pole with the foundation.
[0008] A reinforcing apparatus according to the present invention comprises vertical threaded reinforcing bar rod segments that are partially embedded in the foundation. These rod segments are arranged around the pole and extend upward from the foundation. Similar rod segments are located above and in vertical alignment with the partially embedded rod segments. Means for joining the vertically adjacent rod segments are provided, and may comprise threaded couplings. There are also means for attaching rod segments to the pole at vertically spaced intervals, which may include brackets.
[0009] Brackets mounted to the pole include anchor bolts that fasten the bracket to the pole. U-shape bolts are fastened to the bracket and hold the rod segments to the bracket. The curved portions of the U-bolts may be aligned in the grooves of threaded reinforcing bar rod segments, preventing relative movement of the brackets and the rod segments.
[0010] Additional rod segments may further be installed above the prior rod segments, and likewise there may be completely embedded rod segments below and joined to the partially embedded rod segments.
[0011] In further embodiments, the reinforcing apparatus may comprise substantially vertical base rod segments arranged around the pole, extending upward from proximate to the foundation and having threaded ends, means for attaching the rod segments to the foundation, and means for mounting rod segments to the pole at vertically spaced intervals.
[0012] One embodiment includes substantially vertical threaded bar rod segments attached to a pole with brackets comprising U-bolts. The curved portions of the U-bolts are aligned in the grooves of the threaded reinforcing bar rod segments, preventing relative movement of the brackets and the rod segments.
[0013] A method is also provided for reinforcing a tower monopole. The steps include coring at least three holes in the foundation spaced around the pole for threaded reinforcing bar rod segments. Mounting devices are installed on the uppermost portion of each lowest rod segment that will remain exposed after being placed in the cored hole, and each lowest rod segment is placed into each respective cored hole. A portion of the lowest rod segments is left partially exposed above the foundation's surface and the void around each lowest rod segment in each respective cored hole is grouted. Mounting devices are installed on a plurality of additional threaded reinforcing bar rod segments and the additional rod segments are joined to each of the exposed ends of the lowest rod segments, using a threaded coupling. Holes are then drilled in the pole for the mounting devices and the mounting devices are attached to the pole.
[0014] Features and advantages of the present invention will become more apparent in light of the following detailed description of some embodiments thereof, as illustrated in the accompanying figures. As will be realized, the invention is capable of modifications in various respects, all without departing from the invention. Accordingly, the drawings and the description are to be regarded as illustrative in nature, and not as restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] [0015]FIG. 1 is an elevation view of one embodiment of the present invention, installed on an existing tower monopole.
[0016] [0016]FIG. 2 is a partial elevation view of the embodiment of FIG. 1.
[0017] [0017]FIG. 3 is a plan view of the baseplate of the embodiment of FIG. 1.
[0018] [0018]FIG. 4 is an elevation detail view of the baseplate of FIG. 3.
[0019] [0019]FIG. 5 is a sectional plan view taken along the line 5 - 5 of FIG. 1.
[0020] [0020]FIG. 6 is a sectional plan view taken along the line 6 - 6 of FIG. 1.
[0021] [0021]FIG. 7 is a partial elevation view of the mounting of the embodiment of FIG. 1 to the existing tower monopole.
[0022] [0022]FIG. 8 is an elevation view of a coupling of the embodiment of FIG. 1.
[0023] [0023]FIG. 9 is a partial plan detail view of the mounting arrangement of FIG. 7.
[0024] [0024]FIG. 10 is an elevation detail view of the mounting arrangement of FIG. 7.
DETAILED DESCRIPTION OF THE INVENTION
[0025] The present invention may be embodied in any application where a metal pole requires additional support beyond that provided by the pole itself. Specific embodiments disclosed herein include the mounting of reinforcing rods having threaded ends, such as threaded steel reinforcing bar, to steel tower monopoles. The scope of the invention is not intended to be limited by the materials or dimensions listed herein, but may be carried out using any materials and dimensions that allow the construction and operation of the present invention. Materials and dimensions depend on the particular application.
[0026] In the Figures herein, unique features receive unique numbers, while features that are the same in more than one drawing receive the same numbers throughout. Where a feature is modified between figures or similar features are in different locations, a letter may be added or changed after the feature number to distinguish that feature from the similar feature.
[0027] Referring now to the drawings, FIG. 1 shows the present invention 30 installed on an existing pole 32 . Existing transmission equipment 34 , for which the pole was originally designed, is mounted on the pole 32 . Additional new transmission equipment 36 is to be added, resulting in additional loads based on its own weight and forces from environmental factors such as wind and ice. An existing foundation 36 is substantially below grade 38 .
[0028] [0028]FIG. 2 is an enlarged view showing the foundation 36 and the lowest part of the reinforcing bars 52 . In general, two rods are inadequate, but three rods or more may be used. In the embodiment of FIG. 2 there are four separate rods 52 arranged symmetrically around the pole 32 ; one rod is not visible in FIG. 2. Although the threads are not shown, the reinforcing bars 52 are threaded and are mounted to the pole 32 using spaced mounting devices or brackets 54 . The threaded reinforcing bars 52 extend into the foundation 36 , being placed in cored holes 56 that are subsequently filled with cementitious grout. The threaded reinforcing bars 52 pass through or around the baseplate 58 . The bars 52 are substantially vertical, in that they are installed generally in alignment with the outside surface of the pole 32 . The terms “vertical” and “substantially vertical” are used interchangeably herein.
[0029] A variety of means for attaching a base rod segments to the foundation are available. For example, the attachment may be made using threaded couplings affixed to plates that are anchored to the foundation, with each affixed threaded coupling in vertical alignment with and attached to each base rod segment. A means for attaching the base rod segments to the foundation may comprise plates mounted to and spaced from the foundation, with each base rod segment passing through a plate and fixed in position with a nut threaded onto the base rod segment on the underside of the plate. Further, the attachment apparatus may comprise plates mounted to and spaced from the foundation, with each base rod segment welded to a plate.
[0030] A baseplate 58 is shown in FIG. 3, and is an example of an existing baseplate that was installed with the pole as modified to accommodate the present invention. Baseplates are usually present, but in some cases they are omitted. Existing bolts 70 remain in place. Stiffeners 72 are welded between the baseplate 58 and the pole 32 ; eight stiffeners 72 are used in this embodiment and are detailed in FIG. 4. Four holes 74 are torch-cut in the baseplate 58 to allow the holes 56 in the foundation 36 to be cored and the threaded reinforcing bars 52 to pass through. The holes 74 in the baseplate 58 may be cold-galvanized to protect the baseplate from corrosion.
[0031] The baseplate 58 shown in place on the foundation 36 in the section view of FIG. 5 has the present invention installed around and through it. Threaded reinforcing bars 52 pass through the holes 74 . Brackets 54 attach the threaded reinforcing bars 52 to the pole 32 . FIG. 6 is a section taken at a higher elevation, and shows the brackets 54 and threaded reinforcing bars 52 attached to the pole 32 . An elevation view of the threaded reinforcing bar 52 mounted to the pole 32 with the brackets 54 is shown in FIG. 7.
[0032] The threaded reinforcing bar segments 52 a , 52 b may be joined by the use of threaded couplings 80 . The threaded coupling 80 is backed on each side with a nut 82 a, 82 b to lock the coupling 80 into place. Such couplings 80 may be used at multiple locations and heights, as shown in FIG. 1, and both above grade and below grade. This threaded connection provides a relatively quick and easy means for joining segments of threaded reinforcing bar 52 a, 52 b together.
[0033] The material of the threaded reinforcing bar 52 and the coupling 80 may be hot-dipped galvanized steel, such as DYWIDAG THREADBAR® manufactured by Dycker-hoff & Widmann AG (DYWIDAG and THREADBAR are a registered trademarks of Dyckerhoff & Widmann Aktiensellschaft).
[0034] The bracket 54 is detailed in FIGS. 9 and 10. The bracket 54 comprises a reinforcing clip angle weldment 86 with anchor bolts 88 for connecting to the pole 32 and U-shaped bolts 90 for mounting the weldment 86 to the threaded reinforcing bar 52 . The U-shaped bolts 90 are fastened to the weldments 86 with nuts. The U-shaped bolts 90 are slanted such that their curved portions are lodged in, or in proximate registration with, the grooves 94 of the threaded reinforcing bar 52 . This configuration prevents relative movement between the grooves 94 and the threaded reinforcing bar 52 , since the threaded rod cannot slip through the U-bolt 90 .
[0035] The weldment 86 , anchor bolts 88 , and U-shaped bolts 90 may be steel, for example, either hot-dipped galvanized or stainless steel. The anchor bolts 88 are a type that may be used to secure to structural tube when there is access to only the outside, such as the Hollo-Bolt available from Lindapter North America Inc. of Ann Arbor, Mich.
[0036] A key design factor for the threaded reinforcing bars is the moment exerted on the pole and the bars, and the resulting stresses. Relevant design standards include, among others: AISC—Allowable Stress Design Specification, 9 th Edition (American Institute of Steel Construction); ANSI/TIA/EIA-222-F Standard, Structural Standards for Steel Antenna Towers and Antenna Supporting Structures (American National Standards Institute/Telecommunications Industry Association/Electronic Industries Alliance), and ACI 318-02, Building Code Requirements for Structural Concrete and Commentary (American Concrete Institute).
[0037] One exemplary embodiment is discussed below. This embodiment is provided to help further explain the invention, and should be understood to be illustrative and not limiting to the scope of the invention. This exemplary design is for a monopole having a height of 170 feet. The pole has 12 sides, a bottom diameter of 48 inches, and a top diameter of 16 inches. An allowable stress increase of 1.333 is used throughout the design calculations. The bracket spacing is selected to be 30 inches, with 2-½-inch diameter threaded reinforcing bar extending 90 feet high. The bars are considered to be fixed at the brackets. The design takes into consideration both compression and tension on the bars by setting tension bar force equal to compression bar force. The selected rod dimensions and bracket spacing of this design is confirmed to be acceptable by the following calculations.
[0038] Initially, the strength of the threaded reinforcing bars in compression must be computed. Considering the bracket spacing, the slenderness ratio (kl/r) of the bar is determined. This example uses 30 inches, so the length (l) is 30 inches. Despite considering the bars being fixed at the bracket connections, the k value used is 1.0 and remains so to ensure a conservative design. The radius of gyration (r) is calculated based on the given threaded reinforcing bar and varies depending on the diameter of the bar. With the slenderness ratio calculated, the allowable axial compressive stress (F a ) of the bar is determined. This is completed using one of the following respective equations E2-1 or E2-2 from AISC—Allowable Stress Design Specification, which are chosen based on comparison of the slenderness ratio to C c . Allowable compressive stress (F a ) is calculated using equation E2-1 when the slenderness ratio is smaller than the C c , equation E2-2 when the slenderness ratio exceeds C c .
F a = [ 1 - ( kl / r ) 2 2 C c 2 ] F y 5 3 + 3 ( kl / r ) 8 C c - ( kl / r ) 3 8 C c 3 , kl / r < C c
C c = 2 π 2 E F y E2 - 1 F a = 12 π 2 l 23 ( kl / r ) 2 , kl / r ≥ C c E2 - 2
[0039] F y is the minimum yield strength of the bar and E is the modulus of elasticity.
[0040] The compressive bar capacity is calculated using the following equation:
P
Allow
=ASI×F
a
×A
[0041] where P Allow is the allowable axial capacity of the threaded reinforcing bar, ASI is the allowable stress increase, and A is the cross sectional area of a single bar.
[0042] With the compressive capacity of the threaded reinforcing bar determined, the moment capacity from the bars can be calculated. As stated above, both the compressive and tensile bars are assumed to have equal load in them, up to a limit being the maximum compressive capacity of the bar. Although the tensile bar will be able to resist higher loads within its cross-section, this is ignored because the additional load in the tensile bar is matched in the compressive bar. The compressive bar will exceed its allotted axial capacity, thus ensuring plastic, irreversible deformation in the compressive bar. Using the forces as a couple, a resulting moment capacity is calculated from the bars. The moment is calculated from the following equation:
M Bars = # Bars × P Allow 2 × D Bars 2
[0043] where M Bars is the moment resistance calculated from the bars, # Bars is the total number of bars, and D Bars is the distance between the centers of diametrically opposite reinforcing bars.
[0044] The moment capacity of the monopole is checked to assess its development with respect to the full moment capacity of the threaded reinforcing bars. A ratio of d Pole /D Bars (where d pole is the diameter of the pole) is calculated and is multiplied by the allowable moment capacity of the pole to ensure conservative strain compatibility design. This reduction is validated by the use of a strain ratio calculation when the strains of both the bars and the monopole at their yield strength states are considered. The ratio of the yield strain of the monopole to the buckling strain of the bar typically is greater than 0.95, meaning the monopole will be near its maximum moment capacity when the bars reach their buckling limit. However, as the diameter of the monopole decreases, this ratio becomes smaller, leading to a larger reduction in monopole strength. Thus, d Pole /D Bars accounts for this as it becomes smaller with decreasing pole diameter. With this completed, the moment capacities of the reinforced monopole and the threaded reinforcing bars are summed to determine the system's bending resistance, as follows:
M
Total
=M
Pole
+M
Bars
[0045] where M Pole is the allowable bending stress of the pole times the pole's elastic section modulus times d Pole /D Bars .
[0046] Calculated shear and tension forces at the bracket/pole interface are used to determine bracket dimensions, spacing, and bolt diameters. Spacing may be reduced to prevent excessive bolt shear or increase the compressive bar capacity. For this example, the bracket is 10 inches long, 2¾ inches deep and approximately 6 inches tall. The bolts are ⅝-inch diameter. Stiffener characteristics are determined by calculating the proposed and allowable moments on the baseplate. In this example the height and length of the stiffener is 6 inches, and the thickness is 0.625 inches.
[0047] A variety of connection means to the foundation could be used. For example, a split plate could be placed around the existing baseplate, and threaded anchor rods could be placed through the new split plate and bolted. Likewise, the threaded rods could be screwed into a welded threaded fitting mounted on a separate plate. Modifications could also be made to the existing baseplate if necessary to allow bolting off threaded rods through welded plates spaced from the foundation.
[0048] It should also be understood that not every feature of the reinforcing system described is necessary to implement the invention as claimed in any particular one of the appended claims. Various elements of reinforcing arrangements may be used to fully enable the invention. It should also be understood that throughout this disclosure, where a process or method is shown or described, the steps of the method may be performed in any order or simultaneously, unless it is clear from the context that one step depends on another being performed first.
[0049] Specific embodiments of an invention are described herein. One of ordinary skill in the structural engineering arts will recognize that the invention has other applications in other environments. In fact, many embodiments and implementations are possible. For example, the reinforcing of the present invention may be applied to other types of poles, and the securing of the reinforcing bar with the U-bolt may be used in other applications where slippage needs to be prevented. In addition, the recitation “means for” is intended to evoke a means-plus-function reading of an element in a claim, whereas, any elements that do not specifically use the recitation “means for,” are not intended to be read as means-plus-function elements, even if they otherwise include the word “means.” The following claims are in no way intended to limit the scope of the invention to the specific embodiments described.
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Reinforcing apparatus for tower monopoles. The reinforcing apparatus comprises vertical threaded reinforcing bar rods, or rods with threaded ends, arranged around the pole and embedded in the pole foundation. The rods extend upward and are attached to the pole at spaced intervals using brackets. There are means provided for attaching rod segments to the pole at vertically spaced intervals, such as brackets. The rods comprise distinct rod segments, and means are provided for joining the vertically adjacent rod segments are provided, such as threaded couplings.
Brackets include anchor bolts that fasten the bracket to the pole and U-shape bolts fastened to the bracket to hold the rod segments to the bracket. The curved portions of the U-bolts are aligned in the grooves of the threaded reinforcing bar, preventing relative movement of the bracket and the rod segment. A method is also provided for reinforcing a tower monopole.
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FIELD OF THE INVENTION
[0001] The present invention relates to certain β-hydroxy- and amino-substituted carboxylic acids as matrix metalloproteinase inhibitors, particularly diastereomerically pure β-hydroxy-carboxylic acids, and to processes for their syntheses.
[0002] This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase by using said compounds.
BACKGROUND OF THE INVENTION
[0003] Matrix metalloproteinases (MMPs) are a naturally occurring superfamily of proteinases (enzymes) found in most mammals. The superfamily is composed of at least 26 members of zinc-containing enzymes produced by many cell types and sharing structural and functional features. Based on structural and functional considerations proteinases have been classified into different families and subfamilies (Vartak et al., J. Drug Targeting, 15, 1-20 (2007) and Hooper, FEBS Letters, 354, 1-6 (1994)), such as collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), metalloelastases (MMP-12), the MT-MMPs (MMP-14, -15, -16, -17, -24, and -25), matrilysins (MMP-7 and -26), stromelysins (MMP-3, -10, and -11) and sheddases such as TNF-converting enzymes (TACE and ACE).
[0004] Metalloproteinases are believed to be important in physiological disease processes that involve remodeling such as embryonic development, bone formation, and uterine remodeling during menstruation. One major biological function of MMPs is to catalyze the breakdown of connective tissues or extra-cellular matrix by their ability to hydrolyze various components of tissue or matrix. Apart from their role in degrading connective tissue, MMPs are involved in the activation of zymogen (pro) forms of other MMPs, thereby inducing MMP activation. They are also involved in the biosynthesis of TNF-alpha which is implicated in many pathological conditions.
[0005] MMP-12, also known as macrophage elastase or metalloelastase, is expressed in activated macrophages and has been shown to be secreted from alveolar macrophages from smokers as well as in foam cells in atherosclerotic lesions. MMP-12 knockout mouse studies have shown the development of significant emphysema, thus supporting its role in COPD. MMP-9 (gelatinase B, 92 kDa type IV collagenase) is one member of the MMP family that is released as a proenzyme and subsequently activated via a protease cascade in vivo.
[0006] The concentration of MMP-9 is increased in diseases like asthma, interstitial pulmonary fibrosis (IPF), adult respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD). Because of its proteolytic ability, MMP-9 has been implicated in tissue remodelling of the airways and lungs in chronic inflammatory diseases such as severe asthma and COPD. MMP-9 is also likely to be physiologically important because of its ability to regulate the digestion of components of the extracellular matrix as well as the activity of other proteases and cytokines MMP-9 is secreted in neutrophils, macrophages, and osteoclasts, which are easily induced by cytokines and growth factors, and plays a role in various physiological and pathological processes.
[0007] Over-expression or over-activation of an MMP or an imbalance between an MMP and a natural (i.e., endogenous) tissue inhibitor of a matrix metalloproteinase (TIMP) has been linked to a pathogenesis of diseases characterized by the breakdown of connective tissue or extracellular matrix.
[0008] Inhibition of the activity of one or more MMPs may be of benefit in the treatment of various inflammatory, autoimmune and allergic diseases such as inflammation of the joint, inflammation of the GI tract, inflammation of the skin, collagen remodeling, wound healing disorders, etc.
[0009] The design and therapeutic application of MMP inhibitors has revealed that the requirement of a molecule to be an effective inhibitor of MMP class of enzymes is a functional group (e.g., carboxylic acid, hydroxamic acid, or sulphydryl) capable of chelating to the active site Zn 2+ ion (Whittaker et al., Chem. Rev., 99, 2735-76, (1999)).
[0010] WO 2004/110974 discloses compounds and their physiologically functional derivatives described as inhibitors of matrix metalloproteinase enzymes. WO 2004/113279 discloses alleged inhibitors of matrix metalloproteinase. WO 2005/026120 discloses compounds also described as inhibitors of matrix metalloproteinase. U.S. Pat. No. 6,350,885 discloses tricyclic heteroaromatic compounds and their derivatives believed to be inhibitors of matrix metalloproteinases. WO 98/09940 discloses biphenyl butyric acids and their derivatives described as inhibitors of matrix metalloproteinases. J. Med. Chem ., Vol. 11(6), 1139-1144 (1968), discloses the synthesis and anti-inflammatory activity of 4-(p-biphenylyl)-3-hydroxybutyric acid and related compounds. WO 96/15096 discloses substituted 4-biarylbutyric or 5-biarylpentanoic acids and derivatives as alleged matrix metalloproteinase inhibitors. WO 2006/090235 describes 5-phenyl-pentanoic acid derivatives described as matrix metalloproteinase inhibitors for the treatment of asthma and other diseases.
[0011] Research has been carried out into the identification of inhibitors that are selective, e.g., for a few of the MMP subtypes. An MMP inhibitor of improved selectivity would avoid potential side effects associated with inhibition of MMPs that are not involved in the pathogenesis of the disease being treated.
[0012] Further, the use of more selective MMP inhibitors would require administration of a lower amount of the inhibitor for treatment of the disease than would otherwise be required and, after administration, partitioned in vivo among multiple MMPs. Still further, the administration of a lower amount of the compound would improve the margin of safety between the dose of the inhibitor required for therapeutic activity and the dose of the inhibitor at which toxicity is observed.
[0013] Many drugs exist as asymmetric three-dimensional molecules, i.e., chiral, and will therefore have several stereoisomers, depending upon the number of chiral centers present. The importance of evaluating new chemical entities having chiral centers as single isomers is to understand their effect on pharmacological and toxicological aspects. There are often pharmacodynamic, pharmacokinetic, and/or toxicological differences between enantiomers/diastereomers. Even if natural physiological mediators are achiral, based on their target environment, their receptors/enzymes may demonstrate a preference for only one optically pure enantiomer of agonists, antagonists, or inhibitors. From a pharmacokinetics point of view, chirality can have an influence on drug absorption, distribution, metabolism, and elimination. Pure single isomers may also offer advantages in terms of these pharmacokinetic parameters, thus enabling better developability of such molecules as drug candidates. It is also known that chirality has a significant effect of the physicochemical properties and crystallinity of a chiral molecule, which in turn have profound effects on the pharmacokinetics and developability of the molecule. Besides those mentioned above, regulatory principles guide one to preferably develop single isomers as drug candidates in order to avoid any pharmacological, pharmacokinetic, and toxicological problems that may arise due to interactions of an unwanted isomer with undesirable molecular targets.
[0014] In this context, synthetic strategies to produce pure single isomers offer advantages over analytical techniques of separation of isomers, not only in terms of cost and efficiency but larger amounts of compound can be prepared for elaborate pharmaceutical testing. Thus, compounds of present invention, which are single chiral isomers, have improved potency, improved pharmacokinetics, and/or improved physicochemical properties as compared to racemic compounds.
[0015] The present invention is directed to overcoming problems encountered in the art.
SUMMARY OF THE INVENTION
[0016] The present invention relates to β-hydroxy and amino substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure β-hydroxycarboxylic acids, corresponding processes for the synthesis of and pharmaceutical compositions containing the compounds of the present invention. The present invention relates to matrix metalloproteinase inhibitors useful as effective therapeutic or prophylactic agents in treatment of various inflammatory, autoimmune, and allergic diseases and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase using the compounds.
[0017] The present invention relates to compounds that act as dual MMP-9/12 inhibitors, which have desirable activity profiles and beneficial potency, selectivity, and/or pharmacokinetic properties.
[0018] The present invention includes new chemical entities having chiral centers as single isomers. Synthetic strategies to produce pure single isomers that offer advantages over analytical techniques of separation of isomers, not only in terms of cost and efficiency, but also a larger amount of the compound can be prepared for elaborate pharmaceutical testing are also provided.
[0019] Other aspects will be set forth in the description which follows, and in part will be apparent from the description or may be learned by the practice of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0020] The present invention relates to compounds having the structure of Formula I:
[0000]
[0000] wherein
* denotes or represents a stereogenic or asymmetric center of defined configuration selected from (R,R), (S,S), (R,S), and (S,R); n is an integer from 1 to 5; R 1 is hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, alkoxy, aryloxy, alkenyloxy or alkynyloxy; and R 2 is heterocyclyl, heteroaryl, NR 4 R 5 , —NHC(═Y)R 4 , —NHC(═Y)NR 5 R x , —NHC(═O)OR 4 , NHSO 2 R 4 , C(═Y)NR 4 R 5 , or C(═O)OR 6 ;
wherein
Y is oxygen, sulphur, OR S , —OC(═O)NR 4 R 5 , O-acyl, S(O) m R 4 , —SO 2 N(R 4 ) 2 , cyano, amidino, or guanidine; R x is R 4 or —SO 2 N(R 4 ) 2 ; and R 6 is hydrogen, alkyl, cycloalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl, or cycloalkylalkyl;
wherein
R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclylalkyl, or cycloalkylalkyl; m is an integer from 0 to 2; R 5 is hydrogen or R 4 ; R 3 is hydrogen, fluorine, alkyl, cycloalkylalkyl, or aralkyl; A is OH, OR 4 , —OC(═O)NR 4 R 5 , O-acyl, NH 2 , NR 4 R 5 , —NHC(═Y)R 4 , —NHC(═Y)NR 5 R x , —NHC(═O)OR 4 , or NHSO 2 R 4 ; and Q is optionally substituted aryl or heteroaryl.
[0034] Compounds of Formula I have particularly advantageous properties, which may include biological activities, such as modelling of LPS-included rat neutrophilia, selective inhibition of MMP-9 and MMP-12 activity, and inhibition of these activities without selectivity towards MMP-1 activity. Further, these advantageous properties may include solubilities which enhance preparation and administration of dosage forms, and improved bioavailability, as compared to known compounds, for example, those of WO 2005/026120.
[0035] In one embodiment, the invention relates to compounds of general Formula Ia,
[0000]
[0000] wherein
* denotes or represents a stereogenic or asymmetric center of defined configuration selected from (R,R), (S,S), (R,S), and (S,R); p is an integer from 1 to 3; R 1a is an optionally substituted aryl or heteroaryl; R 2a is a 5-6 membered N-containing heterocyclyl linked through N atom, which is optionally fused to aryl or heteroaryl, or spirofused to cycloalkyl, which can optionally be further substituted with one or more oxo groups, alkyl, cycloalkyl, halo, alkoxy, trifluoroalkyl, or aryl; and Q a is an optionally substituted 5 or 6 membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, or S.
[0041] Compounds of Formula Ia have particularly advantageous properties, which may include biological activities, such as modelling of LPS-included rat neutrophilia, selective inhibition of MMP-9 and MMP-12 activity, and inhibition of these activities without selectivity towards MMP-1 activity. Further, these advantageous properties may include solubilities which enhance preparation and administration of dosage forms, and improved bioavailability, as compared to known compounds, for example, those of WO 2005/026120.
[0042] In another embodiment, the invention relates to compounds of general Formula Ib,
[0000]
[0000] wherein
* denotes or represents a stereogenic or asymmetric center of defined configuration selected from (R,R), (S,S), (R,S), and (S,R); p is an integer from 1 to 3; R 1b is an optionally substituted phenyl or heteroaryl wherein optional substituents can be selected from one or more of alkyl, cycloalkyl, halo, alkoxy, trifluoroalkyl, or aryl; and R 2b is a 5-6 membered N-containing heterocyclyl linked through N atom, which is optionally fused to aryl or heteroaryl, or spirofused to cycloalkyl, which can optionally be further substituted with one or more oxo group, alkyl, cycloalkyl, halo, alkoxy, trifluoroalkyl, or aryl.
[0047] Compounds of Formula Ib have particularly advantageous properties, which may include biological activities, such as modelling of LPS-included rat neutrophilia, selective inhibition of MMP-9 and MMP-12 activity, and inhibition of these activities without selectivity towards MMP-1 activity. Further, these advantageous properties may include solubilities which enhance preparation and administration of dosage forms, and improved bioavailability, as compared to known compounds, for example, those of WO 2005/026120.
[0048] In another embodiment, the invention relates to compounds of general Formula Ic,
[0000]
[0000] wherein
* denotes or represents a stereogenic or asymmetric center of defined configuration selected from (R,R), (S,S), (R,S), and (S,R); p is an integer from 1 to 3; R 1c is optionally substituted phenyl, pyridyl, pyrimidyl, thienyl, or pyrazolyl; wherein optional substitutent can be selected from with one or more alkyl, halo, alkoxy, trifluoroalkyl, or aryl; and R 2c is a 5-6 membered N-containing heterocyclyl linked through N atom, which is optionally fused to aryl or heteroaryl, or spirofused to cycloalkyl, which can optionally be further substituted with one or more oxo group, alkyl, cycloalkyl, halo, alkoxy, trifluoroalkyl, or aryl.
[0053] In compounds of Formula Ic, R 2 , represents 5-6 membered N-containing heterocyclyl linked through N atom, which is optionally fused to aryl or heteroaryl, or spirofused to cycloalkyl, for example, benzotriazinone, isoindoledione, pyrimidinedione, aza-spiro[4.5]decanedione, benzo-oxazinedione, imidazolidinedione, or phthalazinone.
[0054] Compounds of Formula Ic have particularly advantageous properties, which may include biological activities, such as modelling of LPS-included rat neutrophilia, selective inhibition of MMP-9 and MMP-12 activity, and inhibition of these activities without selectivity towards MMP-1 activity. Further, these advantageous properties may include solubilities which enhance preparation and administration of dosage forms, and improved bioavailability, as compared to known compounds, for example, those of WO 2005/026120.
[0055] The diastereomers, rotational isomers, N-oxides, polymorphs, pharmaceutically acceptable salts and pharmaceutically acceptable solvates of these compounds, prodrugs, and metabolites having the same type of activity are also provided, as well as pharmaceutical compositions comprising the compounds, their metabolites, diastereomers, conformational isomers, N-oxides, polymorphs, solvates, or pharmaceutically acceptable salts thereof, in combination with a pharmaceutically acceptable carrier and optionally included excipients.
[0056] In one embodiment, the invention encompasses compounds of Formula (I), which may include, but are not limited to, the following, for example,
(2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4-pyrimidin-5-ylphenyl)pentanoic acid (Compound No. 1); (2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 2); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 3); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 4); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 5); (2S,3R)-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 6); (2S,3R)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 7); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 8); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 9); (2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 10); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 11); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 12); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 13); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 14); (2S,3R)-5-(4′-chloro-3′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 15); (2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 16); (2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 17); (2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 18); (2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 19); (2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-chlorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 20); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 21); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 22); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 23); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 24); (2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 25); (2S,3R)-5-(4′-ethylbiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 26); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 27); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 28); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4-pyrimidin-5-ylphenyl)pentanoic acid (Compound No. 29); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 30); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4-pyridin-3-ylphenyl)pentanoic acid (Compound No. 31); (2S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 32); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 33); (2S,3R)-3-hydroxy-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 34); (2S,3R)-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 35); (2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 36); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 37); (2S,3R)-3-hydroxy-2-{2-[7-(6-methoxypyridin-3-yl)-4-oxo-1,2,3-benzotriazin-3(4H)-yl]ethyl}-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 38); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 39); (2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 40); (2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 41); (2S,3R)-3-hydroxy-2-{2-[5-(6-methoxypyridin-3-yl)-4-oxo-1,2,3-benzotriazin-3(4H)-yl]ethyl}-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 42); (2S,3R)-5-(4′-chloro-3′-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 43); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(1-isobutyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 44); (2S,3R)-5-biphenyl-4-yl-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 45); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 46); (2S,3R)-5-(3,3′-difluoro-4′-methoxybiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 47); (2S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 48); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(1H-tetrazol-1-yl)phenyl]pentanoic acid (Compound No. 49); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 50); (2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 51); (2S,3R)-3-hydroxy-5-[4-(1-isobutyl-1H-pyrazol-4-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 52); (2S,3R)-5-biphenyl-4-yl-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 53); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 54); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-β-fluoro-4-methoxyphenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 55); (2S,3R)-5-(4′-chloro-3-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 56); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[6-(4-methoxyphenyl)pyridin-3-yl]pentanoic acid (Compound No. 57); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-β-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 58); (2S,3R)-5-[6-(4-chlorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 59); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 60); (2S,3R)-5-[4-(4-chlorophenyl)-2-thienyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 61); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)-2-thienyl]pentanoic acid (Compound No. 62); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-{4-[4-(trifluoromethyl)phenyl]-2-thienyl}pentanoic acid (Compound No. 63); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[4-β-fluoro-4-methoxyphenyl)-2-thienyl]-3-hydroxypentanoic acid (Compound No. 64); (2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 65); (2S,3R)-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 66); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 67); (2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 68); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 69); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[2-fluoro-5-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 70); (2S,3R)-5-(4′-chloro-4-fluorobiphenyl-3-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 71); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-fluoro-4′-(trifluoromethyl)biphenyl-3-yl]-3-hydroxypentanoic acid (Compound No. 72); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[4-fluoro-3-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 73); (2S,3R)-5-(4′-chloro-6-fluorobiphenyl-3-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 74); (2S,3R)-5-(3′,6-difluoro-4′-methoxybiphenyl-3-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 75); (2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 76); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 77); (2S,3R)-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 78); (2S,3R)-2-[2-(5-chloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 79); (2S,3R)-2-[2-(4-fluoro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 80); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 81); (2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-phenylpentanoic acid (Compound No. 82); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-phenylpentanoic acid (Compound No. 83); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4(trifluoromethyl)phenyl]pentanoic acid (Compound No. 84); (2S,3R)-5-(4-tert-butylphenyl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 85); (2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 90); (2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 91); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 92); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 93); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 94); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 95); (2S,3R)-5-(2′,4′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 97); (2S,3R)-2-[2-(6-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 98); (2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 99); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-isopropylbiphenyl-4-yl)pentanoic acid (Compound No. 100); (2S,3R)-5-(3′-chloro-4′-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 101); (2S,3R)-5-(4′-butylbiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 102); (2S,3R)-5-(2′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 103); (2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 104); (2S,3R)-3-hydroxy-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 105); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 106); (2S,3R)-5-[6-(3,4-difluorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 107); (2S,3R)-5-[6-(4-chloro-3-fluorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 108); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-(4-fluorophenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 109); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-β-fluoro-4-methylphenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 110); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 111); (2S,3R)-2-[2-(8-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 112); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 113); (2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 114); (2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 115); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 116); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 117); (2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 118); (2S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 119); (2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 121); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 122); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 123); (2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 124); (2S,3R)-3-hydroxy-5-[4-(1-isobutyl-1H-pyrazol-4-yl)phenyl]-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 125); (2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 126); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 127); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 128); (2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 129); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 130); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 131); (2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 132); (2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 133); (2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 134); (2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 135); (2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 136); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 137); (2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 138); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 139); (2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 140); (2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 141); (2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 142); (2S,3S)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 143); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 144); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 145); (2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 146); (2 S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]pentanoic acid (Compound No. 147); (2 S,3R)-5-[4-(6-chloropyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 148); (2 S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 149); (2 S,3R)-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 150); (2 S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 151); (2 S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 152); (2 S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 153); (2 S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]pentanoic acid (Compound No. 154); (2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 155); (2 S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]pentanoic acid (Compound No. 156); (2 S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]pentanoic acid (Compound No. 157); (2 S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 158); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 159); (2 S,3R)-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 160); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 161); (2 S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 162); (2 S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 163); (2 S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 164); (2 S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3 (4H)-yl)ethyl]pentanoic acid (Compound No. 165); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 166); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 167); (2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 168); (2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 169); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 170); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 171); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 172); (2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 173); (2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 174); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 175); (2S,3R)-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)-2-thienyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 176); (2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 177); (2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 178); (2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 179); (2S,3R)-5-[4-(2-chloropyridin-3-yl)phenyl]-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 180); (2S,3R)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 181); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 182); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 183); (2S,3R)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 184); (2S,3R)-3-hydroxy-5-[4-(2-methoxypyrimidin-5-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 185); (2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 186); (2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 187); (2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 188); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 189); (2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 190); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 191); (2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 192); (2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 193); (2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(2-methoxypyrimidin-5-yl)phenyl]pentanoic acid (Compound No. 194); (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(2-methoxypyrimidin-5-yl)phenyl]pentanoic acid (Compound No. 195); (2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(1-oxophthalazin-2(1H)-yl)ethyl]pentanoic acid (Compound No. 196); (2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-β-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)ethyl]pentanoic acid (Compound No. 197); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-{2-[4-oxo-7-(trifluoromethyl)-1,2,3-benzotriazin-3(4H)-yl]ethyl}pentanoic acid (Compound No. 198); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(1-oxophthalazin-2(1H)-yl)ethyl]pentanoic acid (Compound No. 199); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-β-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)ethyl]pentanoic acid (Compound No. 200); (2S,3R)-2-[2-(7,9-dioxo-8-azaspiro[4.5]dec-8-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 201); (2S,3R)-2-[2-(2,4-dioxo-2H-1,3-benzoxazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 202); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)ethyl]pentanoic acid (Compound No. 203); (2S,3R)-5-(4-chloro-3-fluorophenyl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 204); (2R,3S)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 205); (2R,3S)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 206); (2R,3S)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 207); (2S,3S)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 208); (2S,3R)-3-hydroxy-5-[4-(5-methylpyridin-2-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 209); (2S,3R)-5-[4-(6-fluoropyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 210); (2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 211); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 212); (2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 213); (2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 214); (2S,3R)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 215); (2S,3R)-5-(2′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 216); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 217); (2S,3R)-5-(3′-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 218); (2S,3R)-3-hydroxy-5-[4-(2-methoxypyrimidin-5-yl)phenyl]-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 219); (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 220); (2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 221); (2S,3R)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 222); (2S,3R)-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 223); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 224); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 225); (2S,3R)-3-hydroxy-5-[4-(6-hydroxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 226); (2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-{2-[4-oxo-7-(trifluoromethyl)-1,2,3-benzotriazin-3(4H)-yl]ethyl}pentanoic acid (Compound No. 227); (2S,3R)-2-[2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 228); (2S,3R)-3-(acetyloxy)-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 229); (2S,3R)-2-[2-(8-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 230); (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(2,4-dioxo-2H-1,3-benzoxazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 231); and (2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-(2-{[(2-hydroxyphenyl) carbonyl]amino}ethyl)pentanoic acid (Compound No. 232).
[0283] In another embodiment, the present invention relates to a chiral auxiliary (4S)-4-benzyl-1,3-thiazolidin-2-one which would be of versatile utility for asymmetric synthesis. Chiral auxiliaries are utilized in a wide variety of synthetic transformations which include, but are not limited to, asymmetric aldol condensation, stereoselective alkylation, stereoselective Diels-Alder reaction, stereoselective Michael reactions, and stereoselective differentiation of enantiotopic groups in molecules bearing prochiral centers. The chiral auxiliary is used in stoichiometric amounts to induce the stereoselective formation of stereogenic centers.
[0284] In another embodiment, the present invention relates to the therapeutically effective dose of a compound of Formula I in combination with one or more other therapeutic agents used for treating various inflammatory and allergic diseases. Examples of such therapeutic agents include, but are not limited to:
1) Anti-inflammatory agents, experimental or commercial such as (i) nonsteroidal anti-inflammatory agents piroxicam, diclofenac, propionic acids, fenamates, pyrazolones, salicylates, PDE-4/p38 MAP Kinase/Cathepsin inhibitors, CCR-3 antagonists, iNOS inhibitors, tryptase and elastase inhibitors, beta-2 integrin antagonists, cell adhesion inhibitors (especially ICAM), or adenosine 2a agonists; (ii) leukotrienes LTC4/LTD4/LTE4/LTB4-Inhibitors, 5-lipoxygenase inhibitors, and PAF-receptor antagonists; (iii) Cox-2 inhibitors; (iv) other MMP inhibitors; (v) interleukin-1 inhibitors; or (vi) corticosteroids such as alclometasone, amcinonide, amelometasone, beclometasone, betamethasone, budesonide, ciclesonide, clobetasol, cloticasone, cyclomethasone, deflazacort, deprodone, dexbudesonide, diflorasone, difluprednate, fluticasone, flunisolide, halometasone, halopredone, hydrocortisone, methylprednisolone, mometasone, prednicarbate, prednisolone, rimexolone, tixocortol, triamcinolone, ulobetasol, rofleponide, GW 215864, KSR 592, ST-126, dexamethasone, and pharmaceutically acceptable salts or solvates thereof. Preferred corticosteroids include, for example, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, and dexamethasone; 2) Beta-agonists, experimental or commercial, suitable β2-agonists include, for example, (i) one or more of albuterol, salbutamol, biltolterol, pirbuterol, levosalbutamol, tulobuterol, terbutaline, bambuterol, metaproterenol, fenoterol, salmeterol, carmoterol, arformoterol, or formoterol, and pharmaceutically acceptable salts or solvates thereof. One or more β2-agonists may be chosen from those in the art or subsequently discovered. (ii) The β2-agonists may include one or more compounds described in, for example, U.S. Pat. Nos. 3,705,233; 3,644,353; 3,642,896; 3,700,681; 4,579,985; 3,994,974; 3,937,838; 4,419,364; 5,126,375; 5,243,076; 4,992,474; and 4,011,258; 3) antihypertensive agents, (i) ACE inhibitors, e.g., enalapril, lisinopril, valsartan, Telmisartan, and quinapril; (ii) angiotensin II receptor antagonists and agonists, e.g., losartan, candesartan, irbesartan, valsartan, and eprosartan; (iii) β-blockers; and (iv) calcium channel blockers; 4) immunosuppressive agents, for example, cyclosporine, azathioprine, and methotrexate; anti-inflammatory corticosteroids; and 5) anti-infective agents, e.g., antibiotics and antivirals.
DEFINITIONS
[0290] The following definitions apply to terms as used herein.
[0291] The term “alkyl”, unless otherwise specified, refers to a monoradical branched or unbranched saturated hydrocarbon chain having from 1 to 20 carbon atoms. Alkyl groups can be optionally interrupted by atoms or groups independently selected from oxygen, sulfur, a phenylene, sulphinyl, sulphonyl, group or —NR α —, wherein R α can be hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, acyl, aralkyl, —C(═O)OR λ , SO m R ψ , or —C(═O)NR λ R π . This term can be exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-decyl, tetradecyl, and the like. Alkyl groups may be substituted further with one or more substituents selected from alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, oxo, thiocarbonyl, carboxy, carboxyalkyl, aryl, heterocyclyl, heteroaryl, (heterocyclyl) alkyl, cycloalkoxy, —CH═N—O(C 1-6 alkyl), —CH═N—NH(C 1-6 alkyl), —CH═N—NH(C 1-6 alkyl)-C 1-6 alkyl, arylthio, thiol, alkylthio, aryloxy, nitro, aminosulfonyl, aminocarbonylamino, —NHC(═O)R, —NR λ R π , —C(═O)NR λ R π , —NHC(═O)NR λ R π , —C(═O)heteroaryl, C(═O)heterocyclyl, —O—C(═O)NR λ R π {wherein R λ and R π are independently selected from hydrogen, halogen, hydroxy, alkyl, alkenyl, alkynyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, aryl, aralkyl, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, or carboxy}, nitro, or —SO m R ψ (wherein m is an integer from 0-2 and R ψ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl, heterocyclyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl). Unless otherwise constrained by the definition, alkyl substituents may be further substituted by 1-3 substituents selected from alkyl, alkenyl, alkynyl, carboxy, —NR λ R π , —OC(═O)NR λ R π , —NHC(═O)NR λ R π , hydroxy, alkoxy, halogen, CF 3 , cyano, and —SO m R ψ ; or an alkyl group also may be interrupted by 1-5 atoms of groups independently selected from oxygen, sulfur or —NR α — (wherein R α , R λ , R π , m, and R ψ are the same as defined earlier). Unless otherwise constrained by the definition, all substituents may be substituted further by 1-3 substituents selected from alkyl, alkenyl, alkynyl, carboxy, carboxyalkyl, —NR λ R π , —C(═O)NR λ R π , —O—C(═O)NR λ R π , hydroxy, alkoxy, halogen, CF 3 , cyano, and —SO m R ψ (wherein R λ , R π , m, and R ψ are the same as defined earlier); or an alkyl group as defined above that has both substituents as defined above and is also interrupted by 1-5 atoms or groups as defined above.
[0292] The term “alkenyl”, unless otherwise specified, refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group having from 2 to 20 carbon atoms with cis, trans or geminal geometry. Alkenyl groups can be optionally interrupted by atoms or groups independently chosen from oxygen, sulfur, phenylene, sulphinyl, sulphonyl and —NR α — (wherein R α is the same as defined earlier). In the event that alkenyl is attached to a heteroatom, the double bond cannot be alpha to the heteroatom. Alkenyl groups may be substituted further with one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, —NHC(═O)R λ , —NR λ R π , —C(═O)NR λ R π , —NHC(═O)NR λ R π , —O—C(═O)NR λ R π , alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, keto, carboxyalkyl, thiocarbonyl, carboxy, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, heterocyclyl, heteroaryl, heterocyclyl alkyl, heteroaryl alkyl, aminosulfonyl, aminocarbonylamino, alkoxyamino, hydroxyamino, alkoxyamino, nitro, or SO m R ψ (wherein R λ , R π , m and R ψ are as defined earlier). Unless otherwise constrained by the definition, alkenyl substituents optionally may be substituted further by 1-3 substituents selected from alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkoxy, halogen, —CF 3 , cyano, —NR λ R π , —C(═O)NR λ R π , —O—C(═O)NR λ R π , and —SO m R ψ (wherein R λ , R π , m, and R ψ are as defined earlier). Groups, such as ethenyl or vinyl (CH═CH 2 ), 1-propylene, allyl (—CH 2 CH═CH 2 ), iso-propylene (—C(CH 3 )═CH 2 ), bicyclo[2.2.1]heptene, and the like, exemplify this term.
[0293] The term “alkynyl”, unless otherwise specified, refers to a monoradical of an unsaturated hydrocarbon, having from 2 to 20 carbon atoms. Alkynyl groups can be optionally interrupted by atoms or groups independently chosen from oxygen, sulfur, phenylene, sulphinyl, sulphonyl, and —NR α — (wherein R α is the same as defined earlier). In the event that alkynyl groups are attached to a heteroatom, the triple bond cannot be alpha to the heteroatom. Alkynyl groups may be substituted further with one or more substituents selected from alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, oxo, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, aminosulfonyl, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, —NHC(═O)R λ , —NR λ R π , —NHC(═O)NR λ R π , —C(═O)NR λ R π , —O—C(═O)NR λ R π or —SO m R ψ (wherein R λ , R π , m, and R ψ are the same as defined earlier). Unless otherwise constrained by the definition, alkynyl substituents optionally may be substituted further by 1-3 substituents selected from alkyl, alkenyl, alkynyl, carboxy, carboxyalkyl, hydroxy, alkoxy, halogen, CF 3 , —NR λ R π , —C(═O)NR λ R π , —NHC(═O)NR λ R π , —C(═O)NR λ R π , cyano, or —SO m R ψ (wherein R λ , R π , m, and R ψ are the same as defined earlier).
[0294] The term “cycloalkyl”, unless otherwise specified, refers to cyclic alkyl groups of from 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings, which may optionally contain one or more olefinic bonds, unless otherwise constrained by the definition. Such cycloalkyl groups can include, for example, single ring structures, including cyclopropyl, cyclobutyl, cyclooctyl, cyclopentenyl, and the like, or multiple ring structures, including adamantanyl, bicyclo[2.2.1]heptane, or cyclic alkyl groups to which is fused an aryl group, for example, indane and the like. Spiro and fused ring structures can also be included. Cycloalkyl groups may be substituted further with one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, aminosulfonyl, aminocarbonylamino, —NR λ R π , —NHC(═O)NR λ R π , —NHC(═O)R λ , —C(═O)NR λ R π , —O—C(═O)NR λ R π , nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, or SO m R ψ (wherein R λ , R π , m, and R ψ are the same as defined earlier). Unless otherwise constrained by the definition, cycloalkyl substituents optionally may be substituted further by 1-3 substituents selected from alkyl, alkenyl, alkynyl, carboxy, hydroxy, alkoxy, halogen, CF 3 , —NR λ R π , —NHC(═O)NR λ R π , —OC(═O)NR λ R π , cyano, or SO m R ψ (wherein R λ , R π , m, and R ψ are the same as defined earlier). “Cycloalkylalkyl” refers to alkyl-cycloalkyl group linked through alkyl portion, wherein the alkyl and cycloalkyl are the same as defined earlier.
[0295] The term “aralkyl”, unless otherwise specified, refers to alkyl-aryl linked through an alkyl portion (wherein alkyl is as defined above) and the alkyl portion contains 1 to 6 carbon atoms and aryl is as defined below. Examples of aralkyl groups include benzyl, ethylphenyl, propylphenyl, naphthylmethyl, and the like.
[0296] The term “aryl”, unless otherwise specified, refers to aromatic system having 6 to 14 carbon atoms, wherein the ring system can be mono-, bi-, or tricyclic and are carbocyclic aromatic groups. For example, aryl groups include, but are not limited to, phenyl, biphenyl, anthryl, or naphthyl ring and the like, optionally substituted with 1 to 3 substituents selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, acyl, aryloxy, CF 3 , cyano, nitro, COOR ψ , NHC(═O)R λ , —NR λ R π , —C(═O)NR λ R π , —NHC(═O)NR λ R π , —O—C(═O)NR λ R π , —SO m R ψ , carboxy, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl or amino carbonyl amino, mercapto, haloalkyl, optionally substituted aryl, optionally substituted heterocyclylalkyl, thioalkyl, —CONHR π , —OCOR π , —COR π , —NHSO 2 R π , or SO 2 NHR π (wherein R λ , R π , m, and R ψ are the same as defined earlier). Aryl groups optionally may be fused with a cycloalkyl group, wherein the cycloalkyl group may optionally contain heteroatoms selected from O, N, or S. Groups such as phenyl, naphthyl, anthryl, biphenyl, and the like exemplify this term.
[0297] The term “aryloxy” denotes the group O-aryl wherein aryl is the same as defined above.
[0298] The term “heteroaryl”, unless otherwise specified, refers to an aromatic ring structure containing 5 or 6 ring atoms or a bicyclic or tricyclic aromatic group having from 8 to 10 ring atoms, with one or more heteroatoms independently selected from N, O, or S optionally substituted with 1 to 4 substituents selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, acyl, carboxy, aryl, alkoxy, aralkyl, cyano, nitro, heterocyclyl, heteroaryl, —NR λ R π , CH═NOH, (CH 2 ) w C(═O)R η {wherein w is an integer from 0 to 4 and R η is hydrogen, hydroxy, OR λ , NR λ R π , —NHOR ω or —NHOH}, —C(═O)NR λ R π —NHC(═O)NR λ R π , —SO m R ψ , —O—C(═O)NR λ R π , —O—C(═O)R λ , or —O—C(═O)OR λ (wherein m, R ψ , R λ , and R π are as defined earlier and R e ) is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, heteroarylalkyl, or heterocyclylalkyl). Unless otherwise constrained by the definition, the substituents are attached to a ring atom, i.e., carbon or heteroatom in the ring. Examples of heteroaryl groups include oxazolyl, imidazolyl, pyrrolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, thiazolyl, oxadiazolyl, benzoimidazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thienyl, isoxazolyl, triazinyl, furanyl, benzofuranyl, indolyl, benzthiazinyl, benzthiazinonyl, benzoxazinyl, benzoxazinonyl, quinazonyl, carbazolyl phenothiazinyl, phenoxazinyl, benzothiazolyl, or benzoxazolyl, and the like.
[0299] The term “heterocyclyl”, unless otherwise specified, refers to a non-aromatic monocyclic or bicyclic cycloalkyl group having 5 to 10 atoms wherein 1 to 4 carbon atoms in a ring are replaced by heteroatoms selected from O, S, or N, and optionally are benzofused or fused with a heteroaryl having 5 to 6 ring members and/or optionally are substituted, wherein the substituents are selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, acyl, optionally substituted aryl, alkoxy, alkaryl, cyano, nitro, oxo, carboxy, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, —O—C(═O)Rλ, —O—C(═O)ORλ, —C(═O)NRλRπ, SOmRψ, —O—C(═O)NRλRπ, —NHC(═O)NRλRπ, —NRλRπ, mercapto, haloalkyl, thioalkyl, —COORψ, —COONHRλ, —CORλ, —NHSO2Rλ, or SO2NHRλ (wherein m, Rψ, Rλ, and Rπ are as defined earlier) or guanidine. Heterocyclyl can optionally include rings having one or more double bonds. Such ring systems can be mono-, bi-, or tricyclic. Carbonyl or sulfonyl group can replace carbon atoms of heterocyclyl. Unless otherwise constrained by the definition, the substituents are attached to the ring atom, i.e., carbon or heteroatom in the ring. Also, unless otherwise constrained by the definition, the heterocyclyl ring optionally may contain one or more olefinic bonds. Examples of heterocyclyl groups include benzotriazinone, isoindoledione, pyrimidinedione, aza-spiro[4.5]decanedione, benzo-oxazinedione, imidazolidinedione, phthalazinone, oxazolidinyl, tetrahydrofuranyl, dihydrofuranyl, benzoxazinyl, benzthiazinyl, imidazolyl, benzimidazolyl, tetrazolyl, carbaxolyl, indolyl, phenoxazinyl, phenothiazinyl, dihydropyridinyl, dihydroisoxazolyl, dihydrobenzofuryl, azabicyclohexyl, thiazolidinyl, dihydroindolyl, pyridinyl, isoindole 1,3-dione, piperidinyl, tetrahydropyranyl, piperazinyl, 3H-imidazo[4,5-b]pyridine, isoquinolinyl, 1H-pyrrolo[2,3-b]pyridine, or piperazinyl, and the like.
[0300] The term “cycloalkylalkyl” refers to cycloalkyl group linked through alkyl portion, wherein the alkyl having 1 to 6 carbon atoms and cycloalkyl are the same as defined earlier.
[0301] The term “heteroarylalkyl” refers to heteroaryl group linked through alkyl portion, wherein the alkyl having 1 to 6 carbon atoms and heteroaryl are the same as defined earlier.
[0302] The term “heterocyclylalkyl” refers to heterocyclyl group linked through alkyl portion, wherein the alkyl having 1 to 6 carbon atoms and heterocyclyl are the same as defined earlier.
[0303] The term “amino” refers to NH 2 .
[0304] The term “acyl” refers to C(═O)R 4 wherein R 4 is the same as defined earlier.
[0305] The term “thioacyl” refers to C(═S)R 4 wherein R 4 is the same as defined above.
[0306] The term “halogen” refers to fluorine, chlorine, bromine, or iodine.
[0307] The term “leaving group” refers to groups that exhibit or potentially exhibit the properties of being labile under the synthetic conditions and also of being readily separated from synthetic products under defined conditions. Examples of leaving groups include, but are not limited to, halogen (e.g., F, Cl, Br, I), triflates, tosylate, mesylates, alkoxy, thioalkoxy, or hydroxy radicals, and the like.
[0308] The term “protecting groups” refers to moieties that prevent chemical reaction at a location of a molecule intended to be left unaffected during chemical modification of such molecule. Unless otherwise specified, protecting groups may be used on groups, such as hydroxy, amino, or carboxy. Examples of protecting groups are found in T. W. Greene and P. G. M. Wuts, “Protective Groups in Organic Synthesis”, 2 nd Ed., John Wiley and Sons, New York, N.Y., which is incorporated herein by reference. The species of the carboxylic protecting groups, amino protecting groups, or hydroxy protecting groups employed are not critical, as long as the derivatised moiety/moieties is/are stable to conditions of subsequent reactions and can be removed without disrupting the remainder of the molecule.
[0309] Compounds described herein can contain one or more asymmetric carbon atoms and thus occur as diastereomers. These compounds can also exist as conformers/rotamers. All such isomeric forms of these compounds are included herein. Each stereogenic carbon may be of the R or S configuration. Although the specific compounds exemplified in this application may be depicted in a particular stereochemical configuration, compounds having either the opposite stereochemistry at any given chiral center, or mixtures thereof, are envisioned.
[0310] The term “pharmaceutically acceptable salts” forming part of this invention includes the salts of carboxylic acid moiety, which may be prepared by reacting the compound with appropriate base to provide corresponding base addition salts. Examples of such bases are alkali metal hydroxides including potassium hydroxide, sodium hydroxide and lithium hydroxide; or alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide. Further, the salts of organic bases such as lysine, arginine, guanidine, ethanolamine, choline, and the like; inorganic bases, e.g., ammonium or substituted ammonium salts are also included. Wherever appropriate, compounds of the present invention may also form the acid addition salts by treating the said compounds with pharmaceutically acceptable organic and inorganic acids, e.g., hydrohalides such as hydrochloride, hydrobromide, or hydroiodide; other mineral acids and their corresponding salts such as sulphate, nitrate, phosphate, etc.; and alkyl and mono-arylsulphonates such as ethane sulphonate, toluene sulphonate, and benzene sulphonate; and other organic acids and their corresponding salts such as acetate, tartarate, maleate, succinate, citrate, etc.
[0311] The salt forms differ from the compound described herein in certain physical properties such as solubility, but the salts are otherwise equivalent for the purpose of this invention.
[0312] The term “pharmaceutically acceptable solvates” refers to solvates with water (i.e., hydrates) or pharmaceutically acceptable solvents, for example, solvates with ethanol and the like. Such solvates are also encompassed within the scope of the disclosure. Furthermore, some of the crystalline forms for compounds described herein may exist as polymorphs and as such are intended to be included in the scope of the disclosure.
[0313] The term “polymorphs” includes all crystalline forms as well as amorphous forms for compounds described herein, and as such are included in the present invention.
[0314] The phrase “pharmaceutically acceptable carriers” is intended to include non-toxic, inert solid, semi-solid, or liquid filler, diluent, encapsulating material, or formulation auxiliary of any type.
[0315] The term “pharmaceutically acceptable” means approved by regulatory agency of the federal or a state government or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly, in humans.
[0316] Examples of inflammatory conditions and autoimmune disorders in which the compounds of the invention have potentially beneficial effects in treatment methods may include, but are not limited to, diseases of the respiratory tract such as asthma (including allergen-induced asthmatic reactions), cystic fibrosis, bronchitis (including chronic bronchitis), chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome (ARDS), chronic pulmonary inflammation, rhinitis and upper respiratory tract inflammatory disorders (URID), ventilator induced lung injury, silicosis, pulmonary sarcoidosis, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, arthritis, e.g., rheumatoid arthritis, osteoarthritis, infectious arthritis, psoriatic arthritis, traumatic arthritis, rubella arthritis, Reiter's syndrome, gouty arthritis, and prosthetic joint failure, gout, acute synovitis, spondylitis, and non-articular inflammatory conditions, e.g., herniated/ruptured/prolapsed intervertebral disk syndrome, bursitis, tendonitis, tenosynovitic, fibromyalgic syndrome, and other inflammatory conditions associated with ligamentous sprain and regional musculoskeletal strain, inflammatory disorders of the gastrointestinal tract, e.g., ulcerative colitis, diverticulitis, Crohn's disease, inflammatory bowel diseases, irritable bowel syndrome, and gastritis, multiple sclerosis, systemic lupus erythematosus, scleroderma, autoimmune exocrinopathy, autoimmune encephalomyelitis, diabetes, tumor angiogenesis and metastasis, cancer including carcinoma of the breast, colon, rectum, lung, kidney, ovary, stomach, uterus, pancreas, liver, oral, laryngeal, and prostate, melanoma, acute and chronic leukemia, periodontal disease, neurodegenerative disease, Alzheimer's disease, Parkinson's disease, epilepsy, muscle degeneration, inguinal hernia, retinal degeneration, diabetic retinopathy, macular degeneration, inguinal hernia, ocular inflammation, bone resorption diseases, osteoporosis, osteopetrosis, graft vs. host reaction, allograft rejections, sepsis, endotoxemia, toxic shock syndrome, tuberculosis, usual interstitial and cryptogenic organizing pneumonia, bacterial meningitis, systemic cachexia, cachexia secondary to infection or malignancy, cachexia secondary to acquired immune deficiency syndrome (AIDS), malaria, leprosy, leishmaniasis, Lyme disease, glomerulonephritis, glomerulosclerosis, renal fibrosis, liver fibrosis, pancrealitis, hepatitis, endometriosis, pain, e.g., that associated with inflammation and/or trauma, inflammatory diseases of the skin, e.g., dermatitis, dermatosis, skin ulcers, psoriasis, eczema, systemic vasculitis, vascular dementia, thrombosis, atherosclerosis, restenosis, reperfusion injury, plaque calcification, myocarditis, aneurysm, stroke, pulmonary hypertension, left ventricular remodeling, and heart failure. It will be appreciated by those skilled in the art that reference herein to treatment extends to prophylaxis as well as the treatment of established conditions.
[0317] Compounds disclosed herein may be prepared, for example, by techniques well known in the organic synthesis and familiar to a practitioner ordinarily skilled in art of this invention. In addition, the processes described herein may enable the synthesis of the compounds of the present invention. However, these may not be the only means by which the compounds described in the invention may be synthesized. Further, the various synthetic steps described herein may be performed in alternate sequences in order to furnish the desired compounds.
[0000]
[0318] Compounds of Formulae VIIIa and VIIIb can be prepared by following, for example, synthetic routes as depicted in Scheme I. Thus, a compound of Formula II can be converted to a compound of Formula III (wherein P 1 is a silyl protecting group for example, tert-butyldimethylsilane, tert-butyldiphenylsilane, or triisopropylsilane), which can then be converted to a compound of Formula IV (wherein P 1 is defined as above and R′ and R″ together form an acetal protecting group, for example, isopropylidene or cyclohexylidene acetal). The compound of Formula IV can be oxidized to form a compound of Formula V. The compound of Formula V can then be converted to a compound of Formula VI (wherein E is an alkyl group such as methyl, ethyl, and the like), which can then be hydrogenated to form compounds of Formulae VIIa and VIIb. Compounds of Formulae VIIa and VIIb can be reduced to form compounds of Formulae VIIIa and VIIIb.
[0319] Silylation of a compound of Formula II to form a compound of Formula III can be carried out with silylating reagents such as, for example, tert-butyldimethylchlorosilane, triphenylchlorosilane, t-butyldiphenylchlorosilane in the presence of a base, for example, imidazole or triethylamine in an organic solvent, for example, dimethyl formamide, dimethylsulphoxide or acetonitrile.
[0320] Acetonation of a compound of Formula III to form a compound of Formula IV can be carried out with excess acetone as a solvent, in the presence of a mild acid catalyst, for example, anhydrous copper (II) sulphate and camphorsulphonic acid, anhydrous zinc chloride and a small amount of phosphoric acid, or anhydrous ferric chloride. Alternately, one may utilize trans-acetonation with dimethoxypropane in the presence of acid catalysts such as p-toluenesulfonic acid, sulfuric acid, or montmorillonite-K.
[0321] The compound of Formula IV can be oxidized to form a compound of Formula V, for example, by using Swern oxidation (dimethylsulphoxide and oxalyl chloride) or Corey-Kim oxidation (N-chlorosuccinimide and dimethylsulphide) in the presence of a base, for example, triethylamine, diisopropylethylamine in a solvent, for example, dichloromethane or toluene. Alternatively, the compound of Formula IV can be oxidized to a compound of Formula V in, for example, dichloromethane or chloroform with an oxidizing agent, such as Dess-Martin reagent, pyridinium chlorochromate (PCC), or pyridinium dichromate (PDC). Oxidation of the compound of Formula IV to form a compound of Formula V can also be carried out catalytically using, for example, 2,2,6,6,-tetramethylpiperidine N-oxyl (TEMPO) and the 4-substituted derivatives thereof, including, for example, 4-methoxy-TEMPO, 4-ethoxy-TEMPO, 4-acetoxy-TEMPO, 4-acetamino-TEMPO, 4-hydroxy-TEMPO, 4-benzoyloxy-TEMPO, 4-amino-TEMPO, N,N-dimethylamino-TEMPO, or 4-oxo-TEMPO as a catalyst, in the presence of a co-catalyst, for example, potassium bromide or sodium bromide, with an oxidant, for example, sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, sodium hypobromite, or potassium hypobromite in a solvent, for example, methylene chloride, chloroform, ethyl acetate, butyl acetate, acetonitrile, tetrahydrofuran, toluene, acetone, diethyl ether, methyl tert-butyl ether, pentane, hexane, or mixtures of such solvents.
[0322] The compound of Formula V can be converted to a compound of Formula VI, for example, via a Horner-Wadsworth-Emmons reaction, thus a compound of Formula V can be reacted with phosphonate carbanions produced in situ by treating trimethylphosphonoacetate or triethylphosphonoacetate with a base, for example, sodium hydride, potassium hydride, potassium tert-butoxide, sodium tert-butoxide, potassium carbonate, triethylamine in an organic solvent, for example, tetrahydrofuran or dimethoxyethane to give a compound of Formula VI. Alternately, the Wittig reaction can be carried out using the preformed Wittig reagent such as (carboethoxymethylene)-triphenylphosphorane.
[0323] Hydrogenation of a compound of Formula VI to form compounds of Formulae VIIa and VIIb can be carried with palladium on carbon in the presence of hydrogen, in a suitable solvent, for example, methanol, ethanol, propanol, tetrahydrofuran, ethyl acetate, or mixtures thereof.
[0324] Compounds of Formulae VIIa and VIIb can be reduced to give compounds of Formula VIIIa and VIIIb in the presence of a reducing agent, for example, lithium aluminum hydride, lithium triethyl borohydride, or sodium borohydride, in the presence of an additive, for example, lithium chloride or aluminum chloride, in an organic solvent, for example, tetrahydrofuran, diethylether, or diglyme.
[0000]
[0325] Compounds of Formula XX can be prepared, for example, by following synthetic routes as depicted in Scheme II. Thus, a compound of Formula VIIIa (wherein P 1 , R′, and R″ are same as defined earlier), can react with a compound of Formula IX (wherein R 2 is an N-containing heterocyclyl or heteroaryl) to give a compound of Formula X. The compound of Formula X can undergo deprotection to form a compound of Formula XI which, on oxidation, can give a compound of Formula XII. The compound of Formula XII on reaction with a compound of Formula XIII (wherein Q is same as defined earlier, hal is Cl, Br, or I and Ar is phenyl) can form a compound of Formula XIV. The compound of Formula XIV can then react with a compound of Formula XV (wherein R 1 is same as defined earlier) to form a compound of Formula XVI which can then be hydrogenated to form a compound of Formula XVII. The compound of Formula XVII can undergo deprotection to form a compound of Formula XVIII which can then be oxidatively cleaved to form a compound of Formula XIX. The compound of Formula XIX can be deformylated to form a compound of Formula XX.
[0326] The reaction of a compound of Formula VIIIa with a compound of Formula IX to give a compound of Formula X can be carried out using triphenylphosphine or tributylphosphine and diethyl azodicarboxylate, diisoproyl azodicarboxylate, or 1,1′-azodicarbonyldipiperidine in an organic solvent, for example, tetrahydrofuran, dimethylformamide, or toluene.
[0327] The compound of Formula X can be deprotected to form a compound of Formula XI with deprotecting agents, for example, tetrabutylammonium fluoride or potassium fluoride in an organic solvent, for example, tetrahydrofuran, dimethylformamide, diethyl ether, or dioxane, optionally in the presence of crown ethers such as, for example, 18-crown-6. The oxidation of a compound of Formula XI to give a compound of Formula XII can be carried out similarly to the oxidation of a compound of Formula IV to form a compound of Formula V.
[0328] The compound of Formula XII can be converted to a compound of Formula XIV by reacting with a compound of Formula XIII (Wittig reagent, i.e., an ylide, prepared by reacting a phosphonium salt, in turn prepared from triphenylphosphine and alkyl halide, in a solvent, for example, tetrahydrofuran, dimethyl sulphoxide, or diethyl ether, with a strong base, for example, n-butyllithium, sodium hydride, or potassium tert-butoxide).
[0329] The reaction of a compound of Formula XIV with a compound of Formula XV can be carried out in the presence of a metal catalyst, for example, tetrakis(triphenylphosphine) palladium (0), tetrakis(tricyclohexylphosphine) palladium (0), tetrakis(tri-tert-butylphosphine) palladium (0), or palladium acetate and triphenylphosphine in the presence of a base, for example, potassium carbonate or cesium carbonate, in an organic solvent, for example, toluene, dimethyl sulphoxide, dimethylformamide, tetrahydrofuran, dioxane, or diethyl ether.
[0330] Hydrogenation of a compound of Formula XVI to form a compound of Formula XVII can be carried out similarly to hydrogenation of a compound of Formula VI to compounds of Formulae VIIa and VIIb.
[0331] The compound of Formula XVII can be deprotected to form a compound of Formula XVIII with perchloric acid, acetic acid, or hydrochloric acid in solvent(s), for example, acetonitrile, water, tetrahydrofuran, or mixtures thereof.
[0332] Conversion of a compound of Formula XVIII to form a compound of Formula XIX can be carried out by diol cleavage in the presence of, for example, sodium metaperiodate, lead tetraacetate, pyridinium chlorochromate, or manganese dioxide, in co-solvents, for example, tert-butanol-water, methanol-tetrahydrofuran, or tert-butanol-tetrahydrofuran, followed by oxidation with, for example, potassium permanganate or with a mixture of sodium dihydrogen phosphate, sodium chlorite, and hydrogen peroxide.
[0333] The compound of Formula XIX can be deformylated to form a compound of Formula XX in the presence of a base for example, potassium carbonate, sodium carbonate, or triethylamine in a solvent, for example, methanol, tetrahydrofuran, or mixtures thereof
[0000]
[0334] Compounds of Formula XXVI can be prepared by following synthetic routes, for example, as depicted in Scheme III. Thus, a compound of Formula XII can react with a compound of Formula XXI (wherein Q is same as defined earlier and Ar is phenyl) to form a compound of Formula XXII (wherein R 2 is an N-containing heterocyclyl or heteroaryl), which can further be hydrogenated to form a compound of Formula XXIII. The compound of Formula XXIII can be deprotected to form a compound of Formula XXIV, which can then be oxidatively cleaved to give a compound of Formula XXV. The compound of Formula XXV can then be deformylated to form a compound of Formula XXVI.
[0335] The reaction of a compound of Formula XII with a compound of Formula XXI to form a compound of Formula XXII can be carried out similarly to reaction of a compound of Formula XII to a compound of Formula XIV. Hydrogenation of a compound of Formula XXII to give a compound of Formula XXIII can be carried out under similar conditions as that of hydrogenation of a compound of Formula VI to compounds of Formulae VIIa and VIIb.
[0336] Deprotection of a compound of Formula XXIII to give a compound of Formula XXIV can be carried out similarly to deprotection of a compound of Formula XVII to a compound of Formula XVIII. The oxidative cleavage of a compound of Formula XXIV to form a compound of Formula XXV can be carried out under similar condition as that of cleavage of a compound of Formula XVIII to a compound of Formula XIX.
[0337] Deformylation of a compound of Formula XXV to form a compound of Formula XXVI can be carried out similarly to deformylation of a compound of Formula XIX to give a compound of Formula XX.
[0000]
[0338] Compounds of Formula XXXV can be prepared by, for example, following synthetic routes as depicted in Scheme IV. Thus, a compound of Formula VIIIb (wherein P 1 , R′, and R″ are the same as defined earlier), can react with a compound of Formula IX (wherein R 2 is an N-containing heterocyclyl or heteroaryl) to give a compound of Formula XXVII. The compound of Formula XXVII can be deprotected to form a compound of Formula)(XVIII, which on oxidation can give a compound of Formula XXIX. The compound of Formula XXIX on reaction with a compound of Formula XIII can form a compound of Formula XXX which can then react with a compound of Formula XV (wherein R 1 is same as defined earlier) to form a compound of Formula XXXI. The compound of Formula XXXI can then be hydrogenated to form a compound of Formula XXXII which can then undergo deprotection to form a compound of Formula XXXIII. The compound of Formula XXXIII can be oxidatively cleaved to form a compound of Formula XXXIV. The compound of Formula XXXIV can then be deformylated to form a compound of Formula XXXV.
[0339] The reaction of a compound of Formula VIIIb with a compound of Formula IX to give a compound of Formula XXVII can be carried out similarly to the reaction of a compound of Formula VIIIa to form a compound of Formula X.
[0340] Deprotection of a compound of Formula XXVII to give a compound of Formula XXVIII can be carried out similarly to the deprotection of a compound of Formula X to form a compound of Formula XI.
[0341] Oxidation of a compound of Formula XXVIII to give a compound of Formula XXIX can be carried out similarly to the oxidation of a compound of Formula IV to form a compound of Formula V.
[0342] The reaction of a compound of Formula XXIX with a compound of Formula XIII to form a compound of Formula XXX can be carried out under similar condition as that of reaction of a compound of Formula XII to form a compound of Formula XIV.
[0343] Coupling of a compound of Formula XXX with a compound of Formula XV to form a compound of Formula XXXI can be carried out similarly to the coupling of a compound of Formula XIV to form a compound of Formula XVI.
[0344] Hydrogenation of a compound of Formula XXXI to form a compound of Formula XXXII can be carried out similarly to hydrogenation of a compound of Formula VI to form compounds of Formulae VIIa and VIIb. The compound of Formula XXXII can be deprotected to form a compound of Formula XXXIII under similar conditions as that of deprotection of a compound of Formula XVII to form a compound of Formula XVIII.
[0345] Oxidative cleavage of a compound of Formula XXXIII to form a compound of Formula XXXIV can be carried out similarly to cleavage of a compound of Formula XVIII to give a compound of Formula XIX.
[0346] Deformylation of a compound of Formula XXXIV to form a compound of Formula XXXV can be carried out under similar conditions as that of the deformylation of a compound of Formula XIX to form a compound of Formula XX.
[0000]
[0347] Compounds of Formula LIII can be prepared, for example, by following synthetic routes as depicted in Scheme V. Thus, a compound of Formula XXXVI (wherein R 7 and R 8 together form a acetal protecting group, for example, isopropylidene acetal, and R′ and R″ are the same as described earlier) can be oxidized to form a compound of Formula XXXVII which can then be converted to form a compound of Formula XXXVIII (wherein R 9 is alkyl or aryl). The compound of Formula XXXVIII can be hydrogenated to give a compound of Formula XXXIX which can then be hydrolyzed to give a compound of Formula XL. The compound of Formula XL can be oxidized to give a compound of Formula XLI which can then be converted to form a compound of Formula XLII. The compound of Formula XLII can be hydrogenated to form a compound of Formula XLIII which can then be reduced to form a compound of Formula XLIV. The compound of Formula XLIV can then be reacted with a compound of Formula IX (wherein R 2 is an N-containing heterocyclyl or heteroaryl) to afford a compound of Formula XLV which can then be deprotected to form a compound of Formula XLVI. The compound of Formula XLVI can be oxidized to form a compound of Formula XLVII which can then react with a compound of Formula XIII to form a compound of Formula XLVIII. The compound of Formula XLVIII can then be reacted with a compound of Formula XV (wherein R 1 is same as defined earlier) to give a compound of Formula XLIX which can then be hydrogenated to form a compound of Formula L. The compound of Formula L is deprotected to form a compound of Formula LI which can then be oxidatively cleaved to form a compound of Formula LII. The compound of Formula LII is then deformylated to form a compound of Formula LIII.
[0348] Oxidation of a compound of Formula XXXVI to form a compound of Formula XXXVII can be carried out under similar condition as that of oxidation of a compound of Formula IV to form a compound of Formula V. The compound of Formula XXXVII can be converted to a compound of Formula XXXVIII in the presence of, for example, acetic anhydride or benzoic anhydride in presence of base, such as, for example, pyridine, triethylamine, or morpholine.
[0349] The compound of Formula XXXVIII can be hydrogenated to form a compound of Formula XXXIX similarly to the hydrogenation of a compound of Formula VI to give compounds of Formulae VIIa and VIIb. The hydrolysis of a compound of Formula XXXIX to form a compound of Formula XL can be carried out with a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, or sodium methoxide in the presence of a solvent, for example, methanol, ethanol, or isopropanol. The compound of Formula XL can be oxidized to form a compound of Formula XLI similarly to the oxidation of a compound of Formula IV to form a compound of Formula V.
[0350] Conversion of a compound of Formula XLI to form a compound of Formula XLII can be carried out under similar condition as that of conversion of a compound of Formula V to form a compound of Formula VI. The compound of Formula XLII can be hydrogenated to form a compound of Formula XLIII similarly to the hydrogenation of a compound of Formula VI to compounds of Formulae VIIa and VIIb. The reduction of a compound of Formula XLIII to form a compound of Formula XLIV can be carried out under similar condition as that of reduction of compounds of Formulae VIIa and VIIb to form compounds of Formulae VIIIa and VIIIb. The reaction of a compound of Formula XLIV with a compound of Formula IX to form a compound of Formula XLV can be carried out similarly to the reaction of a compound of Formula VIIIa to form a compound of Formula X.
[0351] Selective acetonide deprotection of a compound of Formula XLV to form a compound of Formula XLVI can be carried out with perchloric acid in a solvent, for example, tetrahydrofuran or diethyl ether or trifluoroacetic acid in dichloromethane. Oxidation of a compound of Formula XLVI to form a compound of Formula XLVII can be carried out with, for example, sodium metaperiodate, lead tetraacetate, pyridinium chlorochromate, or manganese dioxide in a solvent, for example, acetone, methanol, ethanol, or tert-butanol.
[0352] The reaction of a compound of Formula XLVII with a compound of Formula XIII to form a compound of Formula XLVIII can be carried out similarly to the reaction of a compound of Formula XII to form a compound of Formula XIV. Coupling of a compound of Formula XLVIII with a compound of Formula XV to form a compound of Formula XLIX can be carried out similarly to the coupling of a compound of Formula XIV to form a compound of Formula XVI. The compound of Formula XLIX can be hydrogenated to form a compound of Formula L under similar conditions to the hydrogenation of a compound of Formula VI to compounds of Formulae VIIa and VIIb. Deprotection of a compound of Formula L to give a compound of Formula LI can be carried out under similar conditions to the deprotection of a compound of Formula XVII to form a compound of Formula XVIII.
[0353] The oxidative cleavage of a compound of Formula LI to form a compound of Formula LII can be done similarly to the cleavage of a compound of Formula XVIII to form a compound of Formula XIX. The compound of Formula LII can be deformylated to a compound of Formula LIII under similar conditions as that of deformylation of a compound of Formula XIX to form a compound of Formula XX.
[0000]
[0354] Compounds of Formula LXVI can be prepared, for example, by following synthetic routes as depicted in Scheme VI. Thus, a compound of Formula XXXVII (wherein R 7 , R 8 , R′, and R″ are same as described earlier) can be converted to form a compound of Formula LIV which can then be hydrogenated to form a compound of Formula LV. The compound of Formula LV can be selectively deprotected to form a compound of Formula LVI which on oxidation, can form a compound of Formula LVII. The compound of Formula LVII can be reacted with a compound of Formula XIII to form a compound of Formula LVIII which can then be coupled with a compound of Formula XV (wherein R 1 is same as defined earlier) to give a compound of Formula LIX. The compound of Formula LIX can be hydrogenated to form a compound of Formula LX which can then be reduced to form a compound of Formula LXI. The compound of Formula LXI can be activated to form a compound of Formula LXII (wherein U is an O-activating group, for example, mesyl, tosyl, or triflate), which can then be reacted with a compound of Formula IXa (wherein R 2 is an N-containing heterocyclyl or heteroaryl and M is a metal, for example, potassium, lithium, or sodium) to form a compound of Formula LXIII. The compound of Formula LXIII can then be deprotected to form a compound of Formula LXIV which can be oxidatively cleaved to form a compound of Formula LXV. The compound of Formula LXV can be deformylated to form a compound of Formula LXVI.
[0355] The compound of Formula XXXVII can be converted to form a compound of Formula LIV under similar conditions as that of conversion of a compound of Formula V to form a compound of Formula VI. Hydrogenation of a compound of Formula LIV to form a compound of Formula LV can be carried out similarly to the hydrogenation of a compound of Formula VI to form compounds of Formulae VIIa and VIIb.
[0356] The compound of Formula LV can be selectively deprotected to form a compound of Formula LVI under similar conditions as that of the deprotection of a compound of Formula XLV to give a compound of Formula XLVI. The compound of Formula LVI can be oxidized to form a compound of Formula LVII similarly to the oxidation of a compound of Formula XLVI to form a compound of Formula XLVII.
[0357] The reaction of a compound of Formula LVII with a compound of Formula XIII to form a compound of Formula LVIII can be carried out under similar conditions to the reaction of a compound of Formula XII to form a compound of Formula XIV. The compound of Formula LVIII can be coupled with a compound of Formula XV to give a compound of Formula LIX under similar conditions as that of the coupling of a compound of Formula XIV to form a compound of Formula XVI. Hydrogenation of a compound of Formula LIX to form a compound of Formula LX can be carried out under similar conditions as that of hydrogenation of a compound of Formula VI to form compounds of Formulae VIIa and VIIb.
[0358] The compound of Formula LX can be reduced to form a compound of Formula LXI under similar conditions as that of reduction of compounds of Formulae VIIa and VIIb to form compounds of Formulae VIIIa and VIIIb.
[0359] A compound of Formula LXI can be activated to form a compound of Formula LXII in a solvent, for example, dichloromethane, toluene, or dichloroethane, using a base, for example, triethylamine, diisopropylamine, or N-methylmorpholine, using a suitable sulphonyl chloride, for example, methanesulphonyl chloride or p-toluene sulphonyl chloride. The reaction of a compound of Formula LXII with a compound of Formula IXa to yield a compound of Formula LXIII can be carried out in an organic solvent, for example, tetrahydrofuran, dimethyl sulphoxide, dimethylformamide, acetonitrile, dioxane, or dimethylacetamide. Alternatively, the reaction of a compound of Formula LXII with a compound of Formula IX to yield a compound of Formula LXIII can be carried out in the presence of a base, for example, sodium hydride, potassium tert-butoxide, sodium (m) ethoxide in an organic solvent, for example, tetrahydrofuran, dimethyl sulphoxide, dimethylformamide, acetonitrile, dioxane, or dimethylacetamide. Alternatively, a compound of Formula LXI can be converted to a compound of Formula LXIII following similar protocols as that of the reaction of a compound of Formula VIIIa with a compound of Formula IX to give a compound of Formula X.
[0360] The compound of Formula LXIII can be deprotected to form a compound of Formula LXIV similarly to the deprotection of a compound of Formula XVII to form a compound of Formula XVIII.
[0361] The oxidative cleavage of a compound of Formula LXIV to give a compound of Formula LXV can be done similarly to the cleavage of a compound of Formula XVIII to form a compound of Formula XIX. The compound of Formula LXV can be deformylated to form a compound of Formula LXVI under similar condition as that of deformylation of a compound of Formula XIX to form a compound of Formula XX.
[0000]
[0362] Compounds of Formula XX can also be prepared, for example, by following alternate synthetic routes as depicted in Scheme VII. Thus, a compound of Formula LXVII can be coupled with a compound of Formula LXVIII to form a compound of Formula LXIX (wherein R 1 and Q are same as defined earlier), which can then be converted to a compound of Formula LXX (Path A) (wherein E is same as defined earlier). Alternately, the compound of Formula LXVIIa can undergo esterification to give a compound of Formula LXIXa, which can be coupled with the compound of Formula XV to form the compound of Formula LXX (Path B) (wherein E is same as defined earlier). The compound of Formula LXX can be hydrogenated to form the compound of Formula LXXI, which can then be reduced to form a compound of Formula LXXII. The compound of Formula LXXII can be oxidized to form a compound of Formula LXXIII, which can then react with a compound of Formula LXXIV (wherein, when R 2 is N-containing heterocyclyl or heteroaryl, Y and W can be oxygen or sulphur, R 10 can be alkyl, aryl, or aralkyl, and n is as defined earlier) to form a compound of Formula LXXV. The compound of Formula LXXII can be further hydrolysed to form a compound of Formula XX.
[0363] Coupling of a compound of Formula LXVII with a compound of Formula LXVIII to form a compound of Formula LXIX can be carried out similarly to the coupling of a compound of Formula XIV to form a compound of Formula XVI.
[0364] Conversion of a compound of Formula LXIX to form a compound of Formula LXX can be carried out under similar conditions to the conversion of a compound of Formula V to form a compound of Formula VI. Esterification of compound of Formula LXVIIIa to gives a compound of Formula LXIXa can be carried out in a solvent, for example, methanol, ethanol, tert-butanol, or benzyl alcohol with a halogenating agent, for example, thionyl chloride or oxalyl chloride. Coupling of a compound of Formula LXIXa with a compound of Formula XV to form a compound of Formula LXX can be carried out similarly to the coupling of a compound of Formula XIV to form a compound of Formula XVI.
[0365] The compound of Formula LXX can be hydrogenated to form a compound of Formula LXXI similarly to the hydrogenation of a compound of Formula VI to form compounds of Formulae VIIa and VIIb. The reduction of a compound of Formula LXXI to form a compound of Formula LXXII can be carried out under similar conditions as that of reduction of compounds of Formulae VIIa and VIIb to form compounds of Formulae VIIIa and VIIIb. The compound of Formula LXXII can be oxidized to form a compound of Formula LXXIII similarly to the oxidation of a compound of Formula IV to form a compound of Formula V.
[0366] The asymmetric aldol addition of a compound of Formula LXXIII with a compound of Formula LXXIV to form a compound of Formula LXXIV can be carried out by generating the enolates with titanium chloride, dibutyl boron triflate, dialkyl boron chloride, or tin(II) triflate, in the presence of a base, for example, diisopropylethylamine, tetramethylethelenediamine, tributylamine, N-ethylpiperidine, 1,4-diazabicyclo[2.2.2]octane, 1,8-Diazabicyclo[5.4.0]undec-7-ene, tetramethylpropylenediamine, or (−) sparteine, in a solvent, for example, dichloromethane or diethyl ether.
[0367] Hydrolysis of a compound of Formula LXXIV to form a compound of Formula XX can be carried out with hydrogen peroxide and lithium hydroxide, in the presence of a solvent, for example, tetrahydrofuran, water, or mixtures thereof.
[0368] Compound Nos. 1 to 81; 86-88; 90-95; 97-119; 121-142; 144-203; 211-213; and 226-232 were prepared following Schemes I and II. Compound Nos. 82 to 85 and 204 were prepared following Schemes I, II, and III. Compound Nos. 143 and 208 were prepared following Scheme IV. Compound Nos. 120 and 205-207 were prepared following Scheme V. Compound Nos. 89 and 96 were prepared following Scheme VI. Compound Nos. 86; 209-210; and 214-225 were prepared following Scheme VII.
[0369] In the above schemes, where specific bases, acids, solvents, condensing agents, reducing agents, deprotecting agents, hydrolyzing agents, metal catalysts, etc., are mentioned, it is to be understood that other acids, bases, solvents, condensing agents, reducing agents, deprotecting agents, hydrolyzing agents, metal catalysts, etc., known to those skilled in the art may also be used. Similarly, the reaction temperature and duration of the reactions may be adjusted according to the requirements that arise during the process.
[0370] The following examples are set forth to demonstrate general synthetic procedures for the preparation of representative compounds of the present invention. The examples are provided to illustrate a particular aspect of the disclosure and do not limit the scope of the present invention.
EXAMPLES
Synthesis of Starting Materials
Synthesis of 6-methyl-1,2,3-benzotriazin-4(3H)-one
[0371] The title compound was prepared following the procedure outlined in J. Med. Chem., 35(14), 2626-2630 (1992).
[0372] The following analogues of 6-methyl-1,2,3-benzotriazin-4(3H)-one were prepared analogously:
8-methyl-1,2,3-benzotriazin-4(3H)-one; 7-methyl-1,2,3-benzotriazin-4(3H)-one; 6-methyl-1,2,3-benzotriazin-4(3H)-one; 8-methoxy-1,2,3-benzotriazin-4(3H)-one; 6-methoxy-1,2,3-benzotriazin-4(3H)-one; 8-chloro-1,2,3-benzotriazin-4(3H)-one; 7-chloro-1,2,3-benzotriazin-4(3H)-one; 6-chloro-1,2,3-benzotriazin-4(3H)-one; 5-chloro-1,2,3-benzotriazin-4(3H)-one; 6,7-difluoro-1,2,3-benzotriazin-4(3H)-one; 8-fluoro-1,2,3-benzotriazin-4(3H)-one; 5-fluoro-1,2,3-benzotriazin-4(3H)-one; 6-fluoro-1,2,3-benzotriazin-4(3H)-one; 5-(6-methoxypyridin-3-yl)-1,2,3-benzotriazin-4(3H)-one; 7-(6-methoxypyridin-3-yl)-1,2,3-benzotriazin-4(3H)-one; and 7-(trifluoromethyl)-1,2,3-benzotriazin-4(3H)-one.
Synthesis of 5-tert-butyl-1H-isoindole-1,3(2H)-dione
[0389] The title compound was prepared following the procedure outlined in Can. J. Chem., Vol. 63, 121-128 (1985).
[0390] Mass (m/z): 204.12 (M + +1)
[0391] The following analogues of 5-tert-butyl-1H-isoindole-1,3(2H)-dione were prepared analogously:
4-fluoro-1H-isoindole-1,3(2H)-dione; and 5-chloro-1H-isoindole-1,3(2H)-dione.
Synthesis of (4-bromobenzyl)(triphenyl)phosphonium bromide
[0394] A mixture of 1-bromo-4-(bromomethyl)benzene (5 g) and triphenylphosphine (5.24 g) in xylene (20 mL) were heated to reflux for 18 hours. The reaction mixture was cooled, filtered, washed with hexane, and dried under vacuum to afford the title compound (8 g). Mass (m/z): 433.9 (M + +1)
[0395] The following Wittig salts were prepared analogously:
[(4-bromo-2-thienyl)methyl]triphenyl phosphonium bromide; [(6-bromopyridin-3-yl)methyl](triphenyl)phosphonium bromide; (4-bromo-2-fluorobenzyl)(triphenyl)phosphonium bromide; 4-tert-butylbenzyl(triphenyl)phosphonium bromide; triphenyl[4-(trifluoromethyl)benzyl]phosphonium bromide; benzyl(triphenyl)phosphonium bromide; (4-bromo-3-fluorobenzyl)(triphenyl)phosphonium bromide; (4-bromo-2-fluorobenzyl)(triphenyl)phosphonium bromide; and (4-chloro-3-fluorobenzyl)(triphenyl)phosphonium bromide.
Synthesis of 4-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)butanoic acid
Step a: Synthesis of ethyl 4-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)butanoate
[0405] In a dry round bottom flask, 1,2,3-benzotriazin-4(3H)-one (50 g), ethyl 4-bromobutanoate (86.2 g) and potassium carbonate (141 g) were taken and dissolved in dimethylformamide (350 mL) and heated to 60° C. to 70° C. for 3 to 4 hours. After cooling to room temperature, water was added to the reaction mixture and extracted with ethyl acetate. The combined organic layer was washed with water and brine and dried over anhydrous sodium sulfate. Solvents were evaporated under reduced pressure and the crude product was purified by silica gel flash column chromatography over silica gel using 20% ethylacetate in hexane as eluant to afford the title compound (68 g).
Step b: Synthesis of 4-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)butanoic acid
[0406] To a stirred solution of compound obtained from step a above (40 g), in a solvent mixture of tetrahydrofuran/methanol/water (3:1:1, 400 mL), lithium hydroxide monohydrate (6.43 g) was added at 0° C. under a nitrogen atmosphere. The reaction mixture was stirred at 0° C. until completion of hydrolysis. The solvents were evaporated, diluted with water, and extracted with ethyl acetate. The aqueous layers were acidified with saturated aqueous sodium hydrogen sulfate solution and extracted with ethyl acetate. The combined layers were washed with water and brine and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure to afford the title compound (28 g).
[0407] The following analogue of 4-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)butanoic acid was prepared analogously:
3-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)propanoic acid.
Synthesis of 3-{4-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-4-oxobutyl}-1,2,3-benzotriazin-4(3H)-one
Step a: Synthesis of (2S)-2-amino-3-phenylpropan-1-ol
[0000]
(Ref: J. Org. Chem., 58, 3568-3571 (1993)).
[0410] To a suspension of sodium borohydride (16.5 g) in dry tetrahydrofuran (600 mL), (L)-phenylalanine (30 g) was added at one portion. The flask was cooled to 0° C. under nitrogen atmosphere. Iodine (46.18 g) solution in tetrahydrofuran (150 mL) was added slowly in drop-wise manner over 40 minutes, resulting in vigorous evolution of H 2 . After the complete addition of iodine, the reaction mixture was heated to reflux for 18 hours and cooled to room temperature. The reaction mixture was quenched with methanol until the reaction mixture became clear. Further, the solution was stirred for 30 minutes at room temperature. The solvents were removed by rotary evaporation to obtain a white paste which was dissolved by 20% aqueous potassium hydroxide (450 mL). The solution was stirred for 4 hours and then dichloromethane was added. The organic layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure to afford 32.5 g of (L)-phenylalaninol as a viscous liquid. The crude product was used as such for the next step.
Step b: Synthesis of (45)-4-benzyl-1,3-thiazolidine-2-thione
[0000]
(Ref: J. Org. Chem., 60(20), 6604-6607 (1995)).
[0412] To a solution of the compound obtained in step a above (32.5 g) in 1N aqueous potassium hydroxide (1 L), carbon disulphide (68 mL, 5.0 equivalence) was added and the reaction mixture was refluxed for 16 hours. After cooling to room temperature, the aqueous solution was extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 15% ethyl acetate in hexane to get the title compound (22.5 g).
Step c: Synthesis of (4S)-4-benzyl-1,3-thiazolidin-2-one
[0413] To a solution of (4S)-4-benzyl-1,3-thiazolidine-2-thione (38 g) in dichloromethane (350 mL) cooled to 0° C., propylene oxide (12.7 mL) and trifluoroacetic acid (14 mL) were added. After stirring the reaction mixture for 2 hours, the solvents were evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 20% ethyl acetate in hexane as eluant to afford the title compound (0.9 g). Mass (m/z): 194.18
Step d: Synthesis of 3-{4-[(45)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-4-oxobutyl}-1,2,3-benzotriazin-4(3H)-one
[0414] To a solution of the compound obtained from step c above (2.1 g) in dichloromethane (25 mL) cooled to 0° C., 4-dimethylaminopridine (0.334 g) and triethylamine (5.7 mL) were added. After stirring the reaction mixture for 10 minutes, 1-β-dimethylaminopropyl)-3-ethylcarbodimide hydrochloride (3.9 g) and 4-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)butanoic acid (3 g) were added, and the reaction mixture was stirred at room temperature for 14 hours. Dichloromethane and water were added to the reaction mixture. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 25% ethyl acetate in hexane as eluant to afford the title compound (4.4 g). Mass (m/z): 409.16
[0415] The following analogue of 3-{4-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-4-oxobutyl}-1,2,3-benzotriazin-4(3H)-one was prepared analogously:
3-{3-[(45)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-3-oxopropyl}-1,2,3-benzotriazin-4(3H)-one
Example 1
Synthesis of (2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4-pyrimidin-5-ylphenyl)pentanoic acid (Compound No. 1)
Step a: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-D-arabinofuranose
[0417] D-Arabinose (200 g) and imidazole (199 g) were placed in a three-neck round bottom flask and connected to high vacuum for 30 minutes. The vacuum was released under nitrogen atmosphere and dimethylformamide (1.8 L) was added to the above mixture at room temperature followed by drop-wise addition of t-butyldiphenylchlorosilane (443 mL) for 10 minutes under a nitrogen atmosphere. The resulting mixture was stirred for 16 hours at the same temperature. Dimethylformamide was evaporated under reduced pressure. The residue was taken up in ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a crude residue which was purified by column chromatography over silica gel using 80% ethyl acetate in hexane as eluant to afford the title compound (273 g).
[0418] Mass (m/z): 389.37 (M + +1)
Step b: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-1,2-O-isopropylidene-β-D-arabinofuranose
[0419] To the solution of the compound obtained from step a above (273 g) in acetone (2.5 L), DL-camphorsulphonic acid (16 g) and anhydrous copper sulphate (346 g) were charged under a nitrogen atmosphere at room temperature. The reaction mixture was stirred for 16 hours at the same temperature. A saturated solution of sodium bicarbonate (2 L) was added drop-wise until a basic pH was attained, and the reaction mixture was further stirred for 2 hours at the same temperature. The resulting mixture was filtered using a Buchner funnel, and the residue was washed with acetone. The filtrate was concentrated, dissolved in ethyl acetate, and washed with water. The organic layer was dried over anhydrous sodium sulphate, filtered, and evaporated under reduced pressure to furnish the title compound (295 g).
[0420] Mass (m/z): 429.41 (M + +1)
Step c: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-1,2-O-isopropylidene-β-D-threo-pentofuranos-3-ulose
[0421] Oxalyl chloride (145 ml) and dichloromethane (1 L) were taken in a three neck round bottom flask and cooled to −75° C. under a nitrogen atmosphere. Dimethylsulfoxide (212 mL) was added drop-wise to the above solution maintaining the reaction temperature at −70° C. The reaction mixture was stirred for 30 minutes at the same temperature, then a solution of the compound obtained from step b above (285 g) in dichloromethane (1 L), was added slowly to the above mixture, maintaining the reaction temperature −70° C. After 20 minutes of the above addition, triethylamine (560 mL) was added drop-wise at the same temperature. Saturated solution of ammonium chloride in water (1.5 L) was then added after 30 minutes and the reaction temperature was allowed to rise to room temperature. The reaction mixture was extracted with dichloromethane. Organic extracts were dried over anhydrous sodium sulphate, filtered, and evaporated under reduced pressure to afford the title compound (285 g).
Step d: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-ethoxy-2-oxoethylidene)-1,2-O-isopropylidene-β-D-arabinofuranose
[0422] To a suspension of sodium hydride (29.4 g, 60% in oil) in tetrahydrofuran (1 L) at 0° C., triethyl phosphonoacetate (200 mL) was charged. After 20 minutes, a solution of the compound obtained from step c above (285 g) in tetrahydrofuran (2 L) was added drop-wise and the reaction mixture was stirred for 1 hour at the same temperature. A saturated solution of ammonium chloride in water (1.5 L) was added to the reaction mixture. The resulting mixture was extracted with ethyl acetate. Combined extracts were dried over anhydrous sodium sulphate and evaporated under reduced pressure to yield a residue which was purified by column chromatography over silica gel using 15% ethyl acetate in hexane as eluant to afford the title compound (275 g).
[0423] Mass (m/z): 497.43 (M + +1)
Step e: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-ethoxy-2-oxoethyl)-1,2-O-isopropylidene-β-D-lyxofuranose and 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-ethoxy-2-oxoethyl)-1,2-O-isopropylidene-α-L-ribofuranose
[0424] 10% Palladium on charcoal (100 g) was added to the solution of the compound obtained from step d above (275 g) in tetrahydrofuran (2 L) and methanol (1 L) at room temperature and hydrogen was supplied at 50 psi (Paar apparatus) for 2 hours. The reaction mixture was filtered through a celite pad and the residue was washed with ethyl acetate. The filtrate was concentrated to afford a mixture of 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-ethoxy-2-oxoethyl)-1,2-O-isopropylidene-β-D-lyxofuranose and 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-ethoxy-2-oxoethyl)-1,2-O-isopropylidene-α-L-ribofuranose (275 g).
[0425] Mass (m/z): 499.42 (M + +1)
Step f: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-hydroxyethyl)-1,2-O-isopropylidene-β-D-lyxofuranose and 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-hydroxyethyl)-1,2-O-isopropylidene-α-L-ribofuranose
[0426] To a suspension of lithium aluminum hydride (48 g) in tetrahydrofuran (1 L), a solution of the compound obtained from step e above (275 g) in tetrahydrofuran (1.5 L) was added at −50° C. The resulting mixture was allowed to attain 0° C. The reaction mixture was stirred for 30 minutes at the same temperature and again cooled to −50° C. Ethyl acetate (2 L) was added slowly while maintaining −50° C. An aqueous solution of ammonium chloride (100 g) in water (2.5 L) was added at the same temperature. The reaction mixture was slowly allowed to warm to room temperature, and the reaction mixture was stirred for 12 hours at the same temperature. The reaction mixture was then filtered through a celite pad and the residue was washed with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate, filtered, concentrated under reduced pressure, and the residue thus obtained was purified by column chromatography over silica gel using 50% ethyl acetate in hexane as eluant to afford the 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-hydroxyethyl)-1,2-O-isopropylidene-β-D-lyxofuranose (130 g) and 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-hydroxyethyl)-1,2-O-isopropylidene-α-L-ribofuranose (40.0 g).
[0427] Mass (m/z): 457.39 (M + +1)
Step g: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-1,2-O-isopropylidene-3-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-β-D-lyxofuranose
[0428] 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-hydroxyethyl)-1,2-O-isopropylidene-β-D-lyxofuranose (35 g), triphenylphosphine (30.8 g) and 1,2,3-benzotriazin-4(3H)-one (12.6 g) were dried in high vacuum in a round bottom flask for 10 minutes. Then the vacuum was released under a nitrogen atmosphere and tetrahydrofuran (70 mL) was added to the above reaction mixture. The reaction mixture was cooled to 0° C. and diisopropyl azodicarboxylate (17 mL) was added slowly. The reaction mixture was stirred for 30 minutes at the same temperature, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated to obtain a residue which was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (50 g).
[0429] Mass (m/z): 586.05 (M + +1)
Step h: Synthesis of 3-deoxy-1,2-O-isopropylidene-3-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-β-D-lyxofuranose
[0430] To a solution of the compound obtained from step g above (50 g) in dry tetrahydrofuran (400 mL) at 0° C., tetra-butyl ammonium fluoride (170 mL) was added. The resulting mixture was initially stirred at 0° C. for 1 hour, and then at room temperature for 4 hours. The reaction mixture was cooled to 0° C., quenched with saturated ammonium chloride, and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulphate and concentrated. The residue thus obtained was purified by column chromatography over silica gel using 80% ethyl acetate in hexane as eluant to furnish the title compound (22 g).
[0431] Mass (m/z): 369.98 (M + +23)
Step i: Synthesis of (5S)-3-deoxy-4,5-O-isopropylidene-3-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-D-arabino-pentodialdo-5,2-furanose
[0432] Oxalyl chloride (13.7 mL) and dichloromethane (300 mL) were taken in a three neck round bottom flask and cooled to −78° C. Dimethylsulfoxide (20.2 mL) was added drop-wise to the reaction mixture. The reaction mixture was warmed to −35° C. for 5 to 10 minutes and again cooled to −78° C. A solution of the compound obtained from step h above (22 g) in dichloromethane (200 mL) was added slowly while maintaining the same temperature. The reaction mixture was stirred for 45 minutes until the reaction temperature reached −35° C. The reaction mixture was again cooled to −78° C. and triethylamine (53 mL) was added. The reaction mixture was stirred for an additional 30 minutes, and the temperature was allowed to reach −35° C. The reaction mixture was quenched with a saturated solution of ammonium chloride and extracted with dichloromethane. The combined organic layers were washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated to furnish the title compound (22 g).
Step j: Synthesis of 3-(2-{(3aS,5R,6S,6aS)-5-[(E)-2-(4-bromophenyl)vinyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0433] To the suspension of sodium hydride (3.3 g, 60% in oil) in tetrahydrofuran (50 mL) cooled to 0° C., (4-bromobenzyl)triphenylphosphonium bromide (48.8 g) in tetrahydrofuran (100 mL) was added. A solution of the compound obtained from step i above (22 g) in tetrahydrofuran (100 mL) was added drop-wise after 20 minutes, and the reaction mixture was stirred for 1 hour at the same temperature. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by column chromatography using 30% ethyl acetate in hexane as eluant to furnish the title compound (24.5 g).
[0434] Mass (m/z): 498.84 (M + +1)
Step k: Synthesis of 3-(2-{(3aS,5R,6S,6aS)-2,2-dimethyl-5-[(E)-2-(4-pyrimidin-5-ylphenyl)vinyl]tetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0435] A mixture of the compound obtained from step j above (0.35 g), pyrimidin-5-ylboronic acid (0.174 g), tetrakistriphenylphosphinepalladium (0) (0.081 g), and potassium carbonate (0.291 g) was dried under high vacuum for 10 minutes and dry dimethylformamide (5 mL) was added at room temperature. The reaction mixture was heated at 120° C. for 2 hours, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under the reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 40% ethyl acetate in hexane as eluant to afford the title compound (0.3 g).
[0436] Mass (m/z): 498.0 (M + +1)
Step l: Synthesis of 3-(2-{(3aS,5R,6S,6aS)-2,2-dimethyl-5-[2-(4-pyrimidin-5-ylphenyl)ethyl]tetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0437] To the solution of the compound obtained from step k above (0.3 g) in a solvent mixture of tetrahydrofuran:methanol (10 mL, 1:1), 10% palladium on charcoal (0.15 g) was added at room temperature and the reaction mixture was hydrogenated with hydrogen at 35 psi for 4 hours in a Paar apparatus. The reaction mixture was filtered through a celite pad and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (0.3 g).
Step m: Synthesis of 3-(2-{(2R,3R,4S,5R)-4,5-dihydroxy-2-[2-(4-pyrimidin-5-ylphenyl)ethyl]tetrahydrofuran-3-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0438] Perchloric acid (0.2 mL) was added to a solution of the compound obtained from step l above (0.3 g) in acetonitrile (4 mL) and water (0.2 mL) at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using sodium bicarbonate solution. The solvents were evaporated under reduced pressure. The residue thus obtained was taken up in ethyl acetate and water. The organic layer was separated and washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.25 g).
Step n: Synthesis of (2S,3R)-3-(formyloxy)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4-pyrimidin-5-ylphenyl)pentanoic acid
[0439] To a solution of the compound obtained from step m above (0.25 g) in tert-butanol:tetrahydrofuran (5 mL:5 mL) at 0° C., a solution of sodium metaperiodate (0.465 g in 5 mL of water) was added. The reaction mixture was stirred for 2 hours at the same temperature and potassium permanganate (0.017 g) was added at 0° C. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated on a rotary evaporator. The residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under the reduced pressure to afford the title compound (0.25 g).
Step o: Synthesis of (2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4-pyrimidin-5-ylphenyl)pentanoic acid
[0440] Potassium carbonate (0.081 g) was added to a solution of the compound obtained from step n above (0.25 g) in methanol (5 mL) and tetrahydrofuran (5 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. Solvents were evaporated and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 60% ethyl acetate in hexane as eluant to afford the title compound (0.030 g).
[0441] Mass (m/z): 446.0 (M + +1).
[0442] 1 HNMR (CD 3 OD): δ 9.09 (s, 1H), 9.03 (s, 1H), 8.30 (d, 1H, J=8 Hz), 8.14 (d, 1H, J=8 Hz), 8.05-8.03 (m, 1H), 7.89-7.87 (m, 1H), 7.61 (d, 2H, J=8 Hz), 7.53-7.59 (m, 1H), 7.35 (d, 2H, J=8 Hz), 4.57-4.52 (m, 2H), 3.79-3.77 (m, 1H), 2.89-2.87 (m, 1H), 2.69-2.67 (m, 1H), 2.47-2.46 (m, 1H), 2.29-2.25 (m, 2H), 1.82-1.77 (m, 2H).
Example 1A
Synthesis of (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 86)
Step a: Synthesis of 3-(2-{(3aS,5R,6S,6aS)-5-[(E)-2-(4-bromophenyl)ethenyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0443] To the suspension of potassium t-butoxide (3.3 g, 60% in oil) in dimethyl sulfoxide (50 mL) cooled to 0° C., 4-bromobenzyl triphenyl-phosphonium bromide (48.8 g) in dimethyl sulfoxide (100 mL) was added. After 20 minutes, the compound obtained from step i of Example 1 above (22 g) was added in dimethyl sulfoxide (100 mL) drop-wise, and the reaction mixture was stirred for 1 hour at the same temperature. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure. Purification was performed on a silica gel column by using 30% ethyl acetate in hexane as eluent to get the title compound (24.5 g).
Step b: Synthesis of 3-{2-[(3aS,5R,6S,6aS)-5-{(E)-2-[4-(6-methoxypyridin-3-yl)phenyl]ethenyl}-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl]ethyl}-1,2,3-benzotriazin-4(3H)-one
[0444] A mixture of the compound obtained from step a above (12 g), 2-methoxy-5-pyridine boronic acid (7.4 g), tetrakistriphenylphosphinepalladium (0) (2.8 g), and potassium carbonate (10 g) was dried under high vacuum for 10 minutes, and dry dimethylformamide (60 ml) was added at room temperature. The reaction mixture was heated at 120° C. for 2 hours, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 40% ethyl acetate in hexane as eluant to afford the title compound (8.5 g).
Step c: Synthesis of 3-{2-[(3aS,5R,6S,6aS)-5-{2-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl]ethyl}-1,2,3-benzotriazin-4(3H)-one
[0445] To the solution of the compound obtained from step b above (8.5 g) in a solvent mixture of tetrahydrofuran:methanol (60 mL:40 mL), 10% palladium on charcoal (4 g) was added at room temperature, and the reaction mixture was hydrogenated with hydrogen at 35 psi for 4 hours in a Paar apparatus. The reaction mixture was filtered through a celite pad and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (8.1 g).
Step d: Synthesis of 3-{2-[(2R,3R,4S,5R)-4,5-dihydroxy-2-{2-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}tetrahydrofuran-3-yl]ethyl}-1,2,3-benzotriazin-4(3H)-one
[0446] Perchloric acid (4.8 mL) was added to a solution of the compound obtained from step c above (8.1 g) in acetonitrile (50 mL) and water (8 mL) at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using sodium bicarbonate solution. The solvents were evaporated under reduced pressure. The residue thus obtained was taken up in ethyl acetate and water. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (8 g).
Step e: Synthesis of (2S,3R)-3-(formyloxy)-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid
[0447] To a solution of the compound obtained from step d above (8 g) in tert-butanol:tetrahydrofuran (40 mL:40 mL) at 0° C., a solution of sodium metaperiodate (14 g in 40 mL of water) was added. The reaction mixture was stirred for 2 hours at the same temperature, and potassium permangnate (518 mg) was added at 0° C. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated on a rotary evaporator. The residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under the reduced pressure, to afford the title compound (8 g).
Step f: Synthesis of (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid
[0448] Potassium carbonate (2.3 g) was added to a solution of the compound obtained from step e above (8 g) in methanol (40 mL) and tetrahydrofuran (30 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The solvents were evaporated, and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 60% ethyl acetate in hexane as eluant to afford the title compound (3 g).
[0449] Mass (m/z): 474.87 (M + +1); 1 H NMR (400 MHz, MeOD): δ 8.32-8.30 (2H, m), 8.16-8.14 (1H, m), 8.04-8.03 (1H, m), 7.92-7.88 (2H, m), 7.46 (2H, d, J=8 Hz), 7.24 (2H, m, J=8 Hz), 6.86 (1H, d, J=8 Hz), 4.57-4.53 (2H, m), 3.93 (3H, s), 3.78-3.83 (1H, m), 2.83-2.80 (1H, m), 2.63-2.60 (1H, m), 2.52-2.49 (1H, m), 2.32-2.28 (2H, m), 1.80-1.76 (2H, m).
Example 1B
Synthesis of (2S,3R)-3-hydroxy-5-[4-(6-hydroxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 226)
[0450] To a solution of the compound obtained from Example 1A above (0.2 g) in dry toluene (5 mL), cooled to 78° C., boron tribromide (0.5 mL) was added and the contents were stirred at room temperature for 4 hours. Ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to obtain a residue which was purified by preparatory thin layer chromatography (2 mm thickness) using 15% methanol in dichloromethane as eluent to get the title compound (60 mg).
[0451] Mass (m/z): 461.23 (M + +1); 1 HNMR (CD 3 OD): 8.30 (d, 1H, J=8 Hz), 8.15 (d, 1H, J=8 Hz), 8.06-8.01 (m, 2H), 7.88 (t, 1H, J=8 Hz), 7.79-7.76 (m, 1H), 7.43 (d, 2H, J=12 Hz), 7.25 (d, 2H, J=12 Hz), 6.75 (d, 1H, J=12 Hz), 4.58-4.51 (m, 2H), 3.82-3.76 (m, 1H), 2.88-2.78 (m, 1H), 2.66-2.57 (m, 1H), 2.54-2.47 (m, 1H), 2.33-2.25 (m, 2H), 1.84-1.70 (m, 2H).
Example 1C
Synthesis of (2S,3R)-3-(acetyloxy)-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 229)
[0452] Diisopropyl azodicarboxylate (63 mg) was added to a solution of the compound obtained from Example 1A above (100 mg), tri-n-butylphosphine (93 mg), and acetic acid (1 mL) in dry tetrahydrofuran (3 mL) at 0° C. The reaction mixture was stirred for 1 hour and concentrated. The residue was taken in ethyl acetate, and washed with water and brine. The organic layer was concentrated to get an oily residue which was purified on preparative thin layer chromatography (2 mm thickness) using 10% methanol in dichloromethane to get the title compound (80 mg).
[0453] Mass (m/z): 517.06 (M + +1); 1 HNMR: δ 8.37 (m, 2H), 8.15 (d, 1H, J=8 Hz), 7.97-7.93 (m, 1H), 7.82-7.80 (m, 1H), 7.41 (d, 2H, J=8 Hz), 7.20 (d, 2H, J=8 Hz), 6.83 (d, 1H, J=8 Hz), 5.28-5.27 (m, 1H), 4.56-4.58 (m, 2H), 4.01 (s, 3H), 2.85-2.80 (m, 1H), 2.55-2.75 (m, 2H), 2.31-2.29 (m, 2H), 2.25-2.10 (m, 2H), 2.063 (s, 3H).
Example 1D
Synthesis of (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 88)
Step a: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1,2-O-(1-methylethylidene)-β-D-lyxofuranose
[0454] 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-(2-hydroxyethyl)-1,2-O-isopropylidene-β-D-lyxofuranose (14 g), triphenylphosphine (12 g), and phthalimide (5 g) were dried in a high vacuum in a round bottom flask for 10 minutes. Then the vacuum was released under a nitrogen atmosphere, and tetrahydrofuran (100 mL) was added to the above reaction mixture. The reaction mixture was cooled to 0° C. and diethyl azodicarboxylate (7.8 mL) was added slowly. The reaction mixture was stirred for 30 minutes at the same temperature, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated to obtain a residue which was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (11 g).
Step b: Synthesis of 3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1,2-O-(1-methylethylidene)-β-D-lyxofuranose
[0455] To a solution of the compound obtained from step a above (11 g) in dry tetrahydrofuran (50 mL) at 0° C., tetra-butyl ammonium fluoride (41.36 mL) was added. The resulting mixture was initially stirred at 0° C. for 1 hour, and then at room temperature for 4 hours. The reaction mixture was cooled to 0° C., quenched with saturated ammonium chloride, and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulphate, and concentrated. The residue thus obtained was purified by column chromatography over silica gel using 80% ethyl acetate in hexane as eluant to furnish the title compound (5 g).
Step c: Synthesis of (5S)-3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-4,5-O-(1-methylethylidene)-D-arabino-pentodialdo-5,2-furanose
[0456] Oxalyl chloride (4.5 mL) and dichloromethane (20 mL) were taken in a three neck round bottom flask and cooled to −78° C. Dimethylsulfoxide (6.6 mL) was added drop-wise to the reaction mixture. The reaction mixture was warmed to −35° C. for 5 to 10 minutes and again cooled to −78° C. A solution of the compound obtained from step b above (7.2 g) in dichloromethane (20 mL) was added slowly while maintaining the same temperature. The reaction mixture was stirred for 45 minutes until the reaction temperature reached −35° C. The reaction mixture was again cooled to −78° C. and triethylamine (17.3 mL) was added. The reaction mixture was stirred for an additional 30 minutes, and the temperature was allowed to reach −35° C. The reaction mixture was quenched with saturated solution of ammonium chloride, and extracted with dichloromethane. The combined organic layers were washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated to furnish the title compound (7.3 g).
Step d: Synthesis of 2-(2-{(3aS,5R,6S,6aS)-5-[(E)-2-(4-bromophenyl)ethenyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0457] To a suspension of potassium t-butoxide (2.3 g) in dimethyl sulfoxide (30 ml) cooled to 0° C., (4-bromobenzyl)triphenylphosphonium bromide (12.2 g) in dimethyl sulfoxide (20 mL) was added. After 20 minutes, a solution of compound obtained from step c above (4.1 g) in dimethyl sulfoxide (10 mL) was added drop-wise, and the reaction mixture was stirred for 1 hour at the same temperature. The reaction mixture was quenched with water, and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure. Purification was performed on silica gel column by using 40% ethyl acetate in hexane as eluant to furnish the title compound (4 g).
Step e: Synthesis of 2-{2-[(3aS,5R,6S,6aS)-5-{(E)-2-[4-(6-methoxypyridin-3-yl)phenyl]ethenyl}-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl]ethyl}-1H-isoindole-1,3(2H)-dione
[0458] A mixture of the compound obtained from step d above (1 g), 2-methoxy-5-pyridine boronic acid (0.614 g), tetrakistriphenylphosphinepalladium (0) (0.115 g), and potassium carbonate (0.832 g) was dried under high vacuum for 10 minutes, and dry dimethylformamide (8 mL) was added at room temperature. The reaction mixture was heated at 120° C. for 2 hours, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (0.62 g).
Step f: Synthesis of 2-{2-[(3aS,5R,6S,6aS)-5-{2-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl]ethyl}-1H-isoindole-1,3(211)-dione
[0459] To a solution of the compound obtained from step e above (0.6 g) in methanol (10 mL), 10% palladium on charcoal (0.05 g) was added at room temperature and the reaction mixture was hydrogenated with hydrogen at 35 psi for 4 hours in a Paar apparatus. The reaction mixture was filtered through a celite pad and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (0.56 g).
Step g: Synthesis of 2-{2-[(2R,3R,4S,5R)-4,5-dihydroxy-2-{2-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}tetrahydrofuran-3-yl]ethyl}-1H-isoindole-1,3(2H)-dione
[0460] Perchloric acid (0.4 mL) was added to a solution of the compound obtained from step f above (0.5 g) in acetonitrile (4 mL) and water (0.8 mL) at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using sodium bicarbonate solution. The solvents were evaporated under reduced pressure. The residue thus obtained was taken up in ethyl acetate and water. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.51 g).
Step h: Synthesis of (1R,2S)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-formyl-1-{2-[4-(6-methoxypyridin-3-yl)phenyl]ethyl}butyl formate
[0461] To a solution of the compound obtained from step g above (0.56 g) in methanol (4 mL) at 0° C., a solution of sodium metaperiodate (0.736 g in 1 mL of water) was added. The reaction mixture was stirred for 2 hours at the same temperature. After stirring the reaction mixture for an additional 1 hour at room temperature, the reaction mixture was evaporated on a rotary evaporator. The residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain the title compound (0.54 g).
Step i: Synthesis of (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-(formyloxy)-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid
[0462] The compound obtained in step h (0.54 g) was taken in acetonitrile (6 mL) and water (1 mL). To this solution, sodium dihydrogen phosphate (0.054 g) was added. The reaction mixture was cooled to 0° C. and hydrogen peroxide (1 mL) and sodium chlorite (0.208 g) were added. After stirring the reaction mixture for an additional 1 hour, the solvents were evaporated on a rotary evaporator; the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to get the title compound (0.5 g).
Step j: Synthesis of (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid
[0463] Potassium carbonate (0.165 g) was added to a solution of the compound obtained from step i above (0.4 g) in methanol (6 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The solvents were evaporated, and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified with preparatory TLC using 7% methanol in ethyl acetate as eluent to get the title compound (0.13 gm).
[0464] Mass (m/z): 474.88 (M + +1); 1 HNMR (CDCl 3 ):— δ 8.35 (s, 1H), 7.83-7.81 (m, 2H), 7.77-7.69 (m, 3H), 7.42 (d, 2H, J=3 Hz), 7.25 (d, 2H, J=6 Hz), 6.80 (d, 1H, J=6 Hz), 3.97 (s, 3H), 3.87-3.78 (m, 3H), 2.89 (m, 1H), 2.69 (m, 1H), 2.57 (m, 1H), 2.15-1.98 (m, 2H), 1.84-1.79 (m, 2H).
Example 1E
Synthesis of (2S,3R)-5-(2′,4′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 97)
Step a: Synthesis of 2-(2-{(3aS,5R,6S,6aS)-5-[(E)-2-(3′,5′-difluorobiphenyl-4-yl)ethenyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0465] A mixture of the compound obtained from step d of Example 1D above (0.2 g), 3,5-difluorophenyl boronic acid (0.135 g), tetrakistriphenylphosphinepalladium (0) (0.023 g), and potassium carbonate (0.2 g) was dried under high vacuum for 10 minutes and dry dimethylformamide (3 mL) was added at room temperature. The reaction mixture was heated at 120° C. for 2 hours, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (0.205 g).
Step b: Synthesis of 2-(2-{(3aS,5R,6S,6aS)-5-[2-(3′,5′-difluorobiphenyl-4-yl)ethyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0466] To the solution of the compound obtained from step a above (0.2 g) in tetrahydrofuran (10 mL), 10% palladium on charcoal (0.1 g) was added at room temperature, and the reaction mixture was hydrogenated with hydrogen at 35 psi for 4 hours in a Paar apparatus. The reaction mixture was filtered through a celite pad, and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (0.2 g).
Step c: Synthesis of 2-(2-{(2R,3R,4S,5R)-2-[2-(3′,5′-difluorobiphenyl-4-yl)ethyl]-4,5-dihydroxytetrahydrofuran-3-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0467] Perchloric acid (0.3 mL) was added to a solution of the compound obtained from step b above (0.2 g) in acetonitrile (6 mL) and water (2 mL) at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using sodium bicarbonate solution. The solvents were evaporated under reduced pressure. The residue thus obtained was taken up in ethyl acetate and water. The organic layer was separated and washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.15 g).
Step d: Synthesis of (1R,2S)-1-[2-(3′,5′-difluorobiphenyl-4-yl)ethyl]-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-formylbutyl formate
[0468] To a solution of the compound obtained from step c above (0.15 g) in methanol (6 mL) at 0° C., a solution of sodium metaperiodate (0.15 g in 1 mL of water) was added. The reaction mixture was stirred for 2 hours at the same temperature. After stirring the reaction mixture for an additional 1 hour at room temperature, the reaction mixture was evaporated on a rotary evaporator. The residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain the title compound (0.12 g).
Step e: Synthesis of (2S,3R)-5-(3′,5′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-(formyloxy)pentanoic acid
[0469] The compound obtained from step d above (0.12 g) was taken in acetonitrile (6 mL) and water (1 mL). To this solution, sodium dihydrogen phosphate (0.05 g) was added. The reaction mixture was cooled to 0° C., and hydrogen peroxide (0.5 mL) and sodium chlorite (0.15 g) were added. After stirring the reaction mixture for an additional 1 hour, the solvents were evaporated on a rotary evaporator and the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure, to get the title compound (0.12 g).
Step f: Synthesis of (2S,3R)-5-(3′,5′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid
[0470] Potassium carbonate (0.06 g) was added to a solution of the compound obtained from step e above (0.12 g) in methanol (10 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The solvents were evaporated, and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified with preparatory thin layer chromatography using 10% methanol in ethyl acetate as eluent to get the title compound (0.025 gm).
[0471] Mass (m/z): 480.13 (M + +1); 1 HNMR (CD 3 OD): δ 7.48-7.76 (m, 4H), 7.47-7.37 (m, 3H), 7.25-7.23 (d, 2H), 7.03-6.98 (m, 2H), 3.78-3.72 (m, 3H), 2.85-2.81 (m 1H), 2.65-2.63 (m, 1H), 2.42-2.40 (m, 1H), 2.10-2.05 (m, 2H), 1.79-1.75 (m, 2H).
Example 2
Synthesis of (2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-phenylpentanoic acid (Compound No. 82)
Step a: Synthesis of 3-{2-[(3aS,5R,6S,6aS)-2,2-dimethyl-5-(2-phenylethyl)tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]ethyl}-1,2,3-benzotriazin-4(3H)-one
[0472] To the solution of the compound obtained from step j of Example 1 (0.3 g) in a solvent mixture of tetrahydrofuran:methanol (10 mL:10 mL) palladium/carbon (0.2 g, 10%) was added at room temperature, and the reaction mixture was hydrogenated at 35 psi for 4 hours in a Paar apparatus. The reaction mixture was filtered through a celite pad and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (0.3 g).
[0473] Mass (m/z): 421 (M + )
Step b: Synthesis of 3-{2-[(2R,3R,4S,5R)-4,5-dihydroxy-2-(2-phenylethyl)tetrahydrofuran-3-yl]ethyl}-1,2,3-benzotriazin-4(3H)-one
[0474] Perchloric acid (0.2 mL) was added to a solution of the compound obtained from step a above (0.3 g) in acetonitrile (4 mL) and water (0.3 mL) at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using a sodium bicarbonate solution. The solvents were evaporated at reduced pressure. The residue thus obtained was taken up in ethyl acetate and water. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.3 g).
Step c: Synthesis of (2S,3R)-3-(formyloxy)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-phenylpentanoic acid
[0475] To a solution of the compound obtained from step b above (0.3 g) in tert-butanol:tetrahydrofuran (3 mL:3 mL) at 0° C., a solution of sodium metaperiodate (0.673 g in 3 mL of water) was added. The reaction mixture was stirred for 2 hours at the same temperature and potassium permanganate (0.025 g) was added at 0° C. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated and the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure, to afford the title compound (0.3 g).
Step d: Synthesis of (2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-phenylpentanoic acid
[0476] Potassium carbonate (0.11 g) was added to a solution of the compound obtained from step c above (0.3 g) in methanol (4 mL) and tetrahydrofuran (4 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The solvents were evaporated, and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 10% methanol in dichloromethane as eluant to afford the title compound (0.020 g).
[0477] Mass (m/z): 368.0 (M + +1); 1 HNMR (CD 3 OD): δ 8.31 (d, 1H, J=8 Hz), 8.15 (d, 1H, J=8 Hz), 8.06-8.02 (m, 1H), 7.91-7.89 (m, 2H), 7.62 (d, 2H, J=8 Hz), 7.36 (d, 1H, J=8 Hz), 7.21-7.07 (m, 1H), 4.57-4.52 (m, 2H), 3.78-3.76 (m, 1H), 2.76-2.75 (m, 1H), 2.57-2.49 (m, 2H), 2.29-2.27 (m, 2H), 1.74-1.71 (m, 2H).
Example 3
Synthesis of (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4(trifluoromethyl)phenyl]pentanoic acid (Compound No. 84)
Step a: Synthesis of 5-O-[tert-butyl(diphenyl)silyl]-3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1,2-O-isopropylidene-β-D-lyxofuranose
[0478] A mixture of the compound obtained from step f of Example 1 (0.14 g), triphenylphosphine (0.080 g), and pthalimide (0.045 g) was taken in a round bottom flask and dried in high vacuum for 10 minutes. The vacuum was released under a nitrogen atmosphere and tetrahydrofuran (5 mL) was added to the reaction mixture. The reaction mixture was cooled to 0° C. and diethyl azodicarboxylate (0.1 mL) was added slowly. The reaction mixture was stirred for 30 minutes at the same temperature, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated. The residue thus obtained was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (0.11 g).
[0479] Mass (m/z): 608 (M + +23)
Step b: Synthesis of 3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1,2-O-isopropylidene-β-D-lyxofuranose
[0480] To a solution of the compound obtained from step a above (0.060 g) in dry tetrahydrofuran (2 mL) at 0° C., tetra-butyl ammonium fluoride (0.2 mL) was added. The resulting mixture was initially stirred at 0° C. for 1 hour, and then at room temperature for 4 hours. The reaction mixture was cooled to 0° C., quenched with saturated ammonium chloride, and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulphate, and concentrated. The residue thus obtained was purified by column chromatography over silica gel using 60% ethyl acetate in hexane as eluant to furnish the title compound (0.4 g).
Step c: Synthesis of (55)-3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-4,5-O-isopropylidene-D-arabino-pentodialdo-5,2-furanose
[0481] In a three-neck round bottom flask, oxalyl chloride (0.6 mL) and dichloromethane (20 mL) were placed and cooled to −78° C. Dimethylsulfoxide (1 mL) was added drop-wise to the reaction mixture. The reaction mixture was warmed to −35° C. for 5 to 10 minutes, and again cooled to −78° C. A solution of the compound obtained from step b above (1 g) in dichloromethane (5 mL) was added slowly while maintaining the same temperature. The reaction mixture was stirred for 45 minutes until the reaction temperature reached −35° C. The reaction mixture was again cooled to −78° C., and triethylamine (2.4 mL) was added. The reaction mixture was stirred for an additional 30 minutes and the temperature was allowed to reach −35° C. The reaction mixture was quenched with a saturated solution of ammonium chloride, and extracted with dichloromethane. The combined organic layer was washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated to furnish the title compound (1.0 g).
Step d: Synthesis of 2-{2-[(3aS,5R,6S,6aS)-2,2-dimethyl-5-{(E)-2-[4-(trifluoromethyl) phenyl]vinyl}tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]ethyl}-1H-isoindole-1,3(2H)-dione
[0482] To a suspension of triphenyl[4-(trifluoromethyl)benzyl]phosphonium bromide (0.795 g) in dimethylsulphoxide (5 mL), potassium tert-butoxide (0.292 g) was added. A solution of the compound obtained from step c above (0.5 g) in tetrahydrofuran (7 mL) was added drop-wise after 20 minutes, and the reaction mixture was stirred for 1 hour at the same temperature. The reaction mixture was quenched with water, and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by column chromatography using 30% ethyl acetate in hexane as eluant to furnish the title compound (0.25 g).
[0483] Mass (m/z): 487 (M + )
Step e: Synthesis of 2-{2-[(3aS,5R,6S,6aS)-2,2-dimethyl-5-{2-[4-(trifluoromethyl)phenyl]ethyl}tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]ethyl}-1H-isoindole-1,3(2H)-dione
[0484] 10% Palladium on charcoal (0.2 g) was added to the solution of compound obtained from step d above (0.25 g) in ethyl acetate (20 mL) at room temperature, and the reaction mixture was hydrogenated at 50 psi for 4 hours in a Paar apparatus. The reaction mixture was filtered through a celite pad, and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (0.225 g).
Step f: Synthesis of 2-{2-[(2R,3R,4S,5R)-4,5-dihydroxy-2-{2-[4-(trifluoromethyl)phenyl]ethyl}tetrahydrofuran-3-yl]ethyl}-1H-isoindole-1,3(2H)-dione
[0485] Perchloric acid (0.2 mL) was added to a solution of the compound obtained from step e above (0.225 g) in acetonitrile (4 mL), water (1 mL), and tetrahydrofuran (0.5 mL) at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using a sodium bicarbonate solution. The solvents were evaporated at reduced pressure. The residue thus obtained was taken in ethyl acetate and water. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.22 g).
Step g: Synthesis of (1R,2S)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-formyl-1-{2-[4-(trifluoromethyl)phenyl]ethyl}butyl formate
[0486] A solution of sodium metaperiodate (0.313 g in 1 mL of water) was added to a solution of the compound obtained from step f above (0.22 g) in methanol:tetrahydrofuran (3 mL:1 mL) at 0° C. The reaction mixture was stirred for 2 hours at same temperature. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated on a rotary evaporator, and the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (0.22 g).
Step h: Synthesis of (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-(formyloxy)-5-[4-(trifluoromethyl)phenyl]pentanoic acid
[0487] To a solution of the compound obtained from step g above (0.22 g) in a solvent mixture of acetonitrile:water (3 mL:1 mL) at 0° C., sodium dihydrogenphosphate (0.021 g), sodium chlorite (0.081 g) and hydrogen peroxide (1 mL, 30% in water) were added. The reaction mixture was stirred for 2 hours at room temperature. The solvents were evaporated under reduced pressure to obtain a residue. Ethyl acetate and water were added to the resulting residue. The organic layer was separated, washed with water and brine, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (0.2 g).
Step i: Synthesis of (2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(trifluoromethyl)phenyl]pentanoic acid
[0488] Potassium carbonate (0.178 g) was added to a solution of the compound obtained from step h above (0.2 g) in methanol (7 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The solvents were evaporated, and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 10% methanol in dichloromethane as eluant to afford the title compound (0.090 g).
[0489] Mass (m/z): 458.0 (M + +23)
[0490] 1 HNMR (CD 3 OD): δ 7.83 (q, 2H, J=3.1 Hz), 7.71 (t, 2H, J=3.2 Hz), 7.51 (d, 2H, J=7.6 Hz), 7.28 (d, 2H, J=7.9 Hz), 3.95-3.76 (m, 3H), 2.93-2.55 (m, 3H), 2.14-1.75 (m, 4H).
Example 4
Synthesis of (2R,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 89)
Step a: Synthesis of 1,2:5,6-Di-O-isopropyliden-α-D-ribo-3-hexulo-furanose
[0491] Oxalyl chloride (25.16 mL) and dichloromethane (200 mL) were taken in a three-neck round bottom flask and cooled to −75° C. under a nitrogen atmosphere. Then dimethylsulfoxide (27.3 mL) was added drop-wise slowly maintaining the temperature at −70° C. The reaction mixture was stirred for 30 minutes at the same temperature, and then diacetone-α-D-glucose (50 g) in dichloromethane (500 mL) was charged slowly, maintaining the temperature at −70° C. After 20 minutes, triethylamine (80 mL) was added drop-wise to the above mixture at the same temperature. A saturated solution of ammonium chloride in water (500 mL) was charged to the reaction mixture after 30 minutes, and the temperature was allowed to rise to room temperature. The reaction mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (45 g).
Step b: Synthesis of 1,2:5,6-Di-O-isopropylidene-3-deoxy-3-(2-ethoxy-2-oxoethylidene)-α-D-ribo-hexofuranose
[0492] To a suspension of sodium hydride (0.155 g, 60% in oil) in tetrahydrofuran (5 mL), triethyl phosphonoacetate (1.55 mL) was charged at 0° C. After 20 minutes, a solution of the compound obtained from step a above (1 g) in tetrahydrofuran (3 mL) was added drop-wise and the reaction mixture was stirred for 1 hour at the same temperature. A saturated solution of ammonium chloride was added to the reaction mixture. The resulting mixture was extracted with ethyl acetate. The combined extracts were dried over anhydrous sodium sulphate, and evaporated under reduced pressure to yield a residue which was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (1.3 g).
[0493] Mass (m/z): 351.1 (M + +23)
Step c: Synthesis of 1,2:5,6-Di-O-isopropylidene-3-deoxy-3-(2-ethoxy-2-oxoethyl)-α-D-allofuranose
[0494] 10% Palladium on charcoal (0.05 g) was added to the solution of the compound obtained from step b above (0.15 g) in ethyl acetate (10 mL) at room temperature, and hydrogen was supplied at 50 psi for 4 hours. The reaction mixture was filtered through a celite pad and the residue was washed with ethyl acetate. The filtrate was concentrated to afford the title compound (0.12 g).
[0495] Mass (m/z): 353.2 (M + +1).
Step d: Synthesis of 3-deoxy-3-(2-ethoxy-2-oxoethyl)-1,2-O-isopropylidene-α-D-allofuranose
[0496] 30% Perchloric acid (4 mL) was added to a solution of the compound obtained from step c above (2.0 g) in tetrahydrofuran (20 mL) at −5° C. to 0° C. The reaction mixture was stirred for 5 hours at −5° C. to 0° C. and then quenched with a saturated solution of sodium bicarbonate (20 mL). The solvents were evaporated, and ethyl acetate and water were added to the resulting residue. The organic layer was separated, washed with brine, dried over anhydrous sodium sulphate, and concentrated to afford the title compound (1.5 g).
[0497] Mass (m/z): 313.2 (M + +1)
Step e: Synthesis of 3-deoxy-3-(2-ethoxy-2-oxoethyl)-1,2-O-isopropylidene-α-D-ribo-pentodialdo-1,4-furanose
[0498] To a solution of the compound obtained from step d above (1.5 g) in methanol (15 mL), an aqueous solution of sodium periodate (1.65 g in 10 mL of water) was added at 0° C. The reaction mixture was stirred for 3 hours and brought from 0° C. to room temperature. The solvents were evaporated. Ethyl acetate and water were added to the residue. The organic layer was separated, washed with brine, dried over anhydrous sodium sulphate, and concentrated to afford the title compound (0.9 g).
[0499] Mass (m/z): 259.2 (M + +1)
Step f: Synthesis of ethyl {(3aR,5R,6R,6aR)-5-[(E)-2-(4-bromophenyl)vinyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}acetate
[0500] To a suspension of (4-bromobenzyl)triphenylphosphonium bromide (2.67 g) in dimethylsulphoxide (15 mL), potassium tert-butoxide (0.508 g) was added at 0° C. After stirring the reaction mixture for 30 minutes at room temperature, a solution of the compound obtained from step e above (0.9 g) in tetrahydrofuran (5 mL) was added drop-wise at 0° C. The reaction mixture was stirred for 2 hours and brought from 0° C. to room temperature, and quenched with ice cold water. The solvents were evaporated, and ethyl acetate and water were added to resulting residue. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure, and the residue thus obtained was purified by column chromatography using 10% ethyl acetate in hexane as eluant to furnish the title compound (1.0 g).
[0501] Mass (m/z): 413.3 (M + +1)
Step g: Synthesis of ethyl {(3aR,5R,6R,6aR)-5-[(E)-2-(4′-chlorobiphenyl-4-yl)vinyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}acetate
[0502] A mixture of the compound obtained from step f above (1.0 g) (4-chlorophenyl)boronic acid (0.76 g), tetrakis(triphenylphosphine)palladium (0) (0.14 g), and potassium carbonate (1.0 g) in dry dimethylformamide (10 mL) was heated at 110° C. for 4 hours. Ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 12% ethyl acetate in hexane as eluant to afford the title compound (0.9 g).
[0503] Mass (m/z): 465.2 (M + +23)
Step h: Synthesis of ethyl {(3aR,5R,6R,6aR)-5-[2-(4′-chlorobiphenyl-4-yl)ethyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}acetate
[0504] To a solution of the compound obtained from step g above (0.8 g) in ethyl acetate (15 mL), 10% palladium on charcoal (0.25 g) was added at room temperature. The system was evacuated with hydrogen and the reaction mixture was stirred for 4 hours at room temperature under a hydrogen atmosphere. The reaction mixture was filtered through a celite pad, and concentrated to afford the title compound (0.75 g).
[0505] Mass (m/z): 415.4 (M + −28)
Step i: Synthesis of 2-{(3aR,5R,6R,6aR)-5-[2-(4′-chlorobiphenyl-4-yl)ethyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethanol
[0506] To a solution of the compound obtained from step h above (0.75 g) in tetrahydrofuran (15 mL), lithium aluminum hydride (0.096 g) was added at 0° C. The resulting mixture was stirred for 3 hours at same temperature, and a saturated solution of ammonium chloride was then added. The reaction mixture was then filtered through silica gel (100 to 200 mesh) and concentrated. Ethyl acetate and water were added to the resulting residue. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to afford the title compound (0.65 g).
[0507] Mass (m/z): 425.2 (M + +23)
Step j: Synthesis of 2-{(3aR,5R,6R,6aR)-5-[2-(4′-chlorobiphenyl-4-yl)ethyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl methanesulfonate
[0508] Triethylamine (0.43 ml) and methanesulfonyl chloride (0.21 mL) were added to a solution of the compound obtained from step i above (0.6 g) in dichloromethane (15 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. Dichloromethane and water were added to reaction mixture. The organic layer was separated, washed with water, dried, and concentrated under reduced pressure to furnish the title compound (0.6 g).
Step k: Synthesis of 2-(2-{(3aR,5R,6R,6aR)-5-[2-(4′-chlorobiphenyl-4-yl)ethyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0509] Potassium phthalimide (0.051 g) was added in one portion to a stirred solution of the compound obtained from step j above (0.12 g) in dimethylformamide (5 mL) at room temperature under a nitrogen atmosphere. The resulting solution was heated at 50° C. for about 14 hours and then cooled to room temperature. Ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed with water and brine, and dried over anhydrous sodium sulphate. The organic phase was evaporated to dryness under reduced pressure. The residue thus obtained was purified by column chromatography using 30% ethyl acetate in hexane as eluant to furnish the title compound (0.1 g).
[0510] Mass (m/z): 549.5 (M + +NH 4 + )
Step l: Synthesis of 2-(2-{(2R,3S,4R,5S)-2-[2-(4′-chlorobiphenyl-4-yl)ethyl]-4,5-dihydroxytetrahydrofuran-3-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0511] Trifluoroacetic acid (1 mL) and water (0.5 mL) were added to the compound obtained from step k above (0.04 g). The reaction mixture was stirred at room temperature for 2 hours. The solvents were evaporated at reduced pressure. The residue thus obtained was taken in ethyl acetate and water. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.028 g).
Step m: Synthesis of (2R,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-(formyloxy)pentanoic acid
[0512] To a solution of the compound obtained from step 1 above (0.028 g) in a tert-butanol:water (2:3; 1.3 mL), sodium metaperiodate (0.051 g) was added at room temperature. The reaction mixture was stirred for 2 hours at the same temperature, and potassium permanganate (0.001 g) was added at 0° C. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated on a rotary evaporator, and the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under the reduced pressure to afford the title compound (0.025 g).
Step n: Synthesis of (2R,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid
[0513] Potassium carbonate (0.007 g) was added to a solution of the compound obtained from step m above (0.025 g) in methanol (1 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The solvents were evaporated and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 10% methanol in dichloromethane as eluant to afford the title compound (0.014 g).
[0514] Mass (m/z): 478.2 (M + +1)
[0515] 1 HNMR (CD 3 OD): δ 7.83 (q, 2H, J=4 Hz), 7.77 (q, 2H, J=4 Hz), 7.56 (d, 2H, J=8 Hz), 7.48 (d, 2H, J=8 Hz), 7.40 (d, 2H, J=8 Hz), 7.26 (d, 1H, J=8 Hz), 3.83-3.70 (m, 3H), 2.85-2.49 (m, 3H), 1.92-1.70 (m, 4H).
Example 5
Synthesis of (2R,3S)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 205)
Step a: Synthesis of 3-O-Acetyl-1,2:5,6-di-O-isopropylidene-α-D-erythrohexofuran-3-enose
[0516] Acetic anhydride (65.77 mL) was added to a solution of the compound obtained from step a of Example 4 (45 g) in pyridine (500 mL) and the reaction mixture was heated at 60° C. for overnight. The reaction mixture was then concentrated to obtain a residue. Ethyl acetate and water were added to the residue. The organic layer was separated and washed with dilute hydrochloric acid, water, and brine. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by silica gel column chromatography using 8% ethyl acetate in hexane as eluant to furnish the title compound (21 g).
[0517] Mass (m/z): 301.19 (M + +1)
Step b: Synthesis of 3-O-acetyl-1,2:5,6-di-O-isopropylidene-α-D-gulofuranose
[0518] To a solution of the compound obtained from step a above (26 g) in ethyl acetate (250 mL), 10% palladium on charcoal (6 g) was added and the reaction mixture was shaken under hydrogen atmosphere at 60 psi for 4 hours on Paar apparatus. The reaction mixture was filtered through a celite bed. The solvents were evaporated to obtain a crude residue which was purified using column chromatography over silica gel using 15% ethyl acetate in hexane as eluant to furnish the title compound (17 g).
[0519] Mass (m/z): 324.97 (M + +Na)
Step c: Synthesis of 1,2:5,6-di-O-isopropylidene-α-D-gulofuranose
[0520] Sodium methoxide (12.5 g) was added to a solution of the compound obtained from step b above (64 g) in methanol (10 mL). The reaction mixture was stirred for 3 hours at 0° C. The reaction mixture was then concentrated. The residue thus obtained was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (31 g).
[0521] Mass (m/z): 261.26 (M + +1)
Step d: Synthesis of 1,2:5,6-di-O-isopropylidene-α-D-xylo-hexofuranos-3-ulose
[0522] Sodium hypochlorite (225 mL, 4% solution) was added drop-wise to a solution of the compound obtained from step c above (30 g), followed by the addition of 2,2,6,6,-tetramethylpiperidine N-oxyl (0.18 g), potassium bromide (10.62 g), and sodium acetate (14.19 g) in ethyl acetate (300 mL) and water (100 mL). After 20 minutes, triethylamine (3.3 mL) was added drop-wise to the above mixture at the same temperature. The reaction mixture was extracted with ethyl acetate after 30 minutes. The organic layer was dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (10.4 g).
Step e: Synthesis of 1,2:5,6-Di-O-isopropylidene-3-deoxy-3-(2-ethoxy-2-oxoethylidene)-α-D-xylo-hexofuranose
[0523] To the solution of the compound obtained from step d above (10.5 g) in tetrahydrofuran, carboethoxymethylene triphenyl-phosphorane (27 g) was added. The reaction mixture was refluxed for 2 hours and concentrated to afford crude compound, which was purified by column chromatography over silica gel using 8% ethyl acetate in hexane as eluant to yield the title compound (5.0 g).
[0524] Mass (m/z): 350.28 (M + +Na)
Step f: Synthesis of 1,2:5,6-Di-O-isopropylidene-3-deoxy-3-(2-ethoxy-2-oxoethyl)-α-D-gulofuranose
[0525] 10% Palladium on charcoal (3 g) was added to a solution of the compound obtained from step e above (12 g) in methanol (50 mL) and the reaction mixture was stirred under hydrogen atmosphere at room temperature for 4 hours. The reaction mixture was filtered through a celite pad and the residue was washed using ethyl acetate. The filtrate was concentrated to furnish the title compound (12 g).
[0526] Mass (m/z): 330.9 (M + +1).
Step g: Synthesis of 1,2:5,6-Di-O-isopropylidene-3-deoxy-3-(2-hydroxyethyl)-α-D-gulofuranose
[0527] To a suspension of lithium aluminum hydride (2.37 g) in tetrahydrofuran (120 mL), a solution of the compound obtained from step f above (12 g) in tetrahydrofuran (100 mL) was added at −50° C. The reaction mixture was allowed to attain the temperature 0° C. and the mixture was stirred for 30 minutes at 0° C. The reaction mixture was quenched using an aqueous solution of ammonium chloride (25 mL). The reaction mixture was slowly allowed to attain room temperature and was further stirred for 12 hours at same temperature. The reaction mixture was filtered through a celite pad, and the residue was washed with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (8.5 g).
Step h: Synthesis of 1,2:5,6-Di-O-isopropylidene-3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-α-D-gulofuranose
[0528] A mixture of the compound obtained from step g above (8.5 g), triphenyl phosphine (21.83 g), and phthalimide (6.73 g) were taken in a round bottom flask and dried in high vacuum for 10 minutes. Then the vacuum was released under a nitrogen atmosphere and tetrahydrofuran (100 mL) was added to the reaction mixture. The reaction mixture was cooled to 0° C. and diisopropyl azodicarboxylate (12.625 g) was added slowly. The reaction mixture was stirred for 30 minutes at the same temperature and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated. The residue thus obtained was purified by column chromatography over silica gel using 40% ethyl acetate in hexane as eluant to afford the title compound (8.5 g).
Step i: Synthesis of 3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1,2-O-(isopropylidene)-α-D-gulofuranose
[0529] 30% Perchloric acid (8.15 mL) was added to a solution of the compound obtained from step h above (0.8 g) in tetrahydrofuran (200 mL). The reaction mixture was stirred for 2 hours at 0° C. to 5° C. and then quenched with a saturated solution of sodium hydrogen carbonate. Ethyl acetate and water were added to the resulting mixture. The organic layer was separated, washed with brine, dried over anhydrous sodium sulphate, and concentrated. The residue thus obtained was purified by column chromatography over silica gel using 60% ethyl acetate in hexane to afford the title compound (5.5 g).
[0530] Mass (m/z): 377.24 (M + +1)
Step j: Synthesis of (5R)-3-deoxy-3-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-4,5-O-(1-methylethylidene)-L-arabino-pentodialdo-5,2-furanose
[0531] To a solution of the compound obtained from step i above (5.5 g) in acetone (100 mL), an aqueous solution of sodium periodate (9.33 g in 100 mL) was added at 0° C. The reaction mixture was stirred for 2 hours, then filtered and concentrated. The residue thus obtained was taken in distilled water and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated to afford the title compound (5.2 g).
Step k: Synthesis of 2-(2-{(3aR,5S,6R,6aR)-5-[(E)-2-(4-bromophenyl)ethenyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0532] A solution of (4-bromobenzyl)triphenylphosphonium bromide (13.3 g) in dimethyl sulphoxide (10 mL) was added drop-wise to a suspension of sodium hydride (1 g of 50% suspension) in dimethyl sulphoxide (20 mL) at 0° C. After 20 minutes, a solution of the compound obtained from step j above (6 g) in dimethylsulphoxide (100 mL) was added drop-wise and the reaction mixture was stirred for 1 hour at the same temperature. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 40% ethyl acetate in hexane to furnish the title compound (5.5 g).
[0533] Mass (m/z): 499.10 (M + +1)
Step l: Synthesis of 2-(2-{(3aR,5S,6R,6aR)-5-[(E)-2-(3′-fluoro-4′-methylbiphenyl-4-yl)ethenyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0534] A mixture of the compound obtained from step k above (0.5 g), 3-fluoro-4-methylphenylboronic acid (0.314 g), tetrakistriphenylphosphinepalladium (0) (0.057 g), and potassium carbonate (0.414 g) was dried under high vacuum for 10 minutes. The vacuum was released under nitrogen atmosphere and dry dimethylformamide (5 mL) was added at room temperature. The reaction mixture was heated at 120° C. for 2 hours, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (0.37 g).
[0535] Mass (m/z): 527.23 (M + +1)
Step m: Synthesis of 2-(2-{(3aR,5S,6R,6aR)-5-[2-(3′-fluoro-4′-methylbiphenyl-4-yl)ethyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0536] 10% Palladium on charcoal (100 g) was added to a solution of the compound obtained from step 1 above (0.37 g) in ethyl acetate (10 mL) at room temperature and the reaction mixture was hydrogenated at 35 psi for 1 hour in a Paar apparatus. The reaction mixture was filtered through a celite pad and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (0.28 g).
Step n: Synthesis of 2-(2-{(2S,3S,4R,5S)-2-[2-(3′-fluoro-4′-methylbiphenyl-4-yl)ethyl]-4,5-dihydroxytetrahydrofuran-3-yl}ethyl)-1H-isoindole-1,3(2H)-dione
[0537] To a solution of the compound obtained from step m above (0.28 g) in acetonitrile (20 mL) and water (2 mL), 30% perchloric acid (0.4 mL) was added at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using a sodium bicarbonate solution. The solvents were evaporated at reduced pressure. The residue thus obtained was taken in ethyl acetate and water. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.418 g) as crude mass which was used further without any purification and characterization.
Step o: Synthesis of (2R,3S)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-(formyloxy)pentanoic acid
[0538] A solution of sodium metaperiodate (0.489 g in 5 mL of water) was added to a solution of the compound, obtained from step n above (0.4 g), in a tert-butanol:tetrahydrofuran (5 mL:5 mL) at 0° C. The reaction mixture was stirred for 2 hours at the same temperature and potassium permanganate (0.033 g) was added at 0° C. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated on a rotary evaporator, and the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (0.31 g) as crude mass which was used further without any purification and characterization.
Step p: Synthesis of (2R,3S)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid
[0539] To a solution of the compound obtained from step o above (0.31 g) in methanol (5 mL), potassium carbonate (0.094 g) was added at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate (50 mL), acidified with sodium hydrogen sulphate, and washed with water (20 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain a residue which was purified by preparative thin layer chromatography using 10% methanol in dichloromethane as eluant to afford the title compound (0.020 g).
[0540] Mass (m/z): 476.07 (M + +1)
[0541] 1 HNMR (CD 3 OD): δ 7.72-7.64 (m, 4H), 7.36-7.34 (m, 2H), 7.18-7.10 (m, 5H), 3.68-3.61 (m, 3H), 2.75-2.71 (m, 1H), 2.55-2.49 (s, 1H), 2.32-2.30 (m, 1H), 2.16 (s, 3H), 1.99-1.94 (m, 2H), 1.70-1.62 (m, 2H).
Example 6
Synthesis of (2S,3S)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 208)
Step a: Synthesis of 5-O—[tert-butyl(diphenyl)silyl]-3-deoxy-1,2-O-isopropylidene-3-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-α-L-ribofuranose
[0542] A mixture of the compound obtained from step f of Example 1 (20 g), triphenyl phosphine (17.6 g), and 1,2,3-benzotriazin-4(3H)-one (7.2 g) was dried in high vacuum in a round bottom flask for 10 minutes. The vacuum was released under a nitrogen atmosphere and tetrahydrofuran (200 mL) was added to the above reaction mixture. The reaction mixture was cooled to 0° C. and diisopropyl azodicarboxylate (9.8 mL) was added slowly. The reaction mixture was stirred for 30 minutes at the same temperature, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, dried over anhydrous sodium sulphate, and concentrated to obtain a residue which was purified by column chromatography over silica gel using 30% ethyl acetate in hexane as eluant to afford the title compound (22 g).
[0543] Mass (m/z): 586.24 (M + +1).
Step b: Synthesis of 3-deoxy-1,2-O-isopropylidene-3-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-α-L-ribofuranose
[0544] To a solution of the compound obtained from step a above (22 g) in dry tetrahydrofuran (200 mL) at 0° C., 1 M solution of tetra-butylammonium fluoride (75 mL) was added. The resulting mixture was stirred at 0° C. for 1 hour and then at room temperature for 4 hours. The reaction mixture was cooled to 0° C., quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulphate, and concentrated. The residue thus obtained was purified by column chromatography over silica gel using 50% ethyl acetate in hexane as eluant to furnish the title compound (6.5 g).
[0545] Mass (m/z): 348.25 (M + +1)
Step c: Synthesis of (5S)-3-deoxy-4,5-O-isopropylidene-3-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-D-ribo-pentodialdo-5,2-furanose
[0546] To a solution of the compound obtained from step b above (6.5 g) in dry dichloromethane (100 mL) cooled to 0° C., Dess-Martin periodinane reagent (11.1 g) was added. The reaction mixture was allowed to stir for 2 hours. The reaction mixture was quenched with sodium thiosulphate and sodium hydrogen carbonate. Dichloromethane was added to the reaction mixture. The organic layer was separated, washed with water and brine solution, dried over sodium sulphate, and evaporated to afford the title compound. (6.5 g)
Step d: Synthesis of 3-(2-{(3aS,5S,6S,6aS)-5-[(E)-2-(4-bromophenyl)vinyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0547] To a suspension of sodium hydride (0.979 g, 60% in oil) in dimethyl sulphoxide (60 mL) cooled to 0° C., (4-bromobenzyl)triphenylphosphonium bromide (14.5 g) was added. The compound obtained from step c above (6.5 g) in tetrahydrofuran (60 mL) was added drop-wise after 20 minutes, and the reaction mixture was stirred for 1 hour at the same temperature. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by column chromatography using 40% ethyl acetate in hexane as eluant to furnish the title compound (4 g).
[0548] Mass (m/z): 498.19 (M + +1)
Step e: Synthesis of 3-(2-{(3aS,5S,6S,6aS)-5-[(E)-2-(4′-methoxybiphenyl-4-yl)vinyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0549] A mixture of the compound obtained from step d above (1 g), 4-methoxyphenyl boronic acid (0.61 g), tetrakistriphenylphosphine palladium (0) (0.232 g), and potassium carbonate (0.832 g) was dried under high vacuum for 10 minutes and dry dimethylformamide (20 mL) was added at room temperature. The reaction mixture was heated at 120° C. for 2 hours, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 50% ethyl acetate in hexane as eluant to afford the title compound (0.62 g).
[0550] Mass (m/z): 526.41 (M + +1)
Step f: Synthesis of 3-(2-{(3aS,5S,6S,6aS)-5-[2-(4′-methoxybiphenyl-4-yl)ethyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0551] To a solution of the compound obtained from step e above (0.62 g) in a solvent mixture of ethyl acetate (20 mL), 10% palladium on charcoal (0.3 g) was added at room temperature, and the reaction mixture was hydrogenated at 35 psi for 4 hours in a Paar apparatus. The reaction mixture was filtered through a celite pad and the residue was washed with methanol. The filtrate was concentrated to afford the title compound (0.6 g).
Step g: Synthesis of 3-(2-{(2S,3R,4S,5R)-4,5-dihydroxy-2-[2-(4′-methoxybiphenyl-4-yl)ethyl]tetrahydrofuran-3-yl}ethyl)-1,2,3-benzotriazin-4(3H)-one
[0552] Perchloric acid (0.2 mL) was added to a solution of the compound obtained from step f above (0.6 g) in acetonitrile (50 mL) and water (10 mL) at room temperature. The reaction mixture was heated to 55° C. for 30 minutes. The reaction mixture was then quenched using a sodium hydrogen carbonate solution. The solvents were evaporated at reduced pressure. The residue thus obtained was taken in ethyl acetate and water. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was concentrated under reduced pressure to yield the title compound (0.6 g).
Step h: Synthesis of (2S,3S)-3-(formyloxy)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4-pyrimidin-5-ylphenyl)pentanoic acid
[0553] To a solution of the compound obtained from step g above (0.6 g) in a tert-butanol:tetrahydrofuran (7 mL:7 mL), a solution of sodium metaperiodate (0.973 g in 7 mL of water) was added at 0° C. The reaction mixture was stirred for 2 hours at the same temperature and potassium permanganate (0.036 g) was added at 0° C. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated and the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (0.5 g).
Step i: Synthesis of (2S,3S)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid
[0554] Potassium carbonate (0.151 g) was added to a solution of the compound obtained from step h above (0.5 g) in methanol (5 mL) and tetrahydrofuran (5 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hours. The solvents were evaporated and the residue was taken into water and ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by preperative thin layer chromatography using 10% methanol in dichloromethane as eluent to afford the title compound (0.008 g).
[0555] Mass (m/z): 474.31 (M + +1);
[0556] 1 HNMR (CD 3 OD): δ 8.32-7.87 (m, 5H), 7.50-7.42 (m, 4H), 7.24-7.20 (m, 2H), 6.97-6.94 (m, 1H), 4.60-4.50 (m, 2H), 3.81 (s, 3H), 3.59 (br t, 1H), 3.0-1.8 (m, 7H).
Example 7
Synthesis of (2S,3R)-3-hydroxy-5-[4-(5-methylpyridin-2-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 209)
Step a: Synthesis of 4-(5-methylpyridin-2-yl)benzaldehyde
[0557] A mixture of 2-bromo-5-methylpyridine (2 g), (4-formylphenyl)boronic acid (3.5 g), tetrakis(triphenylphosphine)palladium(0) (0.672 g), and potassium carbonate (4.8 g) was dried under high vacuum for 10 minutes and dry dimethylformamide (15 mL) was added at room temperature. The reaction mixture was heated at 110° C. for 6 hours, and then quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 20% ethyl acetate in hexane as eluant to afford the title compound (2.8 g).
[0558] Mass (m/z): 198.20
Step b: Synthesis of ethyl (2E)-3-[4-(5-methylpyridin-2-yl)phenyl]prop-2-enoate
[0559] To a suspension of sodium hydride (0.682 g, 60% in oil.) in tetrahydrofuran (20 mL), triethyl phosphonoacetate (3.82 g) was charged at 0° C. After 15 minutes, a solution of the compound obtained from step a above (2.8 g) in tetrahydrofuran (5 mL) was added drop-wise, and the reaction mixture was stirred for 30 minutes at room temperature. A saturated solution of ammonium chloride in water was added to the reaction mixture. The solvent was evaporated and the resulting mixture was extracted with ethyl acetate. The combined extracts were dried over anhydrous sodium sulphate and evaporated under reduced pressure to yield a residue which was purified by column chromatography over silica gel using 15% ethyl acetate in hexane as eluant to afford the title compound (1.8 g).
Step c: Synthesis of ethyl 3-[4-(5-methylpyridin-2-yl)phenyl]propanoate
[0560] 10% Palladium on charcoal (0.8 g) was added to a solution of the compound obtained from step b above (1.8 g) in tetrahydrofuran (15 mL) at room temperature, and hydrogen was supplied at 50 psi in a Paar apparatus for 4 hours. The reaction mixture was filtered through a celite pad and concentrated to afford the title compound (1.8 g).
Step d: Synthesis of 3-[4-(5-methylpyridin-2-yl)phenyl]propan-1-ol
[0561] To a suspension of lithium aluminum hydride (0.424 g) in tetrahydrofuran (20 mL), a solution of the compound obtained from step c above (2 g) in tetrahydrofuran (10 mL) was added at −20° C. The reaction mixture was stirred for 2 hours at 30° C. and a saturated solution of sodium sulphate was added at the same temperature. The reaction mixture was then filtered through a celite pad and the residue was washed with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography over silica gel using 50% ethyl acetate in hexane as eluant to afford the title compound (1.2 g).
Step e: Synthesis of 3-[4-(5-methylpyridin-2-yl)phenyl]propanal
[0562] To a stirred solution of the compound obtained from step d above (1.4 g) in dichloromethane (20 mL), 2,2,6,6,-tetramethylpiperidine N-oxyl (9.6 mg) and potassium bromide (73.4 mg) were added at 0° C. under nitrogen atmosphere. Sodium hypochlorite (13.7 mL, 4% solution) was added at pH 8-9 (maintained by adding aqueous sodium bicarbonate solution). The reaction was stirred for 20 minutes at 0° C. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, water, and brine. The organic layer was dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to afford the title compound (0.9 g).
Step f: Synthesis of 3-{(3S,4R)-3-{[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]carbonyl}-4-hydroxy-6-[4-(5-methylpyridin-2-yl)phenyl]hexyl}-1,2,3-benzotriazin-4(3H)-one
[0563] In a flame-dried flask, 3-{4-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-4-oxobutyl}-1,2,3-benzotriazin-4(3H)-one (1.18 g) was taken up in dichloromethane (10 mL) and cooled to 0° C. Titanium tetrachloride (3.4 mL) in dichloromethane (6 mL) was added drop-wise and the reaction mixture was stirred for 10 to 15 minutes. (−)-Sparteine (1.7 g) was added slowly to the reaction mixture and stirred at 0° C. for 45 minutes. A solution of the compound obtained from step e above (0.65 g) in dichloromethane (10 mL) was added slowly and stirring was continued at 0° C. After 3 hours, the reaction was quenched with the drop-wise addition of a saturated ammonium chloride solution, and dichloromethane was added. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel flash column chromatography using 30% ethyl acetate in hexane as eluant to afford the aldol adduct (0.56 g).
Step g: Synthesis of (2S,3R)-3-hydroxy-5-[4-(5-methylpyridin-2-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid
[0564] To a stirred solution of the compound obtained from step f above (0.2 g) in tetrahydrofuran:water (3:1, 10 mL), aqueous hydrogen peroxide solution (30%, 0.16 mL) was added at 0° C. followed by the addition of lithium hydroxide monohydrate (0.02 g) in water (5 mL). The reaction mixture was stirred at 0° C. for 30 minutes. The reaction mixture was concentrated, and the residue was extracted with ethyl acetate. The aqueous layer was acidified with sodium hydrogen sulphate and extracted with ethyl acetate. The combined layers were washed with water and brine, and dried over anhydrous sodium sulphate. The solvents were evaporated under reduced pressure and the crude residue was purified by silica gel flash column chromatography using 3% methanol in dichloromethane as eluant to afford the title compound (0.035 g).
[0565] Mass (m/z): 459.21 (M + +1);
[0566] 1 HNMR (CD 3 OD): δ 8.40 (s, 1H), 8.30 (d, 1H, J=7.88 Hz), 8.15 (d, 1H, J=8 Hz), 8.05-7.70 (m, 6H), 7.27 (d, 2H, J=7.6 Hz), 4.40-4.0 (m, 2H), 3.80-3.60 (m, 1H), 2.80-2.40 (m, 5H), 2.38 (s, 3H), 1.80-1.60 (m, 2H).
Example 7A
Synthesis of (2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 86)
Step a: Synthesis of methyl (2E)-3-(4-bromophenyl)prop-2-enoate
[0567] To a stirred solution of 4-bromocinnamic acid (16 g) in methanol (150 mL), thionyl chloride (30 mL) was added at 0° C. The reaction mixture was warmed to room temperature and refluxed for 3 hours. After cooling to room temperature, the solvents were evaporated to dryness. The crude compound obtained was used as such for the next step.
Step b: Synthesis of methyl (2E)-3-[4-(6-methoxypyridin-3-yl)phenyl]prop-2-enoate
[0568] The compound obtained from step a above (7.5 g), pyridine-2-methoxy-5-boronic acid (9.48 g), tetrakis(triphenylphosphine)palladium(0) (1.79 g), and potassium carbonate (12.83 g) were taken in dimethylformamide (60 mL) under nitrogen atmosphere. The reaction mixture was refluxed under nitrogen atmosphere for 6 hours. After cooling to room temperature, water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, and the solvents were evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 20% to 30% ethyl acetate in hexane to get the title compound (8.09 g).
Step c: Synthesis of methyl 3-[4-(6-methoxypyridin-3-yl)phenyl]propanoate
[0569] To a solution of compound obtained from step b above (8.1 g) in a mixture of ethyl acetate/methanol/tetrahydrofuran (˜300 mL), 10% Palladium on charcoal (1.6 g) was added and stirred under hydrogen atmosphere at 30 psi in a Paar apparatus for 2.5 hours. The reaction mixture was filtered through a celite pad, washed with ethyl acetate, and the filtrate was concentrated under reduced pressure to obtain the title compound as a white solid which was used as such for the next step.
Step d: Synthesis of 3-[4-(6-methoxypyridin-3-yl)phenyl]propanoic acid
[0570] To a stirred solution of lithium aluminum hydride (2.28 g) in tetrahydrofuran (120 mL), the compound obtained from step c above (8 g) in tetrahydrofuran (50 mL) was added at 0° C. The reaction mixture was stirred at 0° C. for 3 hours. The reaction mixture was quenched carefully with saturated ammonium chloride solution, filtered through celite, and washed with ethyl acetate. The organic layers were separated, washed with brine, and dried over anhydrous sodium sulfate, and solvents were evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 20% to 30% ethyl acetate in hexane to get the title compound as a white crystalline solid (5.1 g).
Step e: Synthesis of 3-[4-(6-methoxypyridin-3-yl)phenyl]propanal
[0571] To a stirred solution of the compound obtained from step d above (9.0 g) in dichloromethane (90 ml), 2,2,6,6,-tetramethylpiperidine N-oxyl (58.77 mg) and potassium bromide (447.57 mg) were added at 0° C. under nitrogen atmosphere. A 4% aqueous sodium hypochlorite (3.497 g) was added at pH 8-9 (maintained by adding saturated aqueous sodium bicarbonate solution). The reaction was stirred for 20 minutes at 0° C. Then, the organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, water, and brine. Finally, the organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the title compound (8.1 g) which was used as such in the next step.
Step f: Synthesis of 3-{(3S,4S)-3-{[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]carbonyl}-4-hydroxy-6-[4-(5-methoxypyridin-2-yl)phenyl]hexyl}-1,2,3-benzotriazin-4(3H)-one
[0572] In a flame-dried flask, 3-{4-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-4-oxobutyl}-1,2,3-benzotriazin-4(3H)-one (2.0 g) was taken up in dichloromethane (10 mL) and cooled to 0° C. Titanium tetrachloride (0.619 mL) in dichloromethane (6 mL) was added drop-wise and the reaction mixture was stirred for 10-15 minutes. (−)-Sparteine (2.7 mL) was added slowly to the reaction mixture and stirred at 0° C. for 45 minutes. A solution of the compound obtained from step e above (1.34 g) in dichloromethane (10 mL) was added slowly and stirring was continued at 0° C. After 3 hours, the reaction was quenched with the drop-wise addition of saturated ammonium chloride solution, and dichloromethane was added. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel flash column chromatography using 30% ethyl acetate in hexane as eluant to afford the aldol adduct (1.21 g).
Step g: Synthesis of (2S,3R)-3-hydroxy-5-[4-(5-methoxypyridin-2-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid
[0573] To a stirred solution of the compound obtained from step f above (1.21 g) in tetrahydrofuran:water (3:1, 15 mL), aqueous hydrogen peroxide solution (30%, 1.02 mL) was added at 0° C., followed by addition of lithium hydroxide monohydrate (114.5 mg) in water (5 mL). The reaction mixture was stirred at 0° C. until the completion of the hydrolysis. The reaction mixture was concentrated and the residue was extracted with ethyl acetate. The aqueous layer was acidified with sodium hydrogen sulphate and extracted with ethyl acetate. The combined layers were washed with water and brine, and dried over anhydrous sodium sulphate. The solvents were evaporated under reduced pressure and the crude residue was purified by silica gel flash column chromatography using 3% methanol in dichloromethane as eluant to afford the title compound (0.61 g).
[0574] Mass (m/z): 474.87 (M + +1);
[0575] 1 H NMR (400 MHz, MeOD): δ 8.32-8.30 (2H, m), 8.16-8.14 (1H, m), 8.04-8.03 (1H, m), 7.92-7.88 (2H, m), 7.46 (2H, d, J=8 Hz), 7.24 (2H, m, J=8 Hz), 6.86 (1H, d, J=8 Hz), 4.57-4.53 (2H, m), 3.93 (3H, s), 3.78-3.83 (1H, m), 2.83-2.80 (1H, m), 2.63-2.60 (1H, m), 2.52-2.49 (1H, m), 2.32-2.28 (2H, m), 1.80-1.76 (2H, m).
Example 7B
Synthesis of (2S,3R)-5-(2′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 216)
Step a: Synthesis of methyl (2E)-3-(4-bromophenyl)prop-2-enoate
[0576] To a stirred solution of 4-bromocinnamic acid (16 g) in methanol (150 mL), thionyl chloride (30 mL) was added at 0° C. The reaction mixture was warmed to room temperature and refluxed for 3 hours. After cooling to room temperature, the solvents were evaporated to dryness. The crude compound obtained was used as such for the next step.
Step b: Synthesis of methyl (2E)-3-(3′,5′-difluorobiphenyl-4-yl)prop-2-enoate
[0577] The compound obtained from step a above (0.75 g), 2,4-difluorophenyl boronic acid (0.737 g), tetrakis(triphenylphosphine)palladium(0) (0.07 g), and potassium carbonate (1.28 g) were taken in dimethylformamide (6 mL) under nitrogen atmosphere. The reaction mixture was refluxed under nitrogen atmosphere for 6 hours. After cooling to room temperature, water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, and the solvents were evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 20% to 30% ethyl acetate in hexane to get the title compound (0.810 g).
Step c: Synthesis of methyl 3-(3′,5′-difluorobiphenyl-4-yl)propanoate
[0578] To a solution of the compound obtained from step b above (0.79 g) in a mixture of ethyl acetate (˜10 mL), 10% Palladium on charcoal (0.2 g) was added and stirred under hydrogen atmosphere at 30 psi for 2.5 hours. The reaction mixture was filtered through a celite pad washed with ethyl acetate and the filtrate was concentrated under reduced pressure to obtain the title compound (0.77 g) as white solid which was used as such for the next step.
Step d: Synthesis of 3-(3′,5′-difluorobiphenyl-4-yl)propanoic acid
[0579] To a stirred solution of lithium aluminum hydride (0.2 g) in tetrahydrofuran (15 mL), the compound obtained from step c above (0.77 g) in tetrahydrofuran (50 mL) was added at 0° C. The reaction mixture was stirred at 0° C. for 3 hours. The reaction mixture was quenched carefully with saturated ammonium chloride solution, filtered through a celite pad, and washed with ethyl acetate. The organic layers were separated, washed with brine, and dried over anhydrous sodium sulfate, and solvents were evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 20% to 30% ethyl acetate in hexane to get the title compound as a white crystalline solid (0.70 g).
Step e: Synthesis of 3-(3′,5′-difluorobiphenyl-4-yl)propanal
[0580] To a stirred solution of the compound obtained from step d above (0.7 g) in dichloromethane (10 mL), 2,2,6,6,-tetramethylpiperidine N-oxyl (4.36 mg) and potassium bromide (33.32 mg) were added at 0° C. under nitrogen atmosphere. Sodium hypochlorite (6.5 mL, 4% solution) was added at pH 8-9 (maintained by adding aqueous sodium bicarbonate solution). The reaction was stirred for 20 minutes at 0° C. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, water, and brine. The organic layer was dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to afford the title compound (0.57 g).
Step f: Synthesis of 3-[(2R,3S)-2-{[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]carbonyl}-5-(3′,5′-difluorobiphenyl-4-yl)-3-hydroxypentyl]-1,2,3-benzotriazin-4(3H)-one
[0581] In a flame-dried flask, 3-{3-[(45)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-3-oxopropyl}-1,2,3-benzotriazin-4(3H)-one (0.25 g) was taken up in dichloromethane (10 mL) and cooled to 0° C. Titanium tetrachloride (0.76 mL, 1 M solution) was added drop-wise and the reaction mixture was stirred for 10 to 15 minutes. (−)-Sparteine (0.36 mL) was added slowly to the reaction mixture and stirred at 0° C. for 20 minutes. A solution of the compound obtained from step e above (0.187 g) in dichloromethane (10 mL) was added slowly and stirring was continued at 0° C. After 3 hours, the reaction was quenched with the drop-wise addition of saturated ammonium chloride solution, and dichloromethane was added. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel flash column chromatography using 30% ethyl acetate in hexane as eluant to afford the title compound (0.24 g).
Step g: Synthesis of (2S,3R)-5-(3′,5′-difluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid
[0582] To a stirred solution of the compound obtained from step f above (0.2 g) in tetrahydrofuran:water (3:1, 10 mL) aqueous hydrogen peroxide solution (30%, 0.16 mL) was added at 0° C., followed by the addition of lithium hydroxide monohydrate (19.53 mg) in water (2 mL). The reaction mixture was stirred at 0° C. until the completion of the hydrolysis. The reaction mixture was concentrated and the residue was extracted with ethyl acetate. The aqueous layer was acidified with sodium hydrogen sulphate and extracted with ethyl acetate. The combined layers were washed with water and brine and dried over anhydrous sodium sulphate. The solvents were evaporated under reduced pressure, and the crude residue was purified by silica gel flash column chromatography using 10% methanol in dichloromethane as eluant to afford the title compound (0.090 g).
[0583] Mass (m/z): 466.06 (M + +1);
[0584] 1 HNMR (CD 3 OD): δ 8.17-8.8.15 (m, 1H), 8.05-8.01 (m, 1H), 7.90-7.88 (m, 1H), 7.86-7.84 (m, 1H), 7.46-7.42 (m, 2H,), 7.40-7.29 (m, 2H,), 7.03-6.98 (m, 2H), 4.82-4.84 (m, 2H), 3.94 (s, 1H), 3.22-3.21 (m, 1H), 2.91-2.89 (m, 1H), 2.78-2.75 (m, 1H), 1.94-1.90 (m, 2H).
Example 7C
Synthesis of (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 217)
Step a: Synthesis of methyl (2E)-3-(4-bromophenyl)prop-2-enoate
[0585] To a stirred solution of 4-bromocinnamic acid (16 g) in methanol (150 mL), thionyl chloride (30 mL) was added at 0° C. The reaction mixture was warmed to room temperature and refluxed for 3 hours. After cooling to room temperature, the solvents were evaporated to dryness. The crude compound obtained was used as such for the next step.
Step b: Synthesis of methyl (2E)-3-(4′-fluorobiphenyl-4-yl)prop-2-enoate
[0586] The compound obtained from step a above (0.75 g), 4-fluorophenyl boronic acid (0.65 g), tetrakis(triphenylphosphine)palladium(0) (0.07 g), and potassium carbonate (1.28 g) were taken in dimethylformamide (6 mL) under nitrogen atmosphere. The reaction mixture was refluxed under nitrogen atmosphere for 6 hours. After cooling to room temperature, water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with water and brine amd dried over anhydrous sodium sulfate, and the solvents were evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 20% to 30% ethyl acetate in hexane to get the title compound (0.720 g).
Step c: Synthesis of methyl 3-(4′-fluorobiphenyl-4-yl) propanoate
[0587] To a solution of the compound obtained from step b above (0.7 g) in a mixture of ethyl acetate (˜20 mL), 10% palladium on charcoal (0.2 g) was added and stirred under hydrogen atmosphere at 30 psi in a Paar apparatus for 2.5 hours. The reaction mixture was filtered through a celite pad, washed with ethyl acetate, and the filtrate was concentrated under reduced pressure to obtain the title compound (0.7 g) as a white solid which was used as such for the next step.
Step d: Synthesis of 3-(4′-fluorobiphenyl-4-yl)propanoic acid
[0588] To a stirred solution of lithium aluminium hydride (0.2 g) in tetrahydrofuran (15 mL), the compound obtained from step c above (0.7 g) in tetrahydrofuran (50 mL) was added at 0° C. The reaction mixture was stirred at 0° C. for 3 hours. The reaction mixture was quenched carefully with saturated ammonium chloride solution, filtered through a celite pad, and washed with ethyl acetate. The organic layers were separated, washed with brine, and dried over anhydrous sodium sulfate, and solvents were evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography using 20% to 30% ethyl acetate in hexane to get the title compound as a white crystalline solid (0.70 g).
Step e: Synthesis of 3-(4′-fluorobiphenyl-4-yl)propanal
[0589] To a stirred solution of the compound obtained from step d above (0.7 g) in dichloromethane (10 mL), 2,2,6,6,-tetramethylpiperidine N-oxyl (4.74 mg) and potassium bromide (36.05 mg) were added at 0° C. under nitrogen atmosphere. Sodium hypochlorite (0.28 g, 4% solution) was added at pH 8-9 (maintained by adding aqueous sodium bicarbonate solution). The reaction mixture was stirred for 20 minutes at 0° C. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, water, and brine. The organic layer was dried over anhydrous sodium sulphate, filtered, and concentrated under reduced pressure to afford the title compound (0.55 g).
Step f: Synthesis of 3-[(2R,3S)-2-{[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]carbonyl}-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentyl]-1,2,3-benzotriazin-4(3H)-one
[0590] In a flame-dried flask, 3-{3-[(4S)-4-benzyl-2-oxo-1,3-thiazolidin-3-yl]-3-oxopropyl}-1,2,3-benzotriazin-4(3H)-one (0.25 g) was taken up in dichloromethane (10 mL) and cooled to 0° C. Titanium tetrachloride (0.76 mL, 1 M solution) was added drop-wise and the reaction mixture was stirred for 10 to 15 minutes. (−)-Sparteine (0.36 mL) was added slowly to the reaction mixture and stirred at 0° C. for 20 minutes. A solution of the compound obtained from step e above (0.17 g) in dichloromethane (10 mL) was added slowly, and stirring was continued at 0° C. After 3 hours, the reaction was quenched with the drop-wise addition of saturated ammonium chloride solution, and dichloromethane was added. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel flash column chromatography using 30% ethyl acetate in hexane as eluant to afford the title compound (0.2 g).
Step g: Synthesis of (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid
[0591] To a stirred solution of the compound obtained from step f above (0.18 g) in tetrahydrofuran:water (3:1, 10 mL), aqueous hydrogen peroxide solution (30%, 0.15 mL) was added at 0° C., followed by the addition of lithium hydroxide monohydrate (17.6 mg) in water (2 mL). The reaction mixture was stirred at 0° C. until the completion of the hydrolysis. The reaction mixture was concentrated and the residue was extracted with ethyl acetate. The aqueous layer was acidified with sodium hydrogen sulphate and extracted with ethyl acetate. The combined layers were washed with water and brine, and dried over anhydrous sodium sulphate. The solvents were evaporated under reduced pressure and the crude residue was purified by silica gel flash column chromatography using 10% methanol in dichloromethane as eluant to afford the title compound (0.075 g).
[0592] Mass (m/z): 448.07 (M + +1);
[0593] 1 HNMR (CD 3 OD): δ 8.25-8.8.30 (d, 1H, J=8 Hz), 8.15-8.12 (d, 1H, J=8 Hz), 8.05-8.00 (t, 1H, J=8 Hz), 7.89-7.85 (t, 1H, J=8 Hz), 7.58-7.55 (m, 1H,), 7.47-7.45 (d, 1H J=8 Hz), 7.28-7.26 (d, 1H, J=8 Hz), 7.89-7.87 (m, 1H), 7.61 (m, 2H), 7.53-7.59 (m, 1H), 7.30-7.25 (d, 2H J=8 Hz), 7.15-7.11 (t, 2H, J=8 Hz), 4.81-4.79 (m, 2H), 3.92 (s, 1H), 3.22-3.16 (m, 1H), 2.92-2.90 (m, 1H), 2.75-2.73 (m, 1H), 1.93-1.87 (m, 2H).
[0594] The following compounds were prepared employing procedures as provided in
Examples 1 to 7C described above
[0595] Compound Nos. 1 to 81, 86-88, 90-95, 97-119, 121-142, 144-203, 211-213, and 226-232 were prepared following Example 1; Compound Nos. 82-83 were prepared following Example 2; Compound Nos 84-85 and 204 were prepared following Example 3; Compound Nos. 89 and 96 were prepared following Example 4; Compound Nos. 120 and 205-207 were prepared following Example 5; Compound Nos. 143 and 208 were prepared following Example 6; and Compound Nos. 86, 209-210, and 214-225 were prepared following Example 7.
[0596] Specific compounds, suitable for use, prepared in the present invention, are listed below:
(2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4-pyrimidin-5-ylphenyl)pentanoic acid (Compound No. 1);
[0598] Mass (m/z): 446.0 (M + +1).
(2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 2)
[0600] Mass (m/z): 531.09 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 3)
[0602] Mass (m/z): 458.82 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 4); (2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 5)
[0605] Mass (m/z): 479.70 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 6)
[0607] Mass (m/z): 458.94 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 7)
[0609] Mass (m/z): 472.87 (M + +1);
(2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 8); (2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 9)
[0612] Mass (m/z): 461.87 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 10)
[0614] Mass (m/z): 473.79 (M + +1);
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 11)
[0616] Mass (m/z): 493.81 (M + +1);
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 12)
[0618] Mass (m/z): 479.77 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 13)
[0620] Mass (m/z): 473.86 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 14)
[0622] Mass (m/z): 510.66 (M + −18);
(2S,3R)-5-(4′-chloro-3′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 15)
[0624] Mass (m/z): 496.10 (M + +1);
(2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 16)
[0626] Mass (m/z): 536.11 (M + +1);
(2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 17)
[0628] Mass (m/z): 530.09 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 18)
[0630] Mass (m/z): 512.04 (M + +1);
(2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 19)
[0632] Mass (m/z): 518.14 (M + +1);
(2S,3R)-2-[2-(5-tert-butyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-chlorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 20)
[0634] Mass (m/z): 534.09 (M + );
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 21)
[0636] Mass (m/z): 512.08 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 22)
[0638] Mass (m/z): 458.14 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 23)
[0640] Mass (m/z): 492.07 (M + +1).
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 24)
[0642] Mass (m/z): 489.11 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 25)
[0644] Mass (m/z): 458.14 (M + +1);
(2S,3R)-5-(4′-ethylbiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 26)
[0646] Mass (m/z): 472.15 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]pentanoic acid (Compound No. 27)
[0648] Mass (m/z): 492.08 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 28)
[0650] Mass (m/z): 478.09 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4-pyrimidin-5-ylphenyl)pentanoic acid (Compound No. 29)
[0652] Mass (m/z): 446.12 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 30)
[0654] Mass (m/z): 448.25 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4-pyridin-3-ylphenyl)pentanoic acid (Compound No. 31)
[0656] Mass (m/z): 445.23 (M + +1);
(2S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 32)
[0658] Mass (m/z): 502.19 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 33)
[0660] Mass (m/z): 489.0 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 34)
[0662] Mass (m/z): 473.0 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 35)
[0664] Mass (m/z): 448.0 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 36)
[0666] Mass (m/z): 505.0 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 37)
[0668] Mass (m/z): 509.0 (M + +1);
(2S,3R)-3-hydroxy-2-{2-[7-(6-methoxypyridin-3-yl)-4-oxo-1,2,3-benzotriazin-3(4H)-yl]ethyl}-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 38)
[0670] Mass (m/z): 582.0 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 39)
[0672] Mass (m/z): 511.0 (M + +1);
(2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 40)
[0674] Mass (m/z): 493.3 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 41)
[0676] Mass (m/z): 489.0 (M + +1);
(2S,3R)-3-hydroxy-2-{2-[5-(6-methoxypyridin-3-yl)-4-oxo-1,2,3-benzotriazin-3(4H)-yl]ethyl}-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 42)
[0678] Mass (m/z): 582.0 (M + +1);
(2S,3R)-5-(4′-chloro-3′-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 43)
[0680] Mass (m/z): 519.0 (M + +23);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(1-isobutyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 44)
[0682] Mass (m/z): 490.0 (M + +1);
(2S,3R)-5-biphenyl-4-yl-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 45)
[0684] Mass (m/z): 444.0 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 46)
[0686] Mass (m/z): 476.0 (M + +1);
(2S,3R)-5-(3,3′-difluoro-4′-methoxybiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 47)
[0688] Mass (m/z): 510.0 (M + +1);
(2S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 48)
[0690] Mass (m/z): 502.0 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(1H-tetrazol-1-yl)phenyl]pentanoic acid (Compound No. 49)
[0692] Mass (m/z): 458.0 (M + +23);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 50)
[0694] Mass (m/z): 493.0 (M + +1);
(2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 51)
[0696] Mass (m/z): 498.0 (M + +23);
(2S,3R)-3-hydroxy-5-[4-(1-isobutyl-1H-pyrazol-4-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 52)
[0698] Mass (m/z): 490.0 (M + +1);
(2S,3R)-5-biphenyl-4-yl-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 53)
[0700] Mass (m/z): 444.0 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 54)
[0702] Mass (m/z): 489.34 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-β-fluoro-4-methoxyphenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 55)
[0704] Mass (m/z): 493.16 (M + +1);
(2S,3R)-5-(4′-chloro-3-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 56)
[0706] Mass (m/z): 496.13 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[6-(4-methoxyphenyl)pyridin-3-yl]pentanoic acid (Compound No. 57)
[0708] Mass (m/z): 475.13 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-β-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 58)
[0710] Mass (m/z): 492.13 (M + +1);
(2S,3R)-5-[6-(4-chlorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 59)
[0712] Mass (m/z): 479.12 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 60)
[0714] Mass (m/z): 476.16 (M + +1);
(2S,3R)-5-[4-(4-chlorophenyl)-2-thienyl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 61)
[0716] Mass (m/z): 484.0 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)-2-thienyl]pentanoic acid (Compound No. 62)
[0718] Mass (m/z): 481.0 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-{4-[4-(trifluoromethyl)phenyl]-2-thienyl}pentanoic acid (Compound No. 63)
[0720] Mass (m/z): 518.0 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[4-β-fluoro-4-methoxyphenyl)-2-thienyl]-3-hydroxypentanoic acid (Compound No. 64)
[0722] Mass (m/z): 498.0 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 65)
[0724] Mass (m/z): 526.0 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 66)
[0726] Mass (m/z): 526.0 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 67)
[0728] Mass (m/z): 492.0 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 68)
[0730] Mass (m/z): 542.29 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 69)
[0732] Mass (m/z): 548.54 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[2-fluoro-5-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 70)
[0734] Mass (m/z): 493.30 (M + +1);
(2S,3R)-5-(4′-chloro-4-fluorobiphenyl-3-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 71)
[0736] Mass (m/z): 495.72 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-fluoro-4′-(trifluoromethyl)biphenyl-3-yl]-3-hydroxypentanoic acid (Compound No. 72)
[0738] Mass (m/z): 530.13 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[4-fluoro-3-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 73)
[0740] Mass (m/z): 493.37 (M + +1);
(2S,3R)-5-(4′-chloro-6-fluorobiphenyl-3-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 74)
[0742] Mass (m/z): 496.26 (M + +1);
(2S,3R)-5-(3′,6-difluoro-4′-methoxybiphenyl-3-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 75)
[0744] Mass (m/z): 509.77 (M + +1);
(2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 76)
[0746] Mass (m/z): 492.56 (M + +1);
(2S,3R)-5-(4′-fluorobiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 77)
[0748] Mass (m/z): 480.0 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 78)
[0750] Mass (m/z): 462.19 (M + +1);
(2S,3R)-2-[2-(5-chloro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 79)
[0752] Mass (m/z): 546.32 (M + +1);
(2S,3R)-2-[2-(4-fluoro-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 80)
[0754] Mass (m/z): 529.25 (M + +1);
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 81)
[0756] Mass (m/z): 498.27 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-phenylpentanoic acid (Compound No. 82)
[0758] Mass (m/z): 368.0 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-phenylpentanoic acid (Compound No. 83)
[0760] Mass (m/z): 368.07 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4(trifluoromethyl)phenyl]pentanoic acid (Compound No. 84)
[0762] Mass (m/z): 458.0 (M + +23);
(2S,3R)-5-(4-tert-butylphenyl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 85)
[0764] Mass (m/z): 424.0 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 86)
[0766] Mass (m/z): 474.87 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 87)
[0768] Mass (m/z): 478.09 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 88)
[0770] Mass (m/z): 474.88 (M + +1);
(2R,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 89)
[0772] Mass (m/z): 478.2 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 90)
[0774] Mass (m/z): 462.32 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 91)
[0776] Mass (m/z): 478.38 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 92)
[0778] Mass (m/z): 514.20 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 93)
[0780] Mass (m/z): 508.29 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 94); (2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 95)
[0783] Mass (m/z): 493.37 (M + +1);
(2R,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 96)
[0785] Mass (m/z): 474.87 (M + +1);
(2S,3R)-5-(2′,4′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 97)
[0787] Mass (m/z): 480.13 (M + +1);
(2S,3R)-2-[2-(6-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 98)
[0789] Mass (m/z): 482.15 (M + +1);
(2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 99)
[0791] Mass (m/z): 482.15 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-(4′-isopropylbiphenyl-4-yl)pentanoic acid (Compound No. 100)
[0793] Mass (m/z): 486.18 (M + +1);
(2S,3R)-5-(3′-chloro-4′-fluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 101)
[0795] Mass (m/z): 496.12 (M + +1);
(2S,3R)-5-(4′-butylbiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 102)
[0797] Mass (m/z): 500.42 (M + +1);
(2S,3R)-5-(2′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 103)
[0799] Mass (m/z): 462.32 (M + +1);
(2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 104)
[0801] Mass (m/z): 466.31 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 105)
[0803] Mass (m/z): 462.38 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 106)
[0805] Mass (m/z): 513.35 (M + +1);
(2S,3R)-5-[6-(3,4-difluorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 107)
[0807] Mass (m/z): 481.32 (M + +1);
(2S,3R)-5-[6-(4-chloro-3-fluorophenyl)pyridin-3-yl]-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 108)
[0809] Mass (m/z): 497.30 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-(4-fluorophenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 109)
[0811] Mass (m/z): 463.35 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-[6-β-fluoro-4-methylphenyl)pyridin-3-yl]-3-hydroxypentanoic acid (Compound No. 110)
[0813] Mass (m/z): 477.34 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 111)
[0815] Mass (m/z): 482.38 (M + +1);
(2S,3R)-2-[2-(8-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 112); (2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]pentanoic acid (Compound No. 113)
[0818] Mass (m/z): 484.39 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 114)
[0820] Mass (m/z): 542.36 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 115)
[0822] Mass (m/z): 472.12 (M + +1);
(2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 116)
[0824] Mass (m/z): 476.23 (M + +1).
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 117)
[0826] Mass (m/z): 494.24 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 118)
[0828] Mass (m/z): 473.38 (M + +1);
(2S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 119)
[0830] Mass (m/z): 516.28 (M + +1);
(2R,3S)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 120)
[0832] Mass (m/z): 474.87 (M + +1);
(2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 121)
[0834] Mass (m/z): 510.23 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 122)
[0836] Mass (m/z): 510.23 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 123)
[0838] Mass (m/z): 512.31 (M + +1);
(2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 124)
[0840] Mass (m/z): 490.30 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(1-isobutyl-1H-pyrazol-4-yl)phenyl]-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 125)
[0842] Mass (m/z): 504.33 (M + +1);
(2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)pentanoic acid (Compound No. 126)
[0844] Mass (m/z): 510.23 (M + +1);
(2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 127)
[0846] Mass (m/z): 492.26 (M + +1).
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 128)
[0848] Mass (m/z): 510.30 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 129)
[0850] Mass (m/z): 504.38 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 130)
[0852] Mass (m/z): 547.29 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 131)
[0854] Mass (m/z): 549.30 (M + +1);
(2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 132)
[0856] Mass (m/z): 547.29 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 133)
[0858] Mass (m/z): 527.40 (M + +1);
(2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-{6-[4-(trifluoromethyl)phenyl]pyridin-3-yl}pentanoic acid (Compound No. 134)
[0860] Mass (m/z): 531.36 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 135)
[0862] Mass (m/z): 488.34 (M + +1);
(2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 136)
[0864] Mass (m/z): 494.33 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 137)
[0866] Mass (m/z): 494.33 (M + +1);
(2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 138)
[0868] Mass (m/z): 476.30 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 139)
[0870] Mass (m/z): 496.30 (M + +1);
(2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 140)
[0872] Mass (m/z): 476.35 (M + +1);
(2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 141); (2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 142)
[0875] Mass (m/z): 490.34 (M + +1);
(2S,3S)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 143)
[0877] Mass (m/z): 475.21 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 144)
[0879] Mass (m/z): 512.32 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 145)
[0881] Mass (m/z): 514.37 (M + +1);
(2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 146)
[0883] Mass (m/z): 506.38 (M + +1);
(2S,3R)-5-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-3-hydroxy-2-[2-(8-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 147)
[0885] Mass (m/z): 532.38 (M + +1);
(2S,3R)-5-[4-(6-chloropyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 148)
[0887] Mass (m/z): 479.36 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 149)
[0889] Mass (m/z): 542.11 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 150)
[0891] Mass (m/z): 542.11 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-(4′-methylbiphenyl-4-yl)pentanoic acid (Compound No. 151)
[0893] Mass (m/z): 488.09 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 152)
[0895] Mass (m/z): 504.06 (M + +1);
(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 153)
[0897] Mass (m/z): 493.01 (M + +1);
(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 154)
[0899] Mass (m/z): 523.02 (M + +1);
(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 155)
[0901] Mass (m/z): 511.04 (M + +1);
(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 156)
[0903] Mass (m/z): 507.05 (M + +1);
(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 157)
[0905] Mass (m/z): 507.05 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 158)
[0907] Mass (m/z): 504.09 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 159)
[0909] Mass (m/z): 508.03 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 160)
[0911] Mass (m/z): 505.11 (M + +1);
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 161)
[0913] Mass (m/z): 510.04 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 162)
[0915] Mass (m/z): 505.11 (M + +1);
(2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 163)
[0917] Mass (m/z): 526.95 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 164)
[0919] Mass (m/z): 529.00 (M + +1);
(2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 165)
[0921] Mass (m/z): 507.03 (M + +1);
(2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 166)
[0923] Mass (m/z): 476.01 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 167)
[0925] Mass (m/z): 489.05 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 168)
[0927] Mass (m/z): 488.06 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 169)
[0929] Mass (m/z): 472.03 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(5-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 170)
[0931] Mass (m/z): 491.98 (M + +1);
(2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 171)
[0933] Mass (m/z): 492.00 (M + +1);
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 172)
[0935] Mass (m/z): 509.98 (M + +1);
(2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 173)
[0937] Mass (m/z): 557.99 (M + +1);
(2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 174)
[0939] Mass (m/z): 506.04 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 175)
[0941] Mass (m/z): 526.91 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(1-methyl-1H-pyrazol-4-yl)-2-thienyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 176); (2S,3R)-5-[2-fluoro-4-(6-methoxypyridin-3-yl)phenyl]-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 177)
[0944] Mass (m/z): 523.01 (M + +1);
(2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 178); (2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(6-methylpyridin-3-yl)phenyl]pentanoic acid (Compound No. 179)
[0947] Mass (m/z): 489.07 (M + +1);
(2S,3R)-5-[4-(2-chloropyridin-3-yl)phenyl]-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 180)
[0949] Mass (m/z): 508.99 (M + +1);
(2S,3R)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 181)
[0951] Mass (m/z): 493.19 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 182)
[0953] Mass (m/z): 496.17 (M + +1);
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 183)
[0955] Mass (m/z): 498.15 (M + +1);
(2S,3R)-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)pentanoic acid (Compound No. 184)
[0957] Mass (m/z): 492.16 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(2-methoxypyrimidin-5-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 185)
[0959] Mass (m/z): 476.13 (M + +1);
(2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(6-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 186)
[0961] Mass (m/z): 480.08 (M + +1);
(2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 187)
[0963] Mass (m/z): 480.15 (M + +1);
(2S,3R)-2-[2-(5-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 188)
[0965] Mass (m/z): 500.07 (M + +1);
(2S,3R)-2-[2-(7-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 189)
[0967] Mass (m/z): 500.13 (M + +1);
(2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 190)
[0969] Mass (m/z): 484.15 (M + +1);
(2S,3R)-2-[2-(6,7-difluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxypentanoic acid (Compound No. 191)
[0971] Mass (m/z): 502.16 (M + +1);
(2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-2-[2-(6-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 192;
[0973] Mass (m/z): 507.22 (M + +23);
(2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 193); (2S,3R)-3-hydroxy-2-[2-(6-methoxy-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-5-[4-(2-methoxypyrimidin-5-yl)phenyl]pentanoic acid (Compound No. 194)
[0976] Mass (m/z): 506.12 (M + +1);
(2S,3R)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxy-5-[4-(2-methoxypyrimidin-5-yl)phenyl]pentanoic acid (Compound No. 195)
[0978] Mass (m/z): 476.18 (M + +1);
(2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-(1-oxophthalazin-2(1H)-yl)ethyl]pentanoic acid (Compound No. 196)
[0980] Mass (m/z): 465.26 (M + +1);
(2S,3R)-5-[2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl]-3-hydroxy-2-[2-β-methyl-2,6-dioxo-3,6-dihydropyrimidin-1 (2H)-yl)ethyl]pentanoic acid (Compound No. 197)
[0982] Mass (m/z): 445.25 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-{2-[4-oxo-7-(trifluoromethyl)-1,2,3-benzotriazin-3(4H)-yl]ethyl}pentanoic acid (Compound No. 198)
[0984] Mass (m/z): 543.22 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(1-oxophthalazin-2(1H)-yl)ethyl]pentanoic acid (Compound No. 199)
[0986] Mass (m/z): 474.25 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-β-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)ethyl]pentanoic acid (Compound No. 200)
[0988] Mass (m/z): 454.24 (M + +1);
(2S,3R)-2-[2-(7,9-dioxo-8-azaspiro[4.5]dec-8-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 201)
[0990] Mass (m/z): 495.27 (M + +1);
(2S,3R)-2-[2-(2,4-dioxo-2H-1,3-benzoxazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 202)
[0992] Mass (m/z): 491.17 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)ethyl]pentanoic acid (Compound No. 203)
[0994] Mass (m/z): 470.12 (M + +1);
(2S,3R)-5-(4-chloro-3-fluorophenyl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 204)
[0996] Mass (m/z): 420.06 (M + +1);
(2R,3S)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 205)
[0998] Mass (m/z): 476.07 (M + +1);
(2R,3S)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-5-(4′-fluorobiphenyl-4-yl)-3-hydroxypentanoic acid (Compound No. 206)
[1000] Mass (m/z): 462.03 (M + +1);
(2R,3S)-5-(3′,4′-difluorobiphenyl-4-yl)-2-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 207)
[1002] Mass (m/z): 480.03 (M + +1);
(2S,3S)-3-hydroxy-5-(4′-methoxybiphenyl-4-yl)-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 208)
[1004] Mass (m/z): 474.31 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(5-methylpyridin-2-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 209)
[1006] Mass (m/z): 459.21 (M + +1);
(2S,3R)-5-[4-(6-fluoropyridin-3-yl)phenyl]-3-hydroxy-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 210)
[1008] Mass (m/z): 463.17 (M + +1);
(2S,3R)-2-[2-(5-fluoro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 211)
[1010] Mass (m/z): 530.33 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[2-(7-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 212)
[1012] Mass (m/z): 492.29 (M + +1);
(2S,3R)-3-hydroxy-5-(6′-methoxy-2,3′-bipyridin-5-yl)-2-[2-(8-methyl-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 213)
[1014] Mass (m/z): 490.34 (M + +1);
(2S,3R)-5-(3′-fluoro-4′-methylbiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 214); (2S,3R)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]-5-[4′-(trifluoromethyl)biphenyl-4-yl]pentanoic acid (Compound No. 215)
[1017] Mass (m/z): 498.09 (M + +1);
(2S,3R)-5-(2′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 216)
[1019] Mass (m/z): 466.06 (M + +1);
(2S,3R)-5-(4′-fluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 217)
[1021] Mass (m/z): 448.07 (M + +1);
(2S,3R)-5-(3′-fluoro-4′-methoxybiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 218)
[1023] Mass (m/z): 478.22 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(2-methoxypyrimidin-5-yl)phenyl]-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 219)
[1025] Mass (m/z): 462.23 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 220)
[1027] Mass (m/z): 461.23 (M + +1)
(2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 221)
[1029] Mass (m/z): 444.24 (M + +1);
(2S,3R)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]-5-[4′-(trifluoromethoxy)biphenyl-4-yl]pentanoic acid (Compound No. 222)
[1031] Mass (m/z): 514.14 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-methylpyridin-3-yl)phenyl]-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 223)
[1033] Mass (m/z): 445.18 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 224)
[1035] Mass (m/z): 464.18 (M + +1);
(2S,3R)-5-(3′,4′-difluorobiphenyl-4-yl)-3-hydroxy-2-[(4-oxo-1,2,3-benzotriazin-3(4H)-yl)methyl]pentanoic acid (Compound No. 225)
[1037] Mass (m/z): 466.20 (M + +1);
(2S,3R)-3-hydroxy-5-[4-(6-hydroxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 226)
[1039] Mass (m/z): 461.23 (M + +1);
(2S,3R)-3-hydroxy-5-(4′-methylbiphenyl-4-yl)-2-{2-[4-oxo-7-(trifluoromethyl)-1,2,3-benzotriazin-3(4H)-yl]ethyl}pentanoic acid (Compound No. 227)
[1041] Mass (m/z): 526.16 (M + +1);
(2S,3R)-2-[2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 228)
[1043] Mass (m/z): 490.17 (M + +1);
(2S,3R)-3-(acetyloxy)-5-[4-(6-methoxypyridin-3-yl)phenyl]-2-[2-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]pentanoic acid (Compound No. 229)
[1045] Mass (m/z): 517.06 (M + +1);
(2S,3R)-2-[2-(8-chloro-4-oxo-1,2,3-benzotriazin-3(4H)-yl)ethyl]-3-hydroxy-5-[4-(6-methoxypyridin-3-yl)phenyl]pentanoic acid (Compound No. 230)
[1047] Mass (m/z): 509.17 (M + +1);
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-2-[2-(2,4-dioxo-2H-1,3-benzoxazin-3(4H)-yl)ethyl]-3-hydroxypentanoic acid (Compound No. 231)
[1049] Mass (m/z): 493.93 (M + +1); and
(2S,3R)-5-(4′-chlorobiphenyl-4-yl)-3-hydroxy-2-(2-{[(2-hydroxyphenyl) carbonyl]amino}ethyl)pentanoic acid (Compound No. 232)
[1051] Mass (m/z): 468.14 (M + +1).
Example
Assay for Matrix Metalloproteinases (MMPs)
[1052] New chemical entities of the present invention and corresponding standards used in the present invention were prepared (stock 10 mM) in 100% DMSO and subsequent dilutions were made in 50% DMSO-50% TCNB (50 mM Tris, 10 mM CaCl 2 , 150 mM NaCl, 0.05% Brij-35, pH 7.5). 1 μl of the compound and 88 μl of TCNB was added to the wells of a 96 well plate to achieve the desired final concentration of NCE (final DMSO concentration should not exceed 0.5%). 1 μl of activated, recombinant MMPs was added to each well (20-100 mg/100 μl reaction mixture) except the “negative well”. (MMP-1, 9, and 14 enzymes require prior activation. For this, the supplied enzyme was incubated with either APMA, final concentration 1 mM, for a time period of 1 hour at 37° C.). Incubation was done at room temperature for 4 to 5 minutes. Reaction was initiated with 10 μl of 100 μM substrate (ES001: Aliquots were freshly diluted in TCNB; stock: 2 mM) and increase in florescence was monitored at excitation wavelength 320 nm followed by emission at 405 nm for 25 to 30 cycles. Increase in florescence (RFU) was calculated for positive, negative, and NCE/standard wells. The percent inhibition compared to controls was calculated and IC 50 values were determined using Graph-prism software.
[1053] The present invention relates to compounds that act as dual MMP-9/12 inhibitors, which have desirable activity profiles and beneficial potency, selectivity, and/or pharmacokinetic properties.
[1054] In particular, compounds disclosed herein exhibited activity in MMP-9 assays from ≦0.02 nM to about 40 μM, or from ≦0.02 nM to about 200 nM, or from ≦0.02 nM to about 20 nM, or from ≦0.02 nM to about 1.0 nM, or from ≦0.02 nM to about 0.3 nM. Compounds disclosed herein exhibited activity in MMP-12 assays from ≦0.02 nM to about 3.8 μM, or from ≦0.02 nM to about 200 nM, or from ≦0.02 nM to about 20 nM, or from ≦0.02 nM to about 1.0 nM, or from ≦0.02 nM to about 0.3 nM. Particular compounds tested (Nos. 2-28, 30, 32-43, 46, 50-51, 55-58, 60-61, 63, 65-69, 76, 79-80, 86-89, 93-96, 98, 106-107, 113-122, 126, 130-132, 134, 136-138, 143-144, 148-150, 155, 157, 159, 173-175, 177, 179, 181-182, 184-186, 190, 192-195, 198, and 210-211) exhibited activity in MMP-1 assays from about 100 nM to about 10 μM, for example, from about 100 nM to about 5 μM, or from about 100 nM to about 2 μM, or from about 100 nM to about 1 μM indicating that compounds of the present invention can be selective over MMP-1 by ≧100 fold.
Assay for In Vivo LPS Induced Rat Neutrophilia Model
[1055] Male wistar rats were treated with vehicle/NCEs (new chemical entities) or standard drug and 2 hours later challenged with lipopolysaccharide (LPS) in phosphate buffered saline (PBS), by oro-intra tracheal route (400 μL of 50 μg/mL). Negative control animals received PBS alone. Intratracheal instillation was done under ketamine and xylazine anaesthesia. Two hours post-LPS challenge, the rats were euthanised and bronchoalveolar lavage (BAL) was performed. The TLC, DLC was done to enumerate neutrophil count in the BAL fluid and results were expressed as percent inhibition using the following formula
[0000]
NeuLPS
-
NeuTEST
NeuLPS
-
NeuPBS
×
100
Where,
[1056] NeuLPS=Neutrophil count in vehicle-treated LPS challenged group
NeuTEST=Neutrophil count in group treated with a given dose of test compound
NeuPBS=Neutrophil in vehicle-treated group challenged with PBS
Solubility Assessment
Equilibrium Solubility:
[1057] The pH-solubility profile of a compound is determined at 37° C. in aqueous media with a pH in the range of 1-7.5. A sufficient number of pH conditions are evaluated to accurately define the pH-solubility profile. Standard buffer solutions described in the USP are considered appropriate for use in solubility studies.
[1058] The compound is weighed and transferred to the flasks. Media are added to each conical flask, and the flask is sealed with a stopper and paraffin film. The volume added is dependant upon the volume required for analysis of the content of the compound. The pH of the solution is measured after addition of the compound. The flask is observed intermittently. If the drug substance is completely dissolved, additional amounts of the compound are added until saturation (undissolved residue) is observed and the pH is measured. Flasks are removed from the water bath after equilibrium is achieved. The saturated solution is filtered through 0.45 μm membrane filter and the samples are analyzed to estimate the content of the test compound.
Pharmacokinetic Screening Assays for Matrix Metalloproteinase (MMP 9/12) Inhibitors
Intrinsic Clearance:
[1059] Intrinsic clearance (or metabolism stability) is assessed by estimating the rate of initial decay of the parent compound in a suitable biological matrix, like human liver microsomes.
[1060] The study reaction consists of NADPH regeneration system and liver microsomes of the various species of interest (human, rat, dog, mouse) added into buffer at a concentration of 0.5 mg/mL. After a short preincubation, the metabolic reaction is initiated by the addition of 5 μL of the substrate stock (100 μM) to yield a final concentration of 0.5 μM in the reaction. Periodic aliquots are drawn every three minutes for 30 minutes, quenched, and the test compound concentration is estimated by LCMS. The rate of disappearance is estimated as the first order slope of the % of parent remaining vs. time graph. The rate of decay is normalized to the unit concentration of the test compound and protein and extrapolated to 1 g of liver by using scaling factors (52.5 mg of CYP microsomal protein per gram of liver).
In Vitro Glucuronidation:
[1061] A comparative assay in the form of intrinsic clearance (see above) with the addition of glucuronic acid and alamethacin to compare primarily the parent disappearance due to glucuronidation. Expressed as rate of clearance and normalized to per gram of liver.
Plasma Protein Binding:
[1062] Assessment by the equilibrium dialysis method where the unbound compound diffuses across a semi-permeable membrane and equilibrates with phosphate buffer (pH 7.4) is estimated, and is subtracted from the total drug in plasma to determine the percentage bound.
[1063] Equilibrium dialysis membranes are soaked overnight and the assembly is prepared. The test drug is spiked into plasma (100 and 1000 ng/mL) and incubated at 37° C. and is transferred into the equilibrium apparatus with plasma added in one compartment and buffer added in the other. The unit is rotated at constant rpm at 37° C. for four hours to allow the unbound compound to dialyse and distribute within the buffer chamber. After four hours the plasma and the buffer are removed from the respective compartments and the test compound concentrations are estimated. The percentage bound is estimated from the test compound concentrations.
[1064] Alternate methods include the ultra filtration method where the compound spiked in plasma (100 and 1000 ng/mL) is filtered with Centricon® filters having molecular weight cut off of 30,000 DA to prepare the retentate and ultra filtrate. The test compound is estimated in both and the percentage bound is calculated.
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The present invention relates to β-hydroxy and amino-substituted carboxylic acids, which act as matrix metalloproteinase inhibitors, particularly diastereomerically pure β-hydroxy carboxylic acids, corresponding processes for their synthesis, and pharmaceutical compositions containing the compounds of the present invention. Compounds of the present invention are useful in the treatment of various inflammatory, autoimmune, and allergic diseases, such as methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis, wound healing disorders, pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by the over-expression and over-activation of a matrix metalloproteinase.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This Application claims priority from U.S. Provisional Application No. 60/496,735, filed Aug. 21, 2003.
FIELD OF THE INVENTION
[0002] The present invention relates to the treatment of Alzheimer's disease and other neurodegenerative and/or neurological disorders in mammals, including humans. This invention also relates to inhibiting, in mammals, including humans, the production of Aβ-peptides that can contribute to the formation of neurological deposits of amyloid protein. More particularly, this invention relates to oxazole compounds useful for the treatment of neurodegenerative and/or neurological disorders, such as Alzheimer's disease and Down's Syndrome, related to Aβ-peptide production.
BACKGROUND OF THE INVENTION
[0003] Dementia results from a wide variety of distinctive pathological processes. The most common pathological processes causing dementia are Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA) and prion-mediated diseases (see, e.g., Haan et al. Clin. NeuroL Neurosurg. 1990, 92(4):305-310; Glenner et al. J Neurol. Sci. 1989, 94:1-28). AD affects nearly half of all people past the age of 85, the most rapidly growing portion of the United States population. As such, the number of AD patients in the United States is expected to increase from about 4 million to about 14 million by the middle of the next century.
[0004] Treatment of AD typically is the support provided by a family member in attendance. Stimulated memory exercises on a regular basis have been shown to slow, but not stop, memory loss. A few drugs, for example Aricep™, provide treatment of AD.
[0005] A hallmark of AD is the accumulation in the brain of extracellular insoluble deposits called amyloid plaques and abnormal lesions within neuronal cells called neurofibrillary tangles. Increased plaque formation is associated with an increased risk of AD. Indeed, the presence of amyloid plaques, together with neurofibrillary tangles, are the basis for definitive pathological diagnosis of AD.
[0006] The major components of amyloid plaques are the amyloid Aβ-peptides, also called Aβ-peptides, which consist of three proteins having 40, 42 or 43 amino acids, designated as the Aβ 1-40 Aβ 1-42 and Aβ 1-43 peptides, respectively. The Aβ-peptides are thought to cause nerve cell destruction, in part, because they are toxic to neurons in vitro and in vivo.
[0007] The Aβ peptides are derived from larger amyloid precursor proteins (APP proteins), which consist of four proteins containing 695, 714, 751 or 771 amino acids, designated as the APP 695 , APP 714 , APP 75 , and APP 771 , respectively. Proteases are believed to produce the Aβ peptides by cleaving specific amino acid sequences within the various APP proteins. The proteases are named “secretases” because the Aβ-peptides they produce are secreted by cells into the extracellular environment. These secretases are each named according to the cleavage(s) they make to produce the Aβ-peptides. The secretase that forms the amino terminal end of the Aβ-peptides is called the beta-secretase. The secretase that forms the carboxyl terminal end of the Aβ-peptides is called the gamma-secretase (Haass, C. and Selkoe, D. J. 1993 Cell 75:1039-1042).
[0008] This invention relates to novel compounds that inhibit Aβ-peptide production, to pharmaceutical compositions comprising such compounds, and to methods of using such compounds to treat neuorodegenerative and/or neurological disorders.
SUMMARY OF THE INVENTION
[0009] The present invention relates to compounds of the formula I
[0010] The ring containing X, Y, U is an aromatic ring in which one of the X, Y, U is a S and the other two of the X, Y, U are N as shown below I-A to I-C.
wherein Z is selected from —C(═O)CHR 1 R 2 , —C(═S)CHR 1 R 2 , —(C═NR 8 )CHR 1 R 2 , —C(═O)C(═O)R 1 and —S(O) 2 —R 1 ;
R 1 is selected from —C 1 -C 20 alkyl, —C 2 -C 20 alkenyl, —C 2 -C 20 alkynyl, —C 1 -C 20 alkoxy, —C 2 -C 20 alkenoxy, —C 2 -C 20 alkynoxy, —C 3 -C 20 cycloalkyl, —C 4 -C 20 cycloalkenyl, (C 10 -C 20 )bi- or tricycloalkyl, (C 10 -C 20 )bi- or tricycloalkenyl, (4-20 membered) heterocycloalkyl, —C 6 -C 20 aryl and (5-20 membered) heteroaryl; wherein R 1 is optionally independently substituted with from one to six fluorine atoms or with from one to three substituents independently selected from the group R 1a ; R 1a is in each instance independently selected from —OH, —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 2 -C 12 alkynyl, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy, —CF 3 , —OCF 3 , —Cl, —Br, —I, —CN, —NO 2 , —NR 9 R 10 , —C(═O)NR 9 R 10 , —SO 2 —NR 9 R 10 , —C(═O)R 11 , —S(O) n —R 11 , —C(═O)OR 12 , —C 3 -C 15 cycloalkyl, —C 4 -C 15 cycloalkenyl, —(C 5 -C 11 )bi- or tricycloalkyl, —(C 7 -C 11 )bi- or tricycloalkenyl, -(4-20 membered) heterocycloalkyl, —C 6 -C 15 aryl, -(5-15 membered) heteroaryl, —C 6 -C 15 aryloxy and -(5-15 membered) heteroaryloxy, wherein said cycloalkyl, cycloalkenyl, bi- or tricycloalkyl, bi- or tricycloalkenyl, heterocycloalkyl, aryl, heteroaryl, aryloxy and heteroaryloxy are each optionally independently substituted with from one to three substituents independently selected from the group R 1b ; R 1b is in each instance independently selected from —OH, —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy, —C 1 -C 6 hydroxyalkyl, —F, —Cl, —Br, —I, —CN, —NO 2 , —NR 9 R 10 , —C(═O)NR 9 R 10 , —C(═O)R 11 , —S(O) n —R 11 , —C 6 -C 15 aryloxy and -(5-15 membered) heteroaryloxy, wherein said alkyl, alkenyl and alkynyl are each optionally independently substituted with from one to six fluorine atoms or with from one to two substituents independently selected from —C 1 -C 4 alkoxy, or with a hydroxy group; R 9 and R 10 are in each instance each independently selected from —H, —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 2 -C 12 alkynyl, —CF 3 , —C(═O)R 11 , —S(O) n —R 11 , —C(═O)OR 12 , —C(═O)NR 11 R 12 , —SO 2 —NR 11 R 12 , —(C zero -C 4 alkylene)-(C 3 -C 20 cycloalkyl), —(C zero -C 4 alkylene)-(C 4 -C 8 cycloalkenyl), —(C zero -C 4 alkylene)-((C 5 -C 11 )bi- or tricycloalkyl), —(C zero -C 4 alkylene)-((C 7 -C 11 )bi- or tricycloalkenyl), —(C zero -C 4 alkylene)-((5-10 membered) heterocycloalkyl), (C zero -C 4 alkylene)-(C 6 -C 10 aryl) and —(C zero -C 4 alkylene)-((5-10 membered) heteroaryl), wherein said aryl, heteroaryl, alkyl, alkenyl and alkynyl are each optionally independently substituted with from one to six fluorine atoms or with from one to two substitutents independently selected from —C 1 -C 4 alkoxy, or with a hydroxy group, and wherein said cycloalkyl, cycloalkenyl, bi-or tricycloalkyl, bi- or tricycloalkenyl, heterocycloalkyl, aryl and heteroaryl are each optionally independently substituted with from one to three substituents independently selected from —OH, —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 2 -C 12 alkynyl, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy, —C 1 -C 6 hydroxyalkyl, —F, —Cl, —Br, —I, —CN, —NO 2 , —CF 3 , —NH 2 , —C(═O)NH 2 , —SO 2 —NR 9 R 10 , —C(═O)H and —C(═O)OH, wherein said alkyl, alkenyl and alkynyl substituents are each optionally independently further substituted with from one to six fluorine atoms or with from one to two substituents independently selected from —C 1 -C 4 alkoxy, or with a hydroxy group; or NR 9 R 10 may in each instance independently optionally form a heterocycloalkyl moiety of from four to ten ring members, said heterocycloalkyl moiety optionally containing one to two further heteroatoms independently selected from N, O and S, and optionally containing from one to three double bonds, wherein the carbon atoms of the heterocycloalkyl moiety of NR 9 R 10 are optionally independently substituted with from one to three substituents independently selected from —OH, —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 2 -C 12 alkynyl, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy, —F, —Cl, —Br, —I, —CF 3 , —NH 2 , —C(═O)NH 2 , —SO 2 —NH 2 , —C(═O)R 11 , —S(O) n —R 11 , (C zero -C 4 alkylene)-(C 6 -C 10 aryl), (C zero -C 4 alkylene)-((5-10 membered heteroaryl), (C zero -C 4 alkylene)-(C 6 -C 10 cycloalkyl) and (C zero -C 4 alkylene)-((5-10 membered) heterocycloakyl, and wherein the (C zero -C 4 alkylene)-((5-10 membered) heterocycloalkyl) substituent and the nitrogen atoms of said heterocycloalkyl moiety of NR 9 R 10 are each optionally independently substituted with one substituent independently selected from —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 2 -C 12 alkynyl, —C(═O)NH 2 , —SO 2 —NH 2 , C(═O)R 11 , —S(O) n —R 11 , (C zero -C 4 alkylene)-(C 6 -C 10 aryl), (C zero -C 4 alkylene)-((5-1 0 membered) heteroaryl), (C zero -C 4 alkylene)-(C 6 -C 10 cycloalkyl) and (C zero -C 4 alkylene)-((5-10 membered) heterocycloalkyl), and wherein said alkyl, alkenyl and alkynyl substituents are each optionally independently further substituted with from one to six fluorine atoms, or with from one to two substituents independently selected from —C 1 -C 4 alkoxy, or with a hydroxy group; R 11 and R 12 are in each instance each independently selected from —C 1 -C 15 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —(C zero -C 4 alkylene)-(C 3 -C 15 cycloalkyl), —(C zero -C 4 alkylene)-(C 4 -C 8 cycloalkenyl), —(C zero -C 4 alkylene)-((C 5 -C 11 )bi- or tricycloalkyl), —(C zero -C 4 alkylene)-((C 7 -C 11 )bi- or tricycloalkenyl), —(C zero -C 4 alkylene)-(C 6 -C 15 aryl), —(C zero -C 4 alkylene)-((5-15 membered) heterocycloalkyl) and —(C zero -C 4 alkylene)-((5-15 membered) heteroaryl); wherein R 11 and R 12 are each optionally independently substituted with from one to three substituents independently selected from the group R 1b ; R 2 is selected from —H, —OH, —NH 2 , —CH 2 OH, —OC(═O)CH 3 , —C(CH 3 ) 2 OH, —C(CH 3 )(CH 2 CH 3 )(OH), —C(OH)(C zero -C 4 alkyl)(C zero -C 4 alkyl), —OC(═O)R 4 and —C(═O)OR 4 , wherein said —OC(═O)R 4 and —OC(═O)OR 4 may optionally be a prodrug of the corresponding OH of R 2 ; R 3 is selected from —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl and —(C zero -C 4 alkylene)-(C 3 -C 6 cycloalkyl), wherein when R 3 is alkyl, alkenyl or alkynyl, R 3 is optionally independently substituted with a substituent independently selected from —C 1 -C 4 alkoxy, —OH, —F and —S(C 1 -C 4 alkyl); R 4 is selected from —C 1 -C 4 alkyl, —CH(OH)(C 1 -C 4 alkyl), -CH(OH)(C 5 -C 6 aryl), —CH(OH)((5-6 membered) heteroaryl), -CH(OH)(C 5 -C 6 cycloalkyl), —CH(OH)((5-6 membered) heterocycloalkyl); R 5 is selected from —H, —C 1 -C 4 alkyl, —C 2 -C 4 alkenyl, —C 2 -C 4 alkynyl, —C(═O)(C 1 -C 4 alkyl), —C 6 -C 10 aryl, -(5-20 membered) heteroaryl, —SO 2 —(C 6 -C 10 aryl), —SO 2 -((5-20 membered) heteroaryl), —SO 2 —CH 2 —(C 6 -C 20 aryl) and —SO 2 —CH 2 -((5-20 membered) heteroaryl); R 7 is selected from —H, —C 1 -C 20 alkyl, —C 2 -C 20 alkenyl, —C 2 -C 20 alkynyl, —C 1 -C 20 alkoxy, —C 2 -C 20 alkenoxy, —C 2 -C 20 alkynoxy, —F, —Cl, —Br, —I, —CN, —NO 2 , —OH, —CF 3 , —NR 9 R 10 , —(C 1 -C 11 alkylene)-NR 9 R 10 , —C(═O)NR 9 R 10 , —C(═O)R 11 , —CHO, —S(O) n —R 11 , —C(═O)OR 12 , —(C zero -C 4 alkylene)-(C 3 -C 20 cycloalkyl), —(C zero -C 4 alkylene)-(C 4 -C 20 cycloalkenyl), —(C zero -C 4 alkylene)-((C 10 -C 20 )bi- or tricycloalkyl), —(C zero -C 4 alkylene)-((C 10 -C 20 )bi- or tricycloalkenyl), —(C zero -C 4 alkylene)-((3-20 membered) heterocycloalkyl), —(C zero -C 4 alkylene)-(C 6 -C 15 aryl), —(C zero -C 11 alkylene)-(C(═O)R 11 , —C 1 -C 11 alkylene)-(COOH), —(C zero -C 11 alkylene)-CHO, —SO 2 NR 9 R 10 , —S—(C 1 -C 20 alkylene)(C═O)OR 8 , —S—(C 1 -C 20 alkylene)-O-(C 1 -C 11 alkyl), —S—(C 1 -C 20 alkylene)-O-(C 5 -C 11 aryl), —SO 2 NR 9 R 10 , —S—(C 1 -C 20 alkylene)-NR 9 R 10 , —(C 1 -C 11 alkylene)-O-(C zero -C 4 alkylene)-O-(C 6 -C 11 aryl), and —(C zero -C 4 alkylene)-((5-15 membered) heteroaryl), wherein said heterocycloalkyl optionally contains from one to four double or triple bonds; wherein R 7 is optionally substituted with from one to six fluorine atoms or with from one to three substituents independently selected from the group R 1a ; R 8 is selected from —H and —C 1 -C 6 alkyl; or, when Z is —C(═NR 8 )CHR 1 R 2 , R 8 and R 1 may together with the nitrogen and carbon atoms to which they are respectively attached optionally form a five to fourteen membered heteroaryl ring or a five to eight membered heterocycloalkyl ring, wherein said heteroaryl or heterocycloalkyl ring optionally contains from one to two further heteroatoms selected from N, O and S, and wherein said heterocycloalkyl ring optionally contains from one to three double bonds, and wherein said heteroaryl or heterocycloalkyl ring is optionally substituted with from one to three substituents independently selected from the group R 1b ; n is 0, 1, 2 and the pharmaceutically acceptable salts of such compounds.
n another embodiment, the compound of Formula I has the following structure:
[0031] Compounds of the Formula I may have optical centers and therefore may occur in different enantiomeric, diastereomeric and meso configurations. The present invention includes all enantiomers, diastereomers, and other stereoisomers of such compounds of the Formula I, as well as racemic and other mixtures thereof. The present invention also includes all tautomers of the Formula I. When the compounds of Formula I of the present invention contain one optical center, the “S” enantiomer is preferred.
[0032] Insofar as the compounds of Formula I of this invention contain basic groups, they can form acid addition salts with various inorganic and organic acids. The present invention also relates to the pharmaceutically acceptable acid addition salts of compounds of the Formula I. Although such salts must be pharmaceutically acceptable for administration to animals, it is often desirable in practice to initially isolate the base compound from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert to the free base compound by treatment with an alkaline reagent, and thereafter, convert the free base to a pharmaceutically acceptable acid addition salt. The acid addition salts of the base compounds of this invention are readily prepared by treating the base compound with a substantially equivalent amount of the chosen mineral or organic acid in an aqueous solvent or in a suitable organic solvent, such as methanol or ethanol. Upon careful evaporation of the solvent, the desired solid salt is readily obtained. The acids which are used to prepare the pharmaceutically acceptable acid addition salts of the aforementioned base compounds of this invention are those which form non-toxic acid addition salts, i.e., salts containing pharmaceutically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or bi-tartrate, succinate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e., 1,1′-methylene-bis-(2-hydroxy-3-naphthoate))salts. Other examples of pharmaceutically acceptable salts of the compounds of this invention are the salts of salicylic acid, oxalic acid, di-p-toluoyl tartaric acid, mandelic acid, sodium, potassium, magnesium, calcium and lithium.
[0033] The present invention also includes isotopically-labeled compounds that are identical to those recited in Formula I, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, chlorine and iodine, such as 2 H, 3 H, 13 C, 11 C, 14 C, 15 N, 18O, 17 O, 18 F, 123 I and 125 I, respectively. The compounds of Formula I of the present invention, prodrugs thereof, pharmaceutically acceptable salts of such compounds or of such prodrugs, and compounds and derivatives of such compounds that contain the aforementioned isotopes and/or other isotopes are within the scope of this invention. Such compounds may be useful as research and diagnostic tools in metabolism pharmacokinetic studies and in binding assays. Certain isotopically-labeled compounds of the Formula I of the present invention, for example, those into which radioactive isotopes such as 3 H and 14 C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., 3 H, and carbon-14, i.e., 14 C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., 2 H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically-labeled compounds of the Formula I of the present invention and prodrugs and derivatives thereof may generally be prepared by carrying out the procedures disclosed in the schemes and discussion of the schemes and/or in the examples and preparations described herein, by substituting a readily available isotopically-labeled reagent for a nonisotopically-labeled reagent in the preparation of said compounds.
[0034] Unless otherwise indicated, as used herein, the terms “halogen” and “halo” include F, Cl, Br and I.
[0035] Unless otherwise indicated, as used herein, the term “alkyl” includes saturated monovalent hydrocarbon radicals having straight or branched moieties. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, cyclopropylmethylene (—CH 2 -cyclopropyl) and t-butyl.
[0036] Unless otherwise indicated, as used herein, the term “alkenyl” includes alkyl moieties having at least one carbon-carbon double bond wherein alkyl is as defined above. Examples of alkenyl include, but are not limited to, ethenyl and propenyl.
[0037] Unless otherwise indicated, as used herein, the term “alkynyl” includes alkyl moieties having at least one carbon-carbon triple bond wherein alkyl is as defined above. Examples of alkynyl groups include, but are not limited to, ethynyl and 2-propynyl.
[0038] Unless otherwise indicated, as used herein, the term “alkoxy”, means “alkyl-O—, wherein “alkyl” is as defined above. Examples of “alkoxy” groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, pentoxy and allyloxy.
[0039] Unless otherwise indicated, as used herein, the term “alkenoxy”, means “alkenyl-O—”, wherein “alkenyl” is as defined above.
[0040] Unless otherwise indicated, as used herein, the term “alkynoxy”, means “alkynyl-O—”, wherein “alkynyl” is as defined above.
[0041] In all of the above defined “C 1 -C x alkyl,” “C 1 -C x alkenyl,” “C 1 -C x alkynyl,” “C 1 -C x alkoxy,” “C 1 -C x alkenoxy,” and “C 1 -C x alkynoxy,” groups, when x is an integer greater than 2, such “C 1 -C x alkyl,” “C 1 -C x alkenyl,” “C 1 -C x alkynyl,” “C 1 -C x alkoxy,” “C 1 -C x alkenoxy,” and “C 1 -C x alkynoxy,” groups, may optionally be replaced with a “polyfluoro C 1 -C x alkyl,” a polyfluoro C 1 -C x alkenyl,” a “polyfluoro C 1 -C x alkynyl,” a “polyfluoro C 1 -C x alkoxy,” a “polyfluoro C 1 -C x alkenoxy,” or a “polyfluoro C 1 -C x alkynoxy,” group. As used herein, the expression “polyfluoro C 1 -C x alkyl” refers to alkyl groups, as defined above, that comprise at least one —CF 2 and/or CF 3 group.
[0042] Unless otherwise indicated, as used herein, the term “cycloalkyl” includes non-aromatic saturated cyclic alkyl moieties wherein alkyl is as defined above. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. “Bicycloalkyl” and “tricycloalkyl” groups are non-aromatic saturated cyclic alkyl moieties consisting of two or three rings, respectively, wherein said rings share at least one carbon atom which may contain a carbon bridge. For purposes of the present invention, and unless otherwise indicated, bicycloalkyl groups include spiro groups and fused ring groups. Examples of bicycloalkyl groups include, but are not limited to, bicyclo-[3.1.0]-hexyl, bicyclo-[2.2.1]-hept-1-yl, norbornyl, spiro[4.5]decyl, spiro[4.4]nonyl, spiro[4.3]octyl, and spiro[4.2]heptyl. An example of a tricycloalkyl group is adamantanyl. Other cycloalkyl, bicycloalkyl, and tricycloalkyl groups are known in the art, and such groups are encompassed by the definitions “cycloalkyl”, “bicycloalkyl” and “tricycloalkyl” herein. “Cycloalkenyl“, “bicycloalkenyl” and “tricycloalkenyl” refer, respectively, to non-aromatic cycloalkyl, bicycloalkyl and tricycloalkyl moieties, respectively, as defined above, except that they each include one or more carbon-carbon double bonds connecting carbon ring members (an ∓endocyclic” double bond) and/or one or more carbon-carbon double bonds connecting a carbon ring member and an adjacent non-ring carbon (an “exocyclic” double bond). Examples of cycloalkenyl groups include, but are not limited to, cyclopentenyl, cyclobutenyl, and cyclohexenyl. A non-limiting example of a bicycloalkenyl group is norbornenyl. Cycloalkyl, cycloalkenyl, bicycloalkyl, and bicycloalkenyl groups also include groups that are substituted with one or more oxo moieties. Examples of such groups with oxo moieties are oxocyclopentyl, oxocyclobutyl, oxocyclopentenyl and norcamphoryl. Other cycloalkenyl, bicycloalkenyl, and tricycloalkenyl groups are known in the art, and such groups are included within the definitions “cycloalkenyl”, “bicycloalkenyl” and “tricycloalkenyl” herein.
[0043] Unless otherwise indicated, as used herein, the term “aryl” includes an organic radical derived from an aromatic hydrocarbon by removal of one hydrogen, such as phenyl (Ph), naphthyl, indenyl, indanyl and fluorenyl. “Aryl” encompasses fused ring groups wherein at least one ring is aromatic.
[0044] Unless otherwise indicated, as used herein, the terms “heterocyclic” and “heterocycloalkyl” refer to non-aromatic cyclic groups containing one or more heteroatoms, prefereably from one to four heteroatoms, each independently selected from O, S and N. “Heterobicycloalkyl” groups are non-aromatic two-ringed cyclic groups, wherein said rings share one or two atoms, and wherein at least one of the rings contains a heteroatom (O, S, or N). Unless otherwise indicated, for purposes of the present invention, heterobicycloalkyl groups include spiro groups and fused ring groups. In one embodiment, each ring in the heterobicycloalkyl group contains up to four heteroatoms (i.e. from zero to four heteroatoms, provided that at least one ring contains at least one heteroatom). The heterocyclic groups of this invention can also include ring systems substituted with one or more oxo moieties. Examples of non-aromatic heterocyclic groups are aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, azepinyl, piperazinyl, 1,2,3,6-tetrahydropyridinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholino, thiomorpholino, thioxanyl, pyrrolinyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, quinolizinyl, quinuclidinyl, 1,4-dioxaspiro[4.5]decyl, 1,4-dioxaspiro[4.4]nonyl, 1,4-dioxaspiro[4.3]octyl, and 1,4-dioxaspiro[4.2]heptyl.
[0045] Unless otherwise indicated, as used herein, “heteroaryl” refers to aromatic groups containing one or more heteroatoms, preferably from one to four heteroatoms, selected from O, S and N. A multicyclic group containing one or more heteroatoms wherein at least one ring of the group is aromatic is a “heteroaryl” group. The heteroaryl groups of this invention can also include ring systems substituted with one or more oxo moieties. Examples of heteroaryl groups are pyridinyl, pyridazinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydroguinolyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, triazinyl, 1,2,4-trizainyl, 1,3,5-triazinyl, isoindolyl, 1-oxoisoindolyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, dihydroquinolyl, tetrahydroquinolyl, dihydroisoquinolyl, tetrahydroisoquinolyl, benzofuryl, furopyridinyl, pyrolopyrimidinyl, and azaindolyl.
[0046] Unless otherwise indicated, as used herein, the term “cycloalkoxy”, means “cycloalkyl-O—”, wherein “cycloalkyl” is as defined above.
[0047] Unless otherwise indicated, as used herein, the term “aryloxy”, means “aryl-O—”, wherein “aryl” is as defined above.
[0048] Unless otherwise indicated, as used herein, the term “heterocycloalkoxy”, means “heterocycloalkyl-O—”, wherein “heterocycloalkyl” is as defined above.
[0049] Unless otherwise indicated, as used herein, the term “heteroaryloxy”, means “heteroaryl-O—”, wherein “heteroaryl” is as defined above.
[0050] The foregoing groups, as derived from the compounds listed above, may be C-attached or N-attached where such is possible. For instance, a group derived from pyrrole may be pyrrol-1-yl (N-attached) or pyrrol-3-yl (C-attached). The terms referring to the groups also encompass all possible tautomers.
[0051] In another aspect, the present invention relates to compounds of the Formula I, wherein Z is —C(═O)CHR 1 R 2 , R 2 is —H, —OH, or OC(═O)CH 3 .
[0052] In another aspect, the present invention relates to compounds of the Formula I, wherein Z is —C(═O)C(═O)R 1 .
[0053] In another aspect, the present invention relates to compounds of the Formula I, wherein Z is —SO 2 R 1 .
[0054] In another aspect, the present invention relates to compounds of the Formula I wherein R 1 is selected from —C 1 -C 20 alkyl, —C 2 -C 20 alkenyl, —C 2 -C 20 alkynyl, —C 3 -C 20 cycloalkyl, (4-20 membered) heterocycloalkyl, —C 6 -C 20 aryl and (5-20 membered) heteroaryl.
[0055] In another aspect, R 1 is selected from —C 1 -C 10 alkyl, —C 2 -C 10 alkenyl, —C 3 -C 10 cycloalkyl, phenyl, thienyl and pyridyl, wherein R 1 is optionally independently substituted with from one to two substituents independently selected from —C 1 -C 4 alkyl, —OCF 3 , —CF 3 , —C 1 -C 4 alkoxy, —F, —Cl, —Br, phenyl and phenoxy, wherein R 1 optionally contains one or two double or triple bonds.
[0056] In another aspect, R 1 is —C 3 -C 7 cycloalkyl, e.g., [2.2.1]-heptanyl.
[0057] In another aspect, R 1 is selected from phenyl and pyridyl, wherein R 1 is optionally independently substituted with from one to two substitutents independently selected from —F, —Cl, OCF 3 , and —CF 3 .
[0058] In another aspect, the present invention relates to compounds of the Formula I wherein R 2 is selected from —H, —OH, and —OC(═O)CH 3 .
[0059] In another aspect, R 2 is selected from —H and —OH.
[0060] In another aspect, R 2 is selected from —OC(═O)CH 3 .
[0061] In another aspect, the present invention relates to compounds of the Formula I wherein R 3 is selected from —C 1 -C 4 alkyl, allyl, and —CH 2 CH 2 SCH 3 .
[0062] In another aspect, the present invention relates to compounds of the Formula I wherein R 5 is H.
[0063] In another aspect, the present invention relates to compounds of the Formula I wherein R 7 is selected from —H, —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 1 -C 20 alkoxy, —F, —Cl, —Br, —I, —CN, —NO 2 , —C 3 -C 15 cycloalkyl, -(3-15 membered) heterocycloalkyl, —C 6 -C 15 aryl, -(5-15 membered) heteroaryl, —CHO, —C(═O)(C 1 -C 15 alkyl), —C(═O)((5-15 membered)heterocycloalkyl), —C(═O)((5-15 membered) heteroaryl), —C(═O)O(C 1 -C 8 alkyl), —C(═O)N(C 1 -C 10 alkyl)(C 1 -C 10 alkyl), —S(O) n -alkyl, —S(O) n -cycloalkyl, —S(O) n -(6 to 14 membered) aryl, —S(O) n -(5 to 14 membered) heteroaryl, wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally independently substituted with from one to three substituents independently selected from —F, —Cl, —Br, —I, —OH, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy, —NR 9 R 10 , —C(═O)R 11 , —S(O) n R 11 , —C(═O)OR 12 , —C(═O)NR 9 R 10 , —S(O) n NR 9 R 10 —C 3 -C 15 cycloalkyl, -(4-15 membered) heterocycloalkyl, —C 6 -C 15 aryl, -(5-15 membered) heteroaryl, (5-15 membered) heterocycloalkoxy, —C 6 -C 12 aryloxy and (6-12 membered) heteroaryloxy.
[0064] In another aspect, wherein R 7 is selected from —H, —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 2 -C 12 alkynyl, —C 1 -C 20 alkoxy, —F, —Cl, —Br, —I, —CN, —NO 2 , —(C zero -C 4 alkylene)(C 3 -C 15 cycloalkyl), -(3-15 membered) heterocycloalkyl, —C 6 -C 15 aryl, -(5-15 membered) heteroaryl, —CHO, —C(═O)(C 1 -C 15 alkyl), —C(═O)((5-15 membered) heterocycloalkyl), —C(═O)(C 5 -C 15 aryl), —C(═O)((5-15 membered) heteroaryl), —C(═O)(C 5 -C 15 cycloalkyl), —C(═O)O(C 1 -C 8 alkyl), —C(═O)N(C 1 -C 10 alkyl)(C 1 -C 10 alkyl), —C(═O)N(C zero -C 10 alkyl)(C 6 -C 10 aryl), —C(═O)N(C zero -C 10 alkyl)((5-10 membered) heteroaryl), —C(═O)N(C zero -C 10 alkyl)((5-10 membered) heterocycloalkyl), —C(═O)N(C zero -C 10 alkyl)(C 5 -C 10 cycloalkyl), —S(O) n —(C 1 -C 6 alkyl), —S(O) n —(C 3 -C 8 cycloalkyl), —S(O) n —(C 6 -C 10 aryl), —S(O) n -((5-10 membered) heteroaryl), wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally independently substituted with from one to three substituents independently selected from —F, —Cl, —Br, —I, —OH, —C 1 -C 10 alkoxy, —C 2 -C 10 alkenoxy, —C 2 -C 10 alkynoxy, —NR 9 R 10 , (C 1 -C 11 alkyl)-NR 9 R 10 , —C(═O)R 11 , —S(O) n R 11 , —C(═O)OR 12 , —C(═O)NR 9 R 10 , —S(O) n NR 9 R 10 —C 3 -C 15 cycloalkyl, -(4-15 membered) heterocycloalkyl, —C 6 -C 15 aryl, -(5-15 membered) heteroaryl, -(4-12 membered) heterocycloalkoxy, —C 6 -C 12 aryloxy and -(6-12 membered) heteroaryloxy.
[0065] In another aspect, R 7 is selected from —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, -C 2 -C 12 alkynyl, —(C zero -C 4 alkylene)(C 3 -C 15 cycloalkyl), and —(C zero -C 4 alkylene)(4-15 membered) heterocycloalkyl, wherein said alkyl, alkenyl, cycloalkyl and heterocycloalkyl are each optionally independently substituted with from one to three substitutents independently selected from —OH, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy and —NR 9 R 10 .
[0066] In another aspect, R 7 is selected from —C 1 -C 12 alkyl, —C 2 -C 12 alkenyl, —C 3 -C 15 cycloalkyl and -(4-15 membered) heterocycloalkyl, wherein said alkyl, alkenyl, cycloalkyl and heterocycloalkyl are each optionally independently substituted with from one to three substitutents independently selected from —OH, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy.
[0067] In another aspect, R 7 is selected from —C 1 -C 12 alkyl, —C 2 -C 12 -alkenyl and —C 3 -C 15 cycloalkyl, wherein said alkyl, alkenyl and cycloalkyl are each optionally independently substituted with from one to three substitutents NR 9 R 10 .
[0068] In another aspect, R 7 is -(4-15 membered) heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with from one to three substitutents independently selected from —OH, —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 1 -C 6 alkoxy, —C 2 -C 6 alkenoxy, —C 2 -C 6 alkynoxy, —(C 6 -C 10 aryl) and -(5-15 membered) heteroaryl.
[0069] Non-limiting examples of the compound of formula I include the following compounds:
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-phenyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-methoxy-phenyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3,4-dimethyl-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-adamantan-1-yl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-chloro-benzyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-phenyl-propylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-trifluoromethyl-benzylsulfanyl)-thiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-methoxy-benzylsulfanyl)-thiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-fluoro-benzylsulfanyl)-thiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-propylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[2-(3-trifluoromethyl-phenoxy)-ethylsulfanyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3,4-dichloro-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-dipropylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-benzylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(2,4-dichloro-phenoxy)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-phenoxy-butylsulfanyl)-thiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[2-(4-bromo-phenoxy)-ethylsulfanyl]-thiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-diethylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-ethylsulfamoyl-[1,3,4]thiadiazol-2-yl )-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-phenethylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-2-(S)-2-hydroxy-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-2-(S)-2-hydroxy-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-2-(S)-hydroxy-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(5-Bromo-pyridin-3-yl)-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Bicyclo[2.2.1]hept-2-yl-acetylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(5-Bromo-pyridin-3-yl)-acetylamino]-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Bicyclo[2.2.1]hept-2-yl-acetylamino)-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-(S)-2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-(R)-2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide; Hydroxy-phenyl-acetic acid [1-(5-methyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butylcarbamoyl]-phenyl-methyl ester; 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-2-(S)-2-hydroxy-acetylamino]-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-2-(R)-2-hydroxy-acetylamino]-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-formyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(2,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2,4,4-trimethyl-pentyl )-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-(S)-2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-(R)-2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-(S)-2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-(R)-2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-(S)-2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-(R)-2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide;
[0124] 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide;
2-(2-(S)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-(R)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-isopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(S)-2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(R)-2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(5-Bromo-pyridin-3-yl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3-Trifluoromethoxy-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide;
[0137] 3-(5-{2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoylamino}-[1,3,4]thiadiazol-2-yl)-3-methyl-butyric acid;
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-oxiranyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-3-oxy-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1,1-dimethyl-3-(2,2,2-trifluoro-ethylamino)-propyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1-methyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1-methyl-butyl)-1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1-methyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-isopropylamino-1-methyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3,3-dimethoxy-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-ethylamino-1-methyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-isopropylamino-1-methyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-hydroxy-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-isopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-ethylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-2-(R)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-2-(S)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-dimethylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-propylamino-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[3-(2-hydroxy-ethylamino)-1,1-dimethyl-propyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-tert-butylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-cyclopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-pyrrolidin-1-yl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-morpholin-4-yl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[3-(1-ethyl-propylamino)-1,1-dimethyl-propyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid [5-(3-cyclopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-hydroxy-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide-2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-{3-[formyl-(2,2,2-trifluoro-ethyl)-amino]-1,1-dimethyl-propyl}-[1,3,4]thiadiazol-2-yl)-amide 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid (5-{3-[formyl-(2,2,2-trifluoro-ethyl)-amino]-1,1-dimethyl-propyl}-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-chloro-1,1-dimethyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-hydroxy-1,1-dimethyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-(5-{2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoylamino)-[1,3,4]thiadiazol-2-ylsulfanyl)-2-methyl-propionic acid ethyl ester; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[(isopropyl-phenyl-carbamoyl)-methylsulfanyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-fluoro-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-trifluoromethyl-pyrimidin-2-ylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-allyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-propenyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-acetyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(3-methyl-butylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-butylamino-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(3,3-dimethyl-butylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-cyclopropylamino-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-oxo-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(4-methyl-piperazin-1-yl)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(4-chloro-benzylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-hydroxy-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(3-chloro-benzylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-benzyloxy-1,1-dimethyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-ethylsulfanyl-[1,3,4]thiadiazol-2-yl)-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(2-dimethylamino-ethylsulfanyl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-ethoxymethyl-[1,3,4]thiadiazol-2-yl)-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-dimethylamino-[1,3,4]thiadiazol-2-yl)-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-isobutyl-[1,3,4]thiadiazol-2-yl)-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-phenyl-[1,3,4]thiadiazol-2-yl)-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-isopropyl-[1,3,4]thiadiazol-2-yl )-butyramide; N-(5-Benzyl-[1,3,4]thiadiazol-2-yl)-2-[2-(3,5-difluoro-phenyl)-acetylamino]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-phenoxymethyl-[1,3,4]thiadiazol-2-yl)-butyramide;
[0205] N-[5-(3-Chloro-phenyl)-[1,3,4]thiadiazol-2-yl]-2-[2-(3,5-difluoro-phenyl)-acetylamino]-butyramide;
N-(5-Cyclobutyl-[1,3,4]thiadiazol-2-yl)-2-[2-(3,5-difluoro-phenyl)-acetylamino]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]thiadiazol-2-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-methoxymethyl-[1,3,4]thiadiazol-2-yl)-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-isopropylsulfanyl-[1,3,4]thiadiazol-2-yl)-butyramide; 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid (5-cyclohexyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid (5-methylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide; 2-(5-{2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoylamino}-[1,3,4]thiadiazol-2-ylsulfanyl)-propionic acid ethyl ester; 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid (5-phenethyl-[1,3,4]thiadiazol-2-yl)-amide; 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid [5-(1-phenoxy-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[3-(toluene-4-sulfonylamino)-[1,2,4]thiadiazol-5-yl]-butyramide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (3-ethylsulfanyl-[1,2,4]thiadiazol-5-yl)-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-morpholin-4-yl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-pyrrolidin-1-yl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide; 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (3-methanesulfonyl-[1,2,4]thiadiazol-5-yl)-amide; and 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [3-(4-nitro-benzenesulfonylamino)-[1,2,4]thiadiazol-5-yl]-amide.
[0221] Compounds of the Formula I of this invention, and their pharmaceutically acceptable salts, have useful pharmaceutical and medicinal properties. The compounds of Formula I, and their pharmaceutically acceptable salts inhibit the production of Aβ-peptide (thus, gamma-secretase activity) in mammals, including humans. Compounds of the Formula I, and their pharmaceutically acceptable salts, are therefore able to function as therapeutic agents in the treatment of the neurodegenerative and/or neurological disorders and diseases enumerated below, for example Alzheimer's disease, in an afflicted mammal, including a human.
[0222] The present invention also relates to a pharmaceutical composition for inhibiting or modulating Aβ-peptide production in a mammal, including a human, comprising an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in inhibiting Aβ-production, and a pharmaceutically acceptable carrier.
[0223] The present invention also relates to a pharmaceutical composition for treating a disease or condition selected from the group consisting of Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis, cerebral amyloid angiopathy, a prion-mediated disease, inclusion body myositis, stroke, multiple sclerosis and Down's Syndrome in a mammal, including a human, comprising an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in inhibiting Aβ-peptide production, and a pharmaceutically acceptable carrier.
[0224] The present invention also relates to a pharmaceutical composition for treating a disease or condition selected from the group consisting of Alzheimer's disease and Down's Syndrome in a mammal, including a human, comprising an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in inhibiting Aβ-peptide production, and a pharmaceutically acceptable carrier.
[0225] The present invention also relates to a pharmaceutical composition for treating a disease or a condition selected from the group consisting of Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis, cerebral amyloid angiopathy, a prion-mediated disease, inclusion body myositis, stroke, multiple sclerosis and Down's Syndrome in a mammal, including a human, comprising an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in treating such disease or condition, and a pharmaceutically acceptable carrier.
[0226] The present invention also relates to a pharmaceutical composition for treating a disease or a condition selected from the group consisting of Alzheimer's disease and Down's Syndrome in a mammal, including a human, comprising an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in treating such disease or condition, and a pharmaceutically acceptable carrier.
[0227] The present invention also relates to a method of inhibiting Aβ-peptide production in a mammal, including a human, comprising administering to said mammal an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in inhibiting Aβ-production.
[0228] The present invention also relates to a method of treating a disease or condition selected from Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis, cerebral amyloid angiopathy, a prion-mediated disease, inclusion body myositis, stroke, multiple sclerosis and Down's Syndrome in a mammal, including a human, comprising administering to said mammal an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in inhibiting Aβ-production.
[0229] The present invention also relates to a method of treating a disease or condition selected from Alzheimer's disease and Down's Syndrome in a mammal, including a human, comprising administering to said mammal an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in inhibiting Aβ-production.
[0230] The present invention also relates to a method of treating a disease or condition selected from Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis, cerebral amyloid angiopathy, a prion-mediated disease, inclusion body myositis, stroke, multiple sclerosis and Down's Syndrome in a mammal, including a human, comprising administering to said mammal an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in treating such condition.
[0231] The present invention also relates to a method of treating a disease or condition selected from Alzheimer's disease and Down's Syndrome in a mammal, including a human, comprising administering to said mammal an amount of a compound of the Formula I, or a pharmaceutically acceptable salt thereof, that is effective in treating such condition.
[0232] The present invention also relates to a pharmaceutical composition for treating a disease or condition associated with Aβ-peptide production in a mammal, including a human, comprising (a) a compound of the Formula I, or a pharmaceutically acceptable salt thereof; (b) a memory enhancement agent, antidepressant, anxiolytic, antipsychotic agent, sleep disorder agent, anti-inflammatory agent, anti-oxidant agent, cholesterol modulating agent or anti-hypertensive agent; and (c) a pharmaceutically acceptable carrier; wherein the active agents “a” and “b” above are present in amounts that render the composition effective in treating such disease or condition.
[0233] The present invention also relates to a pharmaceutical composition for treating a disease or condition selected from the group consisting of Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis, cerebral amyloid angiopathy, a prion-mediated disease, inclusion body myositis, stroke, multiple sclerosis and Down's Syndrome, in a mammal, including a human, comprising (a) a compound of the Formula I, or a pharmaceutically acceptable salt thereof; (b) a memory enhancement agent, antidepressant, anxiolytic, antipsychotic agent, sleep disorder agent, anti-inflammatory agent, anti-oxidant agent, cholesterol modulating agent or anti-hypertensive agent; and (c) a pharmaceutically acceptable carrier; wherein the active agents “a” and “b” above are present in amounts that render the composition effective in treating such disease or condition.
[0234] The present invention also relates to a pharmaceutical composition for treating a disease or condition selected from the group consisting of Alzheimer's disease and Down's Syndrome, in a mammal, including a human, comprising (a) a compound of the Formula I, or a pharmaceutically acceptable salt thereof; (b) a memory enhancement agent, antidepressant, anxiolytic, antipsychotic agent, sleep disorder agent, anti-inflammatory agent, anti-oxidant agent, cholesterol modulating agent or anti-hypertensive agent; and (c) a pharmaceutically acceptable carrier; wherein the active agents “a” and “b” above are present in amounts that render the composition effective in treating such disease or condition.
[0235] The present invention also relates to a method of treating a disease or condition associated with Aβ-peptide production in a mammal, including a human, comprising administering to said mammal (a) a compound of the Formula I, or a pharmaceutically acceptable salt thereof; and (b) a memory enhancement agent, antidepressant, anxiolytic, antipsychotic agent, sleep disorder agent, anti-inflammatory agent, anti-oxidant agent, cholesterol modulating agent or anti-hypertensive agent; wherein the active agents “a” and “b” above are present in amounts that render the composition effective in treating such disease or condition.
[0236] The present invention also relates to a method of treating a disease or condition selected from the group consisting of Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis, cerebral amyloid angiopathy, a prion-mediated disease, inclusion body myositis, stroke, multiple sclerosis and Down's Syndrome, in a mammal, including a human, comprising administering to said mammal (a) a compound of the Formula I, or a pharmaceutically acceptable salt thereof; and (b) a memory enhancement agent, antidepressant, anxiolytic, antipsychotic agent, sleep disorder agent, anti-inflammatory agent, anti-oxidant agent, cholesterol modulating agent or anti-hypertensive agent; wherein the active agents “a” and “b” above are present in amounts that render the composition effective in treating such disease or condition.
[0237] The present invention also relates to a method of treating a disease or condition selected from the group consisting of Alzheimer's disease and Down's Syndrome, in a mammal, including a human, comprising administering to said mammal (a) a compound of the Formula I, or a pharmaceutically acceptable salt thereof; and (b) a memory enhancement agent, antidepressant, anxiolytic, antipsychotic agent, sleep disorder agent, anti-inflammatory agent, anti-oxidant agent, cholesterol modulating agent or anti-hypertensive agent; wherein the active agents “a” and “b” above are present in amounts that render the composition effective in treating such disease or condition.
[0238] Compounds of the Formula I may be used alone or used as a combination with any other drug, including, but not limited to, any memory enhancement agent, e.g., Aricept™, antidepressant agent, e.g., Zoloft™, anxiolytic, antipsychotic agent, e.g., Geodon™, sleep disorder agent, anti-inflammatory agent, e.g., Celebrex™, Bextra™, etc., anti-oxidant agent, cholesterol modulating agent (for example, an agent that lowers LDL or increases HDL), e.g., Lipitor™, or anti-hypertension agent. Accordingly, this invention also provides a pharmaceutical composition for treatment of a mammal, including a human, in need thereof comprising an effective amount of a compound of the Formula I and an effective amount of another drug, for example a memory enhancement agent, e.g., Aricept™, antidepressant agent, e.g., Zoloft™, anxiolytic, antipsychotic agent, e.g., Geodon™, sleep disorder agent, anti-inflammatory agent, e.g., Celebrex™, Bextra™, etc., anti-oxidant agent, cholesterol modulating agent (for example, an agent that lowers LDL or increases HDL), e.g., Lipitor™, or anti-hypertension agent, and a pharmaceutically acceptable carrier. This invention also provides a method for treating dementia, for example Alzheimer's disease, in a mammal, including in a human, comprising administering to the mammal an effective amount of a compound of the Formula I and an effective amount of another drug, for example a memory enhancement agent, e.g., Aricept™, antidepressant agent, e.g., Zoloft™, anxiolytic, antipsychotic agent, e.g., Geodon™, sleep disorder agent, anti-inflammatory agent, e.g., Celebrex™, Bextra™, etc., anti-oxidant agent, cholesterol modulating agent (for example, an agent that lowers LDL or increases HDL), e.g., Lipitor™, or anti-hypertension agent.
[0239] Compounds of the Formula I, or any of the combinations described in the immediately preceding paragraph, may optionally be used in conjunction with a know P-glycoprotein inhibitor, such as verapamil.
[0240] References herein to diseases and conditions “associated with Aβ-peptide production” relate to diseases or conditions that are caused, at least in part, by Aβ-peptide and/or the production thereof. Thus, Aβ-peptide is a contributing factor, but not necessarily the only contributing factor, to “a disease or condition associated with Aβ-peptide production.”
[0241] As used herein, the term “treating” refers to reversing, alleviating or inhibiting the progress of a disease, disorder or condition, or one or more symptoms of such disease, disorder or condition, to which such term applies. As used herein, “treating” may also refer to decreasing the probability or incidence of the occurrence of a disease, disorder or condition in a mammal as compared to an untreated control population, or as compared to the same mammal prior to treatment. For example, as used herein, “treating” may refer to preventing a disease, disorder or condition, and may include delaying or preventing the onset of a disease, disorder or condition, or delaying or preventing the symptoms associated with a disease, disorder or condition. As used herein, “treating” may also refer to reducing the severity of a disease, disorder or condition or symptoms associated with such disease, disorder or condition prior to a mammal's affliction with the disease, disorder or condition. Such prevention or reduction of the severity of a disease, disorder or condition prior to affliction relates to the administration of the composition of the present invention, as described herein, to a subject that is not at the time of administration afflicted with the disease, disorder or condition. As used herein “treating” may also refer to preventing the recurrence of a disease, disorder or condition or of one or more symptoms associated with such disease, disorder or condition. The terms “treatment” and “therapeutically,” as used herein, refer to the act of treating, as “treating” is defined above.
DETAILED DESCRIPTION OF THE INVENTION
[0242] Compounds of the Formula I, and their pharmaceutically acceptable salts, may be prepared as described in the following reaction Schemes and discussion. Unless otherwise indicated, as referred to in the reaction schemes and discussion that follow, R 1 , R 1a , R 1b , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , Z, and n are as defined above.
[0243] The compounds of Formula I may have asymmetric carbon atoms and may therefore exist as racemic mixtures, diastereoisomers, geometric isomers, or as individual optical isomers.
[0244] Separation of a mixture of isomers of compounds of Formula I into single isomers may be accomplished according to conventional methods known in the art.
[0245] The compounds of the Formula I may be prepared by the methods described below, together with synthetic methods known in the art of organic chemistry, or modifications and derivatizations that are familiar to those of ordinary skill in the art. Preferred methods include, but are not limited to, those described below.
[0246] The reactions described below are performed in solvents that are appropriate to the reagents and materials employed and that are suitable for use in the reactions described. In the description of the synthetic methods described below, it is also to be understood that all reaction conditions, whether actual or proposed, including choice of solvent, reaction temperature, reaction duration time, reaction pressure, and other reaction conditions (such as anhydrous conditions, under argon, under nitrogen, etc.), and work up procedures, are those conditions that are standard for that reaction, as would be readily recognized by one of skill in the art. Alternate methods may also be used.
[0247] Scheme I refers to a method of preparation of compounds of the Formula I, 10. An amino-thiadiazole 1 is coupled with a nitrogen-protected amino acid 2a-c using conventional coupling reagents and procedures. The nitrogen protecting group may be a carbamate-type such as butoxycarbonyl (“BOC”, P═O-tert-butyl) or benzyloxycarbonyl (“CBZ”, P═O-benzyl) that is prepared with either di-tert-butyl dicarbonate (Aldrich Chemical Company, Milwaukee Wis.), or benzyl chloroformate (Aldrich) in the presence of either an inorganic or organic base (e.g., sodium carbonate or triethylamine) at 0 to 30° C. in an organic solvent (e.g., methylene chloride) or in a mixture of water and an organic solvent (e.g., ethyl acetate) (see, Muller, Methoden Der Oraanischen Chemie. “Vierte Auglage—Synthesis von Peptiden I”—Houben Weyl—Georg-Thieme Verlag Stuttgart, 1974, Band XV/1).
[0248] The amino-thiadiazoles 1 starting reagents may be prepared according to the procedure similar to the known in literature (references Acta Universitatis Palackianae Olomucensis, Facultas Rerum Naturalium, Chemica (2001); Journal of Medicinal Chemistry (2003), 46(3), 427-440. European Journal of Medicinal Chemistry (2002), 37(8), 689-697. Phosphorus, Sulfur and Silicon and the Related Elements (2002), 177(4), 863-875. Chemistry of Heterocyclic Compounds (New York, N.Y., United States)(Translation of Khimiya Geterotsiklicheskikh Soedinenii) (2001), 37(9), 1102-1106. Journal of the Institution of Chemists (India) (2001), 73(3), 108-110. Russian Journal of General Chemistry (Translation of Zhurnal Obshchei Khimii) (2000), 70(11), 1801-1803. Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry (1989), 28B(1), 78-80. Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry (1981), 20B(6), 518-20. Khimiya Geterotsiklicheskikh Soedinenii, (10), 1416-19; 1986. Journal of the Institution of Chemists (India), 61(2), 54-6; 1989 Journal of the Institution of Chemists (India), 73(5), 193-195; 2001. Chimica Acta Turcica (1984), 12(2), 305-14. Journal of Heterocyclic Chemistry, 21(6), 1689-98; 1984. Journal of Heterocyclic Chemistry (1980), 17(3), 607-8. Journal of Heterocyclic Chemistry (1969), 6(6), 835-40. Huaxue Shijie (2002), 43(7), 366-368. Indian Journal of Chemistry (1970), 8(6), 509-13. Ber. (1942), 75B 87-93. Journal of Medicinal Chemistry (1970), 13(5), 1015-17. Farmaco, Edizione Scientifica (1971), 26(1), 19-28. Journal of the Indian Chemical Society (1989), 66(2), 118-19. Journal of Heterocyclic Chemistry, 12(3), 581-3; 1975 European Journal of Medicinal Chemistry, 10(2), 121-4; 1975. Journal of Heterocyclic Chemistry (1977), 14(5), 853-5. Zhurnal Obshchei Khimii (1980), 50(4), 860-3. European Journal of Medicinal Chemistry (1996), 31(7-8), 597-606. Journal of Heterocyclic Chemistry (1980), 17(3), 607-8. Journal fuer Praktische Chemie (Leipzig), 332(1), 55-64; 1990 ). For example, compounds of formula 1 can be obtained by reacting a compound of formula VlI-IX, with thiosemicarbazide in a suitable solvent such as water, C1-C4 alcohol in the presence of acid, preferably HCl, H 3 PO 4 , polyphosphoric acid, sulfuric acid, MeSO 3 OH, et.c. . Compounds of formula 1 can also be obtained by reacting a compound of formula X with FeCl 3 as described in the reference cited above (Journal of Heterocyclic Chemistry, 12(3), 581-3; 1975; Pharm. Pharmacol. Commun. 2000, 6, 31-33; Russian J. Org. Chem. Vol 33, 1997, pp567-568; Eur. J. Med. Chem (1996) 31, 597-606;). Alternatively, compounds of formula 1 can be obtained by reacting a compound of formula VII, with thiosemicarbazide and phosphorous oxychloride at reflux, followed by hydrolysis (J. Heterocyclic Chem. 8: 835-837.).
[0249] Numerous reagents that are well-known in the art may be used to couple 1 and 2a-c to form 3 by standard peptide coupling methods (2a) or the trimethylaluminum coupling method (2b) or a leaving group (halogen or a mixed anhydride)(2c) known in art of organic chemistry (Scheme I). Activation of the carboxylic acid 2a with oxalyl halide, thionyl chloride, carbodiimidazole, or chloro-(C 1 -C 4 )alkyl-formate, in the prepsence of an appropriate base (e.g., tialkylamine, pyridine, dimethylaminopyridine or sodium carbonate, or the like) or carbodiimides with or without the use of known additives such as N-hydroxysuccinimide, 1-hydroxybenzotriazole, etc. can be used to facilitate coupling. Standard coupling agents include HATU (O-(7-azabenzotriazole-1y)-1,1,3,3,-tetramethyluronium hexafluorophosphate) or PyBOP (benzotriazole-1-yl)-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate) or HBTU (O-benzotriazole-1yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate)/trialkylamine, or 1-hydroxybenzotriazole (HOBT)/1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDAC)/trialkylamine (NEt3), in an appropriate solvent such as methylene chloride, chloroform, tetrahydrofuran (THF), acetonitrile, dimethylforamide (DMF), and the like or a mixture of two solvents to have reagents mixed well to form a clear solution. Peptide coupling agents or resins for solid phase synthesis such as Fmoc (Fluorenylmethylcarbonyl)-protected hydroxylamine bound to polystylene beads are common and well known in the literature. Deprotection of the Fmoc group under standard conditions using 20% piperidine in DMF. References: O-benzotriazol-1-yl-N,N,N,′N′-tetramethyluronium hexafluorophosphate (“HBTU”, Aldrich Chemical Company) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (“HATU”, Aldrich) (See, Fieser, Reagents for Organic Synthesis, 1986, Wiley Interscience, New York, Vol.12, p. 44; Hruby, Biorganic Chemistry: Peptides and Proteins, 1998, Oxford University press, New York, pp. 27-64; Muller, Methoden Der Organischen Chemie, Vierte Auflage—Synthese von Peptiden II—Houben Weyl, George-Thieme Verlag Stuttgart, 1974, Band XV/2). When optically active reagents are employed, reaction conditions, such as temperature, time and the selection of the base, must be carefully controlled to avoid racemization. The protected amino group or carboxylic acid group may be prepared by methods well known in the literature for amino acid protecting groups as described in Organic chemistry Journal, textbook such as “Protective Groups in Organic Syntehsis” by T. W. Green. Alternatively, the coupling can be performed by reacting 1 with an ester 2b in the presence of trialkylaluminum in an appropriate solvent, eg., THF, dioxane, toluene or a mixture of THF/toluene in an open or sealed tube at a temperature between 0° C.-120° C. until the complete conversion to the desired product (3 in Scheme I); preferred temperature is room temperature to 80° C.
[0250] Intermediate 3 of Scheme I, is deprotected to afford aminoamide 4 either through treatment with strong acid in the case of t-butoxycarbonyl or through hydrogenolysis in the case of carbobenzyloxycarbonyl. Specifically, t-BOC-3, on treatment with hydrochloric acid or trifluoroacetic acid in an organic solvent (e.g., dioxane, THF, or methylene chloride), at room temperature to 30° C. for about 1 hour to about 19 hours, affords the corresponding salts 4. Alternatively, CBZ-3 may be deprotected through catalytic hydrogenolysis in the presence of hydrogen (from about 1 to about 10 atmospheres), a heavy metal catalyst (e.g., palladium on carbon or palladium hydroxide on carbon, 1 to 10 percent catalyst loading, present at about 0.01 to about 0.50 times the of substrate), and a solvent (e.g., methanol, ethanol or ethyl acetate) at 20 to 50° C. for about 1 hour to about 19 hours.
[0251] The compound Formula I 10 in Scheme I may be prepared by the reaction of 4 with 9 where L is a leaving group (e.g., halide, mesylate, or triflate) and Z is as defined above. The reaction is carried out at 0 to 30° C. in an organic solvent (e.g., methylene chloride, ethyl acetate, or DMF) in the presence of an organic base (e.g., triethylamine, diisopropylethylamine, or N-methylmorpholine) for about 1 minute to about 24 hours.
[0252] Alternatively, the compound Formula I 10 may be prepared according to the procedure of Scheme II (Z-L is a carboxylic acid or L is a leaving group), employing the general conditions described for Scheme I. In Scheme II, R can be alkyl or benzyl. The coupling of 9 and 11 in Scheme II may be performed at a temperature of about 0 to 30° C. in an organic solvent (e.g., methylene chloride, dichloroethane, ethyl acetate, or DMF) in the presence of a base (e.g., triethylamine or diisopropylethylamine). When R is alkyl, either acidic or basic hydrolysis may be used to covert 12 to 13. If R is benzyl, catalytic hydrogenolysis may also be used to prepare 13.
[0253] The above amide bond formation may be achieved by coupling the ester (12 in Scheme II) with 1 in the presence of trialkylaluminum (e.g., AlMe3) in an appropriate solvent, e.g., THF, toluene or a mixture of THF/toluene, or similar like solvents in an open or sealed tube at a temperature of about 0° C.-110° C. until there is complete conversion to the desired product (10 in Scheme II). Preferably, the temperature is about room temperature to about 80° C.
[0254] The ester group of R 7 may be converted to the corresponding amide using a coupling method similar to those described in Scheme I and II for amide bond formation (acid and amine with coupling agents to form an amide), or employing trimethylaluminum in an appropriate solvent or a mixture of solvents, such as THF/toluene to the corresponding amide (ester with an amine to form an amide). The olefin containing R7 group may be converted to a ketone, CHO, CH2OH, or COOH using ozonolysis followed by either reduction to give alcohol (by quenching with BH3.DMS, Journal of Organic Chemistry (1989), 54(6), 1430-2.), or ketone or aldehyde (by quenching with dimethylsulfide or triphenylphosphine).
[0255] The keto or formyl group of R 7 may be converted to the corresponding amine using a well-established reductive amination method by reacting a ketone with an appropriate amine with or without acid catalyst or Lewis acid catalyst (Ti(iPrO) 4 , ZnCl 2 , NiCl 2 ,/sodium acetate/dry agents (such as activated molecular sieves 4A, anhydrous Na 2 SO 4 or MgSO 4 ), and a reducing agent such as sodium triacetoxy borohydride, sodium cyanoborohydride, sodium borohydride, Zn(BH 4 ) 2 , Bu 3 SnH, Bu 2 SnClH, Bu 2 SnIH, decaborane, silical gel-Zn(BH 4 ) 2 , Et 3 SiH-trifluoroacetic acid, pyridine-BH3, phenylsilane-dibutyltin dichloride, or the corresponding polymer bound-NaBH 4 , polymer bound-NaBH 3 CN, polymer bound-NaB(OAc) 3 H, or any reducing agent (e.g., hydrogenation, Pd(OAc) 2 /potassium formate, Pd/C/H 2 ) that is known in the literature for reducing the imine bond to the corresponding amine in an appropriate solvent, such as dichloroethane, chloroform, 2-methoxyethyl ether, dichloroethane, DMF, THF, MeOH, ethanol, about iso-propanol, t-butanol or toluene, at a temperature between room temperature to reflux, preferably at about room temperature to about 65° C.
[0256] The starting materials used in the procedures of the above Schemes, the syntheses of which are not described above, are either commercially available, known in the art or readily obtainable from known compounds using methods that will be apparent to those skilled in the art.
[0257] The compounds of Formula I, and the intermediates shown in the above reaction schemes, may be isolated and purified by conventional procedures, such as recrystallization or chromatographic separation, such as on silica gel, either with an ethyl acetate/hexane elution gradient, a methylene chloride/methanol elution gradient, or a chloroform/methanol elution gradient. Alternatively, a reverse phase preparative HPLC or chiral HPLC separation technique may be used.
[0258] In each of the reactions discussed or illustrated above, pressure is not critical unless otherwise indicated. Pressures from about 0.5 atmospheres to about 5 atmospheres are generally acceptable, and ambient pressure, i.e., about 1 atmosphere, is preferred as a matter of convenience.
[0259] Pharmaceutically acceptable salts of the compounds of Formula I may be prepared in a conventional manner by treating a solution or suspension of the corresponding free base or acid with one chemical equivalent of a pharmaceutically acceptable acid or base. Conventional concentration or crystallization techniques may be employed to isolate the salts. Suitable acids, include, but are not limited to, acetic, lactic, succinic, maleic, tartaric, citric, gluconic, ascorbic, benzoic, cinnamic, fumaric, sulfuric, phosphoric, hydrochloric, hydrobromic, hydroiodic, sulfamic, sulfonic acids such as methanesulfonic, benzene sulfonic, p-toluenesulfonic and related acids. Suitable bases include, but are not limited to, sodium, potassium and calcium.
[0260] A compound of the Formula I of the present invention may be administered to mammals via either the oral, parenteral (such as subcutaneous, intravenous, intramuscular, intrasternal and infusion techniques), rectal, intranasal, topical or transdermal (e.g., through the use of a patch) routes. In general, these compounds are most desirably administered in doses ranging from about 0.1 mg to about 500 mg per day, in single or divided doses (i.e., from 1 to 4 doses per day), although variations will necessarily occur depending upon the species, weight, age and condition of the subject being treated, as well as the particular route of administration chosen. However, a dosage level that is in the range of about 0.1 mg/kg to about 5 gm/kg body weight per day, preferably from about 0.1 mg/kg to about 100 mg/kg body weight per day, is most desirably employed. Nevertheless, variations may occur depending upon the species of animal being treated and its individual response to said medicament, as well as on the type of pharmaceutical formulation chosen and the time period and interval at which such administration is carried out. In some instances, dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger doses may be employed without causing any harmful side effects, provided that such higher dosage levels are first divided into several small doses for administration throughout the day.
[0261] A compound of the Formula I of the present invention may be administered alone or in combination with pharmaceutically acceptable carriers or diluents by either of the routes previously indicated, and such administration may be carried out in single or multiple doses. Suitable pharmaceutical carriers include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc. The pharmaceutical compositions formed by combining a compound of the Formula I, or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable inert carrier, can then be readily administered in a variety of dosage forms such as tablets, capsules, lozenges, troches, hard candies, powders, sprays, creams, salves, suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups, and the like. Moreover, oral pharmaceutical compositions may be suitably sweetened and/or flavored.
[0262] For oral administration, tablets containing various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate and glycine may be employed along with various disintegrants such as starch (preferably corn, potato or tapioca starch), methylcellulose, alginic acid and certain complex silicates, together with granulation binders such as polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often useful for tabletting purposes. Solid compositions of a similar type may also be employed as fillers in gelatin capsules. Preferred materials in this connection include lactose or milk sugar as well as high molecular weight polyethylene glycols. When aqueous suspensions and/or elixirs are desired for oral administration, the active ingredient may be combined with various sweetening or flavoring agents, coloring matter or dyes, and, if so desired, emulsifying and/or suspending agents as well, together with such diluents as water, ethanol, propylene glycol, glycerin and various like combinations thereof.
[0263] For parenteral administration, solutions containing a compound of the Formula I of the present invention in either sesame or peanut oil or in aqueous propylene glycol may be employed. The aqueous solutions should be suitably buffered (preferably pH greater than 8) if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. These aqueous solutions are suitable for intravenous injection purposes. The oily solutions are suitable for intraarticular, intramuscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is readily accomplished by standard pharmaceutical techniques well known to those skilled in the art.
[0264] The compounds of Formula I of the present invention are useful in inhibiting Aβ-peptide production (thus, gamma-secretase activity) in mammals, and therefore they are able to function as therapeutic agents in the treatment of the aforementioned disorders and diseases in an afflicted mammal.
[0265] The ability of compounds of the Formula I of this invention, and their pharmaceutically acceptable salts, to inhibit Aβ-peptide production (thus, gamma-secretase activity) may be determined using biological assays known to those of ordinary skill in the art, for example the assays described below.
[0266] The activity of compounds of the Formula I of the present invention in inhibiting gamma-secretase activity was determined in a solubilized membrane preparation generally according to the description provided in McLendon et al. Cell-free assays for γ-secretase activity, The FASEB Journal (Vol. 14, December 2000, pp. 2383-2386). Using such assay, compounds of the present invention were determined to have an IC 50 activity for inhibiting gamma-secretase activity of less than about 100 micromolar.
[0267] The following Examples illustrate the present invention. It is to be understood, however, that the invention, as fully described herein and as recited in the claims, is not intended to be limited by the details of the following Examples.
Experimental Procedures
EXAMPLE 1
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide
[0268] A mixture of 3,5-di-fluoro-phenyl acetic acid (51.6 mg, 0.3 mmol), 2-amino-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide (88 mg, 0.3 mmol), HBOT (43 mg, 0.315 mmol), EDC HCl (69 mg, 0.36 mmol.) and triethylamine (0.17 ml) in methylene chloride was stirred at room temperature until product formation or disappearance of starting material. The mixture was quenched with water and extracted with methylene chloride. The organic layer was separated, washed with dilute HCl, brine, dried over sodium sulfate and the solvent was removed at reduced pressure to provide the title compound as a cude oil. The oil was purified by Shimadzu HPLC to provide the title compound as a white solid (56 mg), LC-MS M+1=411.2, 1 H NMR(CDCL3) 8.7 (d,1 H,NH), 6.73(m,2H), 6.6(m,1 H), 4.7(m,1H), 3.5(Abq, 2H), 1.6-1.9(m,2H), 1.3-1.6(m,2H), 1.5(s,9H), 0.92(t,3H) ppm.
EXAMPLE 2
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-phenyl-propylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide
[0269] A mixture of 2-[2-(3,5-difluoro-phenyl)-acetylamino]-pentanoic acid (25.4 mg, 0.2 mmol), 5-(2-phenyl-propylsulfanyl)-[1,3,4]thiadiazol-2-ylamine (50 mg, 0.2 mmol), HBOT (29 mg, 0.21 mmol), EDC HCl (46 mg, 0.24 mmol.) and triethylamine (0.12 ml) in methylene chloride was stirred at room temperature until product formation or disappearance of starting material. The mixture was quenched with water and extracted with methylene chloride. The organic layer was separated, washed with dilute HCl, brine, dried over sodium sulfate and the solvent was removed at reduced pressure to provide the title compound as a cude oil. The oil was purified by Shimadzu HPLC to provide the title compound as a light yellow solid (26 mg), LC-MS M+1=505.0
EXAMPLE 3
2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide
[0270] A mixture of 2-(S)-hydroxyl-3-methyl-butyric acid (35.4 mg, 0.3 mmol), 2-amino-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide (88 mg, 0.3 mmol), HBOT (43 mg, 0.21 mmol), EDC HCl (69 mg, 0.36 mmol.) and triethylamine (0.17 ml) in 2 ml of methylene chloride was stirred at room temperature until product formation or disappearance of starting material. The mixture was quenched with water and extracted with methylene chloride. The organic layer was separated, washed with dilute HCl, brine, dried over sodium sulfate and the solvent was removed at reduced pressure to provide the title compound as a cude oil. The oil was purified by Shimadzu HPLC to provide the title compound as a light yellow solid (44 mg), LC-MS M+1=357.1
[0271] The following compounds were prepared by the methods analogous to those describered in Examples 1, 2, or 3.
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-phenyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=431.1 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-methoxy-phenyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=461.0, RT=2.7 min 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3,4-dimethyl-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=504.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-adamantan-1-yl-[1,3,4]thiadiazol-2-yl)-amid, M+1=489.1 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-chloro-benzyl)-[1,3,4]thiadiazol-2-yl]-amide, M+=478.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-trifluoromethyl-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=545.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-methoxy-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=507.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-fluoro-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=495.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-propylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=476.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[2-(3-trifluoromethyl-phenoxy)-ethylsulfanyl]-[1,3,4]thiadiazol-2-yl}-amide, M+1=574.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3,4-dichloro-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=544.8 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-dipropylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=518.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-benzylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=476.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(2,4-dichloro-phenoxy)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide, M+1=543.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-phenoxy-butylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=535.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[2-(4-bromo-phenoxy)-ethylsulfanyl]-[1,3,4]thiadiazol-2-yl}-amide, M+1=586.8 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-diethylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=490.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-ethylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=461.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-phenethylsulfanyl-[1,3,4]thiadiazol-2-yl)-amide, M+=491.0 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=391.2 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=371.2 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=357.2 2-[2-(3,5-Difluoro-phenyl)-2-(S)-2-hydroxy-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=427.2 2-[2-(3,5-Difluoro-phenyl)-2-(R)-2-hydroxy-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=427.2 2-[2-(5-Bromo-pyridin-3-yl)-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=454.2 2-(2-Bicyclo[2.2.1]hept-2-yl-acetylamino)-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=393.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=383.2 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=329.2 2-[2-(5-Bromo-pyridin-3-yl)-acetylamino]-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=428.2 2-(2-Bicyclo[2.2.1]hept-2-yl-acetylamino)-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=365.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=369.1 2-(S)-(2-(S)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=349.1 2-(S)-(2-(R)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=349.1 Hydroxy-phenyl-acetic acid [1-(5-methyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butylcarbamoyl]-phenyl-methyl ester, M+1=483.2 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=329.2 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=315.1 2-(S)-[2-(R)-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=385.2 2-(S)-[2-(S)-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=385.2 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-ethylsulfanyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.3 min, M+1=401.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(2-dimethylamino-ethylsulfanyl)-[1,3,4]thiadiazol-2-yl]-butyramide, RT=1.4 min, M+1=44.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-ethoxymethyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.1 min, M+1=399.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-dimethylamino-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.0 min, M+1=384.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-isobutyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.3 min, M+1=397.4 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-phenyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.5 min, M+1=417.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-isopropyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.2 min, M+1=383.5 N-(5-Benzyl-[1,3,4]thiadiazol-2-yl)-2-[2-(3,5-difluoro-phenyl)-acetylamino]-butyramide, RT=2.5 min, M+1=431.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-phenoxymethyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.6 min, M+1=447.5 N-[5-(3-Chloro-phenyl)-[1,3,4]thiadiazol-2-yl]-2-[2-(3,5-difluoro-phenyl)-acetylamino]-butyramide, RT=2.7 min, M+1=451.3 N-(5-Cyclobutyl-[1,3,4]thiadiazol-2-yl)-2-[2-(3,5-difluoro-phenyl)-acetylamino]-butyramide, RT=2.4 min, M+1=395.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]thiadiazol-2-yl]-butyramide, RT=2.7 min, M+1=498.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-methoxymethyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.0 min, M+1=385.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-(5-isopropylsulfanyl-[1,3,4]thiadiazol-2-yl)-butyramide, RT=2.6 min, M+1=415.5 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid (5-cyclohexyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=493.5 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid (5-methylsulfamoyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=504.6, RT=2.7 min 2-(5-{2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoylamino}-[1,3,4]thiadiazol-2-ylsulfanyl)-propionic acid ethyl ester, M+1=543.6, RT=3.0 min 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid (5-phenethyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=515.4, RT=3.0 min 2-[2-(3-Phenoxy-phenyl)-acetylamino]-pentanoic acid [5-(1-phenoxy-ethyl)-[1,3,4]thiadiazol-2-yl]-amide, M+1=531.4, RT=3.0 min 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, RT=2.0 min, M+1=385.2 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide, RT=2.3 min, M+1=395.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-formyl-[1,3,4]thiadiazol-2-yl)-amide, RT=2.1 min, M+1=383.2 2-[2-(2,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide, RT=2.4 min, M+1=411.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.6 min, M+1=425.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5- (2,4,4-trimethyl-pentyl)-(1,3,4]thiadiazol-2-yl]-amide, RT=3.0 min, M+1=467.4 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.8 min, M+1=453.5 2-(2-(S)-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.7 min, M+1=413.5 2-(2-(R)-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.7 min, M+1=413.5 2-(2-(R)-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.3 min, M+1=385.5 2-(2-(S)-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.3 min, M+1=385.5 2-(2-(R)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.2 min, M+1=405.5 2-(2-(S)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.2 min, M+1=405.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.7 min, M+1=437.1 2-(2-(R)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.6 min, M+1=433.5 2-(2-(S)-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1-ethyl-pentyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.6 min, M+1=433.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.7 min, M+1=439.5 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, white solid, RT=2.0 min, M+1=419.5 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, white solid, RT=2.6min, M+1=399.5 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, white solid, RT=2.4 min, M+1=385.5 2-[2-(3,5-Difluoro-phenyl)-2-(R)-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, white solid, RT=2.7 min, M+1=455.5 2-[2-(3,5-Difluoro-phenyl)-2-(S)-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, white solid, RT=2.7 min, M+1=455.5 2-[2-(5-Bromo-pyridin-3-yl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=2.5 min, M+1=484.4 2-[2-(3-Trifluoromethoxy-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, RT=3.0 min, M+1=487.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide,LC-MS RT=2.6 min, M+1=423.2 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1-methyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-butyramide, LC-MS RT=2.4 min, M+1=409.2 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.5 min, M+1=425.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1-methyl-butyl)-[1,3,4]thiadiazol-2-yl]-butyramide, LC-MS RT=2.5 min, M+1=411.4 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-butyramide, LC-MS RT=2.6 min, M+1=423.4 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3,3-dimethoxy-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.6 min, M+1=485.0 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide, 1H NMR(CDCl3) δ 7.7 (d,1H), 5.65(m,1 H), 5.1(m,2H), 4.7(m,1H), 3.8(s,1H), 2.5(d,2H), 1.7-2.0(m,2H), 1.5-1.6(m,2H), 1.45(s,6H), 0.98(s,9H), 0.94(t,3H)ppm 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.6 min, M+1=416.9 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.4 min, M+1=383.0 2-[2-(3,5-Difluoro-phenyl)-2-(S)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.9 min, M+1=452.9 2-[2-(3,5-Difluoro-phenyl)-2-(R)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.8 min, M+1=452.9 2-(2-Hydroxy-3,3-dimethyl-butyrylamino)-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide, LC-MS RT=2.2 min, M+1=355.0 2-(2-Hydroxy-3-methyl-butyrylamino)-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide, LC-MS RT=2.0 min, M+1=341.0 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide, LC-MS RT=2.3 min, M+1=410.9 2-(2-Hydroxy-2-phenyl-acetylamino)-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide, LC-MS RT=2.2 min, M+1=374.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-chloro-1,1-dimethyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.6 min, M+1=444.8 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-hydroxy-1,1-dimethyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.1 min, M+1=426.9 2-(5-{2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoylamino}-[1,3,4]thiadiazol-2-ylsulfanyl)-2-methyl-propionic acid ethyl ester, LC-MS RT=2.8 min, M+1=500.8 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[(isopropyl-phenyl-carbamoyl)-methylsulfanyl]-[1,3,4]thiadiazol-2-yl}-amide, LC-MS RT=2.8 min, M+1=561.8 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-fluoro-benzylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.9 min, M+1=494.8 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(4-trifluoromethyl-pyrimidin-2-ylsulfanyl)-[1,3,4]thiadiazol-2-yl]-amide, 1 H NMR(CDCl3/CD3OD)δ 8.74(d, 1 H), 7.37(d, 1H), 6.70(m,2H0, 6.57(m,1H),4.51 (m,1H), 3.43(s,2H), 1.71 (m, 1H), 1.69(m,1H), 1.26(m,2H), 0.87(t,3H) ppm. 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-allyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.6 min, M+1=409.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-propenyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.6 min, M+1=409.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-benzyloxy-1,1-dimethyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=3.0 min, M+1=517.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[3-(toluene-4-sulfonylamino)-[1,2,4]thiadiazol-5-yl]-butyramide, LC-MS RT=2.5 min, M+1=510.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (3-ethylsulfanyl-[1,2,4]thiadiazol-5-yl)-amide, LC-MS RT=2.7 min, M+1=415.2 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (3-methanesulfonyl-[1,2,4]thiadiazol-5-yl)-amide, LC-MS RT=2.3 min, M+1=433.2 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [3-(4-nitro-benzenesulfonylamino)-[1,2,4]thiadiazol-5-yl]-amide, LC-MS RT=2.6 min, M+1=555.3 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (3-p-tolylamino-[1,2,4]thiadiazol-5-yl)-amide, LC-MS RT=2.4 min, M+1=460.4 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (3-methyl-[1,2,4]thiadiazol-5-yl)-amide, LC-MS RT=2.1 min, M+1=369.2
EXAMPLE 4
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-oxiranyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide
[0383] A mixture of 2-[2-(3,5-difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide (196 mg, 0.45 mmol) and ˜60% pure m-chloroperbenzoic acid (109 mg, 0.45 mmol) in methylene chloride was stirred for 4 hr. The mixture was quenched with water, saturated Na 2 S 2 O 3 and extracted with methylene chloride. The organic layer was washed with brine, separated, dried, and concentrated to give 114 mg of crude material with a mixture of desired title compound and undesired N-oxide and recovered starting material. The crude material was purified by HPLC and the title compound was isolated, LC-MS, RT=2.3 min, M=1=453.5.
EXAMPLE 5
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide
[0384] A stream of ozone was generated and passed through a solution of 2-[2-(3,5-difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-yl]-amide (631 mg, 1.445 mmol) in 40 ml of methylene chloride until the mixture turned to blue solution or until the disappearance of starting material at −78° C. The mixture was stirred at −78° C. for 10 min, then the excess ozone was replaced with N 2 at −78° C. The mixture was quenched with excess of dimethylsulfide and stirred at r.t. overnight. The mixture was concentrated to dryness, purified by Shimadzu HPLC to give the title compound as a yellow solid, RT=2.3 min, M+1=439.5.
[0385] 3-(5-{2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoylamino}-[1,3,4]thiadiazol-2-yl)-3-methyl-butyric acid, was prepared as described above in which the ozonolysis provided small quantity of the title compound that was isolated as the title carboxylic acid, RT=2.1 min, M+1=455.5.
[0386] The following examples were prepared by the method analogous to that described in Example 5 starting with an appropriate olefin and ozone, followed by quenching with dimethylsulfide.
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.1 min, M+1=425.5 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1-methyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide, APCI, M+1=411.1 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide, LC-MS RT=2.2 min, M+1=424.9 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.4 min, M+1=454.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-acetyl-[1,3,4]thiadiazol-2-yl)-amide, LC-MS RT=2.3 min, M+1=396.9
EXAMPLE 7
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-oxo-ethyl)-(1,3,4]thiadiazol-2-yl]-amide
[0392] A mixture of 2-[2-(3,5-difluoro-phenyl)-acetylamino]-pentanoic acid [5-(2-hydroxy-1,1-dimethyl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide (40 mg, 0.93 mmol) and Dess-Martin periodinane (1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one) (90 mg) in methylene chloride (3 ml) was stirred at rt for 3 hr. The mixture was quenched with water, methylene chloride and filtered through celite. The filtrate was transferred to separatory funnel and the organic layer was separated, dried and concentrated to give 42 mg of crude material. The crude material was purified by silica gel column chromatography using methylene chloride to 1% methanol in methylene chloride as eluent to give 20 mg of the title compound as a tan glass solid. APCI M+1=425.2.
EXAMPLE 8
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-isopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide
[0393] A mixture of 2-(2-(3,5-difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide (88 mg, 0.2 mmol), isopropylamine (0.09 ml) in dichloroethane (1 ml) and methylene chloride (1 ml) was stirred at r.t. for 10 min, sodium triacetoxyborohydride (76 mg) was added and the resulting mixture was stirred at r.t. overnight. The mixture was quenched with water, diluted with sodium hydroxide, and extracted with methylene chloride. The organic layer was separated, dried over Na 2 SO 4 , filtered and concentrated to dryness. The residue was purified by silica gel column chromatography using 3-5% methanol in methylene chloride, then 5% methanol/0.5% ammonium hydroxide in methylene chloride as eluent to give the title compound as a free base form. The free base was treated with 4 N HCl in doxane (0.1 ml) in methylene chloride (1 ml) and concentrated to dryness. The residue was triturated with hexane, pumped to dryness to give a white solid, LC-MS RT=1.8 min, M+1=481.9.
EXAMPLE 9
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-isopropylamino-1-methyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide
[0394] A mixture of 2-[2-(3,5-difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-methyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl]-amide (63 mg, 0.148 mmol), isopropylamine (0.2 ml) in dichloroethane (1 ml) and methylene chloride (1 ml) was stirred at r.t. for 10 min. Sodium cyanoborohydride (70 mg), acetic acid (0.1 ml), and sodium sulphate were added and the resulting mixture was stirred at 45-50° C. overnight. The mixture was quenched with water, basified with saturated sodium carbonate, extracted with methylene chloride. The organic layer was separated, dried over Na2SO 4 , filtered and concentrated to dryness. The residue was purified by Shimadzu HPLC to give the title compound LC-MS RT=1.7 min, M+1=467.9.
[0395] The following Examples were prepared by the method analogous to that described in Examples 8 or 9 starting from an appropriate aldehyde or ketone and an appropriate amine in an appropriate solvent or a mixture of solvents selected from methylene chloride, dichloroethane, THF, or DMF in the presence of a reducing agent selected from NaBH 3 CN or NaB(OAc) 3 H with or without acetic acid.
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1,1-dimethyl-3-(2,2,2-trifluoro-ethylamino)-propyl]-[1,3,4]thiadiazol-2-yl}-amide, LC-MS, RT=1.6 min, M+1=522.6 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-ethylamino-1-methyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide HCl salt, LC-MS, RT=1.8 min, M+1=440.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-isopropylamino-1-methyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide, HCl salt, LC-MS, RT=1.6 min, M+1=453.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-isopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide, LC-MS, RT=1.7 min, M+1=467.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-ethylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS, RT=1.9 min, M+1=467.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-dimethylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide HCl salt, LC-MS, RT=1.6 min, M+1=468.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-propylamino-propyl)-[1,3,4]thiadiazol-2-yl]-amide, HCl salt, LC-MS, RT=1.9 min, M+1=483.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[3-(2-hydroxy-ethylamino)-1,1-dimethyl-propyl]-[1,3,4]thiadiazol-2-yl}-amide, HCl salt, LC-MS, RT=1.8 min, M+1=484.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-tert-butylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide formic acid salt, LC-MS, RT=1.7 min, M+1=496.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-cyclopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide formic acid salt, LC-MS, RT=1 .9min, M+1=480.2 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-pyrrolidin-1-yl-propyl)-[1,3,4]thiadiazol-2-yl]-amide formic acid salt, LC-MS, RT=1.7 min, M+1=494.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-3-morpholin-4-yl-propyl)-[1,3,4]thiadiazol-2-yl]-amide formic acid salt, LC-MS, RT=1.5 min, M+1=510.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[3-(1-ethyl-propylamino)-1,1-dimethyl-propyl]-[1,3,4]thiadiazol-2-yl}-amide formic acid salt, LC-MS, RT=1.8 min, M+1=510.0 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid [5-(3-cyclopropylamino-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide formic acid salt, LC-MS, RT=1.8 min, M+1=495.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid (5-{3-[formyl-(2,2,2-trifluoro-ethyl)-amino]-1,1-dimethyl-propyl}-[1,3,4]thiadiazol-2-yl)-amide, LC-MS, RT=2.6 min, M+1=549.9 2-[2-(3,5-Difluoro-phenyl)-2-hydroxy-acetylamino]-pentanoic acid (5-{3-[formyl-(2,2,2-trifluoro-ethyl)-amino]-1,1-dimethyl-propyl}-[1,3,4]thiadiazol-2-yl)-amide, LC-MS, RT=2.5 min, M+1=566.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(3-methyl-butylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide, HCl salt, LC-MS, RT=1.9 min, M+1=468.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-butylamino-ethyl)-[1,3,4]thiadiazol-2-yl]-amide, HCl salt, LC-MS, RT=1.9 min, M+1=454.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(3,3-dimethyl-butylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide HCl salt, LC-MS, RT=2.2 min, M+1=482.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-cyclopropylamino-ethyl)-[1,3,4]thiadiazol-2-yl]-amide HCl salt, LC-MS, RT=1.7 min, M+1=437.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(4-methyl-piperazin-1-yl)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide formic acid salt, LC-MS, RT=1.7 min, M+1=481.0 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(4-chloro-benzylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide formic acid salt, LC-MS, RT=2.3 min, M+1=521.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid {5-[1-(3-chloro-benzylamino)-ethyl]-[1,3,4]thiadiazol-2-yl}-amide HCl salt, LC-MS, RT=2.2 min, M+1=521.9
EXAMPLE 10
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-N-[5-(3-hydroxy-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-butyramide
[0419] A mixture of 2-[2-(3,5-difluoro-phenyl)-acetylamino]-N-[5-(1,1-dimethyl-3-oxo-propyl)-[1,3,4]thiadiazol-2-yl)]-butyramide (100 mg) and sodium borohydride (40 mg) in methanol was stirred at rt for 5 min. The mixture was quenched with water, extracted with methylene chloride. The organic layer was separated, dried, filtered and concentrated to give 90 mg of the tilte compound that was purified by silica gel column chromatography using hexane/EtOAc=3/2 to EtOAc as eluent to give 80 mg of the title compound, LC-MS RT=2.1 min, M+1=426.9
[0420] The following examples were prepared by the method analogous to that described in Example 10 starting from an appropriate aldehyde or ketone with excess of sodium borohydride in methanol.
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(3-hydroxy-1,1-dimethyl-propyl)-[1,3,4]thiadiazol-2-yl]-amide, LC-MS RT=2.2 min, M+1=440.9 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1-hydroxy-ethyl)-[1,3,4]thiadiazol-2-yl]-amide LC-MS RT=1.9 min, M+1=398.9
EXAMPLE 11
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-morpholin-4-yl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide
[0423] A mixture of 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-oxo-ethyl)-[1,3,4]thiadiazol-2-yl]-amide (41 mg), morpholine (25 mg), acetic acid (0.02 ml) in methylene chloride (1 ml) was stirred at room temperature for 1 hr, and sodium triacetoxyborohydride (42 mg) was added. The mixture was stirred at room temperature for at least two days. The mixture was quenched with diluted NaOH and extracted with methylene chloride. The organic layer was separated, concentrated to dryness and the residue was purified by silica gel column chromatography using 35% to 65% ethyl acetate in hexane as eluent to give the title compound. The title compound was prepared as the corresponding HCl salt by adding HCl/doxane, followed by concentration to give a solid. LC_MS retention time 1.7 min M+1=497.0, M−1=495.0.
EXAMPLE 12
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-pyrrolidin-1-yl-ethyl)-[1,3,4]thiadiazol-2-yl]-amide
[0424] A mixture of 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [5-(1,1-dimethyl-2-oxo-ethyl)-[1,3,4]thiadiazol-2-yl]-amide (22 mg), pyrrolidine (0.02 ml), acetic acid (0.01 ml) in methylene chloride (1 ml) was stirred at room temperature for 1 hr, and sodium triacetoxyborohydride (28 mg) was added. The mixture was stirred at room temperature for at least two days. The mixture was quenched with diluted NaOH and extracted with methylene chloride. The organic layer was separated, concentrated to dryness and the residue was purified by silica gel column chromatography using 35% to 65% ethyl acetate in hexane as eluent to give the title compound. The title compound was prepared as the corresponding HCl salt by adding HCl/doxane, followed by concentration to give a solid. LC_MS retention time 2.0 min M+1=480.0.
Preparation A
1-(5-tert-Butyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butyl]-carbamic acid tert-butyl ester
[0425] A mixture of 2-tert-butoxycarbonylamino-pentanoic acid (5.432g, 25 mmol.), 5-tert-butyl-[1,3,4]thiadiazol-2-ylamine (3.925g, 25 mmol), HBOT (3.540g, 26.25 mmol), EDC HCl (5.73g, 30 mmol.) and triethylamine (14 ml) in methylene chloride was stirred at room temperature until product formation or disappearance of starting material. The mixture was quenched with water and extracted with methylene chloride. The organic layer was separated, washed with dilute HCl, brine, dried over sodium sulfate and the solvent was removed at reduced pressure to provide the title compound (9.2671 g), LC-MS M+1=357.2.
[0426] The following examples were prepared by the method analogous to that in Preparation A.
[1-(5-Methyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butyl]-carbamic acid tert-butyl ester, M+1=315.4, 1H NMR(CDCl3) d 6.6(d,1H,NH), 4.4(m,1H), 2.7(s,3H), 1.2-1.9(m,4H), 1.3(s,9H), 0.95(t,3H) ppm. [1-(5-Cyclopropyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butyl]-carbamic acid tert-butyl ester, M+1=341.3 [1-(5-Ethyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butyl]-carbamic acid tert-butyl ester, M+1=329.4, 1H NMR(CDCl3) d 7.0(s,1H,NH), 4.4(m,1H), 3.06(q,2H), 1.3-1.9(m,4H), 1.4(t,3H), 1.28(s,9H), 0.94(t,3H) ppm. [1-(5-tert-Butyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butyl]-carbamic acid tert-butyl ester, LC-MS M+1=357.2 {1-[5-(1,1-Dimethyl-butyl)-[1,3,4]thiadiazol-2-ylcarbamoyl]-butyl}-carbamic acid tert-butyl ester, LC-MS RT=2.9 min, M+1=385.5 {1-[5-(1,1-Dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-ylcarbamoyl]-butyl}-carbamic acid tert-butyl ester, LC-MS RT=2.8 min, M+1=383.4 {1-[5-(1,1-Dimethyl-but-3-enyl)-[1,3,4]thiadiazol-2-ylcarbamoyl]-propyl}-carbamic acid tert-butyl ester, LC-MS RT=2.6 min, M+1=369.4
Preparation B
2-Amino-pentanoic acid (5-tert-butyl-[1,3,4]thiadiazol-2-yl)-amide
[0434] A mixture of [1-(5-tert-butyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-butyl]-carbamic acid tert-butyl ester (8.9 g) in dioxane (60 ml) was treated with 4 N HCl in 1,4-dioxane (20 ml). The mixture was stirred at rt overnight, then concentrated to dryness and pumped in vacuo to give the title compounds as a white solid (7.0908g, 93%), APCI M+1=257.4
[0435] The following examples were prepared by the method analogous to that described in Preparation B.
2-Amino-pentanoic acid (5-methyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=215.3 2-Amino-pentanoic acid (5-ethyl-[1,3,4]thiadiazol-2-yl)-amide, M+1=229.3 2-Amino-pentanoic acid (5-cyclopropyl-[1,3,4]thiadiazol-2-yl)-amide, 1H NMR (CDCl3) d 4.15 (m,1H), 2.4(m,1H), 1.95(m,2H), 1.5(m,2H), 1.2-1.35(m,2H), 1.29(m,2H), 0.98(t,3H) ppm. 2-Amino-pentanoic acid [5-(1,1-dimethyl-butyl)-[1,3,4]thiadiazol-2-yl]-amide, 1H NMR (CDCl3) d 4.14 (m,1H), 1.95(m,2H), 1.7(m,2H), 1.5(m,2H), 1.45(s,6H), 1.25(m,2H), 1.01(t,3H), 0.89(t,3H) ppm.
[0440] Based on a reading of the present description and claims, certain modifications to the compounds, compositions and methods described herein will be apparent to one of ordinary skill in the art. The claims appended hereto are intended to encompass these modifications.
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The present invention relates to compounds of the Formula
wherein R 3 , R 5 , R 7 , U, X, Y and Z are as defined. Compounds of the Formula I have activity inhibiting production of Aβ-peptide. This invention also relates to pharmaceutical compositions and methods of treating diseases, for example, neurodegenerative diseases, e.g., Alzheimer's disease, in a mammal comprising compounds of the Formula I.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 12/851,940 filed on Aug. 6, 2010 which claims the benefit of U.S. Provisional Patent Application No. 61/232,882, filed on Aug. 11, 2009. The entire disclosures of the above applications are incorporated herein by reference.
FIELD
[0002] The present disclosure relates to a driveline for a motor vehicle having a system for disconnecting a hypoid ring gear from rotating at driveline speed. In particular, a power transfer device such as a power take-off unit or a transfer case includes a coupling for ceasing the transfer of torque from a power source to the hypoid ring gear of a secondary driveline while another disconnect selectively interrupts the flow of power from a vehicle wheel to the hypoid ring gear on the secondary driveline.
BACKGROUND
[0003] Typical power take-off units transfer power from a transaxle in receipt of torque from a vehicle power source. The power take-off unit transfers power to a propeller shaft through a gear arrangement that typically includes a hypoid cross-axis gearset. Other gear arrangements such as parallel axis gears may be provided within the power take-off unit to provide additional torque reduction.
[0004] Power take-off units have traditionally been connected to the transaxle output differential. Accordingly, at least some of the components of the power take-off unit rotate at the transaxle differential output speed. Power losses occur through the hypoid gear churning through a lubricating fluid. Efficiency losses due to bearing preload and gear mesh conditions are also incurred while the components of the power take-off unit are rotated.
[0005] Similar energy losses occur when other driveline components are rotated. For example, many rear driven axles include hypoid gearsets having a ring gear at least partially immersed in a lubricating fluid. In at least some full-time all-wheel drive configurations, the rear drive axle hypoid gearset continuously rotates during all modes of operation and transmits a certain level of torque. In other applications, the rear axle hypoid gearset still rotates but without the transmission of torque whenever the vehicle is moving. In other configurations, a transfer case selectively transfers power to a front drive axle equipped with a front drive axle hypoid gearset. Regardless of the particular configuration, churning and parasitic losses convert energy that could have been transferred to the wheels into heat energy that is not beneficially captured by the vehicle. As such, an opportunity may exist to provide a more energy efficient vehicle driveline.
SUMMARY
[0006] A vehicle drive train includes a first driveline being adapted to transfer torque to a first set of wheels and includes a first power disconnection device, A second driveline is adapted to transfer torque to a second set of wheels and includes a differential gearset having an output coupled to a second power disconnection device. A hypoid gearset is positioned within the second driveline in a power path between the first and second power disconnection devices. The second power disconnection device includes an active multi-plate clutch having a first set of clutch plates fixed for rotation with the differential gearset output. The clutch further includes a second set of clutch plates fixed for rotation with an output shaft adapted to transfer torque to one of the wheels of the second set of wheels. A valve is operable to limit a flow of coolant to the multi-plate clutch when the second power disconnection device operates in the disconnected mode.
[0007] In another form, a vehicle drive train includes a first driveline adapted to transfer torque from a power source to a first set of wheels and includes a power take-off unit. A second driveline includes a hypoid gearset in receipt of torque from the first driveline. The power take-off unit includes a first power disconnection device selectively ceasing the transfer of torque to the hypoid gearset. The second driveline transfers torque to a second set of wheels and includes a second power disconnection device selectively interrupting a transfer of torque from the second set of wheels to the hypoid gearset. The second power disconnection device includes a multi-plate clutch controlled by a ball ramp actuator selectively providing a first rate of axial apply plate travel per degree of rotation and a second lesser rate of axial apply plate travel per degree of rotation.
[0008] Further areas of applicability will become apparent from the description provided herein. It should be understood that the description and specific examples are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.
DRAWINGS
[0009] The drawings described herein are for illustration purposes only and are not intended to limit the scope of the present disclosure in any way.
[0010] FIG. 1 is a schematic of an exemplary vehicle equipped with a vehicle drive train of the present disclosure;
[0011] FIG. 2 is a fragmentary cross-sectional view of a rear drive axle including a disconnect coupling;
[0012] FIG. 3 is a fragmentary cross-sectional view of a ball ramp actuation mechanism;
[0013] FIG. 4 is a fragmentary sectional view of another portion of the ball ramp mechanism;
[0014] FIG. 5 is a partial fragmentary cross-sectional view of a rear drive axle having a clutch lubrication flow valve; and
[0015] FIG. 6 is a fragmentary cross-sectional view of the axle and the clutch lubrication flow valve having a flow reducer in a position to restrict fluid flow.
DETAILED DESCRIPTION
[0016] The following description is merely exemplary in nature and is not intended to limit the present disclosure, application, or uses. It should be understood that throughout the drawings, corresponding reference numerals indicate like or corresponding parts and features.
[0017] In general, the present disclosure relates to a coupling and hypoid disconnect system for a driveline of a motor vehicle. A power take-off unit may be equipped with an active coupling or a dog clutch/synchronizer to disconnect the power source from a portion of the driveline and to reconnect through synchronization of said driveline. Additionally, another active coupling may be provided to disconnect a portion of the driveline from the vehicle wheels. The hypoid gearing of the vehicle driveline may be separated from the driving source of power to reduce churning losses and other mechanical inefficiencies.
[0018] With particular reference to FIG. 1 of the drawings, a drive train 10 of a four-wheel drive vehicle is shown. Drive train 10 includes a front driveline 12 and a rear driveline 14 both drivable from a source of power, such as an engine 16 through a transmission 18 which may be of either the manual or automatic type. In the particular embodiment shown, drive train 10 is a four-wheel system incorporating a power transmission device 20 for transmitting drive torque from engine 16 and transmission 18 to front driveline 12 and rear driveline 14 . Power transmission device 20 is shown as a power take-off unit.
[0019] Front driveline 12 is shown to include a pair of front wheels 24 individually driven by a first axle shaft 26 and a second axle shaft 28 . Front driveline 12 also includes a reduction speed gearset 30 and a differential assembly 32 . Power transmission device 20 includes a clutch 34 and a right-angled drive assembly 36 . Clutch 34 may be configured as a dog clutch, a synchronized clutch, a roller clutch, a multi-plate clutch, or another torque transferring disconnection mechanism. If speed synchronization may be accomplished between the rotating members to be connected, a simple dog clutch may suffice. However, under certain conditions, the reconnection of a previously disconnected driveline may become more challenging due to rotational speed differences across the power disconnection device. For example, front wheel slip may occur that will result in the front driveline speed being greater than the rotational speed of rear driveline components being driven by the rear wheels. In this case, a speed differential will be realized across the power disconnection device making it difficult or impossible for a dog clutch to be actuated from a non-torque transferring mode to a torque transferring mode. Accordingly, a roller clutch or synchronizer may be implemented at any of the locations depicted as a dog clutch or similar power disconnection device. By implementing the roller clutch or synchronizer, a controller may initiate reconnection and torque transfer once a specified range of speed difference between the two members being connected is met. This control arrangement may result in improved system performance including a reduction in the time required to operate the vehicle in one of the drive modes.
[0020] Rear driveline 14 includes a propeller shaft 38 connected at a first end to right-angled drive assembly 36 and at an opposite end to a rear axle assembly 40 . Rear driveline 14 also includes a pair of rear wheels 42 individually driven by a first rear axle shaft 44 and a second rear axle shaft 46 . Rear axle assembly 40 also includes a hypoid ring and pinion gearset 48 driving a differential assembly 50 . A disconnect coupling 52 may selectively drivingly connect and disconnect second rear axle shaft 46 from ring and pinion gearset 48 and differential assembly 50 .
[0021] FIG. 2-4 depict portions of rear axle assembly 40 . A housing 60 rotatably supports a pinion shaft 62 of ring and pinion gearset 48 via bearings 64 , 66 . A pinion gear 68 is integrally formed with pinion shaft 62 . Ring and pinion gearset 48 also includes a ring gear 70 in meshed engagement with pinion gear 68 and fixed for rotation with a carrier 72 . Carrier 72 is rotatably supported within housing 60 by bearings 74 . Differential assembly 50 includes a pair of pinion gears 76 supported on a cross pin 78 fixed to carrier 72 . First and second side gears 80 , 82 are in meshed engagement with pinion gears 76 . Second side gear 82 is fixed for rotation with a stub shaft 84 . Bearing 74 rotatably supports stub shaft 84 within housing 60 . Seals 86 engage stub shaft 84 and separate a cavity 88 containing disconnect coupling 52 from a cavity 89 containing differential assembly 50 .
[0022] Disconnect coupling 52 includes a drum 90 fixed for rotation with stub shaft 84 . A driven spindle 94 is rotatably supported within a removable portion 96 of housing 60 by bearings 98 . A hub 100 is fixed for rotation with driven spindle 94 via a splined connection 102 . Disconnect coupling 52 also includes a plurality of outer friction plates 104 fixed for rotation with and axially moveable relative to drum 90 as well as a plurality of inner friction plates 106 fixed for rotation with and being axially moveable relative to hub 100 . Outer friction plates 104 are interleaved with inner friction plates 106 .
[0023] A clutch actuator 110 is operable to selectively apply a force to an actuator plate 112 for compressing outer clutch plates 104 and inner clutch plates 106 to transfer torque between stub shaft 84 and driven spindle 94 . A spring 113 is positioned to engage hub 100 and actuator plate 112 to urge actuator plate 112 away from clutch plates 104 , 106 . Actuator 110 includes an electric motor 114 driving a ball ramp mechanism 115 via a worm gear 116 and sector gear 117 . Ball ramp mechanism 115 includes a first cam plate 118 spaced apart from a second cam plate 120 . First cam plate 118 includes a plurality of tapered grooves 122 . Second cam plate 120 includes a corresponding pair of tapered grooves 124 that are circumferentially spaced apart from one another and positioned to oppose first grooves 122 . Balls 126 are positioned within pairs of tapered grooves 122 , 124 . Relative rotation between first cam plate 118 and second cam plate 120 causes second cam plate 120 to translate and axially move actuator plate 112 .
[0024] As shown in FIG. 4 , first tapered grooves 122 include a relatively steep ramp angle portion 128 adjacent to a relatively shallow ramp angle portion 130 . Second grooves 124 also include corresponding steep and shallow ramp angle portions 132 and 134 , respectively. To reduce frictional losses across disconnect coupling 52 when the coupling is operated in an open or disconnected mode, it may be advantageous to space outer friction plates 104 from inner friction plates 106 a maximum distance from one another. The shape and depth of first grooves 122 and second grooves 124 acting with spring 113 may accomplish this task. However, a relatively large distance needs to be traversed when torque transfer across disconnect coupling 52 is desired. The steep ramp angle portions 128 , 132 function to accomplish this goal by axially translating second cam plate 120 a relatively large amount based on a relatively small amount of relative rotation between first cam plate 118 and second cam plate 120 . Once most of the clearance between outer clutch plates 104 , inner clutch plates 106 and actuator plate 112 has been removed, balls 126 act on the relatively shallow ramp angle portions 130 , 134 to apply an amplified force and control the torque generated by disconnect coupling 52 .
[0025] Clutch actuator 110 may alternatively include a hydraulic motor, or some other source of energy to cause relative rotation between first cam plate 118 and second cam plate 120 . Furthermore, it should be appreciated that ball ramp mechanism 115 may be replaced by a hydraulic actuation system with similar behavior. In a first step, a piston in the hydraulic system travels quickly with a small available force. In a second step, the piston travels slowly, but with a high possible actuation force. An exemplary system is described within U.S. Patent Application Publication No. 2009/038908 which is hereby incorporated by reference.
[0026] During vehicle operation, it may be advantageous to reduce the churning losses associated with driving ring and pinion gearset 48 and right-angled drive assembly 36 . A controller 140 is in communication with a variety of vehicle sensors 142 providing data indicative of parameters such as vehicle speed, four-wheel drive mode, wheel slip, vehicle acceleration and the like. At the appropriate time, controller 140 outputs a signal to control clutch 34 and place it in a deactuated mode where torque is not transferred from engine 16 to rear driveline 14 . Controller 140 also signals clutch actuator 110 associated with disconnect coupling 52 such that energy associated with rotating rear wheels 42 will not be transferred to ring and pinion gearset 48 or differential assembly 50 . Accordingly, the hypoid gearsets do not rotate at the rotational output speed of differential assembly 32 , nor do they rotate at the rotational speed of rear wheels 42 . The hypoid gearsets are disconnected from all sources of power and are not driven at all.
[0027] It is contemplated that any one or more of the previously described clutches including interleaved inner and outer clutch plates may be either a wet clutch or a dry clutch. Wet clutches are lubricated and cooled with a fluid that may be pumped or sloshed across the friction surfaces of the inner and outer clutch plates. The wet clutches provide excellent torque transfer characteristics and operate in a sealed environment containing the lubricant. A pump (not shown) may provide pressurized fluid to cool the wet clutch. Alternatively, the fluid acting on the clutch plates may be the same fluid used to lubricate members of the gear train including the ring and pinion gears.
[0028] When a wet plate clutch is used as a disconnect device and active all wheel drive coupling, viscous drag torque losses are associated with the plates of the wet clutch shearing through the fluid in contact with the plates. To reduce the drag losses within the wet clutch, the inner and outer plates may be axially spaced apart from one another a relatively large distance, as previously discussed. To further reduce the fluid shearing losses, actuator 110 may include a valve 150 associated with a clutch lubrication pickup tube 152 . Lubrication pickup tube 152 is stationary within housing 60 and may be fixed to first cam plate 118 . Valve 150 functions to control lubricant flow in the vicinity of outer clutch plates 104 and inner clutch plates 106 . When disconnect coupling 52 is in a torque transferring mode, a substantial flow of lubricant is allowed. When disconnect coupling 52 is in the open or disconnected mode, valve 150 functions to restrict or discontinue the flow of lubricant to the friction plates 104 , 106 . With the lubricant flow restricted or stopped, fluid previously positioned between outer clutch plates 104 and inner clutch plates 106 will drain such that the shearing losses will be further reduced. More particularly, and as shown in FIGS. 5 and 6 , it is contemplated that valve 150 includes a flow reducer 154 fixed to second cam plate 120 . Flow reducer 154 is shown rotated out of a flow restricting position in FIG. 5 . FIG. 6 depicts flow reducer 154 blocking at least a portion of pickup tube 152 . The angular orientation of second cam plate 120 determines the position of flow reducer 154 .
[0029] By positioning actuator 110 within housing 60 as previously discussed, the forces generated by disconnect coupling 52 and its associated actuator 110 are retained and reacted in housing portion 96 thus minimizing any losses across support bearings 74 or 98 , thereby improving system control and accuracy. Furthermore, the actuation forces related to operating disconnect coupling 52 are not influenced by forces generated by ring and pinion gearset 48 or differential assembly 50 , thus improving control accuracy and reducing drag losses.
[0030] It should be appreciated that the concepts previously discussed regarding the operation and location of multiple disconnects in relation to a transverse oriented engine and transmission as depicted in FIG. 1 may also be applied to a longitudinal engine arrangement. While a number of vehicle drivelines have been previously described, it should be appreciated that the particular configurations discussed are merely exemplary. As such, it is contemplated that other combinations of the components shown in the Figures may be arranged with one another to construct a drive train not explicitly shown but within the scope of the present disclosure.
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A vehicle drive train includes a first power disconnection device and a first driveline for transferring torque to a first set of wheels. A second driveline for transferring torque to a second set of wheels includes a differential gearset having an output coupled to a second power disconnection device. A hypoid gearset is positioned within the second driveline in a power path between the first and second power disconnection devices. The second power disconnection device includes a clutch having a first set of clutch plates fixed for rotation with the differential gearset output. The clutch further includes a second set of clutch plates fixed for rotation with a shaft adapted to transfer torque to one of the wheels of the second set of wheels. A valve limits a flow of coolant to the clutch when the second power disconnection device operates in a disconnected mode.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention generally relates to a digital-audio-signal coding device, a digital-audio-signal coding method and a medium in which a digital-audio-signal coding program is stored, and, in particular, to compressing/coding of a digital audio signal used for a DVD, digital broadcast and so forth.
2. Description of the Related Art
In the related art, a human psychoacoustic characteristic is used in high-quality compression/coding of a digital audio signal. This characteristic is such that a small sound is inaudible as a result of being masked by a large sound. That is, when a large sound develops at a certain frequency, small sounds at vicinity frequencies are inaudible by the human ear as a result of being masked. The limit of a sound pressure level below which any signal is inaudible due to masking is called a masking threshold. Further, regardless of masking, the human ear is most sensitive to sounds having frequencies in vicinity of 4 kHz, and the sensitivity decreases as the frequency of the sound moves further away from 4 kHz. This feature is expressed by the limit of a sound pressure level at which the sound is audible in an otherwise quiet environment, and this limit is called an absolute hearing threshold.
Such matters will now be described in accordance with FIG. 1 which shows an intensity distribution of an audio signal. The thick solid line (A) represents the intensity distribution of the audio signal. The broken line (B) represents the masking threshold for the audio signal. The thin solid line (C) represents the absolute hearing threshold. As shown in the figure, for the human ear, only the sounds having the sound pressure levels higher than the respective masking levels for the audio signal and also higher than the absolute hearing level are audible by the human ear. Accordingly, even when only the information from the portions in which the sound pressure levels are higher than the respective masking levels for the audio signal and also higher than the absolute hearing level is extracted from the intensity distribution of the audio signal, the thus-obtained signal can be sensed as being the same as the original audio signal, acoustically.
This is equivalent to allocation of coding bits only to the hatched portions in FIG. 1 in coding of the audio signal. This bit allocation is performed in units of scalefactor bands (D) which are obtained as a result of the entire band of the audio signal being divided. The lateral width of each hatched portion corresponds to the respective scalefactor-band width.
In each scalefactor band, the sounds having the intensities lower than the lower limit of the respective hatched portion are inaudible using the human ear. Accordingly, as long as the error in intensity between the original signal and the coded and decoded signal does not exceed this lower limit, the difference therebetween cannot be sensed by the human ear. In this sense, the lower limit of a sound pressure level for each scalefactor band is called an allowable distortion level. When quantizing and compressing an audio signal, it is possible to compress the audio signal without degrading the sound quality of the original sound as a result of performing quantization in such a way that the quantization-error intensity of the coded and decoded sound with respect to the original sound does not exceed the allowable distortion level for each scalefactor band. Therefore, allocating coding bits only to the hatched portions is equivalent to quantizing the original audio signal in such a manner that the quantization-error intensity in each scalefactor band is just equal to the allowable distortion level.
Of such a method of coding an audio signal, MPEG (Moving Picture Experts Group) Audio, Dolby Digital and so forth are known. In any method, the feature described above is used. Among them, the method of MPEG-2 Audio AAC (Advanced Audio Coding) standardized in ISO/IEC 13818-7: 1997(E), ‘Information technology—Generic coding of moving pictures and associated audio information—, Part 7: Advanced Audio Coding (AAC)’ (simply referred to as ISO/IEC 13818-7, hereinafter) is presently said to have the highest coding efficiency. The entire contents of ISO/IEC 13818-7 are hereby incorporated by reference.
FIG. 2 is a block diagram showing a basic arrangement of an AAC (Advanced Audio Coding) encoder. An audio signal input to the AAC encoder is a sequence of blocks of samples which are produced along the time axis such that adjacent blocks overlap with one another. (The frequency with which the samples of sound are taken, which samples constitute the digital audio signal, is called ‘sampling frequency of the digital audio signal’.) Each block of the audio signal is transformed into a number of spectral scalefactor-band components via a filter bank 73 . A psychoacoustic model 71 calculates an allowable distortion level for each scalefactor-band component of the audio signal. A gain control 72 and the filter bank 73 map the blocks of the audio signal into the frequency domain through MDCT (Modified Discrete Cosine Transform). A TNS (Temporal Noise Shaping) 74 and a predictor 76 perform predictive coding. An intensity/coupling 75 and an MS stereo (Middle Side Stereo) (abbreviated as M/S, hereinafter) 77 perform stereophonic correlation coding. Then, scalefactors are determined by a scalefactor module 78 , and a quantizer 79 quantizes the audio signal based on the scalefactors. The scalefactors correspond to the allowable distortion level shown in FIG. 1, and are determined for the respective scalefactor bands. After the quantization, based on a predetermined Huffman-code table, a noiseless coding module 80 provides Huffman codes for the scalefactors and for the quantized values, and performs noiseless coding. Finally, a multiplexer 81 forms a code bitstream.
MDCT performed by the filterbank 73 is such that DCT is performed on the audio signal in such a way that adjacent transformation ranges are overlapped by 50% along the time axis, as shown in FIG. 3 . Thereby, distortion developing at a boundary portion between adjacent transformation ranges can be suppressed. Further, the number of MDCT coefficients generated is half the number of samples included in the transformation range. In AAC, either a long transformation range (defined by a long window) or short transformation ranges (each defined by a short window) is/are used for mapping the audio signal into the frequency domain. The portion of each block of the input audio signal defined by the long window is called a long block, and the portion of each block of the input audio signal defined by the short window is called a short block, wherein the long block includes 2048 samples and the short block includes 256 samples. In MDCT, defining long blocks from an audio signal, each for a first predetermined number of samples (2048 samples, in the above-mentioned example, as shown in FIG. 4) with a long window, for performing MDCT on the audio signal using the thus-defined long blocks for mapping the audio signal into the frequency domain will be referred to as ‘using the long block type’, and defining short blocks from an audio signal, each for a second predetermined number (smaller than the first predetermined number) of samples (256 samples, in the above-mentioned example, as shown in FIG. 5) with a short window, for performing MDCT on the audio signal using thus-defined short blocks for mapping the audio signal into the frequency domain will be referred to as ‘using the short block type’, hereinafter. The number of MDCT coefficients generated from the long block is 1024, and the number of MDCT coefficients generated from each short block is 128. When the short block type is used, 8 short blocks are defined successively at any time (as shown in FIG. 5 ). Thereby, the number of MDCT coefficients generated is the same when using the short block type and using the long block type.
Generally, for a steady portion in which variation in signal waveform is a little as shown in FIG. 4, the long block type is used. For an attack portion in which variation in signal waveform is violent as shown in FIG. 5, the short block type is used. Which thereof is used is important. When the long block type is used for a signal such as that shown in FIG. 5, noise called pre-echo develops preceding an attack portion. When the short block type is used for a signal such as that shown in FIG. 4, suitable bit allocation is not performed due to lack of resolution in the frequency domain, the coding efficiency decreases, and noise develops, too. Such drawbacks are remarkable especially for a low-frequency sound.
When the short block type is used, grouping is performed. The grouping is to group the above-mentioned 8 successive short blocks into groups, each group including one or a plurality of successive blocks, the scalefactor for which is the same. By treating a plurality of blocks, for which the scalefactor is common, as those included in one group, it is possible to improve the information amount reducing effect. Specifically, when the Huffman codes are allocated to the scalefactors in the noiseless coding module 80 shown in FIG. 2, allocation is performed not in short-block units but in the group unit. FIG. 6 shows an example of grouping. In the case of FIG. 6, the number of groups is 3, the 0-th group includes 5 blocks, the 1-th group includes 1 block, and the 2-th group includes 2 blocks. When grouping is not performed appropriately, increase in the number of codes and/or degradation of the sound quality occur. When the number of groups is too large with respect to the number of blocks, the scalefactors which otherwise can be coded in common will be coded repeatedly, and, thereby, the coding efficiency decreases. When the number of groups is too small with respect to the number of blocks, common scalefactors are used even when variation of the audio signal is violent. As a result, the sound quality is degraded. In ISO/IEC13818-7, with regard to grouping, although rules for syntax of codes are included, no specific standards/methods for grouping are included.
As described above, when coding is performed, the long block type and short block type are appropriately used for an input audio signal. Deciding whether the long or short block type is used is performed by the psychoacoustic model 71 in FIG. 2 . ISO/IEC 13818-7 includes an example of a method for making a decision as to whether the long or short block type is used for each target block. This deciding processing will now be described in general.
Step 1: Reconstruction of an Audio Signal
1024 samples for a long block (128 samples for a short block) are newly read, and, together with 1024 samples (128 samples) already read for the preceding block, a series of signals having 2048 samples (256 samples) is reconstructed.
Step 2: Windowing by Hann Window and FFT
The 2048 samples (256 samples) of audio signal reconstructed in the step 1 is windowed by a Hann window, FFT (Fast Fourier Transform) is performed on the signal, and 1024(128) FFT coefficients are calculated.
Step 3: Calculation of Predicted Values for FFT Coefficient
From the real parts and imaginary parts of the FFT coefficients for the preceding two blocks, the real parts and imaginary parts of the FFT coefficients for the target block are predicted, and 1024 (128) predicted values are calculated for each of them.
Step 4: Calculation of Unpredictability
From the real parts and imaginary parts of the FFT coefficients calculated in the step 2 and the predicted values for the real parts and imaginary part of the FFT coefficients calculated in the step 3, unpredictability is calculated for each of them. Unpredictability has a value in the range of 0 to 1. When unpredictability is close to 0, this indicates that the tonality of the signal is high. When unpredictability is close to 1, this indicates that the tonality of the signal is low.
Step 5: Calculation of the Intensity of the Audio Signal and Unpredictability for Each Scalefactor Band
The scalefactor bands are ones corresponding to those shown in FIG. 1 . For each scalefactor band, the intensity of the audio signal is calculated based on the respective FFT coefficients calculated in the step 2. Then, the unpredictability calculated in the step 4 is weighted with the intensity, and the unpredictability is calculated for each scalefactor band.
Step 6: Convolution of the Intensity and Unpredictability with Spreading Function
Influences of the intensities and unpredictabilities in the other scalefactor bands for each scalefactor band are obtained using the spreading function, and they are convolved, and are normalized, respectively.
Step 7: Calculation of Tonality Index
For each scalefactor band b, based on the convolved unpredictability (cb(b)) calculated in the step 6, the tonality index tb(b) (=−0.299-0.43 log e (cb(b)) is calculated. Further, the tonality index is limited to the range of 0 to 1. The tonality index indicates a degree of tonality of the audio signal. When the index is close to 1, this means that the tonality of the audio signal is high. When the index is close to 0, this means that the tonality of the audio signal is low.
Step 8: Calculation of S/N Ratio
For each scalefactor band, based on the tonality index calculated in the step 7, an S/N ratio is calculated. Here, a property that the masking effect is larger for low-tonality signal components than for high-tonality signal components is used.
Step 9: Calculation of Intensity Ratio
For each scalefactor band, based on the S/N ratio calculated in the step 8, the ratio between the convolved audio signal intensity and masking threshold is calculated.
Step 10: Calculation of Allowable Distortion Level
For each scalefactor band, based on the audio signal intensity calculated in the step 6, and the ratio between the audio signal intensity and masking threshold calculated in the step 9, the masking threshold is calculated.
Step 11: Consideration of Pre-echo Adjustment and Absolute Hearing Threshold
Pre-echo adjustment is performed on the masking threshold calculated in the step 10 using the allowable distortion level of the preceding block. Then, the larger one between the thus-obtained adjusted value and the absolute hearing threshold is used as the allowable distortion level of the currently processed block.
Step 12: Calculation of Perceptual Entropy (PE)
For each block type, that is, for the long block type and for the short block type, a perceptual entropy (PE) defined by the following equation is calculated: PE = - ∑ b w ( b ) · log 10 nb ( b ) e ( b ) + 1
In the above equation, w(b) represents the width of the scalefactor band b, nb(b) represents the allowable distortion level in the scalefactor band b calculated in the step 11, and e(b) represents the audio signal intensity in the scalefactor band b calculated in the step 5. It can be considered that PE corresponds to the sum total of the areas of the bit allocation ranges (hatched portions) shown in FIG. 1 .
Step 13: Decision of Long/Short Block Type (see a flow chart shown in FIG. 7 for decision as to whether the long or short block type is used).
When the value of PE (obtained in a step S 10 in FIG. 7) calculated for the long block type in the step 12 is larger than a predetermined constant (switch_pe), the short block type is used for the target block (in steps S 11 and S 12 , in FIG. 7 ). When the value of PE calculated for the long block type in the step 12 is not larger than the predetermined constant (switch_pe), the long block type is used for the target block (in steps S 11 and S 13 , in FIG. 7 ). The constant, switch_pe, is determined depending on the application.
The above-described method is the method for decision as to whether the long or short block type is used, described in ISO/IEC13818-7. However, in this method, an appropriate decision is not always reached. That is, the long block type is selected to be used even in a case where the short block type should be selected, or, the short block type is selected to be used even in a case where the long block type should be selected. As a result, the sound quality may be degraded.
Japanese Laid-Open Patent Application No. 9-232964 discloses a method in which an input signal is taken at every predetermined section, the sum of squares is obtained for each section, and a transitional condition is detected from the degree of change in the signal of the sum of squares between at least two sections. Thereby, it is possible to detect the transient condition, that is, to detect when a block type to be used is changed between the long and short block types, merely as a result of calculating the sum of squares of the input signal on the time axis without performing orthogonal transformation processing or filtering processing. However, this method uses only the sum of squares of an input signal but does not consider the perceptual entropy. Therefore, a decision not necessarily suitable for the acoustic property may be made, and the sound quality may be degraded.
A method will now be described. In the method, the short blocks of a block of an input audio signal are grouped in a manner such that the difference between the maximum value and minimum value in perceptual entropy of the short blocks in the same group is smaller than a threshold. Then, when the result thereof is such that the number of groups is 1, or this condition and another condition are satisfied, the block of the input audio signal is mapped into the frequency domain using the long block type. In the other cases, the block of the input audio signal is mapped into the frequency domain using the short block type. This method is performed by an arrangement shown in FIG. 8 B. An entropy calculating portion 31 calculates the perceptual entropy for each short block. A grouping portion 32 groups ones of the short blocks. A difference calculating portion 33 calculates the difference between the maximum value and minimum value in perceptual entropy of the short blocks included in the thus-obtained group. A grouping determining portion determines, based on the thus-obtained difference, whether the grouping is allowed. A long/short-block-type deciding portion 35 decides to use the long or short block when the number of the thus-allowed groups is 1.
This method will now be described in detail in accordance with FIG. 8A showing an operation flow of this method. As an example of an input audio signal, audio data shown in FIG. 9 is used. In FIG. 9, corresponding consecutive numbers are given to 8 successive short blocks. The perceptual entropy PE(i) of the audio data shown in FIG. 9 for each short block i is shown in FIG. 10 .
First, 8 short blocks are obtained from a block of an input audio signal, as shown in FIG. 9 . Then, for the 8 short blocks, the perceptual entropies are calculated, respectively, and are represented by PE(i) (0≦i≦7), in sequence, in a step S 20 . This calculation can be achieved as a result of the method described in the steps 1 through 12 of the method for deciding as to whether the long or short block type is used for each target block in ISO/IEC13818-7 described above being performed on each short block. Then, initializing is performed such that group_len[ 0 ]=1, and group_len[gnum]=0 (0≦gnum≦7) in a step S 21 , wherein gnum represents a respective one of consecutive numbers of groups resulting from grouping, and group_len[gnum] represents the number of the short blocks included in the gnum-th group. Then, initializing is performed such that gnum=0, min=PE( 0 ) and max=PE( 0 ), in a step S 22 . These min and max represent the minimum value and the maximum value of PE(i), respectively. Then, the index i is initialized so that i=1, in a step S 23 . This index corresponds to a respective one of the consecutive numbers of the short blocks.
Then, min and max are updated with PE(i). That is, when PE(i)<min, min=PE(i), and when PE(i)> max, max=PE(i), in a step S 24 . Then, a decision is made as to grouping, in a step S 25 . That is, the difference, max−min, is obtained, is compared with a predetermined threshold th, and, when the difference is equal to or larger than the threshold th, the operation proceeds to a step S 26 so that the short blocks i−1 and i are included in different groups. When the difference is smaller than the threshold th, a decision is made such that the short blocks i−1 and i are included in the same group, and the operation proceeds to a step S 27 . In this example, it is assumed that th=50. That is, grouping is performed such that the difference between the maximum value and minimum value of PE(i) becomes smaller than 50. A decision is made such that the short blocks 0 and 1 are included in the same group, and the operation proceeds to the step S 27 . Because gnum=0 in this time, the short blocks 0 and 1 are included in the 0-th group. Then, the value of group_len[gnum] is incremented by 1 in a step S 28 . This means that the number of short blocks included in the gnum-th group is increased by 1. In this example, because initializing is performed such that gnum=0 and group_len[ 0 ]=1 in the steps S 21 and S 22 , group_len [ 0 ]=2 in the step S 27 . This corresponds to the matter that the two blocks, block 0 and block 1 , are already fixed as the short blocks included in the 0-th group.
Then, the index i is incremented by 1 in a step S 28 . Then, when i is smaller than 7, the operation returns to the step S 24 , in a step S 29 .
Then, operations similar to those described above are repeated until i=4. When i=4, in the example shown in FIGS. 9 and 10, min=96 and max=137 in the step S 24 . Then, in the step S 25 , max−min=41<50=th. As a result, the operation proceeds to the step 27 from the step 25 . Then, in the step S 27 , group_len[ 0 ]=5. This corresponds to the matter that the five blocks, blocks 0 , 1 , 2 , 3 and 4 , are fixed as the short blocks included in the 0 -th group. Then, after i=5 in the step S 28 , the operation again returns to the step S 24 through the step S 29 . Then, because PE( 5 )=152 at this time, min=96 and max=152. Then, in the step S 25 , max−min=56>50=th, in the step S 25 . As a result, the operation proceeds to the step S 26 . This means that the short blocks 4 and 5 are included in different groups. In the step S 26 , the value of gnum is incremented by 1, and each of min and max is replaced by the latest PE(i). Here, gnum=1, min=152 and max=152. The matter that gnum=1 corresponds to the matter that the group includes the short block 5 is the 1-th group.
Then, in the step S 27 , group_len[ 1 ] is incremented by 1. Because the group_len[ 1 ] is initialized to be 0 in the step S 21 , again group_len[ 1 ]=1, here. This corresponds to the matter that one block, the block 5 is fixed as the short block included in the 1-th group.
Then, similarly, i=6 in the step S 28 in FIG. 8A, and the operation returns to the step S 24 from the step S 29 . Then, at this time, because PE( 6 )=269, min=152 and max=269. Then, in the step S 25 , max−min=117>50=th, and, as a result, the operation proceeds to the step S 26 . That is, the short blocks 5 and 6 are included in different groups. Then, in the step s 26 , gnum=2, min=269 and max=269. Then, in the step S 27 , group_len[ 2 ]=1. Then, in the step S 28 , i=7. Then, similarly to the above, because PE( 7 )=231 in the step S 24 , min=231 and max=269. Then, in the step S 25 , max−min=38<50=th. As a result, the operation proceeds to the step S 27 . That is, both the short blocks 6 and 7 are included in the 2-th group. Correspondingly thereto, group_len[ 2 ]=2 in the step S 27 . Then, in the next step S 28 , i=8. Then, in the step S 29 , the operation is decided to proceed to the step S 30 . Thus, grouping is completed for all the 8 short blocks.
In this example, in the end, gnum=2, group_len[ 0 ]=5, group_len[ 1 ]=1 and group_len[ 2 ]=2. That is, the number of groups is 3, the 0-th group includes 5 short blocks, the 1-th group includes one short block and the 2-th group includes two short blocks.
How to decide, from the number of groups as the result of grouping, whether the long or short block type is used will now be described. In the step S 30 , it is determined whether or not the value of gnum is 0. When the value of gnum is 0, the number of groups is 1. When the value of gnum is not 0, the number of groups is equal to or larger than 2. Therefore, when gnum=0, the operation proceeds to a step 31 , and it is decided to perform MDCT on the block of the input audio signal using the long block type, that is, a single long block is obtained from the block of the input audio signal for performing MDCT on-the input audio signal. When gnum≠0, the operation proceeds to a step 32 , and it is decided to perform MDCT on the block of the input audio signal using the short block type, that is, 8 short blocks are obtained from the block of the input audio signal for performing MDCT on the input audio signal.
However, also in this method, there is a case where an appropriate decision as to whether the long or short block type is used cannot be performed. This case is a case where audio data including low frequency components having high tonalities is coded. MDCT using the short block type results in increase in the resolution in the time domain, but decrease in the resolution in the frequency domain. Further, the human ear has a masking property such that the resolution is high in a low-frequency range, and, in particular, only a very narrow frequency-band component is masked in audio data having high tonality. When audio data including low frequency components having high tonalities is mapped into the frequency domain using the short block type, due to decrease to the resolution in the frequency domain when the short block type is used, the energy of the original audio data is dispersed in surrounding frequency bands. Then, when the energy thus spreads to the outside of the masking range in low-frequency components of the human ear, the human ear senses degradation in the sound quality. This indicates that decision as to whether the long or short block type is used based only on the perceptual entropies of the short blocks is not sufficient, and, it is necessary to consider to further combine tonality of audio data and the frequency-dependency of the masking property.
SUMMARY OF THE INVENTION
The present invention has been devised for solving these problems, and, an object of the present invention is to provide, with the tonality of an input audio data and frequency dependency of masking property of the human ear in mind, conditions for enabling an appropriate decision as to whether the long or short block type is used without resulting in degradation in the sound quality, and to provide a digital-audio-signal coding device, a digital-audio-signal coding method and a medium in which a digital-audio-signal coding program is stored, in which it is possible to make a decision as to whether the long or short block type is used appropriately depending on the sampling frequency of input audio data.
In order to achieve the above-mentioned objects, a device for coding a digital audio signal according to the present invention comprises:
a converting portion which converts each of blocks of an input digital audio signal into a number of frequency-band components, the blocks being produced from the signal along a time axis;
a bit-allocating portion which allocates coding bits to each frequency band;
a scalefactor determining portion which determines a scalefactor in accordance with the number of the coding bits thus allocated; and
a quantizing portion which quantizes the digital audio signal using the thus-determined scalefactors,
wherein:
the converting portion comprises a block-type deciding portion which makes a decision as to whether a long or short block type is used for mapping the input digital audio signal into the frequency domain;
the block-type deciding portion comprises:
a tonality-index calculating portion which calculates a tonality index of the digital audio signal in each of a predetermined one or plurality of frequency bands of the number of frequency bands;
a comparing portion which compares each of the thus-calculated tonality indexes with a predetermined one or plurality of thresholds; and
a deciding portion which makes a decision as to whether the long or short block type is used based on the thus-obtained comparison result.
The block-type deciding portion may further comprise a parameter deciding portion which decides parameters and/or a determining expression to be used in a process of making a decision as to whether the long or short block type is used, depending on the sampling frequency of the input digital audio signal.
The block-type deciding portion may further comprise a decision method deciding portion which makes a decision that a decision be made as to whether the long or short block is used using the tonality indexes, when the sampling frequency of the input digital audio signal is larger than a predetermined threshold.
The parameter deciding portion may increase the number of the frequency bands to be used and shifts the frequency bands to be selected to higher ones, when the sampling frequency is lower.
Thereby, the following problems can be solved: When the number of frequency bands used for the decision is small, only the tonality in the limited number of frequency bands is considered. Accordingly, in a case where the tonality is high in other frequency bands, and, therefore, the long block type should be used, a decision is made to use the short block type. Further, when the number of frequency bands used for the decision is large, a decision is made to use the long block type only in a special case where the tonality is high in every frequency band thereof.
As a result, it is possible to provide appropriate determination conditions for making a decision as to whether the long or short block type is used, with the tonality of input audio data and frequency dependency of masking property of the human ear in mind, so that the use of the thus-provided determination conditions does not result in degradation in the sound quality.
Other objects and further features of the present invention will become more apparent from the following detailed description when read in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a diagram explaining a relationship between the absolute hearing threshold and masking threshold in a spectral distribution of an audio signal;
FIG. 2 is a block diagram showing a basic structure of an AAC encoder;
FIG. 3 shows transformation ranges in MDCT;
FIG. 4 shows transformation ranges in MDCT for a signal waveform having a gentle variation;
FIG. 5 shows transformation ranges in MDCT for a signal waveform having a violent variation;
FIG. 6 shows an example of grouping;
FIG. 7 is a flow chart showing operations for making decisions as to whether the long or short block type is used, described in ISO/IEC13818-7;
FIG. 8A is a flow chart showing operations for making decisions as to whether the long or short block type is used in the related art;
FIG. 8B is a block diagram showing an example of an arrangement for performing the operations shown in FIG. 8A;
FIG. 9 shows a waveform of an example of one block of an input audio signal;
FIG. 10 shows the perceptual entropy of each short block of the input audio signal shown in FIG. 9 :
FIG. 11 is a block diagram partially showing a digital-audio-signal processing device according to the present invention;
FIG. 12 is a flow chart of operations of the digital-audio-signal processing device in a first embodiment of the present invention;
FIG. 13 shows a manner of providing scalefactor-band identifying numbers;
FIG. 14 shows an example of tonality indexes of an audio signal in each short block;
FIG. 15 is a flow chart of operations of the digital-audio-signal processing device in a second embodiment of the present invention;
FIG. 16 shows another example of tonality indexes of an audio signal in each short block;
FIG. 17 is a flow chart of operations of the digital-audio-signal processing device in a third embodiment of the present invention (but it is also possible to consider this flow chart to be a flow chart of other operations of the digital-audio-signal processing device in the second embodiment of the present invention);
FIG. 18A is a block diagram partially showing the digital-audio-signal processing device in a fourth embodiment of the present invention;
FIG. 18B is a flow chart showing operations performed by the arrangement shown in FIG. 18A; and
FIG. 19 is a block diagram showing one example of a hardware configuration of the digital-audio-signal processing device according to the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 11 is a block diagram partially showing an arrangement of a digital-audio-signal coding device according to the present invention. The digital-audio-signal coding device according to the present invention may have the same arrangement as the AAC encoder described above using FIG. 2 in accordance with ISO/IEC13818-7 except that the psychoacoustic model 71 includes the arrangement for making a decision as to whether the long or short block type is used according to the present invention shown in FIG. 11 and described below. Similarly, the digital-audio-signal coding method according to the present invention may be the same as that performed by the AAC encoder described above using FIG. 2 in accordance with ISO/IEC13818-7 except that the method for making a decision as to whether the long or short block type is used according to the present invention described below is used.
The digital-audio-signal coding device according to the present invention includes a block obtaining portion 11 . An audio signal, input to the block obtaining portion 11 is a sequence of blocks of samples which are produced along the time axis. The block obtaining portion 11 obtains, from each block of the input audio signal, a predetermined number of successive blocks, in the embodiments described below, 8 successive blocks, such that adjacent blocks overlap with one another, as shown in FIG. 9 . The digital-audio-signal coding device further includes a tonality-index calculating portion 12 which calculates the tonality index of each one of the thus-obtained blocks using the above-mentioned calculation equation, a comparing portion 13 which compares the thus-calculated tonality index with a predetermined threshold, a long/short-block-type deciding portion 14 which make a decision as to whether the long or short block type is used based on the thus-obtained comparison result, and a control portion which controls operations of each portion. FIG. 12 is a flow chart showing operations of the digital-audio-signal coding device in the first embodiment.
The operations of the first embodiment of the present invention will now be described using FIGS. 11 and 12.
In the operations, 8 short blocks are obtained from a block of an input audio signal, and, then, for each short block, it is determined whether the tonality index(es) of audio components included in a predetermined one or a plurality of scalefactor-band components are larger than thresholds predetermined for the respective scalefactor bands. Then, when at least one short block exists for which the tonality indexes are larger than the predetermined thresholds for all the predetermined one or plurality of scalefactor-band components, it is decided to use the long block type for the block of the input audio signal, that is, a single long block is obtained from the block of the input audio signal for mapping the input audio signal into the frequency domain. This method will now be described in detail in accordance with FIG. 12 showing an operation flow of the method. Similarly to the above-mentioned method, the audio data shown in FIGS. 9 and 10 are used as an example of an input audio signal.
First, for each of the successive 8 short blocks i (0≦i ≦7) of the input audio signal, obtained from the block obtaining portion 11 , the tonality indexes in the respective sfb are calculated, and, thus, tb[i][sfb] is obtained in a step S 40 . The sfb's are respective ones of consecutive numbers for identifying the respective scalefactor bands, as shown in FIG. 13 . The calculation of the tonality indexes is performed, by the tonality-index calculating portion 12 , in accordance with the step 7 in the above-described method of deciding as to whether the long or short block type is used for each target block in ISO/IEC13818-7. Then, initializing is performed such that tonal —flag= 0, in a step S 41 . Further, the number i of the short block is initialized to be 0, in a step S 42 . Then, for the short block i, it is determined whether or not, in a predetermined one or a plurality of scalefactor bands, the respective tonality indexes are larger than thresholds predetermined for the respective scalefactor bands, in a step S 43 . In the example of FIG. 12, the determination is performed by the comparing portion 13 for the scalefactor bands, sfb of which are 7, 8 and 9, and the thresholds for the tonality indexes thereof are assumed to be th 7 , th 8 and th 9 , respectively.
In this example, it is assumed that, for the respective short blocks i, the tonality indexes in the scalefactor bands, sfb of which are 7, 8 and 9, are those shown in FIG. 14 . Further, it is assumed that th 7 =0.6, th 8 =0.9, th 9 =0.8. Then, when i=0 at first, tb[ 0 ][ 7 ]=0.12<0.6=th 7 , tb[ 0 ][ 8 ]=0.08<0.9=th 8 , tb[ 0 ][ 9 ]=0.15<0.8=th 9 . Therefore, the result of the determination in the step S 43 is NO. Then, the operation proceeds next to a step S 45 . Then, the value of i is incremented by 1 so that i=1, and, the operation passes through the determination in a step S 46 , and returns to the step S 43 .
Then, operations similar to those described above are repeated until i=5. After i=6 in the step S 45 , the operation passes through the determination in the step S 46 , and returns to the step S 43 . Then, because tb[ 6 ][ 7 ]=0.67>0.6=th 7 , tb[ 6 ][ 8 ]=0.95>0.9=th 8 and tb[ 6 ][ 9 ]=0.89>0.8=th 9 , the result of the determination in the step S 43 is YES. Then, the operation proceeds to a step S 44 . Then, tonal_flag=1. Then, i =7, in the step S 45 . Then, the operation passes through the step S 46 and returns to the step S 43 . When i=7, because tb[ 7 ][ 7 ]=0.42<0.6=th 7 , tb[ 7 ][ 8 ]=0.84<0.9=th 8 and tb[ 7 ][ 9 ]=0.81>0.8=th 9 , the result of the determination in the step S 43 is NO. Then, the operation proceeds to the step S 45 . It is noted that tonal_flag=1 is maintained. Then, after i=8 in the step S 45 , the operation passes through the determination of the step S 46 , and, at this time, proceeds to a step S 47 . Then, the value of tonal_flag is examined. In this example, because tonal_flag=1, the determination of the step S 47 is YES, and the operation proceeds to a step S 48 . Therefore, it is decided to use the long block type for the block of the input audio signal for performing MDCT on the input audio signal. When tonal_flag≠1, the determination of the step S 47 is NO, and the operation proceeds to a step S 49 . Therefore, in the step S 49 , a decision as to whether the long or short block type is used is made by another method such as the method described in ISO/IEC13818-7. For example, at this time, when a decision as to whether the long or short block type is used is made in the method shown in FIG. 8A, the short blocks of the block of the input audio signal are grouped in a manner such that the difference between the maximum value and minimum value in perceptual entropy for the short blocks in the same group is smaller than a threshold. Then, when the result thereof is such that the number of groups is 1, or this condition and another condition are satisfied, MDCT is performed on the input audio signal using the long block type for the block of the input audio signal. In the other cases, MDCT is performed on the input audio signal using the short block type for the block of the input audio signal.
However, in this method, when the number of scalefactor bands used for the decision is small, the tonality in only a limited number of scalefactor bands is considered. Accordingly, in a case where the tonality is high in other scalefactor bands, and, therefore, the long block type should be used, a decision is made to use the short block type. Further, when the number of scalefactor bands used for the decision is large, a decision is made to use the long block type only in a special case where the tonality is high in every scalefactor band thereof. The reason why such problems occur is that the tonality index being larger than a predetermined threshold in every one of predetermined one or a plurality of scalefactor bands is used as a condition for the decision.
Further, generally, when the sampling frequency of an input audio signal is low, the resolution in the frequency domain in each scalefactor band is high. Therefore, as the sampling frequency becomes lower, the signal of a certain frequency is included in a higher scalefactor band. Therefore, when scalefactor bands and thresholds for tonality indexes used for making a decision as to whether the long or short block type is used are fixed regardless of the sampling frequency, an appropriate decision cannot be made. Further, in a case where a sampling frequency is sufficiently low, decisions using tonality indexes are not needed. This is because, in this case, the resolutions in scalefactor bands are sufficiently high, thereby, the matter that, due to decrease in the resolution in the frequency domain when the short block type is used, the energy of the original audio data is dispersed to surrounding frequency bands, and the energy thus spreads to the outside of the masking range in low-frequency components of the human ear, does not occur.
The operations of a second embodiment of the present invention will now be described using FIGS. 11 and 15.
First, successive 8 short blocks i (0≦i≦7) are obtained from the block of the input audio signal by the block obtaining portion 11 . For each of the thus-obtained 8 short blocks, the tonality indexes in the respective scalefactor bands sfb are calculated by the tonality-index calculating portion 12 . First, the tonality index tb[i][sfb] in the scalefactor band sfb of the short block i is obtained, in a step S 50 , wherein, as shown in FIG. 13, sfb represents consecutive numbers for identifying the respective scalefactor bands. The calculation of the tonality indexes is performed in accordance with the method described in the step 7 of the above-described long/short-block-type deciding method for a target block in ISO/IEC13818-7. Initializing is performed such that tonal_flag=0 in a step S 51 . Further, the number i (representing a respective one of consecutive numbers of the short blocks) is initialized so that i=0 in a step S 52 . Then, for the short block i, the comparing portion 13 determines whether, in each of the predetermined one or plurality of scalefactor bands, the tonality index is larger than a respective one of thresholds predetermined for the respective scalefactor bands, in a step S 53 . In the example of FIG. 15, this determination is performed for the scalefactor bands, sfb of which are 6, 7, 8 and 9, and, the threshold for the tonality index for each scalefactor band is determined as follows: th 61 for sfb=6, th 71 and th 72 for sfb=7, th 81 and th 82 for sfb=8, and th 91 for sfb=9. Further, it is determined whether or not the following logical determination expression (condition) is satisfied; {tb[i][ 6 ]>th 61 AND tb[i][ 7 ]>th 71 } OR {tb[i][ 7 ]>th 72 AND tb[i][ 8 ]>th 81 } OR {tb[i][ 8 ]>th 82 AND tb[i][ 9 ]>th 91 }, in a step S 53 .
In this example, it is assumed that, for each short block i, the values of the tonality indexes in the scalefactor bands, sfb of which are 6, 7, 8 and 9, are those shown in FIG. 14 . Further, it is determined that th 61 =0.7, th 71 =0.8, th 72 =0.8, th 81 =0.9, th 82 =0.8 and th 91 =0.9. Then, the logical determination expression in the step S 53 is {tb[i][ 6 ]>0.7 AND tb[i][ 7 ]>0.8} OR {tb[i][ 7 ]>0.8 AND tb[i][ 8 ]>0.9} OR {tb[i][ 8 ]>0.8 AND tb[i][ 9 ]>0.9}. In this expression, the determination expression, tb[i][ 7 ]>0.8, occurs twice. Further, for tb[i][ 8 ], the two different determination expressions, tb[i][ 8 ]>0.9 and tb[i][ 8 ]>0.8, exist.
In the example of FIG. 14, when i=0 at first, tb[ 0 ][ 6 ]=0.09, tb[ 0 ][ 7 ]=0.12, tb[ 0 ][ 8 ]=0.08, tb[ 0 ][ 9 ]=0.15. Therefore, the determination in the step S 53 by the comparing portion 13 is NO. Then, the operation proceeds to a next step S 55 . Then, in the step S 55 , the value of i is incremented by 1 so that i=1, and the operation passes through the determination in a step 56 , and returns to the step S 53 .
Operations similar to those described above are repeated until i=5. After i=6 in a step S 55 , the operation pass through the determination in the step 56, and returns to the step S 53 . Then, tb[ 6 ][ 6 ]=0.67, tb[ 6 ][ 7 ]=0.82, tb[ 6 ][ 8 ]=0.95, tb[ 6 ][ 9 ]=0.89. Therefore, the determination in the step S 53 by the comparing portion 13 is YES. Then, the operation proceeds to a next step S 54 . Then, tonal_flag=1 in the step s 54 . Then, i=7 in the step S 55 , the operation passes through the step S 56 and returns to the step S 53 . When i=7, tb[ 7 ][ 6 ]=0.23, tb[ 7 ][ 7 ]=0.42, tb[ 7 ][ 8 ]=0.84, tb[ 7 ][ 9 ]=0.81. Therefore, the determination in the step S 53 by the comparing portion 13 is NO. Then, the operation proceeds to the step S 55 . However, tonal_flag=1 is maintained. Then, after i=8 in the step S 55 , the operation passes through the determination in the step S 56 , and, then, at this time, proceeds to a step S 57 . Then, the value of tonal_flag is examined in the step S 57 . In this example, because tonal_flag=1, the result of the determination in the step S 57 is YES, and the operation proceeds to a step S 58 . Then, by the long/short-block-type deciding portion 14 , it is decided to use the long block type for the block of the input audio signal, that is, a single long block is obtained from the block of the input audio signal for performing MDCT on the input audio signal.
Then, as another example, a case where the values of the tonality indexes in the scalefactor bands, sfb of which are 6, 7, 8 and 9, are those shown in FIG. 16 . However, it is not changed that th 61 =0.7, th 71 =0.8, th 72 =0.8, th 81 =0.9, th 82 =0.8 and th 91 =0.9. In this case, different from the example shown in FIG. 14, no short block i, for which {tb[i][ 6 ]>0.7 AND tb[i][ 7 ]>0.8} OR {tb[ 1 ][ 7 ]>0.8 AND tb[i][ 8 ]>0.9} OR {tb[i][ 8 ]>0.8 AND tb[i][ 9 ]>0.9} is satisfied, exists. Therefore, the determination in the step S 53 by the comparing means 13 is always NO, and, as a result, the operation never passes through the step S 54 . As a result, the value of tonal_flag is maintained to be the initial value so that tonal_flag=0, and, therewith, the operation proceeds to the step S 57 .
Then, because the result of the determination in the step S 57 is NO, the operation proceeds to a next step S 59 , and, a decision as to whether the long or short block type is used is made by another method such as the method described in ISO/IEC13818-7 or the like, in the step S 59 . For example, at this time, when a decision as to whether the long or short block type is used is made in the method shown in FIG. 8A, the short blocks of the block of the input audio signal are grouped in a manner such that the difference between the maximum value and minimum value in perceptual entropy for the short blocks in the same group is smaller than a threshold. Then, when the result thereof is such that the number of groups is 1, or this condition and another condition are satisfied, it is decided to use the long block type, that is, a single long block is obtained from the block of the input audio signal for performing MDCT on the input audio signal. In the other cases, it is decided to use the short block type, that is, a plurality of short blocks are obtained from the block of the input audio signal for performing MDCT on the input audio signal.
The scalefactor bands used in the decision as to whether the long or short block type is used are not limited to those, sfb of which are 6, 7, 8 and 9. Further, the respective thresholds are not limited to th 61 =0.7, th 71 =0.8, th 72 =0.8, th 81 =0.9, th 82 =0.8 and th 91 =0.9. Furthermore, the arrangement of the logical determination expression is not limited to the above-mentioned example. Various arrangements such as {tb[i][ 6 ]>th 61 AND tb[i][ 7 ]>th 71 AND tb[i][ 8 ]>th 81 } OR {tb[i][ 8 ]>th 82 AND tb[i][ 9 ]>th 91 }, tb[i][ 6 ]>th 61 OR th[i][ 7 ]>th 71 OR tb[i][ 8 ]>th 81 OR tb[i][ 9 ]>th 91 , simply tb[i][ 6 ]>th 61 , or the like can be used.
A third embodiment of the present invention will now be described using FIG. 17 . Here, a method is provided by which a decision as to whether the long or short block type is used can be made appropriately depending on the sampling frequency of an input audio signal. In this method, the scalefactor bands to be used for the decision using the tonality indexes, thresholds for the tonality indexes determined for the respective scalefactor bands, and logical determination expression used in the decision using the tonality indexes, in a step S 53 in FIG. 15, are determined individually for each sampling frequency.
A specific example thereof will now be described using a flow chart shown in FIG. 17 . Here, a case is considered where the sampling frequency of an input audio signal is lower than that for which the example shown in FIG. 15 is used. The flow chart shown in FIG. 17 is the same as that shown in FIG. 15 except that the step S 53 in FIG. 15 is replaced by a step S 63 .
As described above, when the sampling frequency of an input audio signal is low, the resolution in the frequency domain in each scalefactor band is high. Therefore, as the sampling frequency becomes lower, the signal of a certain frequency is included in a higher (larger-sfb) scalefactor band. Therefore, when the above-described example is used for an input audio signal, the sampling frequency of which is lower, the number of scalefactor bands used for the decision using the tonality indexes is increased, and these scalefactor bands are higher (larger-sfb) ones.
In the step S 63 in FIG. 17, sfb=8, 9, 10, 11 and 12. Further, the thresholds for the tonality indexes are determined as follows: th 81 for sfb=8, th 91 and th 92 for sfb=9, th 101 , th 102 and th 103 for sfb=10, th 111 and th 112 for sfb=11 and th 121 for sfb=12. Similarly to the example shown in FIG. 15, specific values are predetermined for the respective thresholds, th 81 , th 91 , . . . Then, the logical determination expression for making a decision as to whether the long or short block type is used is determined to be {tb[i][ 8 ]>th 81 AND tb[i][ 9 ]>th 91 AND tb[i][ 10 ]>th 101 } OR {tb[i][ 9 ]>th 92 AND tb[i][ 10 ]>th 102 AND tb[i][ 11 ]>th 111 } OR {tb[i][ 10 ]>th 103 AND tb[i][ 11 ]>th 112 AND tb[i][ 12 ]>th 121 }.
Except for the decision in the step S 63 , a decision is made as to whether the long or short block type is used through operations similar to those in the example shown in FIG. 15 .
Similarly, for another sampling frequency, a decision is made as to whether the long or short block type is used through operations the same as those shown in FIG. 15 except that the step S 53 (S 63 in FIG. 17) is replaced by another one suitable for the sampling frequency.
In a case where the sampling frequency of an input audio signal is further lowered, because the resolutions in the scalefactor bands are sufficiently high as described above, a decision using tonality indexes is not needed. Therefore, when the sampling frequency of an input audio signal is lower than a predetermined threshold, a method using tonality indexes is not used, and, a decision as to whether the long or short block type is used is made only by another method. Specifically, when the threshold predetermined for the sampling frequency is such that th_sf 24 kHz, for example, the sampling frequency of an input audio signal is compared therewith, and, when the sampling frequency is lower than 24 kHz, a method for making a decision as to whether the long or short block type is to be used based on tonality indexes is not used, and a decision as to whether the long or short block type is used is made only by a method using other means (for example, the method shown in FIG. 8 A). When the sampling frequency is equal to or higher than 24 kHz, both a method for making a decision as to whether the long or short block type is used using tonality indexes and a method for making a decision as to whether the long or short block type is used using other means (for example, the method shown in FIG. 8A) are used. When both a method for making a decision as to whether the long or short block type is used using tonality indexes and a method for making a decision as to whether the long or short block type is used using other means (for example, the method shown in FIG. 8A) are used, a decision as to whether the long or short block type is used is made using scalefactor bands used for a decision based on tonality indexes, thresholds for the tonality indexes determined for the respective scalefactor bands, and logical determination expression for making a decision as to whether the long or short block type is used, wherein the scalefactor bands used for a decision based on tonality indexes, thresholds for the tonality indexes determined for the respective scalefactor bands, and logical determination expression for making a decision as to whether the long or short block type is used are determined individually for each sampling frequency. A relationship with a result of decision using other means is that described in the description of the example shown in FIG. 15 (the steps S 57 , S 58 and S 59 ). That is, when the decision is made to use the long block type in a method using tonality indexes, the input audio signal is mapped into the frequency domain using the long block type for the block of the input audio signal regardless of the decision made in a method using other means. When the decision is not made to use the long block type in the method using tonality indexes, the input audio signal is mapped into the frequency domain using a block type in accordance with the decision made in the method using other means for the block of the input audio signal.
FIGS. 18A and 18B illustrate such a method (a fourth embodiment of the present invention). The arrangement shown in FIG. 11 may be replaced by the arrangement shown in FIG. 18 A. When the sampling frequency of an input audio signal is lower than a first threshold Th 1 (YES in a step S 70 in FIG. 18 B), it is decided by a decision method deciding portion 21 shown in FIG. 18A that a decision is made as to whether the long or short block type is used in a method using other means in a step S 59 shown in FIG. 18B performed by another arrangement 22 shown in FIG. 18A (for example, the arrangement shown in FIG. 8A for performing the method shown in FIG. 8 A). When the sampling frequency of an input audio signal is equal to or higher than the first threshold Th 1 (NO in the step S 70 in FIG. 18 B), the sampling frequency is compared with a second threshold Th 2 higher than the first threshold Th 1 in a step S 71 . When the sampling frequency is lower than the second threshold Th 2 (YES in the step S 71 in FIG. 18 B), it is decided by a parameter deciding portion 23 shown in FIG. 18A that a decision is made as to whether the long or short block type is used in a method shown in FIG. 17 performed by the arrangement (shown in FIG. 11) 24 shown in FIG. 18A in a step S 73 , in which the scalefactor bands, sfb of which are 8, 9, 10, 11 and 12 are selected; the thresholds for the tonality indexes are determined as follows: th 81 for sfb=8, th 91 and th 92 for sfb=9, th 101 , th 102 and th 103 for sfb=10, th 111 and th 112 for sfb=11 and th 121 for sfb=12; and the logical determination expression for making a decision as to whether the long or short block type is used is determined to be {tb[i][ 8 ]>th 81 AND tb[i][ 9 ]>th 91 AND tb[i][ 10 ]>th 101 } OR {tb[i][ 9 ]>th 92 AND tb[i][ 10 ]>th 102 AND tb[i][ 11 ]>th 111 } OR {tb[i][ 10 ]>th 103 AND tb[i][ 11 ]>th 112 AND tb[i][ 12 ]>th 12 }. When the sampling frequency is equal to or higher than the second threshold Th 2 (NO in the step S 71 in FIG. 18 B), it is decided by the parameter deciding portion 23 shown in FIG. 18A that a decision is made as to whether the long or short block type is used in a method shown in FIG. 15 performed by the arrangement (shown in FIG. 11) 24 shown in FIG. 18A in a step S 72 , in which the scalefactor bands, sfb of which are 6, 7, 8 and 9 are selected; the threshold for the tonality index for each scalefactor band is determined as follows: th 61 for sfb=6, th 71 and th 72 for sfb=7, th 81 and th 82 for sfb=8, and th 91 for sfb=9; and the logical determination expression for making a decision as to whether the long or short block type is used is determined to be: {tb[i][ 6 ]>th 61 AND tb[i][ 7 ]>th 71 } OR {tb[i][ 7 ]>th 72 AND tb[i][ 8 ]>th 81 } OR {tb[i][ 8 ]>th 82 AND tb[i][ 9 ]>th 91 }.
The present invention can be practiced using a general purpose computer that is specially configured by software executed thereby to carry out the above-described functions of the digital-audio-signal coding method in any embodiment according to the present invention.
FIG. 19 shows such a general purpose computer that is specially configured by executing software stored in a computer-readable medium. The computer includes an interface (abbreviated to I/F, hereinafter) 51 , a CPU 52 , a ROM 53 , a RAM 54 , a display device 55 , a hard disk 56 , a keyboard 57 and a CD-ROM drive 58 .
Program code instructions for carrying out the digital-audio-signal coding method in any embodiment according to the present invention are stored in a computer-readable medium such as a CD-ROM 59 . When a control signal is input to this computer via the I/F 51 from an external apparatus, the instructions are read by the CD-ROM drive 58 , and are transferred to the RAM 54 and then executed by the CPU 52 , in response to instructions input by an operator via the keyboard 57 or automatically. Thus, the CPU 52 performs coding processing in the digital-audio-signal coding method according to the present invention in accordance with the instructions, stores the result of the processing in the RAM 54 and/or the hard disk 56 , and outputs the result on the display device 55 , if necessary. Thus, by using a medium in which program code instructions for carrying out the digital-audio-signal coding method according to the present invention are stored, it is possible to practice the present invention using a general purpose computer.
Further, the present invention is not limited to the above-described embodiments and variations and modifications may be made without departing from the scope of the present invention.
The present application is based on Japanese priority application No. 11-077703, filed on Mar. 23, 1999, the entire contents of which are hereby incorporated by reference.
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A converting portion converts each of blocks of an input digital audio signal into a number of spectral frequency-band components, the blocks being produced from the signal along a time axis. A bit-allocating portion allocates coding bits to each frequency band. A scalefactor is determined in accordance with the number of the coding bits allocated. The digital audio signal is quantized using the scalefactors. Each block of the input digital audio signal is converted into the number of spectral frequency-band components. A tonality index of the digital audio signal is calculated in each of a predetermined one or plurality of frequency bands. The tonality index is compared with a predetermined one or plurality of thresholds. A decision to use the long or short block type is based on the thus-obtained comparison result.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to U.S. Provisional Patent Application No. 60/703,778, filed on Jul. 29, 2005, which is incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to a connector for connecting to a transformer having a single stud hole with superimposed multiple threads. More particularly, the present invention relates to a transformer stud connector, having an easy-off stud mounting hole, for installing on studs of different sizes and which permits the connector to disengage the stud and slide off without the need for moving the connector from side to side.
BACKGROUND OF THE INVENTION
[0003] Electrical transformers are typically used to distribute electrical power from main utility lines for secondary distribution. The transformer accepts the main utility line on the primary side of the transformer and distributes the power from a secondary side of the transformer. An electrical step-down is provided by the transformer so as to provide for the proper secondary distribution of electrical power for residential and commercial use.
[0004] The transformer is normally housed in a steel cabinet. A threaded copper stud extends from the secondary side of the transformer from which secondary distribution is provided. Plural electrical conductors, connected to the threaded stud, provide for distribution of power to the end user.
[0005] In order to connect the conductor to the stud, a transformer stud connector is employed. These transformer stud connectors are elongate, electrically conductive members which are inserted over the copper stud extending from the secondary side of the transformer. The stud connector may be threadingly attached to the transformer stud. Extending longitudinally therefrom are a plurality of conductor accommodating ports wherein the ends of conductors may be inserted. Each conductor port has an associated set screw to effect mechanical and electrical connection to the transformer stud connector. Examples of transformer stud connectors are shown in U.S. Pat. Nos. 5,931,708; 5,848,913; 5,690,516; DES 377,782; DES 346,150; and DES 309,664.
[0006] In a typical arrangement, the utility distribution transformer has threaded studs typically ⅝-11 or 1-14, oversized applications can have larger 1 ¼-12, 1 ½-12 threaded studs or possibly a custom size dictated by customer needs. A connector, sometimes referred to as a bus bar, is used to connect to the stud and provide ports for multiple wire connections. The connector is threaded with the same pitch tread but the threaded hole is equal or larger to the diameter of the transformer stud. This allows the connector to be slipped on to the stud, known as a slip fit connector, instead of being spun onto the treaded shaft. This allows the connector to be installed and removed without having to remove any of the conductors. An orthogonally mounted set screwis typically used to secure the connector to the studded shaft. However, slip fit connectors, due to the presence of threads around the inside of the stud hole can sometime be difficult to remove from the stud. In many cases, once the setscrews securing the connector are loosened, the connector must still be wiggled up and down or side to side to get the connector to slide off. This can make removal of the connector a difficult and time consuming process as well as damaging the connector and stud threads by repeated contact between the threads while trying to wiggle the connector off of the stud. This problem can be exacerbated when the connector is adapted to receive more than one size stud due to the close tolerances that are required for the stud connector hole when more than one size stud can be accommodated within the connector.
[0007] In prior art connectors, various means were provided so that a single connector could be used to service studs of various sizes. One way is to provide at least two threaded holes, one for each of the stud sizes serviced by the connector. However, the disadvantage of such design is that it requires at least two holes, and therefore needs to be larger than necessary. Also, because by design the stud hole has to meet a certain depth to accommodate the stud, the portion of the connector receiving the threaded stud in not usable for conductor connections, thus additionally requiring a longer connector to accommodate an equal number of conductors. This problem is exacerbated for connectors having multiple threaded holes. In addition, a multi hole connector does not address the problems of easy installation and removal.
[0008] A further prior art design utilizes a tear-drop design of two holes which overlap and therefore produce a large diameter threaded hole having an arc-section of a smaller hole at the bottom of the larger hole, which extends beyond the perimeter of the larger hole. The disadvantage of this design is that it requires pre-drilling a smaller hole, followed by drilling of the second larger hole, partially overlapping the smaller hole. Alternately, the larger hole can be bored first, followed by milling or broaching of the bottom arc section to create the “tear-drop”. Both methods therefore require a two-step process, which adds complexity and expense to the manufacturing process.
[0009] A third alternative prior art design utilizes a slider system mounted to the connector which has grooved sides at various levels on the connector body. By moving the slider, in the grooves, various gap sizes between the slider and the connector body can be formed. However, this design requires a second element, the slider, to be added to the connector, which adds complexity and expense to the manufacturing process.
[0010] It is therefore desirable to provide a transformer stud connector, which can be mounted on studs of various sizes without the complexity, or cost of prior art designs, has a more compact design, provides greater physical contact between the connector and the stud and provides for easy installation and removal of the connector with out extra effort or steps on the part of the user.
SUMMARY OF THE INVENTION
[0011] The present invention provides a connector, which can be attached to transformer studs of various sizes with a single threaded hole.
[0012] The present invention uses a single hole or bore within the body of a connector to accept two or more threaded studs of different thread sizes. Furthermore, the present invention can accommodate one or more different size studs while still providing a connector that has a compact design, provides increased physical contact between the stud and connector, is easily manufactured and can be easily installed and removed from a stud without undue effort on the part of the installer. This is accomplished in the present invention by producing a stud connector having an elongated passageway with three bore centers, wherein the thread center is slightly offset from the elongated passageway diameter and the elongated passageway being just slightly larger than the stud to be received. Furthermore, the elongated passageway includes more than one thread size milled into the offset bore diameter.
[0013] To that end there is provided an electrically conductive transformer stud connector comprising, a body with an elongated passageway centered at a first point, for receiving a transformer stud having threads of a particular root distance, a first thread corresponding to the transformer stud threads of a particular size within the elongated passageway wherein the elongated passageway is centered at a second point that is vertically offset from the first point by a distance equal to the root distance.
[0014] The present invention further provides a method of making an electrically conductive transformer stud connector comprising forming a cylindrical elongated passageway within a connector body centered at a particular point for receiving a stud of a predetermined root distance, forming a first threaded region corresponding to a predetermined thread size and pitch centered at a point that is vertically offset from the particular point, forming a second threaded region overlapping the first threaded region corresponding to a second predetermined thread size and pitch wherein the first threaded region and the second threaded region overlap along a single line of tangency.
[0015] As shown by way of a preferred embodiment herein, the connector of the present invention includes a single elongated passageway with an offset bore cradle for accommodating more than one thread size which is easy to install and remove.
BRIEF DESCRIPTION OF DRAWINGS
[0016] FIG. 1 is a perspective view of a portion of the connector according to the present invention.
[0017] FIG. 2 is a cross-sectional drawing of a connector according to the present invention.
[0018] FIG. 3 is a cross-sectional drawing of a connector according to the present invention having a stud installed.
[0019] FIG. 4 is a cross-sectional drawing of a connector according to the present invention having an alternate stud installed.
[0020] FIG. 5 is a schematic drawing of the threaded hole of the connector according to the present invention depicting the thread arrangement.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0021] Referring to FIG. 1 , there is shown a perspective view of the connector according to the present invention. Shown is connector body 10 having a longitudinal bore 12 including threads 14 disposed along the inner diameter. Set screws 16 protrude from the top of connector body 10 and can be screwed into connector body 10 to contact transformer stud (not shown). As shown in FIG. 1 , and which will be further described with respect to FIG. 2 , threads 14 are helically disposed about a portion of the circumference of longitudinal bore 12 . In a preferred embodiment, the threads 14 are helically disposed around up to approximately 130° of longitudinal bore 12 , but threads 14 may also be disposed in a parallel or non-helical arrangement. There is further shown side surface 18 of the connector body 10 , which, when mounted to a transformer stud faces the transformer.
[0022] The connector body 10 is an integrally formed metallic member, preferably formed of aluminum or other material, having high electrical conductivity. Transformer stud connector body 10 includes central, generally elongate cylindrical bore 12 . The central bore 12 is internally threaded to accommodate the extending, externally threaded transformer stud (not shown). The length of bore 12 need only be approximately the length of the extending portion of the stud so that when the body is placed over the stud, the stud and the bore extend generally the same distance.
[0023] Transformer stud connector body 10 will typically include conductor-accommodating ports 11 for receiving conductors located on the cantilevered step portions 13 of connector body 10 . In this way, additional conductor accommodating ports 11 can be added without extending the length of connector body 10 .
[0024] Each conductor port will also include a securement device such as a set screw 17 for securing the conductor. Each set screw aperture is in communication with the respective conductor receiving port so that set screws 17 may be inserted therein to mechanically and electrically secure the ends of the conductors within the stud connector body 10 . In a typical arrangement, each of the ports extends from one side surface of the connector body 10 . The conductor ports are generally positioned on similarly facing surfaces so that conductors inserted into the ports can be inserted from the same direction.
[0025] Referring now to FIG. 2 , the transformer stud connector body 10 is depicted as having a central region with a longitudinal bore 12 , and two cantilevered step portions 13 . The longitudinal bore 12 includes an aperture 20 for receiving at least one particular size stud. In the particular example described with respect to FIG. 2 , the longitudinal bore 12 is drilled to accept at maximum, a 1 inch stud. In the case of a 1-inch diameter stud, the aperture 20 is drilled to a diameter of 1.060 inches.
[0026] In accordance with the present invention, to accommodate the stud, once aperture 20 is drilled, the threads for a particular size thread are tapped into aperture 20 . In the exemplary embodiment of the present invention described, two threads, a larger diameter thread 22 having a center point 23 and a smaller diameter thread 24 , are tapped into aperture 20 . The location of the larger diameter thread 22 is located with respect to the aperture center 21 . The larger diameter thread 22 center 23 is offset from the aperture center 21 by a distance 26 that corresponds to the root distance between the valley and crest of the stud thread that is received into the larger diameter thread 22 . The third center 28 of the smaller diameter thread 24 is located such that the smaller thread crest is tangent to the larger diameter thread crest at a point 25 along the base of aperture 20 . By offsetting the center 23 of larger diameter thread 22 a cradle 27 is formed at the base of aperture 20 .
[0027] By offsetting the tapped threads from the center 21 of aperture 20 , the majority of the inside circumference of aperture 20 remains smooth, i.e., without threads. Therefore, it is easier to slip connector 10 onto the transformer stud since there is a smaller area of the inner circumference that is covered by threads that may catch onto the threads of the stud during installation or removal of the connector 10 . In addition, aperture 20 can be drilled to a smaller dimension. In the example described, the aperture is only 0.060″ larger than the stud size to be accommodated whereas it normally would be oversized at least ⅛″ and typically ¼″. Further, the size of the larger diameter thread 22 is the same size as the stud to be accommodated, it is not oversized. Due to the large diameter thread 22 being the same size as the stud diameter and the center 23 of the large diameter thread 22 being only slightly offset from the aperture center 21 , the arc 29 for the larger diameter thread 22 spans up to about 130° of the aperture 20 inner circumference depending on thread profile. Therefore, because the radius of the large diameter thread 22 matches the stud diameter the contact surface in cradle 27 between the connector threads 14 and the stud is maximized, resulting in enhanced electrical conductivity.
[0028] Turning again to FIG. 2 , connector 10 includes a set screw 16 for securing the connector to the threaded stud. The set screw 16 is received into the connector body in a threaded bore 34 and can thus be raised or lowered by rotating the set screw 16 . In this way, the set screw 16 can be adjusted to contact a threaded stud within longitudinal bore 12 .
[0029] In a preferred embodiment of the present invention, the connector 10 is produced by forming the longitudinal bore 12 by drilling into the connector body 10 to create a void or aperture 20 . Thereafter, a first tap or milling operation is performed to form the larger diameter thread 22 , which in the preferred embodiment may be a 1-14 thread. Once the large diameter thread 22 is formed, a milling operation is performed to form the small diameter thread 24 , which in the preferred embodiment may be ⅝-11 thread. As will be further shown and described with respect to FIG. 5 , the threaded regions are positioned within the connector body 10 by offsetting the large diameter thread center 23 from the aperture center 21 by a distance equal to the root distance between the valley and crest of the larger thread size chosen. The third center 28 of the smaller diameter thread 24 is located such that the smaller diameter thread crest is tangent to the larger thread crest at a point 25 along the base of aperture 20 , which is typically directly opposite the set screw 16 . In a three dimensional frame of reference with respect to the two threads 22 and 24 , multiple points 25 would extend along a tangent line within cradle 27 .
[0030] Removal of the overlapping thread sections could be done by a milling/threading/tapping operation on the side of aperture 20 where interlocking of the second stud in desired, typically opposite the set screw 16 . Alternately, the overlapping thread sections can be formed at other locations around the entire inner diameter of longitudinal bore 12 .
[0031] While the preferred embodiment of the connector according to the present invention is described with respect to a particular large and small thread pitch. It would be clear to one skilled in the art that any standard or non-standard thread pitches could be overlapped in the manner described. Likewise the present invention need not be limited to overlapping two particular thread pitches, but may include more than two particular thread pitches that are formed within aperture 20 .
[0032] Turning now to FIG. 3 , there is shown a transformer stud 30 installed within aperture 20 , which has a diameter slightly smaller than aperture 20 , such that the connector 10 can be slipped over stud 30 without the stud and connector threads becoming engaged. Once the stud is fully inserted within the connector, set screw 16 is rotated to bear against stud 30 , thereby causing the threads on stud 30 to engage the complementary pitch threads 14 within aperture 20 and thus secure the connector 10 to the stud. It should be noted that while a standard flat tip set screw is depicted, to minimize thread distortion, a saddle typed stud clamping screw can be used. The saddle type screw utilizes a saddle piece featuring the same type of thread pattern to allow for normal fit over the stud thread, therefore avoiding any thread damage and providing a more positive mechanical and electrical connection.
[0033] Turning now to FIG. 4 , there is shown a transformer stud 40 installed within aperture 20 , which has a diameter smaller than aperture 20 , such that the connector can be slipped over stud 40 without the stud and connector threads becoming engaged. Once the stud is fully inserted within the connector, set screw 16 is rotated to bear against stud 40 , thereby causing the threads on stud 40 to engage the complementary pitch threads 14 within aperture 20 and thus secure the connector to the stud. Stud 40 engages the small diameter threaded region 24 of aperture 20 which are overlapped with the large diameter threads 22 that are engaged by stud 30 of FIG. 3 along the various tangent points 25 in thread cradle 27 .
[0034] Turning now to FIG. 5 , there is shown a side view of an exemplary stud thread 50 shown depicting the thread pitch of a one inch diameter stud. In the view depicted the stud thread crest 52 and valley 54 are shown. The crest 52 and valley 54 are separated by a root distance 56 that corresponds to the offset distance between aperture center 21 and large diameter thread center 23 . It should be recognized by one skilled in the art that the stud 50 , root distance 56 and offset distance 26 can be varied to suit a particular stud size. However, regardless of the size of the root distance 56 , the offset 26 and root distance 56 are preferably equal, for a connector designed for a particular stud size.
[0035] Various changes to the foregoing described and shown structures would now be evident to those skilled in the art. Accordingly, the particularly disclosed scope of the invention is set forth in the following claims.
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A connector is attachable to an extending transformer stud. The connector includes a single hole or bore within the body of a connector to accept threaded transformer studs of different thread sizes. The connector can accommodate different size studs while still providing a compact design. The connector provides increased physical contact with the stud. The connector can be easily installed and removed from a stud without undue effort on the part of the installer. The stud connector includes an elongated passageway with three bore centers, wherein the thread center is slightly offset from the elongated passageway center and the elongated passageway having a diameter just slightly larger than the stud to be received. The elongated passageway includes more than one thread size milled or tapped into the bore circumference.
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The United States government may have certain rights in this invention. This invention was made, in part, with funding from the National Institutes of Health.
FIELD OF THE INVENTION
This application relates to compositions for antiviral or other therapy and to methods for glycoprotein structural modifications which prolong the half-life of those proteins in the circulation by blocking specific liver clearance mechanisms. Specifically, this application relates to compositions useful in the treatment of Human Immunodeficiency Virus (HIV) infections.
BACKGROUND OF THE INVENTION
The primary immunologic abnormality in HIV-infected patients with an infection in the active stage is the progressive depletion and functional impairment of T lymphocytes expressing the CD4 cell surface glycoprotein (Lane et al. (1985) Ann. Rev. Immunol. 3:477). Generally, T lymphocytes expressing the CD4 surface glycoprotein have a helper/inducer T cell phenotype (Reinherz et al. (1980) Cell 19:821), but such T cells can also have cytotoxic/suppressor activity (Thomas et al. (1981) J. Exp. Med. 154:459). It is believed that the loss of the helper/inducer functions in immunocompromised AIDS or ARC patients leads to the opportunistic infections and malignancies associated with AIDS.
Molecular studies of HIV infection of T cells have shown that HIV specifically and selectively infects T cells expressing CD4. It was also observed that CD4-specific monoclonal antibodies could block HIV infection and syncytia formation (Dalgeish et al. (1984) Nature 312:767; McDougal et al. (1985) J. Immunol. 135:3151). Maddon et al. (1986) Cell 47:333 showed that cells normally non-permissive for HIV infection which expressed a stable cDNA encoding CD4 became permissive for HIV infection. These results showed that CD4 was required for HIV infection. McDougal et al. (1986) Science 231:382, demonstrated complex formation between CD4 and gp120, the major HIV envelope glycoprotein.
cDNA encoding CD4 has been cloned and sequenced (Maddon et al. (1985) Cell 42:93). Sequence analysis shows an N-terminal signal peptide sequence, domains which exhibit homology to certain immunoglobulin variable-region domains, potential glycosylation sites at about 273 and about 303 in the amino acid sequence, a potential trans-membrane domain from about 375 to about 395, and a potential cytoplasmic domain extending through the C-terminus of the protein. Peterson and Seed (1988) Cell 54:65 performed site-directed mutagenesis of the CD4 protein to determine HIV binding sites, and correlated this information with epitopes recognized by CD4-specific monoclonal antibodies. Amino acid substitutions in the region of amino acids 45-47 of the protein appeared to destroy both HIV binding and syncytium formation.
Secreted, soluble forms of CD4 have been synthesized using truncated coding sequences. CD4 derivatives of about 370 amino acids have been produced; these are glycosylated when produced in appropriate host cells. Such molecules bind HIV gp120 effectively and can block HIV infection of susceptible cells (See, e.g., Smith et al. (1987) Science 238:1704; Fisher et al. (1988) Nature 331:76; and Hussey et al. (1988) Nature 331:78). Soluble truncated CD4 proteins as short as 113 amino acids, which are not glycosylated, can block HIV-mediated cell fusion (Chao et al. (1989) J. Biol. Chem. 264:5812). Thus it is clear that intact oligosaccharide side chains are not required for HIV binding or for cell fusion events.
The use of soluble forms of CD4 has been proposed for AIDS treatment or prophylaxis (See e.g., EP 0 385,909, published Sep. 5, 1990). Soluble forms of CD4 are known to have a short half-life in circulation in relation to certain serum proteins. Because the in vivo plasma half-life of soluble CD4 has been shown to be relatively short, various strategies have been employed to stabilize the protein against clearance. (See, e.g., WO 89/03222; WO 89/02922; WO 90/01035; and WO 90/05534). Conjugates have been prepared in which polyethylene glycol or other hydrophilic polymers are attached to the CD4 either via amino acid free functional groups or via sugar moieties in the oligosaccharide side chains of the glycosylated soluble CD4 protein. A second approach to stabilizing the CD4 protein in circulation has been to produce fusion proteins including a soluble CD4 portion and a portion from a protein of long circulating half-life, such as an immunoglobulin. Such fusions exhibited longer plasma half-lives in animal models than sCD4 without added domains.
Therapeutic proteins may be removed from circulation by a number of routes. For some pharmacologically active proteins, there are specific receptors which mediate removal from circulation. Proteins which are glycosylated may be cleared by lectin-like receptors in the liver, which exhibit specificity only for the carbohydrate portion of those molecules. Nonspecific clearance by the kidney of proteins and peptides (particularly nonglycosylated proteins and peptides) below about 50 kDa has also been documented. It has been noted that asialo-glycoproteins are cleared more quickly by liver than native glycoproteins or proteins lacking glycosylation (Bocci (1990) Advanced Drug Delivery Reviews 4:149). The sialic acid residues of erythropoietin appear to contribute to its stable circulation (Fukuda et al. (1989) Blood 73:84). In contrast, studies of tissue-type plasminogen activator (tPA) showed that the oligosaccharide sidechains were not the primary determinants for clearance from solution, but rather rapid clearance was dependent on the amino acid sequence within one or more domains of the molecule. The presence and type of glycosylation made a secondary, less significant contribution to clearance (Larsen et al. (1989) Blood 73:1842).
Mammalian glycoproteins often have N-acetylneuraminic acid (sialic acid) as the external (terminal) residue of the oligosaccharide chains which may be N-linked or O-linked (See, e.g., Osawa and Tsuji (1987) Ann. Rev. Biochem. 56:21).
Where the nature of the oligosaccharide is the primary determinant for clearance from circulation, generally glycoproteins with terminal sialic acid residues removed (asialoglycoproteins) are cleared more quickly than their intact counterparts. Circulating glycoproteins are exposed to sialidase(s) (or neuraminidase) which can remove terminal sialic acid residues. Typically the removal of the sialic acid exposes galactose residues, and these residues are recognized and bound by galactose-specific receptors in hepatocytes (reviewed in Ashwell and Harford (1982) Ann. Rev. Biochem. 51:531). Liver also contains other sugar-specific receptors which mediate removal of glycoproteins from circulation. Specificities of such receptors also include N-acetylglucosamine, mannose, fucose and phosphomannose. Glycoproteins cleared by the galactose receptors of hepatocytes undergo substantial degradation and then enter the bile; glycoproteins cleared by the mannose receptor of Kupffer cells enter the reticuloendothelial system (reviewed in Ashwell and Harford (1982) Ann. Rev. Biochem. 51:53).
Studies with asialo-ceruloplasmin and derivatives showed that asialo-ceruloplasmin in which galactose residues were oxidized by treatment with galactose oxidase and horseradish peroxidase and asialoagalacto-ceruloplasmin exhibited extended circulating half-lives as compared with asialo-ceruloplasmin (Morell et al. (1968) J. Biol. Chem. 243:155). Efficient removal by the galactose receptor appears to require at least two exposed galactose residues. In contrast, transferrin is a glycoprotein in which the sialylation state of the oligosaccharide is not key to rapid clearance from circulation (Morell et al. (1971) J. Biol. Chem. 246:1461).
From the foregoing cited examples of glycoproteins for which sialylation is the key determinant of clearance from circulation and those for which sialylation has no bearing on clearance or for which oligosaccharides play a relatively insignificant role in clearance, one may conclude that the fate of a particular glycoprotein in circulation and its apparent mechanism for clearance must be determined empirically. Similarly, strategies for prolonging the circulation of a particular glycoprotein must be evaluated on a case-by-case basis. The mechanism for clearance must be evaluated and the strategies for slowing or avoiding clearance must take into account maintenance of desired biological activity or function, potential toxicity, potential immunogenicity and cost.
A problem solved by the present invention is the prolongation of the circulating half-life of soluble CD4 derivatives, thus reducing the quantity of injected material and frequency of injection required for maintenance of therapeutically effective levels of circulating sCD4 for treatment or prophylaxis of HIV-infected individuals. The short in vivo plasma half-life of sCD4 is undesirable from the standpoint of the frequency and the amount of soluble CD4 protein which would be required in the prophylaxis or treatment of AIDS. The present invention provides means to prolong the circulating half-life of sCD4 with the most conservative but still effective change to the glycoprotein structure and with the substantial maintenance of gp120 binding activity.
SUMMARY OF THE INVENTION
It is an object of this invention to provide a means for stabilizing glycoproteins in circulation when the glycosylation of that protein provides the primary determinant for clearance. Increased half-life is achieved in such glycoproteins by treatments which block or inhibit removal of the protein by sugar-specific receptor, such as the galactose and mannose receptors in the liver. In particular, the prolonging of soluble CD4 derivatives in circulation is described. Prolonged circulating half-lives are desirable in therapeutic proteins because frequency and/or size of dose can be reduced when half-life is longer.
It is also an object of this invention to provide a modified soluble CD4 derivative with increased plasma half-life as compared with the unmodified derivative. Increased half-life of sCD4 is achieved in general by means which block or inhibit removal of sCD4 by galactose, mannose or other sugar-specific receptors. More specifically, means are provided for modification of terminal galactose or mannose residues of glycosylated sCD4 or its derivatives such that removal by sugar-specific receptors in the liver is inhibited or prevented. Modifications that result in increased half-life include, but are not limited to, exposure of galactose residues followed by oxidation or derivatization of the galactose such that binding of the modified sCD4 to galactose receptor is inhibited or blocked. A preferred embodiment is one in which the terminal sialic acid residues of the oligosaccharide side chains of the soluble CD4 or soluble CD4 derivative have been removed with neuraminidase treatment, and then the exposed galactose residues are oxidized by galactose oxidase and horseradish peroxidase treatment. The oxidation of the exposed galactose residues has the effect of preventing rapid clearance of the modified CD4 from circulation by specific galactose receptors in the liver. It is understood that other structural modifications of terminal galactose residues, including but not limited to addition of a functional group or small molecule or mild oxidation treatment, which have the effect of blocking, inhibiting or preventing recognition of terminal galactose residues without destroying the HIV gp120-binding activity are functionally equivalent. It is also contemplated that structural modification of one or more sialic acid residues of oligosaccharide portions of a soluble CD4 molecule may be made with the result that terminal sialic acid residues are not removed by neuraminidase; as a result the persistence of the modified sCD4 in circulation is increased. This invention also encompasses the modification of terminal mannose residues so as to inhibit or prevent clearance via the mannose receptor of liver.
Furthermore, a modified sCD4 may be prepared in which sialic acid (e.g., with neuraminidase) and galactose residues (e.g., with galactosidase) are removed to expose mannose residues. Those exposed mannose residues may be structurally altered by the addition of a functional group or small molecule or by mild oxidation treatment, with the result that recognition of this modified sCD4 by the mannose receptor and removal from circulation of liver is prevented or inhibited. For all modified sCD4 molecules, solubility in pharmacological and physiological fluids must be maintained and the biological activity of HIV gp120/160 binding must likewise be maintained.
An object of this invention is a therapeutic composition comprising a concentration of a modified sCD4 effective for binding HIV gp120/gp160 and a pharmaceutically acceptable carrier. Preferably, the half-life in human circulation of said modified sCD4 is greater than about 24 hours. A preferred sCD4 is one which has been treated to remove sufficient sialic acid to expose at least two galactose residues and which has been further treated, e.g., with galactose oxidase and horseradish peroxidase so that clearance of the modified sCD4 from circulation by the galactose-specific receptor of liver is inhibited or prevented.
A further object of the invention is as method for increasing the half-life of a glycoprotein in circulation in a mammal, where the glycoprotein is normally cleared from circulation by the galactose receptor of liver when in an asialo-glycoprotein form. The method comprises the steps of treating said glycoprotein to remove terminal sialic acid residues to produce an asialo-glycoprotein, and oxidizing any galactose residues of said asialo-glycoprotein to produce an oxidized asialo-glycoprotein, whereby removal of said oxidized asialo-glycoprotein by the galactose receptor of liver is inhibited. In a preferred embodiment which specifically exemplifies the prolonging of sCD4 in circulation, sialic acid residues are removed by neuraminidase treatment and the galactose residues are oxidized by treatment with galactose oxidase and horseradish peroxidase.
In principle, the teachings for the structural modification of sCD4 to prolong circulating half-life can be applied to any pharmacologically active protein for which a longer circulating half-life is advantageous, in which intact oligosaccharide chains are not required for the desired biological activity, and for which the oligosaccharide carries the signal of primary importance for clearance from the bloodstream.
DETAILED DESCRIPTION OF THE INVENTION
CD4, as defined herein, is the full-length CD4 polypeptide having the biological activities of native human CD4. Amino acid sequence variations and derivatizations which allow the maintenance of the biological activities of the CD4 protein are included within the definition. Native, CD4, and recombinant CD4 which is synthesized in recombinant eukaryotic cells is a glycoprotein. Maddon et al. (1985), supra, notes that there are two sites for N-linked glycosylation, at about 275 and at about 305. EP 372 752 gives the sugar content of a CD4 molecule, but the exact structure of the oligosaccharide chain(s) is not known. However, it is generally understood in the art that sialic acid (N-acetylneuraminic acid) residues will be terminal in the oligosaccharide side chain of a mature glycoprotein synthesized in a mammalian cell, and that galactose residues will be exposed when sialic acid is absent or removed (See, e.g., Osawa and Tsuji (1987) supra). The art knows that exact oligosaccharide structure of a glycoprotein may vary with respect to sugars present, the glycosylation enzymes present and the relative proportions of each according to the choice of the particular eukaryotic cell in which the recombinant CD4 (or soluble CD4) is synthesized.
As defined herein soluble CD4 (sCD4) is a variant of the CD4 protein which is soluble in water-based pharmaceutical preparations (or pharmaceutically acceptable solvents or compositions which include components in addition to water) and in physiological fluids, including plasma, at a level which is sufficient to achieve a therapeutically effective concentration in circulation. sCD4 proteins include those in which part or all of the transmembrane domain of the primary structure of CD4 has been deleted, for example through truncation of the coding sequence; the cytoplasmic domain of the protein may likewise be deleted without the loss of the desired biological activity of HIV gp120 binding. sCD4 molecules capable of being glycosylated when synthesized in appropriate host cells are described in Smith et al. (1987), supra; Fisher et al. (1988), supra, Hussey et al. (1988), supra; EP Publication No. 385 909, supra; Deen et al. (1988) Nature 331:82-84; all of which are incorporated by reference herein. Unless otherwise noted and like the native full-length CD4, the sCD4 molecule is glycosylated. In any case, the HIV gp120 binding activity of the native CD4 is substantially maintained in the soluble CD4 derivative and modified sCD4 of the present invention. Peterson and Seed (1988), supra, e.g., address the issue of amino acid substitutions and deletions in the N-terminal region of the CD4 and the effects on gp120 binding. It is believed that some form of glycosylation is necessary for protection of sCD4 from degradation in circulation and/or clearance by the kidneys. Thus, sCD4 of the present invention must retain some level of glycosylation: preferably the minimal structural modification of the glycosylation is made which acts to prolong circulating half-life.
For the purposes of monitoring sCD4 molecules or derivatives in an animal model (e.g., in the rat, as described in the Examples), radio-iodinated sCD4 is prepared using, e.g., Bolton-Hunger reagent and instructions for use from Nuclear England Nuclear (Boston, Mass.), or according to any other technique well-known to the art.
Modified sCD4 molecules of the present invention are those with structural alterations (modifications) of the oligosaccharide portions of the glycoprotein which result in prolonged circulating half-life by blocking or inhibiting clearance via sugar-specific receptors of the liver. Preferably the sCD4 glycoproteins are synthesized in a recombinant mammalian host. The chemical and/or enzymatic treatments to produce the structural modifications of the oligosaccharide should not substantially alter the binding reaction of sCD4 with the HIV target protein. It is preferred that the circulating half-life of a modified sCD4 of the present invention be at least about 24-48 hours in humans (or at least about 6-12 hours as measured in a rat animal model). It is most preferable that the structural modification of the oligosaccharide so as to prolong circulating half-life is the most conservative structural change which will achieve this end. A variety of chemical derivatization procedures, or chemical and/or enzymatic procedures, as understood in the art, may be employed to produce the modified sCD4 molecules of the present invention. The modified sCD4 specifically exemplified in the present invention is oxidized asialo-sCD4, in which the terminal galactose residues have been oxidized by treatment with galactose oxidase and horseradish peroxidase. As for full-length CD4, there may be variations in amino acid sequence so long as glycosylation and gp120 binding activity are maintained.
Asialo-sCD4 is a modification of the sCD4 in which the sialic acid residues are wholly or partially absent from the oligosaccharide portion of the molecule so that at least two terminal galactose residues are exposed. Sialic acid residues may be removed by sialidase or neuraminidase treatment; asialo-sCD4 may also be produced by synthesizing sCD4 in a host cell which is unable to add the terminal sialic acid residues during oligosaccharide synthesis. Most preferably, at least two galactose residues are exposed.
Agalacto-asialo-sCD4 is a sCD4 derivative in which terminal sialic acid and galactose residues are absent, either as a result of enzymatic or chemical removal or through synthesis of the sCD4 in a host cell which is deficient in sialic acid and galactose addition. Where galactose residues are terminal in the oligosaccharide portion of a glycoprotein, those galactose residues may be removed with β-galactosidase.
Oxidized asialo-sCD4 is an asialo-sCD4 derivative in which the galactose residues have been oxidized by mild oxidation conditions, for example with galactose oxidase and horseradish peroxidase. Although not wishing to be bound by any particular mechanism, it is believed that such treatment oxidizes the C6 position of the galactose and prevents recognition and removal of the molecule from circulation by the galactose receptor of the liver; thus prolonging the half-life of the modified sCD4 in circulation so that said molecule, either injected alone or in conjunction with any other HIV treatment, is therapeutically effective. Mild oxidation conditions include any chemical or enzymatic oxidation which oxidizes the terminal sugar residue without substantial effect on the gp120 binding function of the sCD4 protein or any protective function of glycosylation on the protein.
Other structural modifications of the oligosaccharide portion of a sCD4 molecule which prolong the circulating half-life by preventing and/or inhibiting removal of sCD4 by the galactose or mannose receptors are within the scope of the invention. While the experimental results described in this specification are consistent with the model for the clearance of asialo-sCD4 from circulation by the hepatocyte galactose receptor, Applicants do not want to be bound by this model. It is understood that other mechanisms may contribute to clearance. It is likely that treatment of the asialo-sCD4 with galactose oxidase and horseradish peroxidase prevented binding of terminal sugar residues by the galactose receptor. Such modifications can include the structural modification of sialic acid of the glycoprotein so that neuraminidases cannot remove the terminal sialic acid residues to expose the galactose residues which could then mediate clearance by virtue of their recognition by the galactose specific receptor of liver. An asialo-sCD4 can be modified by the addition of functional groups to the galactose so that recognition and removal from circulation by the galactose receptor is prevented or inhibited. Chemical modification or derivatization of the C6 position of galactose is preferred to maximize half-life and minimize clearance without significantly affecting gp120 binding function and without eliciting negative physiological reactions; minimal and mild treatment is preferred. Functional groups or other structure-modifying molecules in this invention to be added to the oligosaccharide portion of an sCD4 exclude any polymeric substituents. Also contemplated are analogous structural changes to terminal mannose residues of asialoagalacto-sCD4 which will inhibit or prevent clearance from circulation via the mannose receptor of Kupffer cells of the liver. The binding of modified sCD4 molecules to gp120 will not be affected by the structural modifications to the oligosaccharide portion of the molecule.
For any modified sCD4 molecule of the present invention it is most desirable that an immunological response will not be elicited in a human patient exposed to the modified sCD4. It is also required that the HIV gp120 binding activity is not significantly decreased to detrimentally affect the therapeutic function of sCD4 by the structural modification employed to confer prolonged circulation. It is also most desirable that any structural modification of a sCD4 molecule does not result in toxicity in a patient to which that modified sCD4 is administered. Clearly for use in therapeutics, the modified sCD4 should have minimal toxic, irritant or other side effects on administration to humans. The ability of a modified sCD4 molecule to bind HIV gp120 can be determined using a test such as that described in EP 372 752, published Jun. 13, 1990, which document is incorporated by reference herein.
The circulating half-life of a protein (or glycoprotein) is the time for the initial blood concentration of that protein to fall to half the initial concentration.
As it relates to the modified sCD4 molecules of the present invention, the term biological activity refers to the ability of the sCD4-related molecule to bind the HIV gp120 (or gp160) with substantially the same affinity as the unmodified sCD4 molecule. Modifications which substantially decrease the biological activity of sCD4 are to be avoided. Once the modified sCD4 has bound the HIV gp120, the bound HIV cannot infect a susceptible cell, thus preventing the spread of viral infection. Similarly, an HIV-infected cell expressing gp120 on its surface and where gp120 is bound to an sCD4 molecule, cannot participate in syncytium formation with a cell expressing CD4 on its surface. The inhibition of syncytium formation further contributes to the therapeutic effect of an sCD4-related protein in an HIV-infected individual. Bound complexes of modified sCD4 with HIV via gp120 or with a patient's cells via surface gp120 may also be targeted for removal from the circulation, for example, using an extracorporeal device with means for removal of sCD4-gp120 complexes, either associated with viral particles or with cells in circulation. Similarly, HIV particles or HIV-infected cells may be targeted for destruction via bound modified sCD4 molecules.
The modified sCD4 molecules of this invention may be purified by any means known to the art before formation into therapeutic compositions. Therapeutic compositions are formulated using a modified sCD4 with a prolonged circulating half-life and a physiologically acceptable carrier; such compositions can be sterilized by any means known to the art which does not significantly alter either the desired biological activity or the prolonged half-life in circulation. In addition, the modified sCD4 molecules of the present invention may be used in conjunction with other compositions useful in the treatment or prophylaxis of AIDS in HIV-infected individuals. Such other compositions include, but are not limited to, AZT, DDC, DDI, neutralizing antibodies, immunocytotoxins, gp120 fragments and HIV vaccine preparations.
For glycoproteins other than sCD4 for which a derivative with prolonged circulating half-life is desired, the skilled artisan can apply the teachings of this disclosure. In a rat model system, as described herein, the artisan can determine whether the galactose receptor is the primary means of clearance by preparing a radiolabeled, desialylated derivative, testing for bile excretion and also for competition by asialofetuin of liver-associated counts. Inhibition of clearance with co-injection of asialofetuin and appearance of asialoglycoprotein-associated radioactivity indicates clearance by the liver galactose receptor. Then, for example, the glycoprotein of interest can be desialylated, preferably oxidized under mile conditions, e.g., with galactose oxidase and horseradish peroxidase, and prolonged half-life can be confirmed in the animal model as described herein. Analogous appropriate tests and treatments will be readily apparent to the skilled artisan when clearance by another sugar receptor is the mode of clearance. For any glycoprotein in which sialic acid residues are normally present, treatment with sialotransferase under appropriate conditions to ensure complete sialylation will also prolong circulating half-life.
In principle, the teachings presented herein may be applied to any sCD4 modified to improve circulating half-life and/or HIV gp120/gp160 binding in such a way that glycosylation during synthesis is not prevented. Furthermore, mixtures of sCD4-related molecules and modified sCD4 molecules may be combined in a therapeutic composition useful for prophylaxis or treatment of HIV infection and/or for alleviation of the detrimental effects of HIV infection. A uniform modified glycoprotein may be incorporated in a therapeutic composition or a mixture of modified glycoprotein may be formulated in such a composition, so long as the desired therapeutic action is achieved by those molecules and so long as clearance by sugar-specific receptors mediating clearance is inhibited or prevented by the modification or modifications made to said glycoprotein. This methodology is applicable to therapeutic sCD4 molecules or to other therapeutically useful glycoproteins which are cleared from circulation by sugar-specific receptors.
It will be readily apparent to those of ordinary skill in the art that assays, reagents, procedures and techniques other than those specifically described herein, can be employed to obtain the same or equivalent results and achieve the goals described herein. For example, chemical means of oxidation or removal of sialic acid can be readily substituted for enzymatic means specifically described. All such alternatives are encompassed by the spirit and scope of this invention.
EXAMPLE 1
Fate of Circulating Soluble CD4
This example describes the elucidation of the clearance mechanism for circulating recombinant soluble CD4 (sCD4) in the rat animal model. The recombinant sCD4 used herein is the product of a truncated coding sequence of CD4. The terms [ 125 -I]-sCD4 and sCD4 are used interchangeably but only radiolabelled sCD4 was used in these experiments. The [ 125 I]-sCD4 used in the experiments described herein was obtained from Biogen, Cambridge, Mass., and was stored at -70° C. prior to use. The radioactive sCD4 used in these experiments had a specific activity of about 10 microcuries per microgram of protein.
The rat is the model animal system used to study sCD4 clearance from circulation. The studies are performed using the following general scheme.
Rats are fasted overnight and then weighed before a clearance experiment is begun. Then each rat is anaesthetized by intraperitoneal injection of an appropriate amount of an aesthetic, e.g., 5.2 mg sodium pentobarbital per 100 g body weight.
sCD4 is prepared for injection by preparing 0.15M sodium chloride (NS) to which 1 mg bovine serum album (BSA) is added.
Then [ 125 I]-sCD4 is added, preferably about 100,000 cpm as measured in a gamma counter. It is necessary to add sCD4 to solutions already containing BSA and to pretreat equipment with BSA because otherwise the sCD4 tends to adhere to the walls of test tubes, pipet tips, etc. The use of BSA as a carrier protein tends to reduce the amount of sCD4-radioactivity adhering to tubes, etc.
The sCD4 sample is drawn up into a BSA-coated 1 cc syringe, and a second syringe is prepared with 1 ml NS containing I mg/ml BSA to flush the IV tubing after sCD4 injection. A peristaltic pump and tubing are prepared with 0.15M NaCl.
When the rat is thoroughly anaesthetized, the peritoneum is opened and the abdominal cavity is exposed with a 2.5 inch vertical cut. The are is flushed with 0.15M NaCl and covered with an NS-soaked gauze sponge which is kept moist throughout the experiment. An IV is secured in the tail. The sample is injected and the IV tubing is then flushed with NS. Timing is started half-way through the 1 ml NS flush. A NS flush continues at 7 ml/h throughout the course of the experiment. The peristaltic pump is stopped at the end of the experiment. For long term experiments, the sample and the 1 ml flush are administered under anesthesia without opening the peritoneal cavity. At the end of a long-term (greater than 2 hr) experiments, the animal is again anesthetized, and the peritoneal cavity is opened, the portal vessels are ligated with suture and the animal is exsanguinated by intracardiac puncture, simultaneously collecting blood in a measured volume that is placed in vials containing EDTA as anticoagulant. In all cases, the portal vessels were ligated after opening the peritoneal cavity, and this ligation signals the end of the experiment.
To collect a blood sample, the heart is pierced and about 5 ml blood is collected. A measured volume is placed in a glass counting vial before the blood clots and radioactivity is determined by gamma counting.
The liver is removed immediately after the blood sample is taken if a liver sample is desired. The hepatic portal vein is sutured before the liver is actually removed. The liver is rinsed in distilled water, blotted, weighed and placed in a glass counting vial. If desired, spleen, kidneys, intestine can be removed, rinsed, blotted and counted in a gamma counter.
All glassware, tubing, pipets, etc. are also counted.
For determination of [ 125 I]-sCD4-related counts appearing in the bile, the bile duct is cannulated and means for collecting bile are prepared in the rat before the sCD4 sample is injected.
To look at clearance, rats were injected with sCD4 with or without infusion of either the glycoprotein fetuin or asialofetuin. At the noted times after injection of the sCD4, rats were sacrificed and the radioactivity in the blood samples and in livers was determined. Table 1 summarizes the results of this experiment. The asialofetuin infusion resulted in about a 46% increase in blood-associated sCD4 radioactivity.
These results suggested that there might be heterogeneity in the [ 125 I]-sCD4 molecules. The relative increase in radioactivity in the bloodstream at 10 min after injection with sCD4 and asialofetuin as compared with injection of sCD4 alone or injection of sCD4 and fetuin suggests that a major mode of clearance is the galactose receptor in hepatocytes. It is proposed that sCD4 molecules with complete sialylation had a long half-life and that those with uncovered galactose residues have a short half-life in circulation.
EXAMPLE 2
Preparation of Control and Asialo-sCD4
To further study the mechanism for clearance of sCD4, a desialylated preparation of [ 125 -I]-sCD4 was made for comparison with an untreated control preparation.
10 microliters of [ 125 I]-sCD4 containing about 0.2 ug protein was added to 2.2 ml 0.1M sodium acetate (pH 4.5) containing 1 mg/ml BSA. 1 ml of this mixture was transferred to each of two 15 ml conical centrifuge tubes and 1 ml 0.1M sodium acetate was added to each. Then a 20 microliter aliquot of neuraminidase Type V (Sigma Chemical Co., St. Louis, Mo.) (about 0.1 units) was added to one of the tubes, and the other served as an untreated control. From this point on in the preparation, the tubes were treated in parallel. Both tubes were incubated at 37° C. for 2 hr. Each mixture was then dialyzed using tubing with an exclusion limit of 12,000-14,000 d against 1 liter TC-PBS buffer overnight at 4° C. TC-PBS contains 6.5 mM sodium phosphate, 3.5 mM potassium phosphate, 0.14M sodium chloride (pH 7.40). The dialysates were then collected, stored at 4° C., and the radioactivity in aliquots of each were determined by liquid scintillation counting (10 microliters of control sCD4=21325; 10 microliters of asialo-sCD4=19490 cpm). Treatment of the sCD4 with neuraminidase yielded substantially desialylated sCD4 (asialo-sCD4). The control sample was assumed to be fully sialylated sCD4.
In some experiments a second neuraminidase treatment followed that described above. After the first two hour incubation, an additional 200 microliters neuraminidase (1 unit) was added and incubation was continued an additional two hours at 37° C.
To determine the radioactivity associated with relatively high molecular weight material, aliquots of the asialo-sCD4 and of the control sCD4 were precipitated with trichloroacetic acid as follows: 10 microliters of BSA (1 mg) was added to a borosilicate tube (5 ml size) and then a 890 microliter aliquot of dialyzed sCD4 and TC-PBS was added. After mixing, 100 microliters of cold 100% TCA was added, the samples were mixed and held on ice for 10 min. Then each tube was centrifuged for 10 min. 500 microliter supernatant samples, pellets, and the syringe used to measure the sample were then counted.
Rats R11 and R14 were injected with asialo-CD4 (twice digested with neuraminidase). It appears that the neuraminidase treatment to remove terminal sialic acid residues results in a significant relative increase in liver-associated radioactivity and a substantial relative decrease in bloodstream-associated radioactivity at 10 min post-injection. The results in Tables 1 and 2 suggest that circulating sCD4 is removed by the galactose receptor of the liver. The results also suggest some heterogeneity in the sCD4 preparation with respect to sialylation levels of the recombinant sCD4.
To attempt to lengthen the circulating lifetime of sCD4 by preventing recognition and binding of asialo-sCD4 by the hepatocyte galactose receptor, asialo-sCD4 was treated with galactose oxidase and horseradish peroxidase to oxidize the carbinol residues of galactose residues to aldehydes. It was found necessary to incorporate protease inhibitors in the oxidation reaction mixtures. The oxidations were performed as follows:
Galactose oxidase (Sigma Chemical Co., St. Louis, Mo.) was diluted to 0.5 units/ml in 0.1M sodium phosphate (pH 7.0). Horseradish peroxidase (Sigma Chemical Co., St. Louis, Mo.) was diluted to 0.5 units/microliter in 0.1M sodium phosphate (pH 7.0). Digestions were performed in 0.15M sodium chloride, 45 mM sodium acetate, 20 mM sodium phosphate (pH 7.0). The final quantities of galactose oxidase and horseradish peroxidase were 15 units per oxidation reaction and 20 units per oxidation reaction, respectively. All glassware, pipets, etc. were precoated with a 1 mg/ml solution of BSA. A reaction volume of 1.0 ml contained 150 microliters of asialo-sCD4 (about 0.5 ug), 30 microliters (0.15 units) galactose oxidase, 20 units horseradish peroxidase, and 1 mg BSA. The following protease inhibitors were added to the oxidation reactions as follows: 20 microliters 0.1M phenylmethylsulfonyl fluoride in toluene, 20 microliters 0.1M 1,10-phenanthroline, 4 microliters 0.5M iodoacetamide in water. Control reactions included one without GO and HPO, and one without asialo-sCD4. Reactions were carried out in 15 ml conical centrifuge tubes precoated with BSA. After incubation for 66 hr at 25° C., reaction mixtures were individually dialyzed to remove low molecular weight reaction products, toluene, etc. and to adjust the buffer environment to tissue culture-PBS. Immediately before injection, the control asialo-sCD4 sample was prepared by combining the two control reaction tubes; thus the control asialo-sCD4 was exposed to GO and HPO for no more than about 1 min. Analysis of the reaction products showed that there was insignificant proteolytic activity in the enzyme preparations if the above-noted protease inhibitors were included.
Rats were injected with oxidized asialo-sCD4 and control asialo-sCD4. Radioactivity in liver and blood samples was determined at intervals after injection. The results are summarized in Table 3. At 20 min post-injection, there was approximately five-fold more label in the bloodstream for the asialo-sCD4 treated with GO and HPO as compared with control asialo-sCD4. The persistence of the oxidized asialo-sCD4 in circulation was clearly greater than that of asialo-sCD4 or sCD4 (See, e.g., Tables 1 and 3).
The appearance of [ 125 I]-label in the bile was monitored in one rat injected with sCD4 and one injected with GO/HPO oxidized asialo-sCD4. Bile samples were collected at 15 min intervals over 2 hr post-injection and radioactivity was measured in each. The results are presented in Table 4. Over seven times as many [ 125 I]-sCD4-associated counts as [ 125 I]-oxidized asialo-sCD4 enter the bile within the first two hours post-injection. The relative radioactivity associated with liver and bile is nearly twice as great for injection of the intact sCD4 as for the injection of oxidized asialo-sCD4. Thus, the oxidation of the galactose moieties of asialo-sCD4 appears to interfere with clearance from the bloodstream by hepatocytes. The results obtained in the foregoing experiments are consistent with clearance of asialo-sCD4 by the galactose receptor in hepatocytes.
The estimated half-life of sCD4 in the circulation of rat is less than 15 min, at least in the early phase of clearance. The estimated half-life of asialo-sCD4 is less than 5 min; clearance is linear. In contrast, the estimated half-life in circulation for oxidized asialo-sCD4 is greater than 6 hrs. Thus, treatment of asialo-sCD4 with galactose oxidase and horseradish peroxidase dramatically increases circulating half-life.
Deglycosylated sCD4 was prepared to determine the effect of removal of the oligosaccharide side chains from the sCD4 proteins on circulating half-life and to determine the route of clearance of the sCD4 polypeptide from the bloodstream. 500 microliters of asialo-sCD4 was mixed with 4.2 microliter of Endoglycosidase F in 5mM EDTA 50% glycerol (New England Nuclear, Boston, Mass.), 12.5 microliters of 0.2M EDTA and double distilled water to 1 ml. The corresponding control was identical except that 4.2 microliters of 5 mM EDTA in 50% glycerol was substituted for the endoglycosidase F. All tubes, dialysis tubing, pipet tips, etc. were precoated with BSA as above prior to use. Reaction and control tubes were incubated at 37° C. for 2 hr. Then mixtures were dialyzed against 5 mM EDTA for 5 hr and then against TC-PBS overnight at 4° C.
sCD4 was also treated to remove all oligosaccharides with a combination of Endoglycosidase F (New England Nuclear, Boston, Mass.) and N-glycosidase F (BEM, Indianapolis, Ind.). As above, all glassware and pipet tips were precoated with BSA. To a volume of 1 ml in 50 mM sodium phosphate (pH 7.0), there was mixed 50 microliters of sCD4 mix and 195 microliter enzyme mix. The control in which oligosaccharides were not removed contained 195 microliters 100 mM sodium phosphate, 25 mM EDTA, 50% glycerol in place of the enzyme mix. sCD4 mix was made by mixing 20 microliters of sCD4 with 110 microliters of 1 mg/ml BSA.
One rat was injected with the substantially deglycosylated sCD4 and another with the control sCD4 treated in parallel. Blood samples were taken at intervals and radioactivity was determined. The results are summarized in Table 5. It appears that the sCD4 polypeptide is cleared from the bloodstream somewhat more quickly than the corresponding intact glycoprotein molecule. These results suggest that clearance by the kidney, degradation and excretion in the urine is greater for the substantially deglycosylated sCD4 than for control glycosylated sCD4.
TABLE 1__________________________________________________________________________Distribution of [.sup.125 I]-sCD4in Liver and Blood SamplesTime Input % Input % InputRat Post-Injection Counts Counts Associated Counts in MaterialNumber(min) (cpm) with Liver 1 ml Blood Injected__________________________________________________________________________R1 5 98,976 27.2% 2.2% sCD4R2 5 113,076 26.1% 2.3%R4 10 125,480 12.3% 4.0% sCD4 plus Asialo-FetuinR5 10 126,053 19.8% 2.7% sCD4 plus Fetuin__________________________________________________________________________
TABLE 2__________________________________________________________________________Distribution of [.sup.125 I]-Asialo-sCD4in Liver and Blood Samples Input % InputTime Radio- Radioactivity % InputRat Post-Injection activity Associated Counts in MaterialNumber(min) (cpm) with Liver 1 ml Blood Injected__________________________________________________________________________R11 10 124,954 61.8% 0.6% Asialo-sCD4R14 10 129,942 49.1% 0.6% Asialo-sCD4__________________________________________________________________________
TABLE 3__________________________________________________________________________Distribution of [.sup.125 I]-sCD4in Liver and Blood for Asialo-sCD4with Intact and with Oxidized Galactose ResiduesTime Input % Input % InputRat Post-Injection Counts Counts Associated Counts in MaterialNumber(min) (cpm) with Liver 1 ml Blood Injected__________________________________________________________________________R26 10 141,621 64.6% 0.64% Asialo-sCD4R27 20 140,393 54.3% 0.48%R25 20 102,695 23.3% 2.6%R28 120 144,118 17.8% 1.9% GO/HPO-treatedR23 360 204,864 14.5% 1.6% Asialo-sCD4R29 1080 138,563 10.5% 0.2%__________________________________________________________________________
TABLE 4__________________________________________________________________________sCD4 Excretion Into BileTime After Injection R3 (sCD4) R28 (GO/HPO-Asialo-sCD4)__________________________________________________________________________ 15 min 1476 536 30 min 6397 772 45 min 8624 1094 60 min 7611 1183 75 min 6629 1038 90 min 4719 928105 min 3716 884120 min 2980 760Total Bile: 42152 (38% input) 7195 (5% input)Total Bile & Liver: 48963 34774Total Input Counts: 111,638 144,118Approximate Percent of 40-45% 24%Input Counts Associatedwith Bile and Liver__________________________________________________________________________
TABLE 5__________________________________________________________________________Effect of Deglycosylation of sCD4(Endoglycosidase F + N-glycosidase F-treated Asialo-sCD4)on Distribution of [.sup.125 I]-sCD4 in Liver and BloodTime Total % InputPost- Input % Input % Input Count inRat Injection Counts Counts Associated Counts in Urine & MaterialNumber(min) (cpm) with Liver 1 ml Blood Bladder Injected__________________________________________________________________________R32 5 127,613 ND* 1.3% ND Deglyco- sylated sCD415 ND 0.81 ND30 ND 0.75 ND60 ND 0.53 ND90 ND 0.44 ND120 6.3% 0.23 25.4%R33 5 111,190 ND 2.0% ND sCD415 ND 1.13% ND30 13.3% 0.82% 0.1%__________________________________________________________________________ *ND = Not Determined
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A method for extending soluble CD4 serum half-life in mammals is described. The method comprises modifying soluble CD4 glycosylation so as to inhibit clearance from serum. In a preferred embodiment, clearance by hepatocyte galactose receptors is inhibited by removal of soluble CD4 terminal sialic residues followed by oxidation of exposed galactose residues. The modified soluble CD4 molecules are demonstrated to possess extended serum half-life.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an integrated circuit (IC) having circuitry with programmable functions and programmable interconnections. More specifically, the present invention relates to a method and apparatus for converting to and from variable-width data paths.
2. Related Art
In the past, multi-gigabit transceivers (MGTs) have not been included on programmable logic devices (PLDs) for various reasons, where a PLD is any IC which has programmable functions and programmable interconnections. However, commonly owned, copending U.S. patent application Ser. No. 10/090,250 filed on Mar. 1, 2002 entitled “High Speed Configurable Transceiver Architecture” by Suresh M. Menon et al., describes the manner in which MGTs can be included on a PLD, such as a field programmable gate array (FPGA). It would therefore be desirable to optimize the data paths between the core logic of a PLD and the MGTs located on the PLD.
PLD commonly includes one or more data paths, or collections of digital signals routed through the system during processing. The size of a collection, called the “data width” or “data path width” herein, depends on a number of factors. One factor in determining the data path width is the significance of the signals (i.e., the information that the signals represent, and the format of the signals). Another factor is the required speed of operation of the design. Yet another factor is the size constraints introduced by the design. Other factors may also possibly affect the data path width.
In some cases, it may be desirable to modify the width of a data path at some point in the design, changing the extent to which data is propagated in parallel. This may be necessary, for example, because of: different operating speeds in different portions of the design, or different constraints on the data width in different portions of the design. It may also be beneficial for this data width modification to be programmable and to be done dynamically.
It would therefore be desirable to have a PLD capable of implementing a variable-width data path.
SUMMARY
The present invention provides a method and system for converting data on a first bus of a first fixed or variable width to data on a second bus of a second fixed or variable width. An exemplary embodiment of the present invention includes: an integrated circuit (IC) with programmable circuitry having programmable functions and programmable interconnections. The IC further includes: a first module having an output with a first fixed data width or first variable data width; a second module having an input with a second fixed data width or a second variable data width; and a data width converter receiving data from the output of the first module and sending the data to the input of the second module, the data width converter configured to convert data from the first fixed data width or first variable data width to the second fixed data width or the second variable data width, where the first fixed data width is not equal to the second fixed data width.
An embodiment of the present invention provides an integrated circuit (IC) including: programmable circuitry having programmable functions and programmable interconnections, where the programmable circuitry includes a first transmit port having a first fixed data width or a first variable data width, and a first receive port having a second fixed data width or a second variable data width; a transceiver with a second transmit port having a third fixed data width or a third variable data width, and a second receive port having a fourth fixed data width or a fourth variable data width; a transmit converter coupling the first transmit port of the programmable circuitry and the second receive port of the transceiver, where the transmit converter is operably configured to convert the first fixed data width to the fourth variable data width, the first variable data width to the fourth fixed data width, or the first variable data width to the fourth variable data width; and a receive converter coupling the first receive port of the programmable circuitry and the second transmit port of the transceiver. The IC may also have the receive converter operably configured to convert the third fixed data width to the second variable data width, the third variable data width to the second fixed data width, or the third variable data width to the second variable data width.
Further, in another embodiment, the transmit converter couples the first transmit port of the programmable circuitry and the second receive port of the transceiver, where the transmit converter is operably configured to convert the first fixed data width to the fourth fixed data width; and the receive converter couples the first receive port of the programmable circuitry and the second transmit port of the transceiver. The receive converter operably configured to convert the fourth fixed data width to the second fixed data width.
The present invention will be more fully understood in view of the following description and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram of a programmable logic device in accordance with one embodiment of the present invention.
FIG. 2-1 is a block diagram of a multi-gigabit transceiver and variable-width interface in accordance with one embodiment of the present invention.
FIG. 2-2 is a block diagram of another embodiment of the present invention;
FIG. 2-3 is a block diagram of yet another embodiment of the present invention;
FIGS. 3A , 3 B, 3 C and 3 D show the clock waveforms (CLK 1248 ) used to control variable-width 1-bit, 2-bit, 4-bit and 8-bit data paths, respectively, as well as the clock waveform (CLK 2 ) used to control fixed-width 2-bit data paths in accordance with one embodiment of the present invention.
FIG. 4 is a circuit diagram of a transmit variable-width interface in accordance with one embodiment of the present invention.
FIG. 5 is a circuit diagram of a transmit width control circuit used to control the transmit variable-width interface of FIG. 4 , in accordance with one embodiment of the present invention.
FIG. 6 is a waveform diagram illustrating the relationship between the CLK 2 signal, the CLK 1248 signal and a delayed CLK 1248 signal (CLK 1248 D), which is enabled when an 8-bit variable-width data path is selected in accordance with one embodiment of the present invention.
FIGS. 7A , 7 B, 7 C, and 7 D are waveform diagrams illustrating the timing of the transmit variable-width interface of FIG. 4 for 1-bit, 2-bit, 4-bit and 8-bit data paths, respectively, in accordance with one embodiment of the present invention.
FIG. 8 is a circuit diagram of a receive variable-width interface in accordance with one embodiment of the present invention.
FIG. 9 is a circuit diagram of a receive width control circuit used to control the receive variable-width interface of FIG. 8 , in accordance with one embodiment of the present invention.
FIGS. 10A , 10 B, 10 C, and 10 D are waveform diagrams illustrating the timing of the receive variable-width interface of FIG. 8 for 1-bit, 2-bit, 4-bit and 8-bit data paths, respectively, in accordance with one embodiment of the present invention.
FIG. 11 is a waveform diagram of three clock signals (CLK — A, CLK — B and CLK — C) used to control the 8-bit wide data path of the receive variable-width interface of FIG. 8 in accordance with one embodiment of the present invention.
DETAILED DESCRIPTION
FIG. 1 is a block diagram of a programmable logic device (PLD) 100 in accordance with one embodiment of the present invention. In the described embodiment, PLD 100 is a field programmable gate array (FPGA) that includes select I/O blocks (labeled I/O), digital clock managers (labeled DCM) and multi-gigabit transceivers (labeled MGT) located around the perimeter of the device. Each MGT includes a full-duplex differential data channel, such as channel 115 . PLD 100 also includes core block 150 , which includes an array of configurable logic blocks (CLBs), programmable routing circuitry, and optional embedded hardwire circuitry, for example, processor block 130 , in the described embodiment. Variable-width interface circuits (labeled VWIF) are located between each of the MGTs and core block 150 . Select I/O blocks I/O, digital clock managers DCM and core block 150 are well known to those of ordinary skill in the art. These conventional elements of PLD 100 are described in detail in “Virtex™-II Platform FPGA Handbook”, December 2000, pages 33–75, and in the Virtex II Pro™ Platform FPGA Handbook, October 2002, available from Xilinx Inc., 2100 Logic Drive, San Jose, Calif. 95124.
PLDs, such as FPGAs, have not previously included multi-gigabit transceivers or variable-width interfaces. As described in more detail below, some of the variable-width interfaces (VWIFs) enables a data path between core block 150 and the corresponding MGT to have a selectable data path width. For example, variable-width interface VWIF 111 enable data paths to core block 150 having widths of N, 2N, 4N or 8N, where N is an integer. Both the transmit and receive data paths between VWIF 111 and MGT 110 have widths equal to M, where M is an integer. In the examples described below, M is equal to 2N, although this is not necessary.
In other embodiments of the present invention, the VWIFs may connect the core block 150 to I/Os, e.g., 122 and 124 , and/or a processor block 130 to one or more CLBs 132 in the core block 150 . VWIF 124 has data paths to/from core block 150 having variable widths of N, 2N, 4N or 8N and data paths to/from I/O 122 having fixed data width M. VWIF 128 has data paths to/from core block 150 having variable widths of N, 2N, 4N or 8N and data paths to/from I/O 122 having variable widths of N, 2N, 4N or 8N. VWIF 134 has data paths to/from CLBs 132 in core block 150 having variable widths of N, 2N, 4N or 8N and data paths to/from processor block 130 , embedded in core block 150 , having fixed data width M. In yet other embodiments processor block 130 may be replaced by a digital signal processor (DSP), a Block random access memory (BRAM), RAM, non-volatile memory, one or more CLBs, and application specific integrated circuit or other hardwired circuitry.
FIG. 2-1 is a block diagram illustrating multi-gigabit transceiver 110 and variable-width interface 111 in accordance with one embodiment of the present invention. MGT 110 includes a physical media access (PMA) sublayer 201 , which includes a serializer/deserializer (SERDES) 211 having a 20-bit wide serializer data input port 212 , a 1-bit wide serializer data output port 213 , a 1-bit wide deserializer data input port 214 , and a 20-bit wide deserializer data output port 215 . MGT 110 also includes a physical coding sublayer (PCS) 202 , which includes transmit processing block 221 and receive processing block 222 coupled to the 20-bit wide serializer data input port 212 and the 20-bit wide deserializer data output port 215 , respectively. Although MGTs have not previously been included on programmable logic devices, the various elements of MGTs are well known to those of ordinary skill in the art.
Transmit processing block 221 includes a 16-bit wide transmit data input bus 231 , and receive processing block 222 includes a 16-bit wide receive data output bus 232 . Thus, in the described embodiment, M is equal to 16. The widths of transmit data input bus 231 and receive data output bus 232 are fixed in the described embodiment. Transmit data input bus 231 and receive data output bus 232 are coupled to variable-width interface 111 . More specifically, transmit data input bus 231 is coupled to transmit variable-width interface 241 , and receive data output bus 232 is coupled to receive variable-width interface 242 . Both transmit variable-width interface 241 and receive variable-width interface 242 are coupled to the programmable interconnect resources 250 of core block 150 .
In accordance with one embodiment, variable-width interface 111 supports a variable-width transmit data path 251 , which is created from programmable interconnect resources 250 , having a width of 8-bits, 16-bits, 32-bits or 64-bits. Similarly, variable-width interface 111 supports a variable-width receive data path 252 , which is created from programmable interconnect resources 250 , having a width of 8-bits, 16-bits, 32-bits or 64-bits. Thus, in the described embodiment, N is equal to 8. The variable-width data paths 251 – 252 can be controlled to have the same width, or different widths, in different embodiments of the present invention. Advantageously, the variable-width data paths 251 – 252 can have a smaller width, the same width, or a wider width with respect to the width of data paths 231 – 232 . This provides flexibility in operating PLD 100 .
Simplified representations of transmit variable-width interface 241 and receive variable-width interface 242 will now be described in more detail. As described above, M is equal to 16 and N is equal to 8 in the example illustrated by FIG. 2-1 . However, the following simplified examples describe a transmit variable-width interface and a receive variable-width interface having a width M equal to two and a width N equal to 1. Given these examples, one of ordinary skill can easily expand these interfaces to create larger interfaces, such as the one defined by FIG. 2-1 . With N equal to 1, variable-width data paths 251 – 252 can have widths equal to 1-bit, 2-bits, 4-bits and 8-bits. With M equal to 2, fixed-width data paths 231 – 232 have widths equal to 2-bits. FIGS. 3A , 3 B, 3 C and 3 D show the clock waveforms (CLK 1248 ) used to control the variable-width 1-bit, 2-bit, 4-bit and 8-bit data paths, respectively, as well as the clock waveform (CLK 2 ) used to control the fixed-width 2-bit data paths within variable-width interface 111 . The waveforms shown in FIGS. 3K–3D indicate not only the relative frequencies of the two clock signals CLK 2 and CLK 1248 , but also their phase relationship.
The described design assumes that all flip-flops (described below) in transmit variable-width interface 241 and receive variable-width interface 242 are positive edge triggered. The described design also assumes that in order to eliminate flip-flop hold time as a critical design issue, it is required that rising (positive) edges of the CLK 2 and CLK 1248 signals are not aligned. The latter requirement is met by defining the clock waveforms CLK 2 and CLK 1248 such that the rising edges of the slower clock signal are aligned with falling edges of the faster clock signal. In the case of the 2-bit data path ( FIG. 3B ), either clock signal CLK 2 or clock signal CLK 1248 may be regarded as the “faster” or “slower” clock signal for the purpose of this requirement.
An alternative embodiment of FIG. 2-1 is shown in FIG. 2-2 . The MGT 110 of FIG. 2-1 is replaced by a transceiver 312 having a SERDES circuit 314 . The transceiver 312 is any conventional transceiver as known to one of ordinary skill in the arts. There is a 1-bit serial input and a 1-bit serial output into/out of transceiver 312 as shown by label 310 . Data bus or data path 324 has a width of M 1 bits. Data bus or data path 326 has a width of M 2 bits. M 1 and M 2 are positive integers. Data buses 324 and 326 may have fixed or variable widths and may be created using programmable interconnect resources. Data bus 324 is coupled to transmit (TX) variable-width interface (I/F) 320 (similar to TX variable-width I/F 241 ), and data bus 326 is coupled to receive (RX) variable-width interface (I/F) 322 (similar to RX variable-width I/F 242 ). Both transmit variable-width interface 320 and receive variable-width interface 322 are coupled to core block 150 via the programmable interconnect resources that create data bus 332 with width of N 1 bits and data bus 334 with width of N 2 bits, where N 1 and N 2 are positive integers.
In one example of the alternative embodiment, N 1 equals N 2 , and N 1 has a width selectable from a group having widths of 8-bits, 16-bits, 32-bits, and 64-bits. M 1 equals M 2 , and M 1 has a width selectable from a group having widths of 16-bits and 32-bits. The TX Variable Width I/F 320 and the RX Variable Width I/F 322 may be included in core block 150 , and data buses 324 and/or 326 may be created from programmable interconnect resources to be either 16 or 32 bits. In other embodiments, M 1 , M 2 , N 1 and N 2 have various combinations of positive integers and fixed or variable data widths. In an alternative embodiment the TX Variable Width I/F 320 and the RX Variable Width I/F 322 may be hardwired circuitry. In yet another embodiment, the TX Variable Width I/F 320 and the RX Variable Width I/F 322 may be combined into one module, buses 324 and 326 may be combined into a bi-directional bus, and buses 332 and 334 may be combined into another bi-directional bus.
Yet another embodiment of the present invention is shown in FIG. 2-3 . Two modules 340 and 360 are connected together by data width converters 348 and 350 . The modules 340 and 360 and data width converters 348 and 350 are located on an integrated circuit having programmable logic and programmable interconnections. Modules 340 and 360 , for example, may include CLBs, serdes circuitry, a transceiver, an I/O module, an embedded microprocessor core, a hardwired digital signal processing core, or other programmable and/or hardwired circuitry. The data width converters 348 and 350 may be hardwired or formed using programmable logic. In addition the data width converters 348 and 350 may be combined into one data width converter circuit. Also buses 346 and 348 may be combined into one bi-directional bus and buses 352 and 354 may be combined into another bi-directional bus. The data width converter, e.g., 348 or 350 , receives a first fixed or variable data width and converts the data width to a second fixed or variable data width. The data width conversion circuitry used has been explained earlier with reference to FIGS. 2-1 and 2 - 2 .
Module 340 has an input port IN 342 and an output port OUT 344 . For illustration purposes, let module 340 be an embedded microprocessor such as in Virtex II Pro™ FPGA from Xilinx Corp. of San Jose, CA. Bus 346 of width M 3 may be an input data bus into IN 342 , and bus 348 of width M 4 may be an output address bus from OUT 344 of the microprocessor. Module 360 in this example is part of the FPGA's programmable logic fabric, which may include a block random access memory (BRAM). Module 360 has output port OUT 362 and input port IN 364 , which may represent the address (IN 364 ) to the BRAM and the data (OUT 362 ) retrieved from the address. IN 364 receives the address from bus 354 of width N 4 and OUT 362 sends data to bus 352 of width N 3 . N 3 , N 4 , M 3 , and M 4 are positive integers.
Data width converter 350 receives the address on bus 348 of width M 4 and converts it to an address on bus 354 of width N 4 . The address, in this example, on bus 348 is typically a fixed data width, although in cases of other types of modules, bus 348 can be of a fixed or variable data width. The address on bus 354 is of a fixed or variable data width. Module 360 receives the address and retrieves the data at the address from BRAM. The data is then put on bus 352 of fixed or variable width N 3 and then converted to typically a fixed width M 3 on bus 346 by data converter 348 in order to be used by the microprocessor in module 340 . Again bus 346 may be fixed or variable for other types of modules 340 .
In a programmable FPGA environment, the clock waveforms defined in FIGS. 3A–3D may be generated without additional external components using a single digital clock manager DCM ( FIG. 1 ) located on PLD 100 . Each DCM is similar in functionality to a phase-locked loop (PLL).
Transmit Interface
FIG. 4 is a circuit diagram of a transmit variable-width interface 400 in accordance with one embodiment of the present invention. This interface 400 roughly corresponds with transmit variable-width interface 241 illustrated in FIG. 2-1 . Transmit variable-width interface 400 includes flip-flops A 00 –A 7 , multiplexers MO–M 1 , flip-flops B 0 –B 1 and half-cycle delay 401 . Flip-flops A 00 –A 01 receive input data signal D[0], and flip-flops A 7 –A 1 receive input data signals D[7:1], respectively, from a data path corresponding to variable-width data path 251 . Flip-flops A 00 –A 7 are clocked by the CLK 1248 signal, and provide output data signals D 00 –D 7 , respectively. Multiplexer M 0 receives data values D 00 , D 2 , D 4 and D 6 on the “00”, “01”, “11” and “10” input terminals, respectively. Multiplexer M 0 is controlled by control signals S 1 and S 0 . Multiplexer M 1 receives data values D 01 , D 1 , D 3 , D 5 and D 7 on the “100”, “000”, “001”, “011” and “010” input terminals, respectively. Multiplexer M 1 is controlled by control signals S 2 , S 1 and S 0 . Multiplexers M 0 and M 1 route data signals to flip-flops BO and B 1 , respectively. Flip-flops B 0 and B 1 are clocked in response to the CLK 2 signal, and provide the output signals P 0 and P 1 , respectively.
FIG. 5 is a circuit diagram of a transmit width control circuit 500 used to control transmit variable-width interface 400 of FIG. 4 . Transmit width control circuit 500 generates the control signals required to operate transmit variable-width interface 400 . Transmit width control circuit 500 includes OR gates 501 – 502 , AND gates 511 – 514 and inverters 521 – 522 , which are configured as illustrated to generate the enable signals E 4 — 7 , E 2 — 3 , E 1 , E 01 , and E 00 and the select signals S 2 , S 1 and S 0 .
The data inputs to the transmit variable-width interface 400 include D[7:0] (for the 8-bit data path), D[3:0] (for the 4-bit data path), D[1:0] (for the 2-bit data path), and D[0] (for the 1-bit data path). The clock inputs to transmit variable-width interface 400 include the CLK 1248 clock signal (for the input variable-width data path), and the CLK 2 signal (for the output 2-bit data path). The control inputs to interface 400 include width control signals X 1 , X 2 , X 4 , and X 8 (for variable data-width selection). One and only one of width control signals X 1 , X 2 , X 4 or X 8 is set to a logic high (“1”) value, thereby identifying the selected data path width as 1-bit, 2-bits, 4-bits or 8-bits, respectively. Although the X 2 control signal is not directly used in the described example, it is understood that this control signal X 2 can be used in other variations. Transmit variable-width interface 400 provides a 2-bit output signal P[1:0].
Transmit variable-width interface 400 and control circuit 500 operate as follows. First, the user determines the desired width of the data path into interface 400 . The values of the width control signals X 1 , X 2 , X 4 and X 8 ; the CLK 1248 signal; and the input data values are then determined by this desired width. Table 1 below summarizes the values of the width control signals, the CLK 1248 signal, and the input data values for the selected widths of 1-bit, 2-bits, 4-bits and 8-bits.
TABLE 1
Width
X8
X4
X2
X1
CLK1248
Data
1-bit
0
0
0
1
FIG. 3A
D[0]
2-bits
0
0
1
0
FIG. 3B
D[1:0]
4-bits
0
1
0
0
FIG. 3C
D[3:0]
8-bits
1
0
0
0
FIG. 3D
D[7:0]
The CLK 1248 D clock signal is generated as follows. Half cycle delay flip-flop 401 includes a clock terminal coupled to receive the CLK 2 signal, a data input terminal coupled to receive the CLK 1248 signal, and an enable terminal coupled to receive the X 8 width control signal. If the X 8 width control signal has a logic “0” value (i.e., during 1-bit, 2-bit and 4-bit operation), then the CLK 1248 D signal is held at a reset value of “0”. However, if the X 8 width control signal has a logic “1” value, then flip-flop 401 is enabled. In this case, delay flip-flop 401 causes the CLK 1248 D signal to lag the CLK 1248 signal by one half cycle of the CLK 2 signal. FIG. 6 is a waveform diagram illustrating the relationship between the CLK 2 , CLK 1248 and CLK 1248 D signals when the X 8 width control signal has a logic “1” value.
The various widths of transmit variable-width interface 400 will now be described in detail.
1-Bit Data Path
When transmit variable-width interface 400 is configured to have a 1-bit width, the X 8 , X 4 , X 2 , X 1 signals have values of (0,0,0,1) as illustrated in Table 1. In this case, transmit width control circuit 500 generates enable signals E 4 — 7 , E 2 — 3 , E 1 , E 01 and E 00 , and select signals S 2 , S 1 and S 0 as illustrated in Table 2. Note that the symbol “#” identifies the inverse of a signal. Also note that the enable signals are labeled to identify the flip-flops A 00 –A 7 ( FIG. 4 ) that they enable. Thus, enable signal E 4 — 7 enables flip-flops A 4 –A 7 , enable signal E 2 — 3 enables flip-flops A 2 –A 3 , enable signal E 1 enables flip-flop A 1 , enable signal E 01 enables flip-flop A 01 , and enable signal E 00 enables flip-flop A 00 .
TABLE 2
E4 — 7
E2 — 3
E1
E01
E00
S2
S1
S0
0
0
0
CLK2
CLK2#
1
0
0
Turning to FIG. 4 , these enable and select values have the following effect in transmit variable-width interface 400 . The logic “0” enable signals E 4 — 7 , E 2 — 3 and E 1 disable flip-flops A 1 –A 7 . Enable signals E 01 and E 00 alternately enable flip-flops A 00 and A 01 during alternate half-cycles of the CLK 2 signal. Each time that flip-flop A 01 is enabled, a rising edge of the CLK 1248 signal causes the applied 1-bit data value D[0] to be latched into flip-flop A 01 , and provided as data signal D 01 . The data signal D 01 is applied to the “100” input terminal of multiplexer M 1 . Data signal D 01 is routed through multiplexer M 1 to flip-flop B 1 in response to select signals S 2 , S 1 , S 0 , which have a value of (1,0,0).
Similarly, each time that flip-flop A 00 is enabled, a rising edge of the CLK 1248 signal causes the applied 1-bit data value D[0] to be latched into flip-flop A 00 , and provided as output signal D 00 . Data signal D 00 is applied to the “00” input terminal of multiplexer M 0 . Data signal D 00 is routed through multiplexer M 0 to flip-flop B 0 in response to select signals S 1 and S 0 , which have a value of (0,0).
Flip-flops B 0 and B 1 are clocked in response to the rising edges of the CLK 2 signal, thereby providing the data signals D 00 and D 01 as output signals P 0 and P 1 , respectively. The timing of transmit variable-width interface 400 for a 1-bit data path is illustrated in FIG. 7 A. Note that the offset between the rising edges of the CLK 1248 and the CLK 2 signals (which is equal to half the period of the CLK 1248 clock signal) allows the interface 400 to exhibit adequate set-up and hold times even if the CLK 1248 and CLK 2 signals exhibit small amounts of skew.
2-Bit Data Path
When transmit variable-width interface 400 is configured to have a 2-bit width, the X 8 , X 4 , X 2 , X 1 signals have values of (0,0,1,0) as illustrated in Table 1. In this case, width control circuit 500 generates enable signals E 4 — 7 , E 2 — 3 , E 1 , E 01 and E 00 , and select signals S 2 , S 1 and S 0 as illustrated in Table 3.
TABLE 3
E4 — 7
E2 — 3
E1
E01
E00
S2
S1
S0
0
0
1
0
1
0
0
0
Turning to FIG. 4 , these enable and select values have the following effect in transmit variable-width interface 400 . The logic “0” enable signals E 4 — 7 , E 2 — 3 , and E 01 disable flip-flops A 01 and A 2 –A 7 . Enable signals E 1 and E 00 enable flip-flops A 1 and A 00 , respectively. Each rising edge of the CLK 1248 signal causes the bits D[1] and D[0] of the applied 2-bit data value D[1:0] to be latched into flip-flops A 1 and A 00 , and provided as data signals D 1 and D 00 , respectively. The data signal D 1 is applied to the “000” input terminal of multiplexer M 1 . Data signal D 1 is routed through multiplexer M 1 to flip-flop B 1 in response to select signals S 2 , S 1 , S 0 , which have a value of (0,0,0).
Similarly, data signal D 00 is applied to the “00” input terminal of multiplexer MO. Data signal D 00 is routed through multiplexer M 0 to flip-flop B 0 in response to select signals S 1 and S 0 , which have a value of (0,0).
Flip-flops B 0 and B 1 are clocked in response to the rising edges of the CLK 2 signal, thereby providing the data signals D 1 and D 00 as output signals P 0 and P 1 , respectively. The timing of transmit variable-width interface 400 for a 2-bit data path is illustrated in FIG. 7B . Note that the offset between the rising edges of the CLK 1248 and the CLK 2 signals (which is equal to half the period of the CLK 1248 clock signal) allows the interface 400 to exhibit adequate set-up and hold times even if the CLK 1248 and CLK 2 signals exhibit small amounts of skew.
4-Bit Data Path
When transmit variable-width interface 400 is configured to have a 4-bit width, the X 8 , X 4 , X 2 , X 1 signals have values of (0,1,0,0) as illustrated in Table 1. In this case, width control circuit 500 generates enable signals E 4 — 7 , E 2 — 3 , E 1 , E 01 and E 00 , and select signals S 2 , S 1 and S 0 as illustrated in Table 4.
TABLE 4
E4 — 7
E2 — 3
E1
E01
E00
S2
S1
S0
0
1
1
0
1
0
0
CLK1248
Turning to FIG. 4 , these enable and select values have the following effect in transmit variable-width interface 400 . The logic “0” enable signals E 4 — 7 and E 01 disable flip-flops A 01 and A 4 –A 7 . Enable signals E 2 — 3 , E 1 and E 00 enable flip-flops A 3 , A 2 , A 1 and A 00 . Each rising edge of the CLK 1248 signal causes the bits D[3], D[2], D[1] and D[0] of the applied 4-bit data value D[3:0] to be latched into flip-flops A 3 , A 2 , A 1 , and A 00 , and provided as data signals D 3 , D 2 , D 1 and D 00 , respectively. The data signals D 3 and D 1 are applied to the “001” and “000” input terminals of multiplexer M 1 . The data signals D 2 and D 00 are applied to the “01” and “00” input terminals of multiplexer M 0 .
When the CLK 1248 signal has a value of “1”, data signals D 3 and D 2 are routed through multiplexers M 1 and M 0 , respectively, to flip-flops B 1 and B 0 , respectively, in response to select signals S 2 , S 1 , S 0 , which have a value of (0,0,1).
When the CLK 1248 signal has a value of “0”, data signals D 1 and D 00 are routed through multiplexers M 1 and M 0 , respectively, to flip-flops B 1 and B 0 , respectively, in response to select signals S 2 , S 1 , S 0 , which have a value of (0,0,0).
Flip-flops B 0 and B 1 are clocked in response to the rising edges of the CLK 2 signal, thereby providing the data signals D 3 and D 2 as output signals P 0 and P 1 , respectively, in response to a rising edge of the CLK 2 signal, and providing the data signals D 1 and D 00 as output signals P 0 and P 1 , respectively, in response to the next rising edge of the CLK 2 signal. The timing of transmit variable-width interface 400 for a 4-bit data path is illustrated in FIG. 7C . Note that the offset between the rising edges of the CLK 1248 and the CLK 2 signals (which is equal to one quarter of the period of the CLK 1248 clock signal) allows the interface 400 to exhibit adequate set-up and hold times even if the CLK 1248 and CLK 2 signals exhibit small amounts of skew.
8-Bit Data Path
When transmit variable-width interface 400 is configured to have an 8-bit width, the X 8 , X 4 , X 2 , X 1 signals have values of (1,0,0,0) as illustrated in Table 1. In this case, width control circuit 500 generates enable signals E 4 — 7 , E 2 — 3 , E 1 , E 01 and E 00 , and select signals S 2 , S 1 and S 0 as illustrated in Table 5.
TABLE 5
E4 — 7
E2 — 3
E1
E01
E00
S2
S1
S0
1
1
1
0
1
0
CLK1248
CLK1248D
Turning to FIG. 4 , these enable and select values have the following effect in transmit variable-width interface 400 . The logic “0” enable signal E 01 disables flip-flop A 01 . The logic “1” enable signals E 4 — 7 , E 2 — 3 , E 1 and E 00 enable flip-flops A 1 –A 7 and A 00 . Each rising edge of the CLK 1248 signal causes the bits D[7], D[6], D[5], D[4], D[3], D[2], D[1] and D[0] of the applied 8-bit data value D[7:0] to be latched into flip-flops A 7 , A 6 , A 5 , A 4 , A 3 , A 2 , A 1 , and A 00 , and provided as data signals D 7 , D 6 , D 5 , D 4 , D 3 , D 2 , D 1 and D 00 , respectively. The data signals D 7 , D 5 , D 3 and D 1 are applied to the “010”, “011”, “001” and “000” input terminals of multiplexer M 1 , respectively. The data signals D 6 , D 4 , D 2 and D 00 are applied to the “10”, “11”, “01” and “00” input terminals of multiplexer M 0 , respectively.
The timing of transmit variable-width interface 400 for an 8-bit data path is illustrated in FIG. 7D . At time T 0 , the rising edge of the CLK 1248 signal causes the data values D[7:0] (i.e., A–H) to be latched into flip-flops A 7 –A 1 and A 00 as data signals D 7 –D 1 and D 00 . Prior to time T 1 , the CLK 1248 signal has a logic “1” value and the CLK 1248 D signal has a logic “0” value. As a result, the S 2 , S 1 , S 0 signals have a value of (0,1,0), thereby routing data signal D 7 (i.e., A) and data signal D 6 (i.e., B) through multiplexers M 1 and M 0 , respectively, to flip-flops B 1 and B 0 , respectively. At time T 1 , the rising edge of the CLK 2 signal causes these data signals A and B to be latched into flip-flops B 1 and B 0 , respectively, and provided as output signals P 1 and P 0 .
Just prior to time T 2 , the CLK 1248 signal has a logic “1” value and the CLK 1248 D signal has a logic “1” value. As a result, the S 2 , S 1 , S 0 signals have a value of (0,1,1), thereby routing data signal D 5 (i.e., C) and data signal D 4 (i.e., D) through multiplexers M 1 and M 0 , respectively, to flip-flops B 1 and B 0 , respectively. At time T 2 , the rising edge of the CLK 2 signal causes these data signals C and D to be latched into flip-flops B 1 and B 0 , respectively, and provided as output signals P 1 and P 0 .
Just prior to time T 3 , the CLK 1248 signal has a logic “0” value and the CLK 1248 D signal has a logic “1” value. As a result, the S 2 , S 1 , S 0 signals have a value of (0,0,1), thereby routing data signal D 3 (i.e., E) and data signal D 2 (i.e., F) through multiplexers M 1 and M 0 , respectively, to flip-flops B 1 and B 0 , respectively. At time T 3 , the rising edge of the CLK 2 signal causes these data signals E and F to be latched into flip-flops B 1 and B 0 , respectively, and provided as output signals P 1 and P 0 .
Just prior to time T 4 , the CLK 1248 signal has a logic “0” value and the CLK 1248 D signal has a logic “0” value. As a result, the S 2 , S 1 , S 0 signals have a value of (0,0,0), thereby routing data signal D 1 (i.e., G) and data signal D 00 (i.e., H) through multiplexers M 1 and M 0 , respectively, to flip-flops B 1 and B 0 , respectively. At time T 4 , the rising edge of the CLK 2 signal causes these data signals G and H to be latched into flip-flops B 1 and B 0 , respectively, and provided as output signals P 1 and P 0 .
This process is repeated for the next 8-bit data value (i.e., data signals I-P), as illustrated. Note that the offset between the rising edges of the CLK 1248 and the CLK 2 signals (which is equal to one eighth of the period of the CLK 1248 clock signal) allows transmit variable-width interface 400 to exhibit adequate set-up and hold times even if the CLK 1248 and CLK 2 signals exhibit small amounts of skew.
In the foregoing manner, transmit variable-width interface 400 supports variable data widths of 1-bit, 2-bits, 4-bits and 8-bits in core block 150 , and a fixed data width of 2-bits in MGT 110 .
Receive Interface
FIG. 8 is a circuit diagram of a receive variable-width interface 800 in accordance with one embodiment of the present invention. This interface 800 roughly corresponds with receive variable-width interface 242 illustrated in FIG. 2-1 . Receive variable-width interface operates in response to clock signals CK 2 and CK 1248 . These clock signals CK 2 and CK 1248 are different signals than the clock signals CLK 2 and CLK 1248 described above. However, for purposes of the present description, clock signals CK 2 and CK 1248 have the same phase relationships as clock signals CLK 2 and CLK 1248 , respectively, illustrated in FIGS. 3A–3D .
Receive variable-width interface 800 includes flip-flops J 2 –J 7 , multiplexer M 2 , flip-flops K 0 –K 7 and half-cycle delay 801 . Flip-flops J 2 , J 4 and J 6 receive input data signal Q[0], and flip-flops J 3 , J 5 and J 7 receive input data signal Q[1], from a data path corresponding to fixed width data path 232 ( FIG. 2-1 ). Flip-flops J 2 –J 7 are clocked by the CK 2 signal, and provide output data signals R 2 –R 7 , respectively. Multiplexer M 2 receives data signals Q 0 , R 2 and R 3 on the “0-”, “10” and “11”, input terminals, respectively. Multiplexer M 2 is controlled by control signals T 1 and T 0 . Multiplexer M 2 routes a data signal R 0 to flip-flop KO. Data signals R 1 –R 7 are provided to flip-flops K 1 –K 7 , respectively. Flip-flops K 7 –K 0 are clocked in response to the CK 1248 signal, and provide the output signals R[7:0], respectively.
FIG. 9 is a receive width control circuit 900 used to control receive variable-width interface 800 of FIG. 8 . Receive width control circuit 900 generates the control signals required to operate receive variable-width interface 800 . Receive width control circuit 900 includes inverters 901 – 903 , AND gates 911 – 914 , and OR gates 921 – 922 , which are configured as illustrated.
A 2-bit input data signal Q[1:0] is provided to interface 800 . The data outputs of the variable-width data path include R[7:0] (for the 8-bit data path), R[3:0] (for the 4-bit data path), R[1:0] (for the 2-bit data path), and R[0] (for the 1-bit data path). The clock inputs to receive variable-width interface 800 include the CK 1248 clock signal (for the output variable-width data path), and the CK 2 signal (for the input 2-bit data path). The control inputs to interface 800 include width control signals Y 1 , Y 2 , Y 4 , and Y 8 (for variable data-width selection). One and only one of width control signals Y 1 , Y 2 , Y 4 or Y 8 is set to a logic high (“1”) value, thereby identifying the selected data path width as 1-bit, 2-bits, 4-bits or 8-bits, respectively.
Receive variable-width interface 800 and receive width control circuit 900 operate as follows. First, the user determines the desired width of the data path out of interface 800 . The values of the width control signals Y 1 , Y 2 , Y 4 and Y 8 , the CK 1248 signal, and the input data values are then determined by this desired width. Table 6 below summarizes the values of the width control signals, the CK 1248 signal, and the output data values for the selected widths of 1-bit, 2-bits, 4-bits and 8-bits.
TABLE 6
Width
Y8
Y4
Y2
Y1
CK1248
Data
1-bit
0
0
0
1
FIG. 3A
R[0]
2-bits
0
0
1
0
FIG. 3B
R[1:0]
4-bits
0
1
0
0
FIG. 3C
R[3:0]
8-bits
1
0
0
0
FIG. 3D
R[7:0]
Half cycle delay flip-flop 801 generates the CK 1248 D clock signal in the same manner as flip-flop 401 (See, FIG. 6 ). The various widths of receive variable-width interface 800 will now be described in detail.
1-Bit Data Path
When receive variable-width interface 800 is configured to have a 1-bit output width, the Y 8 , Y 4 , Y 2 , Y 1 signals have values of (0,0,0,1) as illustrated in Table 6. In this case, width control circuit 900 generates enable signals EJ 6 — 7 , EJ 4 — 5 , EJ 2 — 3 , EK 4 — 7 , EK 2 — 3 and EK 1 , and select signals T 1 and T 0 as illustrated in Table 7. The enable signals are labeled to identify the flip-flops J 2 –J 7 and K 0 –K 7 ( FIG. 8 ) that they enable. Thus, enable signal EJ 6 — 7 enables flip-flops J 6 and J 7 , enable signal EJ 4 — 5 enables flip-flops J 4 and J 5 , enable signal EJ 2 — 3 enables flip-flops J 2 and J 3 , enable signal EK 1 enables flip-flop K 1 , enable signal EK 2 — 3 enables flip-flops K 2 and K 3 , and enable signal EK 4 — 7 enables flip-flops K 4 –K 7 . Flip-flop K 0 is always enabled.
TABLE 7
EJ6 — 7
EJ4 — 5
EJ2 — 3
EK4 — 7
EK2 — 3
EK1
T1
T0
0
0
1
0
0
0
1
CK2
Turning to FIG. 8 , these enable and select values have the following effect in receive variable-width interface 800 . The logic “0” enable signals EJ 6 — 7 , EJ 4 — 5 , EK 4 — 7 , EK 2 — 3 and EK 1 disable flip-flops J 4 –J 7 and K 1 –K 7 . The logic “1” enable signal EJ 2 — 3 enables flip-flops J 2 and J 3 . The received data signals Q 0 and Q 1 are latched into flip-flops J 2 and J 3 as data signals R 2 and R 3 , respectively, in response to rising edges of the CK 2 signal. Flip-flops J 2 and J 3 then provide these data signals R 2 and R 3 to the “10” and “11” input terminals, respectively, of multiplexer M 2 . The control signals T 1 –T 0 provided to multiplexer M 2 transition between values of “11” and “10” in response to the rising and falling edges of the CK 2 signal (see Table 7). Thus, multiplexer M 2 will route the R 3 data signal, and then the R 2 data signal, to flip-flop K 0 as the data signal R 0 . Flip-flop K 0 latches the R 0 data signal on rising edges of the CK 1248 clock signal, thereby providing the 1-bit R[0] data signal. The timing of receive variable-width interface 800 for a 1-bit data path is illustrated in FIG. 10A . Note that the offset between the rising edges of the CK 1248 and the CK 2 signals (which is equal to half the period of the CK 1248 clock signal) allows the interface 800 to exhibit adequate set-up and hold times even if the CK 1248 and CK 2 signals exhibit small amounts of skew.
2-Bit Data Path
When receive variable-width interface 800 is configured to have a 2-bit output width, the Y 8 , Y 4 , Y 2 , Y 1 signals have values of (0,0,1,0) as illustrated in Table 6. In this case, width control circuit 900 generates enable signals EJ 6 — 7 , EJ 4 — 5 , EJ 2 — 3 , EK 4 — 7 , EK 2 — 3 , and EK 1 , and select signals T 1 and T 0 as illustrated in Table 8.
TABLE 8
EJ6 — 7
EJ4 — 5
EJ2 — 3
EK4 — 7
EK2 — 3
EK1
T1
T0
0
0
0
0
0
1
0
CK2
Turning to FIG. 8 , these enable and select values have the following effect in receive variable-width interface 800 . The logic “0” enable signals EJ 6 — 7 , EJ 4 — 5 , EJ 2 — 3 , EK 4 — 7 , and EK 2 — 3 disable flip-flops J 2 –J 7 and K 2 –K 7 . The logic “1” enable signal EK 1 enables flip-flop K 1 . The received data signal Q 1 is routed directly to flip-flop K 1 as data signal R 1 , and the received data signal Q 0 is routed to flip-flop K 0 through multiplexer M 2 as data signal R 0 . Note that the logic “0” value of the T 1 select signal causes multiplexer M 2 to route the Q 0 signal, regardless of the state of the CK 2 signal. That is, flip-flops J 2 –J 3 are bypassed in the 2-bit data path. The R 1 and R 0 data signals are latched into flip-flops K 1 and K 0 , respectively, in response to rising edges of the CK 1248 clock signal, and provided as 2-bit output signal R[1:0]. The timing of interface 800 for a 2-bit data path is illustrated in FIG. 10B .
4-Bit Data Path
When receive variable-width interface 800 is configured to have a 4-bit output width, the Y 8 , Y 4 , Y 2 , Y 1 signals have values of (0,1,0,0) as illustrated in Table 6. In this case, width control circuit 900 generates enable signals EJ 6 — 7 , EJ 4 — 5 , EJ 2 — 3 , EK 4 — 7 , EK 2 — 3 , and EK 1 , and select signals T 1 and T 0 as illustrated in Table 9.
TABLE 9
EJ6 — 7
EJ4 — 5
EJ2 — 3
EK4 — 7
EK2 — 3
EK1
T1
T0
0
0
CK1248#
0
1
1
0
CK2
Turning to FIG. 8 , these enable and select values have the following effect in receive variable-width interface 800 . The logic “0” enable signals EJ 6 — 7 , EJ 4 — 5 and EK 4 — 7 , disable flip-flops J 4 –J 7 and K 4 –K 7 . The logic “1” enable signals EK 1 and EK 2 — 3 enable flip-flops K 1 –K 3 . The received data signals Q 1 and Q 0 are latched into flip-flops J 3 and J 2 , respectively, as data signals R 3 and R 2 , respectively, when the CK 1248 signal has a logic low value (CK 1248 #=“1”) and the CK 2 signal has a rising edge. On the same rising edge of the CK 2 signal, the Q 1 and Q 0 data signals transition to represent two new data values. These two new data values propagate directly to flip-flops K 1 and K 0 as data signals R 1 and R 0 well before the next rising edge of the CK 1248 signal. At the next rising edge of the CK 1248 signal, the R 3 and R 2 data values in flip-flops J 3 and J 2 are latched into flip-flops K 3 and K 2 , respectively, and the data values R 1 and R 0 are latched into flip-flops K 1 and K 0 , respectively. These data values are provided at the output terminals of flip-flops K 3 –K 0 as the output data signal R[3:0]. The timing of receive variable-width interface 800 for a 4-bit data path is illustrated in FIG. 10C .
8-Bit Data Path
When receive variable-width interface 800 is configured to have a 8-bit output width, the Y 8 , Y 4 , Y 2 , Y 1 signals have values of (1,0,0,0) as illustrated in Table 6. In this case, width control circuit 900 generates enable signals EJ 6 — 7 , EJ 4 — 5 , EJ 2 — 3 , EK 4 — 7 , EK 2 — 3 , and EK 1 , and select signals T 1 and TO as illustrated in Table 10.
TABLE 10
EJ6 — 7
EJ4 — 5
EJ2 — 3
EK4 — 7
EK2 — 3
EK1
T1
T0
CLK — A
CLK — B
CLK — C
1
1
1
0
CK2
In Table 10, CLK — A is equal to the logical AND of CK 1248 D and CK 1248 ; CLK — B is equal to the logical AND of CK 1248 D and CK 1248 #; and CLK — C is equal to the logical AND of CK 1248 # and CK 1248 D#. These clock signals are illustrated in FIG. 11 . Turning to FIG. 8 , these enable and select values have the following effect in receive variable-width interface 800 . The logic “1” enable signals EK 4 — 7 , EK 2 — 3 and EK 1 enable flip-flops K 1 –K 7 . The CLK — A, CLK — B and CLK — C signals sequentially enable flip-flop sets J 6 –J 7 , J 4 -J 5 , and J 2 –J 3 , respectively. Successive rising edges of the CK 2 signal (starting with the second rising edge of the CK 2 signal after a rising edge of the CK 1248 signal) latch data signals Q 1 and Q 0 into: flip-flops J 7 and J 6 (at time T 2 in FIGS. 10D and 11 ); then flip-flops J 5 and J 4 (at time T 3 in FIGS. 10D and 11 ); and then flip-flops J 3 and J 2 (at time T 4 in FIGS. 10D and 11 ). The edge of the CK 2 signal that stores data signals Q 1 and Q 0 into flip-flops J 3 and J 2 also latches new values Q 1 and Q 0 , which propagate directly to flip-flops K 1 and K 0 sufficiently fast to satisfy the setup time requirements of R 1 and R 0 , prior to the next rising edge of the CK 1248 signal. The next rising edge of the CK 1248 signal then stores the data values R 7 –R 0 into flip-flops K 7 –K 0 , which are then provided as output data value R[7:0]. The timing of interface 800 for an 8-bit data path is illustrated in FIG. 10D .
By changing the values of data width selectors Y 1 , Y 2 , Y 4 and Y 8 , interface 800 can be configured to operate using any of several supported data widths. Separate data width selectors may be provided for transmit variable-width interface 400 and receive variable-width interface 800 . In one embodiment using a programmable FPGA environment, interfaces 400 and 800 advantageously avoid the use of programmable resources for the implementation of these interfaces, thereby enabling these interfaces to be implemented in an efficient manner. In another embodiment the programmable resources of the FPGA may be used to allow use of the data-width converters for more applications.
Variations on the above implementations are possible. For example, the clock waveforms of FIGS. 3A–3D may be defined differently, depending on whether the data paths are positive-edge or negative-edge triggered, and whether it is required to avoid hold-time design issues.
The implementation of interface 400 described in connection with FIGS. 4 and 5 assume that the input data value D[7:0] should be provided directly to flip-flop inputs. If it is permissible to go to flip-flop inputs via minimal logic (i.e., a multiplexer), then flip-flops A 1 and A 01 may be merged into a single flip-flop, with other suitable modifications to the design. Such modifications would include the addition of a multiplexer that provides either the D[1] or D[0] data signal to the merged flip-flop, depending on the configuration of the data path.
The implementation described in FIGS. 8 and 9 makes certain assumptions about propagation delays from the source of Q[1:0]. Different assumptions might lead to not propagating Q[1:0] directly to flip-flops K 1 and K 0 for the 2-bit, 4-bit, and 8-bit data paths, or conversely, to bypassing flip-flops J 2 and J 3 for the 1-bit data path. Similarly, assumptions about propagation delays from P[1:0] in FIG. 4 could lead to bypassing flip-flops B 1 and/or B 0 in some cases.
The implementation in FIG. 8 defined the enable inputs so that each of flip-flops J 2 –J 7 is written at most once per CK 1248 cycle. An alternative design style would be to organize flip-flops J 2 –J 7 as a shift register, unconditionally loaded (shifted) by each rising edge of CK 2 and periodically loaded into flip-flops K 0 –K 7 by the rising edge of CK 1248 . It is also possible to use a shift register methodology in transmit variable-width interface 400 of FIG. 4 as well.
In addition, interfaces 400 and 800 may be extended to support other data widths, or it may be constrained to support only a subset of the data widths.
Although the invention has been described in connection with several embodiments, it is understood that this invention is not limited to the embodiments disclosed, but is capable of various modifications, which would be apparent to a person skilled in the art. Logically equivalent but structurally different implementations are possible. Moreover, other variations in design style or detail may be possible. Thus, the invention is limited only by the following claims.
|
An integrated circuit (IC) with programmable circuitry having programmable functions and programmable interconnections. The IC further includes: a first module having an output with a first fixed data width or first variable data width; a second module having an input with a second fixed data width or a second variable data width; and a data width converter receiving data from the output of the first module and sending the data to the input of the second module, the data width converter configured to convert data from the first fixed data width or first variable data width to the second fixed data width or the second variable data width.
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FIELD OF THE INVENTION
[0001] This disclosure pertains to a method of enhancing brightness of paper produced from mechanical or recycled pulps.
BACKGROUND OF THE INVENTION
[0002] Bleaching of mechanical and recycled pulps during a papermaking process enhances the brightness of paper produced from these pulps. Mechanical pulps include groundwood (GW), refiner mechanical pulp (RMP), thermomechanical pulp (TMP), chemithermomechanical pulp (CTMP), chemimechanical pulp (CMP), variations thereof (e.g., stone GW, pressurized GW, thermo-RMP, pressure RMP, pressure TMP, chemi-RMP, long fiber CMP, thermomechanical chemi pulp); recycled pulp; and compositions containing mechanical, chemical and recycled pulps. Recycled pulps include any pulp obtained from recycled paper, for example newspapers.
[0003] Some common bleaching chemicals utilized during a bleaching stage of a papermaking process include: sodium hydrosulfite; ammonium hydrosulfite; magnesium hydrosulfite; calcium hydrosulfite; zinc hydrosulfite; chlorine; chlorine dioxide; hydrogen peroxide; oxygen; and calcium hypochlorite.
[0004] The efficacy, however, of these bleaching chemicals is retarded by transitional metal ions in the pulp that react with the bleaching chemicals. More specifically, these reactions cause decomposition of the bleaching chemicals. Therefore, a need exists to prevent this decomposition so that an optimum brightness of paper can be achieved.
SUMMARY OF THE INVENTION
[0005] The present invention provides for a method of enhancing brightness of paper made from mechanical pulps that comprises the step of: adding an effective amount of one or more chelants and one or more surfactants to a bleaching stage in a papermaking process that involves the addition of hydrosulfite.
[0006] The present invention also provides for a method of enhancing brightness of paper made from recycled pulps that comprises the step of: adding an effective amount of one or more chelants and one or more surfactants to a bleaching stage of a papermaking process that involves the addition of hydrosulfite.
DETAILED DESCRIPTION OF THE INVENTION
[0007] “Bleaching” means a process of purifying and whitening pulp by chemical treatment to remove or change existing coloring material so that the pulp takes on a higher brightness characteristic.
[0008] “DTMPA” means diethylenetriaminepentaacetic acid.
[0009] “DTMPA” means diethylenetriaminepentakis(methylphosphonic acid).
[0010] “EDTA” means ethylendiaminetetraacetic acid.
[0011] “AMP” means aminotris(methylphosphonic acid).
[0012] “o.d.” means oven dry.
[0013] Conventional methods for bleaching pulp and making paper from pulps, whether that be virgin mechanical or recycled pulps, are well known in the art. Bleaching may be one stage or multistage. In multi-stage bleaching, the pulp is sequentially exposed to different types of bleaching chemicals, for example, hydrogen peroxide first, and hydrosulfite second.
[0014] As stated above, brightness in both mechanical and recycled pulps is achieved by adding an effective amount of both chelants and surfactants to a bleaching stage in a papermaking process that involves the addition of hydrosulfite. In one embodiment, the chelants and surfactants are added as a mixture or sequentially. The chelants may be added to the bleaching stage at a dose of 0.01 to 10 lbs/ton of o.d. pulp, preferably 1 to 4 lbs/ton of o.d. pulp. The surfactants may be added at a dose of 0.01 to 10 lbs/ton of o.d. pulp, preferably 0.5 to 2 lb/ton of o.d. pulp.
[0015] In another embodiment, the chelants are selected from the group consisting of: aminophosphonates, aminophosphates, aminocarboxylates, DTMPA, AMP, DTMPA-polyacrylate blends, EDTA, and DTPA.
[0016] In another embodiment, the surfactants are selected from the group consisting of: anionic; long-chain carboxylic acids; alkylarylsulfonates; alkylsulfates; alkylsulfonates; arylsulfonates; cationic; tertiary alkylammonium; alkylpyridinium salts; ampholitic species; alkylaminoacids; non-ionic; oxyalkylated alcohols; polyethyleneglycol esters of fatty acids; oxyalkylated; and alkylphenols. In a preferred embodiment, the surfactants are selected from the group consisting of: polyalkoxylated long-chain alcohols; ethoxylated alcohols; and propoxylated alcohols.
[0017] In a preferred embodiment, the chelants and surfactants are added as a single product comprising: 15% pentasodium DTPA, 3% etoxylated, propoxylated hexadecanol and 17% sodium xylenesulfonate at pH about 7.
[0018] In another embodiment, the chelants and surfactants are added as separate products, one chelant comprising: 29% pentasodium DTMPA and 14% sodium polyacrylate at pH about 6 and one surfactant comprising 16% ethoxylated, propoxylated hexadecanol at pH about 8.
[0019] The present invention will be further described in the following examples and tables. The examples are not intended to limit the invention prescribed by the appended claims.
EXAMPLES
[0020] The efficacy of the combination of chelants and surfactants were studied in a hydrosulfite bleaching experiment conducted according to the following protocol.
[0021] The experiments must be conducted in an oxygen-free atmosphere to achieve reproducible results. Oxygen from air quickly oxidizes sodium hydrosulfite in the solution to sulfate and sulfite.
[0022] The following procedure was followed for all examples: (1) weigh out a pulp sample (5 g dry pulp per sample, calculate actual weight based on the consistency) in a 250-ml glass bottle; (2) add water and additives when needed, mix well; (3) close the bottle and degas them the sample with a flow of nitrogen for 10 min; (4) degas deionized (“DI”) water for 10 min; (5) place desired amount of hydrosulfite in a 100-ml flask, close it, fill with nitrogen, then add required amount of degassed DI water through a syringe and mix. Recommended concentration of hydrosulfite provides for about 1% in the bleached sample after adding 5 ml stock solution; (6) add 5 ml of hydrosulfite solution to the pulp sample via syringe in a flow of nitrogen; (7) mix well quickly; (8) immerse in water bath for desired reaction time; (9) transfer the bleached pulp onto cheesecloth placed in a Büchner funnel and wash it with 2 L DI water under vacuum; and (10) prepare handsheets from a 0.5% pulp slurry (IL DI water) for brightness measurements.
[0023] The handsheets were equilibrated at constant humidity 50% and 23° C. and brightness measured (standard TAPPI R457 brightness, E313 yellowness, Elrepho-3000 instrument, Datacolor International, Charlotte, N.C.).
[0024] The doses in the following tables are calculated based on o.d. pulp, 40% active chelants and 80% active surfactants. For the interpretation of these tables, the following legend should be utilized: Br0—initial brightness, BrGain—gain in brightness vs. Control; Chelant 1—29% DTMPA/14% sodium polyacrylate, pH 5.8; Chelant 2—38% tetrasodium EDTA; Surfactant 1—79% C12-14 secondary alcohols, ethoxylated; Surfactant 2—70% ethoxylated oxoalcohols (“bottoms” from the oxo-process). TMP1 and TMP2 refer to TMP from different mills.
TABLE 1 TMP1, 4.6%, 70° C., 1 h, 0.9% sodium hydrosulfite % Chelant 1 % Surfactant 1 Br BrGain 0 0 53.6 0.0 0.05 0 54.0 0.4 0.025 0.01 54.5 0.9 0.05 0.01 54.5 0.9 0.075 0.01 55.0 1.4 0.025 0.02 54.5 0.8 0.05 0.02 54.2 0.6 0.075 0.02 54.6 1.0 0.1 0.02 54.4 0.8 0 0.005 53.5 −0.1 0 0.01 53.8 0.2 0 0.02 54.2 0.5
[0025]
TABLE 2
TMP2, 3.5%, 50 min, 65° C., 1.0% sodium hydrosulfite
Chemicals
Br
Control
66.90
0.2% Chelant 2
67.54
0.05% Chelant 1
67.59
0.05% Chelant 1 + 0.01% Surfactant 1
67.72
0.05% Chelant 1 + 0.01% Surfactant 2
67.86
[0026]
TABLE 3
TMP - Deinked Pulp (Recycling), 3.9%, 30 min,
70° C., 0.7% sodium hydrosulfite
Surfactant
Chelant 1
Chelant 2
Br
Control
0.0%
0.0%
62.70
N/A
0.0%
0.05%
63.42
0.025% Surfactant 1
0.0%
0.05%
63.65
0.025% Surfactant 2
0.0%
0.05%
63.79
N/A
0.025%
0.025%
63.65
0.01% Surfactant 2
0.025%
0.025%
63.90
[0027]
TABLE 4
TMP - Deinked Pulp (Recycling), 3.9%, 30 min,
70° C., 0.7% sodium hydrosulfite
Chemicals
Br
Control
62.67
0.025% Surfactant 1
63.16
0.01% Surfactant 1
62.93
0.05% Chelant 1 + 0.025% Surfactant 1
63.95
0.05% Chelant 1 + 0.01% Surfactant 1
63.84
0.1% Chelant 1 + 0.01% Surfactant 1
64.00
0.05% Chelant 1 + 0.025% Surfactant 2
64.21
[0028]
TABLE 5
TMP - Deinked Pulp (Recycling), 3.9%, 30 min,
70° C., 0.7% sodium hydrosulfite
Chemicals
Br
Control
62.18
0.2% Chelant 2
63.31
0.05% Chelant 1 + 0.05% Surfactant 2
63.66
0.1% Chelant 1 + 0.025% Surfactant 2
63.89
Control
62.68
0.2% Chelant 2
63.90
0.05% Chelant 1 + 0.05% Surfactant 2
63.73
0.05% Chelant 1 + 0.025% Surfactant 2
63.78
0.1% Chelant 1 + 0.025% Surfactant 2
64.00
[0029]
TABLE 6
TMP - Deinked Pulp (Recycling), 3.9%, 30 min,
70° C., 0.7% sodium hydrosulfite
Bleach
Br
Control
62.09
0.05% Surfactant 2
62.18
0.01% Surfactant 2
62.12
0.1% Chelant 1
62.64
0.05% Chelant 1
62.44
0.05% Chelant 1 + 0.01% Surfactant 2
62.86
0.05% Chelant 1 + 0.05% Surfactant 1
63.45
0.2% Chelant 2
63.32
[0030] As shown in Table 1, the addition of a phosphonate chelant and a surfactant to a mechanical type pulp has a synergistic effect on brightness. Table 2 also shows improved performance of a chelant when a surfactant was added.
[0031] With respect to recycled pulps, tables 3 through 6 demonstrate that the addition both a chelant and a surfactant have a synergistic effect on brightness.
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A method of enhancing brightness of paper made from mechanical pulps or recycled pulps that comprise: adding an effective amount of one or more chelants and one or more surfactants to a bleaching stage of a papermaking process that involves the addition of hydrosulfite is disclosed.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a Continuation-in-Part of application Ser. No. 763,000, filed Sep. 20, 1991 (now U.S. Pat. No. 5,261,255), which is a Continuation of application Ser. No. 388,069, filed Jul. 21, 1989 (now U.S. Pat. No. 5,050,375), which is a Continuation-in-Part of abandoned application Ser. No. 123,280, filed Nov. 20, 1987, which was a Continuation-in-Part of application Ser. No. 813,486, filed Dec. 26, 1985 (now U.S. Pat. No. 4,714,032). It is also related to application Ser. No. 294,424, filed Jan. 9, 1989 (now U.S. Pat. No. 4,898,107), which is a Continuation-in-Part of abandoned application Ser. No. 100,531, filed Sep. 24, 1987, which was a also a Continuation-in-Part of application Ser. No. 813,486 (now U.S. Pat. No. 4,714,032).
BACKGROUND OF THE INVENTION
This and the referenced inventions are addressed to the related national problems of energy security and air quality. In particular, it is addressed to potential domestic energy resources which are not utilized, or under utilized, because of impurities, notably moisture and chlorine.
Fuels (with the exception of nuclear fuels) are said to be carbonaceous, i.e., having a carbon skeleton. The fluid fuels: oil and gas, are essentially mixtures of hydrocarbons whereas solid fuels have considerable oxygen in their molecular structure.
Coals are "ranked" according to their geological age. Those of high rank (oldest) have high carbon and low oxygen contents, little affinity for water, and are mineral-like. Anthracite and bituminous coals are considered high rank. As rank (age) decreases coals have decreasing carbon and increasing oxygen contents and affinity for water, and become more fibrous. Sub-bituminous and lignites are low rank coals. Although not called coal, peat is a fossil fuel still lower in age or rank.
Sub-bituminous coals and lignites are important commercial fuels, usually mined at low cost. (Powder River Basin sub-bituminous has another attractive feature--it is low in sulfur and in considerable demand by utilities having difficulty meeting sulfur dioxide emission regulations.) However, their high moisture contents, and correspondingly low heating values, make them expensive to ship to market and inefficient to burn.
Heating values are misleadingly reported as though water were only a diluent. Besides dilution, additional energy is wasted evaporating it, making this impurity an even greater drawback than is apparent, especially for solid fuels shipped at high expense.
Still further down the ranking scale are a variety of organic wastes and by-products (biomass), whose aggregate dry heating value, although not usually counted as an energy resource, could make an appreciable contribution to the domestic supply. Among these are Municipal Solid Waste, Industrial Wastes, Construction and Demolition Wastes, Paper Mill and Sewage Sludges. To these can be added the variety of woody or cellulosic by-products of agriculture and forestry, and industry based upon them. Compared with even lowest ranked fossil fuels, they have lower contents of carbon and higher contents of oxygen. Most are also fibrous and normally associated with substantial water.
Inventors and entrepreneurs have responded to the moisture/heating value drawback of low rank coals by putting forward a variety of carbonization processes, in which moisture and oxygen are driven off by heat. In other words, the carbonaceous raw material has been enriched in carbon. Although heating value is improved, the product tends to be troubled by dusting and spontaneous combustion. By product water, heavily contaminated with complex organic chemicals, presents a difficult disposal problem (addressed in my U.S. Pat. No. 5,000,099). These carbonizations, moreover, handle and process raw material and product as solid fuels, through a sequence of solids moving, heating, cooling, crushing, screening, etc. steps, at considerable expense and opportunity for pollution and loss.
In contrast to the ease, economy and cleanliness with which fluid fuels are pipelined around the country, solids are burdened with open mechanical excavators, conveyors, bulldozers, crushers, hoppers, railroad cars, pilers, reclaimers, grinders, etc. all of which require labor and create noise, dust, loss and polluted runoff. The existing mechanical culture of solid fuels utilization needs lump fuel of limited size range. In crushing oversize material to conform, considerable undersized must be rejected. These "fines" have little market and comprise not only a loss of material but an environmental debit.
The DOE and private entrepreneurs have tried to address the often overlooked form penalty, which solid fuels have to bear relative to fluid fuels: oil and gas. One of the most extensive of such attempts has comprised programs to convert coal into a liquid slurry fuel, called Coal-Water-Fuel (CWF), which has been successfully fired in boilers and furnaces designed for oil. Specially prepared CWFs have also been fired in experimental diesel engines and gas turbine combustors. Unfortunately, most coals require extensive beneficiation and expensive additives, making the cost of energy, in CWF form, roughly double that of the coal from which it is made. At the time of this application world oil prices are so low that this technically feasible substitution is uneconomic.
High rank coals (anthracite and bituminous) can be ground and slurried to a pumpable solids concentration of 50% or higher. As rank decreases (sub-bituminous toward lignite), there is a deterioration in slurryability. Poor slurrying characteristics of low rank and waste fuels are associated with their fibrous and hydrophillic nature. However, it was pointed out in my U.S. Pat. No. 4,380,960 that a slurry of a hydrophillic fuel can be concentrated by heating to a temperature at which molecular rearrangement occurs, with splitting off of carbon dioxide and water, resulting in a less hydrophilic and fibrous fuel (char) for which the maximum pumpable concentration is considerably increased. I have called this process "Slurry Carbonization".
The Energy and Environmental Research Center (EERC) of the University of North Dakota has extensively studied the slurry carbonization (which they call Hydrothermal Treatment or Hot Water Drying) of North Dakota and other lignites. In a continuous pilot unit EERC, under contract with the DOE, has carbonized a slurry of low ash sub bituminous coal which, after concentration, the Allison Division of General Motors used successfully to fuel a commercial-scale gas turbine with solid fuel for the first time.
The EERC has also studied the slurry carbonization of such woody by-products as sawdust, obtaining around 300% improvement in the concentration (and energy density) of pumpable slurries.
Compounding coal's form handicap in the energy market are its impurities. A variable content of ash inflates shipping, emissions control, maintenance and disposal costs. Moisture is costly to ship and lowers boiler efficiencies. Sulfur and nitrogen contents are considered responsible for acid rain and require expensive control devices to meet clean air standards. Chlorine in some coals causes expensive boiler tube corrosion, and/or requires costly alloy. Moreover, chlorine is implicated in some of a long list of, as yet unregulated, trace toxics believed present in air emissions from coal burning (the most notorious being dioxins). The National Committee for Geochemistry of the National Research Council identified in 1980 the elements: arsenic, boron, cadmium, lead, mercury, molybdenum and selenium as "of greatest environmental concern" with respect to coal, and the elements: vanadium, chromium, nickel, copper, zinc and fluorine "of moderate concern".
The Illinois Basin is a major, well-located source of bituminous coal. While sulfur and chlorine contents vary from seam-to-seam, both tend to be relatively high. As environmental pressures have increased, the extensive mining industry in the area has suffered loss of business and jobs. A large research budget administered by the Illinois Clean Coal Institute (ICCI), formerly Center for Research on Sulfur in Coal (CRSC), has not produced an economical remedy for these impurities. My U.S. Pat. Nos. 4,714,032 and 5,050,375 specifically target the environmentally sound utilization of Illinois No. 6 coal with respect to sulfur and nitrogen oxides. The invention of this application addresses the removal of other impurities, particularly chlorine.
Conversion of MSW to energy is also impeded by impurities. Water contents are high and extremely variable. Ash contents are also high. About half of the 1000 metric tons of mercury used annually in the U.S. goes into disposable batteries, most of which wind up in MSW. Discarded batteries are also significant sources of cadmium and lead. Toxic lead, cadmium and mercury appear in the flue gas and have to be controlled by scrubbers and filters. Chlorine, originating with chlorinated plastics such as PVC (40% chlorine), averages about 0.5% but can range to as high as 1.8%. It engenders corrosive conditions in the firebox, requires alkali scrubbers and contributes to the formation of dioxins, furans and probably other dangerous air pollutants. Environmentalists are particularly sensitive to mercury vapor in flue gas; there is controvery over whether its methylated form is adequately accounted for.
In addition, bottom ash is sometimes classified as hazardous on the basis of the Environmental Protection Agency (EPA) TCLP leaching test and fly ash almost always is. Toxic metals which find their way into the ash include lead, arsenic, cadmium, selenium, chromium and mercury. Literature discloses that hazardous ash can be made to pass the TCLP test by heating it to or above its melting point, a process known as "vitrification".
Since, with coal burning, emissions of sulfur oxides are frequently a problem while MSW and fuel derived from it (RDF) are low in sulfur, there have been numerous attempts to blend the fuels so that flue gas from burning the blend (a practice known as co-firing) complies with sulfur oxide regulations. The sulfur advantage of co-firing has been overshadowed, however, by practical boiler problems, including higher requirement for excess air, poorer combustion control, increased slagging and corrosion. More recently there has been a revival of interest because of some evidence that sulfur oxides from the coal inhibits the formation of dioxins from chlorine in the RDF. However, RDF produced by conventional dry RR cannot be pulverized so as to be co-fired with pulverized coal, restricting the practice to the generally older and smaller stoker and moving grate boilers.
The world has thousands of sites at which garbage has been dumped for decades, and even centuries. Although dumping practice has improved and come to be known as "landfilling", much discarded refuse lies decaying under conditions now considered environmentally unsatisfactory. There is public pressure to remedy such old dump and landfill sites, which is bound to increase. Besides the potential hazards, much recyclable material and potential energy lies buried, awaiting economic means of recovery.
Many of the papermill sludges (besides being penalized by high water and ash contents) also contain serious amounts of chlorine and thus share the corrosion and air toxics risks hampering recovery of energy from MSW. Another potential biomass fuel high in chlorine is manure.
Although chlorine receives the lion's share of attention, MSW (as well as Industrial and Construction and Demolition Wastes) may contain lesser amounts of other halogens. In particular, fluorine from fluorinated (or chlorofluorinated) polymers may, in some cases, have toxic and/or fouling consequences. Both fluorine and bromine occur in some coals.
Environmentalists have long promoted tree farms, or other biomass crops, as renewable energy resources (which have the virtue of "recycling" carbon dioxide rather than adding to the production of greenhouse gases). The predominant impurity in renewable biomass fuels is water, which seriously detracts from, or even nullifies, their net energy value in atmospheric boilers. They generally have a low ash content which, nevertheless, can cause serious problems with low melting slags, frequently associated with sodium and/or potassium.
SUMMARY OF THE INVENTION
As already disclosed in my U.S. Pat. Nos. 4,714,032, 4,898,107, 5,000,099 and 5,050,375, the energy potential of an aqueous slurry of a carbonaceous fuel can best be realized by continuously burning or oxidizing it under pressure, as in a reactor integrated with a gas turbine, with or without the indirect transfer of reaction heat, as to boiling feedwater. The thermal efficiency of the process is a function of the energy density of the fuel, as expressed in Btu/Lb or cal/gr of slurry. Dry basis heating values vary somewhat but the main determinant of energy density is the concentration of solid fuel particles in the slurry. In other words, it is inversely proportional to water content. This concentration is limited by viscosity, which needs to be low enough that the slurry can be pumped, heated, controlled and dispersed into a reactor or combustor. Such a slurry is described herein as having a "processable viscosity".
In addition, conventional utilization is often impaired by impurities other than water, particularly sulfur, chlorine, nitrogen and slag-forming cations, such as sodium and potassium. The effects of sulfur are ameliorated by methods described in the patents cited above. This invention also decreases sulfur and nitrogen but is addressed specifically to the reduction of water, chlorine and slag-forming cations.
The viscosity restraint is tolerable with respect to high rank coals, permitting concentrations of around 50% without additives and up to about 70% with them. As rank decreases, slurry concentration or energy density, at processable viscosity, deteriorates, making such fuels increasingly unattractive for conventional use.
I have discovered that numerous solid and waste carbonaceous materials, which are unattractive fuels for conventional combustion by virtue of form, bulk, location, low heating value, moisture and poor slurryability, can be converted into useful high energy density slurry fuels. I have also discovered that, simultaneously, sodium, potassium, calcium, nitrogen, sulfur, chlorine and other difficultly soluble impurities, in amounts which would impair utilization by virtue of corrosion, slag formation and/or toxic emissions, can be significantly reduced.
These important enhancements result from providing he fuel as a slurry, which is heated under pressure, usually in the presence of an alkali, to a temperature at which a significant molecular rearrangement occurs, characterized by the splitting off of a substantial proportion of the oxygen as carbon dioxide. The temperature necessary for this rearrangement varies with the source but is usually between 500° F. and 650° F. The aggressively hydrolyzing conditions free chlorine (even from such stable polymers as PVC), sulfur and other anions to react with the alkali and to dissolve in the aqueous phase. Previously bound cations, such as sodium and potassium, are likewise made accessible to aqueous dissolution. The aqueous slurry form, as well as its heat treatment, allows the vast experience of industrial and academic chemistry to be brought to bear on undesirable impurities (including those which may not yet be identified). For example, agents specific to the extraction or neutralization of one or more impurities, including acids, peroxides and sequestering agents, may be added before, during or after heating. The carbonaceous matrix loses much of its fibrous character, and is broken up into smaller particles of char, resulting in a slurry of dramatically improved rheology, i.e., capable of a much higher concentration (or energy density) at processable viscosity.
Some biomass organics, such as sludges, may be supplied as slurries. Others, such as manure, may be semi-solid and become slurries when mixed with additional water or dilute waste. If solid, the raw fuel is shredded, chipped, ground and/or pulped to permit preparation of a processable slurry. If the slurry contains appreciable inorganic material, separable by virtue of density or other physical property, appropriate separation is performed. (In the case of MSW, the shredding, slurrying and density separation are called "wet Resource Recovery".) Because of the fine division of solids and the fluidity of the slurry, removal of toxic metals, which have a relatively high specific gravity, is essentially complete. (If justified, separated inorganics may be purified for recycling or other utilization.) When the raw fuel contains appreciable halogens, sulfur, or other acid-forming anions, alkali is added, if not already present.
This invention is particularly advantageous for co-firing a low rank coal with MSW or RDF. After carbonization and concentration, slurried blends of fossil and biomass fuels (because of bi-modality of particles) frequently exhibit higher energy density, at a specified viscosity, than slurries of either alone. The proportions of the base fuels may be adjusted to meet sulfur and nitrogen oxide emissions goals without concern for excessive slagging or corrosion. The char slurry fuel has excellent uniformity so that excess air needed for co-firing is minimized and can be controlled more precisely. Moreover, slurried fuels are fired through burners similar to those used with fuel oil and/or pulverized coal (PC), and thus are not limited to stoker or moving grate boilers.
Dense inorganics are preferably separated before blending, which may occur before carbonization or after. When carbonized in admixture, alkali naturally occurring in some low rank coals decreases the amount to be added, or makes it unnecessary. Similar synergism occurs when co-processing low rank coals with other biomass fuels in this manner.
(Conventionally, "co-firing" simply means burning a coal and a biomass fuel together. Application of the term to this invention may be misleading because the base fuels are often synergistically carbonized together before "co-firing".)
Since raw RDF contains chlorine (which can form hydrochloric acid) and most other biomass fuels contain the alkaline elements, sodium and potassium, they are a natural fit to be co-processed through slurry carbonization. Not only are both turned into uniform, high energy density liquid slurry fuels, but their chemical impurities tend to neutralize one another. (Depending on proportions, some additional alkali may be required.) It is most logical to extend the co-processing of this low sulfur fuel mixture to include otherwise non-compliant fossil fuel.
Should the char slurry resulting from the process be essentially free of harmful dissolved salts, it may be concentrated to the maximum viscosity suitable for charging to oxidation or other use. If, on the other hand, it contains appreciable dissolved salts and/or minerals which would cause operating difficulty in oxidation, or result in release of pollutants, the solid char is separated essentially completely from the aqueous phase and re-slurried, to maximum processable viscosity, in clean water. In some cases it may be desirable to wash the wet char with clean water before re-slurrying. The concentrated or re-slurried char is valuable liquid fuel, preferably converted to useful energy via pressurized oxidation.
There is a further novel and significant property of chars, produced from low ranked fuels and biomass in accordance with this invention. They are extremely reactive, even in the presence of water or steam. This reactivity makes it possible to release their chemical energy under pressure spontaneously, without the ignition and high temperature flames characteristic of conventional combustion. This controlled-temperature reaction, which I call Thermal Oxidation, minimizes the formation of sulfur and nitrogen oxides and chlororganic pollutants, the volatilization of toxic metals and the formation of adherent deposits.
In the field of conventional combustion at atmospheric pressure, it is known to introduce the combustion air in two or more stages, the principal justification being a mitigation of the formation of nitrogen oxides. In effect, the first-stage (primary) air converts the solid fuel (not necessarily completely) to a fuel gas, combustion being completed with secondary and/or tertiary air in a subsequent stage, or stages. When char slurries are prepared in accordance with this invention, they are so reactive that it is possible, particularly under pressure, to oxidize essentially all of the carbon in a first, or primary stage, with a fraction of the oxygen theoretically required for complete oxidation, and at a temperature usually in the range of 900°-1600° F., significantly lower than conventional partial or complete combustions. It is then possible to separate ash particles from the gas, before oxidation is completed with the balance of the compressed oxidant in a second-stage, which may occur in the reactor of a gas turbine. Resulting heat and pressure energy are then converted to useful mechanical and/or electrical energy.
While, with any of the embodiments described in this application, oxygen or enriched air may be used in place of air, it also may be advantageous to divert to an air separation unit, for enrichment in oxygen, only that part of the oxidant to be used in the primary stage, leaving that to be used as secondary or tertiary oxidant in its natural state.
When, however, the char slurry, as from MSW or sewage sludge, contains such quantities of toxic metals as might render its ash hazardous, primary oxidant (air and/or oxygen) to a first oxidation stage may be increased to result in an inlet zone reaction temperature above the melting point of a majority of ash constituents, resulting in ash particles being converted to molten particles (slag) which remain suspended, for a brief time, in the gaseous phase. The temperature is then reduced to a level at which the molten particles re-solidify, by means of a quench stream of secondary and/or tertiary oxidant, steam, water and/or cooled gas. Quenching occurs before separation of ash particles from the gaseous product of the oxidation.
An object of the invention is to decrease the nation's dependency on imported oil. Another object is to provide an improved means of obtaining heat and power from low grade fuels. A further object is to provide an improved means of disposing of Municipal Solid Waste and other wastes. A further object is to facilitate the remediation of existing landfills by providing a safe and economic disposition of the reclaimed, dirt-contaminated MSW. Another object is to improve the economics of utilizing fuels contaminated with moisture and chlorine. A further object is to provide a means of ameliorating the discharge of chlororganic pollutants and toxic metals into the atmosphere. A further object is to provide an efficient and continuous method of vitrifying a potentially hazardous ash. A further object is to provide an economical means of producing hot, clean, pressurized gas for driving a gas turbine. Additional objects will be apparent from a consideration of the drawings and explanations thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic elevational diagram of an embodiment for converting a solid waste, exemplified by Municipal Solid Waste, into a high energy density, chlorine-reduced char slurry suitable for pressurized oxidation.
FIG. 2 is a schematic elevational diagram of an embodiment for recovering energy from a solid waste comprising slurrying and separation of dense inorganic impurities, heating under pressure in the presence of alkali, concentration of char slurry to a high energy density and recovery of electrical energy through thermal oxidation in a steam injected gas turbine with Heat Recovery Steam Generator.
FIG. 3 is a schematic elevational diagram of a combined cycle energy conversion embodiment comprising a gas turbine, Heat Recovery Steam Generator and condensing steam turbine generator.
FIG. 4 is a schematic elevational diagram of a combined cycle energy conversion embodiment in which thermal oxidation of char slurry is conducted in two stages, with particulate removal between stages.
FIG. 5 is a schematic elevational diagram of an alternative energy conversion embodiment comprising a pressurized circulating fluidized bed boiler and condensing steam turbine generator.
DESCRIPTION OF PREFERRED EMBODIMENTS
The embodiment of FIG. 1 is representative of the operation of the invention with respect to a solid waste containing non-combustibles heavier than water and one or more anions, such as chlorine, having corrosion and/or air pollution consequences, and/or one or more cations conducive to slagging at temperatures of oxidation or combustion. Municipal Solid Waste (MSW), which may have been reclaimed from an existing landfill or modified by curbside recycling, and/or any pre-separation deemed justified, is used for purposes of illustration.
Waste is charged to the apparatus by a conveying means 101. Make-up water is introduced through a line 102. MSW is shredded and mixed with fresh and recycled water in a wet Resource Recovery (RR) section 103, such as that licensed by Newest, Inc. In the wet RR heavy debris and dirt are settled out, being separated into discards, which exit via a conduit 104, and ferrous and non-ferrous metals, which exit via a conduit 105. The slurry from which debris and heavy metals have been settled is pulped, diluted and subjected to selective density separation in a series of density classifiers, such as hydroclones, resulting in the discharge, through a conduit 106, of wet solids rich in glass, and the discharge, through a conduit 107, of wet solids rich in aluminum. Also within the wet RR 103, the remaining slurry of essentially carbonaceous constituents undergoes preliminary concentration to about the maximum processable viscosity, water separated therefrom being recycled internally to the initial mixing operation.
The carbonaceous slurry leaves the wet RR 103 by means of a line 108, and is joined by an alkali solution or slurry, such as lime slurry, from a line 109. If not already present, alkali is added in an amount at least the chemical equivalent of the acid-forming anions in the organic slurry. Alkalis are excellent agents for assisting the release and solution of acid-forming anions. In some cases, however, removal of cations, including slag-formers and potentially toxic metals, may take precedence. In such cases, solubizing agents effective for such elements including, but not limited to, certain acids and chelating agents may supplement or substitute for the addition of alkali by means of the line 109.
Depending upon relative elevations, a transfer pump (not shown) may be required in the line 108 or a line 110 conducting the carbonaceous slurry to a storage tank 111. If perishable, the carbonaceous slurry may be sterilized, as by heating by the injection of low pressure steam into it through a line 112. Sterilization may be necessary because of the time the carbonaceous slurry may be held in the storage tank 111 to permit continuous production of char slurry product. The tank 111 may be insulated to conserve sensible heat and be provided with one or more mixers and/or a circulating pump (not shown) to aid in maintaining uniformity of slurry properties.
A charge pump 113 draws carbonaceous slurry from the tank 111 and provides sufficient pressure to move it through subsequent pressurized equipment and maintain it essentially in liquid phase. The carbonaceous slurry flows from the pump 113, through a line 114, to the cold side of a low temperature heat exchanger 115, in which it is indirectly heated by, and to an approach to the temperature of, char slurry from a line 125. From the exchanger 115 the partially heated carbonaceous slurry flows to the cold side of a high temperature heat exchanger 116, in which it is indirectly heated by, and to an approach to, the temperature of carbonized (char) slurry from a line 120, exiting therefrom via a line 117.
The difference in free energies between a prototype carbonaceous biomass molecule and the resulting char molecule plus evolved gas (mainly carbon dioxide), indicates that the process is exothermic. In theory, this heat of reaction could result in the char slurry being sufficiently hotter than the raw slurry to provide the necessary driving force to operate the exchanger 116, without the necessity for an external source of heat. In practice, considering heat losses and the variability in raw material properties, the amount and location of heat evolution, it is preferrable to assure a controlled carbonization temperature by supplying a small amount of external heat. This function is symbolized in FIG. 1 by a heater 118 in which the requisite heat is transferred indirectly, as by condensing high pressure steam, a heat transfer fluid such as Dowtherm, a fired heater, electric resistance elements, or a coil heated by hot flue gas or turbine exhaust from associated equipment, or directly by the injection of high pressure steam, hot flue gas from a pressurized burner or a small amount of air or oxygen-containing gas.
Depending upon physical arrangement, piping between the heater 118 and the hot side inlet of the heat exchanger 116 may provide sufficient time for the carbonization to be complete. If a particular carbonaceous slurry requires more time at temperature than so provided, an enlarged section, or coil, of pipe 119, may be inserted to provide a few minutes additional reaction time. Now much reduced in viscosity, the char slurry and gas evolved by carbonization reactions (or as modified by the injection of heating agent) flow through the line 120 to the hot side of the high temperature heat exchanger 116, in which they supply heat indirectly to the carbonaceous slurry which has been partially heated in the low temperature exchanger 115. They are cooled thereby to a temperature corresponding to a pressure sufficient that, after being separated in a high pressure flash drum 122, the evolved gas can flow through a control device 123 and a line 124 to a pressurized oxidation reactor.
Char slurry flows from the bottom of the drum 122 via the line 125 to the hot side of the low temperature heat exchanger 116 in which it indirectly transfers heat to incoming carbonaceous slurry, as previously described. The cooled char slurry, at a temperature near its atmospheric boiling point, flows through a line 126, under control of a flow controlling device 127, which is operated to maintain the level in the drum 122 within a desired range. Although the preponderance of gas was separated in the drum 122, a little remaining in solution in the char slurry (mainly carbon dioxide) separates out, along with an equilibrium quantity of steam, in a low pressure flash drum 128. This gas flows via a line 129 to the storage tank 111 in which it is largely absorbed in the carbonaceous slurry, or to alternative disposition.
The char slurry flows through a line 130 to a comminution device 131 which breaks up any particles large enough to cause difficulty, such as plugging, in subsequent utilization, from which it flows via a line 132 to a liquid-solids separating device 133, which may be one of several types of continuous centrifuges or filters or one or more hydroclones. The separating device is operated to essentially free the solid char particles from aqueous phase, which exits the device 133 through a line 134. Part or all of the aqueous phase is pumped by a recycle pump 135 through a line 136 as recycle water to the RR section 103. Part or all of the aqueous phase may alternatively be withdrawn from the apparatus through a flow control device 137 as a purge of salts, dissolved organic compounds and/or fine solid particles unseparated in the device 133. Such purge may go to conventional waste water treatment or have its combustible content oxidized from it by one of the processes described in my U.S. Pat. No. 4,898,107.
The separating device 133 may have provision for washing the wet char solids with clean water in order to further reduce its content of undesirable anions and/or cations. In such case washings join with the aqueous phase in being recycled and/or purged. A recycle water storage tank (not shown) may be useful or necessary for purposes of operating continuity.
Char solids discharged from the device 133 fall through a conduit 138 and are reslurried in clean water from a line 139, with the aid of a mixing device 140, to a maximum viscosity deemed suitable for subsequent processing and flow via a line 141 to a surge tank 142, in which the high energy density, chlorine-reduced char slurry is accumulated for transport through a line 143 for conversion into thermal and/or electrical energy. The tank 142 may be insulated to conserve sensible heat and be provided with one or more mixers and/or a circulating pump (not shown) to aid in maintaining uniformity of slurry properties.
Essentially the same method is utilized to recover energy from a coal whose market value is adversely affected by chlorine and/or sulfur and/or slag-forming ash ingredients. However, in place of the RR section 103, conventional coal washing and beneficiation practice may be used to minimize inorganic impurities, adjusted to deliver to the line 108, or the pump 113, a ground coal slurry of approximately maximum processable viscosity. While the response of coals to carbonization differs, it is to be expected that the majority of the chlorine and an appreciable proportion of the sulfur will be extracted into the aqueous stream separated in the device 133, and that undesirable cations will also be reduced.
In the case of forestry and agricultural byproducts, chipping, pulping and degritting, as known to the pulp and paper industry, may be employed to produce the raw carbonaceous slurry and deliver it to the line 108. Since these fuels are normally low in chlorine and sulfur, addition of alkali through the line 109 may be omitted. Nevertheless, a substantial proportion of sodium and potassium in the raw fuel will be rendered soluble in, and be separated with, the aqueous recycle and/or purge, and the char slurry will have processable viscosity at a high energy density.
In the case of a pre-existing slurry, such as a sewage or paper mill sludge, the equipment devoted to slurrying and density separation of inorganic contaminents may be omitted, i.e., those items preceding the line 110, or limited to simple degritting. Alkali, or other solubilizing agent, would be added through the line 109 only if the raw feedstock contains appreciable acid-forming anions or potentially troublesome cations, and available alkali is not already present. If no danger of bacterial decomposition exists, it is unnecessary to inject steam as through the line 112.
Similarly, should the resulting char slurry be free of large particles liable to plug downstream apparatus, the comminutor 131 may be omitted. If the raw feed does not contain appreciable amounts of extractable anions or cations, the char slurry may merely be concentrated in the device 133 to a maximum processable viscosity, rather than separated essentially completely and reslurried in clean water. In such case a single or multi-stage hydroclone (which may provide a counterflow of wash water) may economically accomplish the concentration.
The preferred disposition of the concentrated char slurry is as fuel to pressurized oxidation. Nevertheless, it can be burned in atmospheric furnaces and boilers of various kinds, without corrosion and with a positive contribution to heat release, rather than the negative thermal impact which the raw slurry would have had in similar equipment. Should the char slurry be destined for burning in an atmospheric furnace or boiler, the schematic flow arrangement, after slurrying and separation of heavy inorganics, would be simplified by combining the heat exchangers 115 and 116, eliminating the flash drum 122, separating all gas produced in the low pressure flash drum 128 and conducting it to a suitable use or incineration in the furnace or boiler.
On the other hand, for char slurry destined for pressurized oxidation or combustion, a somewhat higher overall thermal efficiency would be realized by performing the comminution (if required), and separation of char from aqueous phase and subsequent reslurrying, under essentially the same pressure as the high pressure flash in the drum 122, so that the slurry (as well as the gas) can flow without pumping to the oxidation or combustion reactor. The char slurry would then be delivered at saturation temperature, considerably hotter than its atmospheric boiling point. However, additional heat would have to be provided, as by the heater 118, to replace that formerly transferred in (now redundant) low temperature heat exchanger 116.
The embodiment of FIG. 2 incorporates the embodiment of FIG. 1 and the conversion of the high energy density char slurry to electricity, by means of thermal oxidation in the presence of injected steam, separation of ash particles from the hot gas and conversion of its heat and pressure energy to electricity.
A solid waste, low rank or chlorine-containing fuel, or matures thereof is transported via a conveying means 201, along with make-up water from a line 202, into a grinding, mixing and slurrying facility 203, along with recycled water from a line 204. In the facility 203, which may be a wet RR (as described more fully in connection with FIG. 1) and/or washing and beneficiation apparatus, particle size is reduced and heavy inorganic impurities are separated and removed via a transport means 205. A largely carbonaceous slurry of approximately maximum processable viscosity leaves the facility 203 through a line 206 and may be alkalized by injecting a solution or slurry of alkali through a line 207. If bacterial decomposition could be a problem, the slurry may be sterilized by the injection of low pressure steam through a line 208. If operating continuity requires, a surge tank (not shown) can be inserted between the line 206 and a carbonization charge pump 209.
The pump 209 imparts to the carbonaceous slurry sufficient pressure to cause it to flow through a carbonization section 210, as more fully described in connection with FIG. 1, and maintains it essentially in liquid phase. Gas evolved during carbonization is separated within the section 210 and delivered for suitable disposal through a control device 211. Excess aqueous phase leaves the section 210 and may be recycled through the line 204 and/or purged from the apparatus through a line 212. Concentrated or reslurried char slurry is pumped from the section 210 by a reactor charge pump 213, which delivers it through a line 214 to a dispersing and mixing device 215. Should the char slurry in the line 214 be at a temperature near to its atmospheric boiling point, and it is economic to transfer to it process heat which would otherwise have been wasted, a heat exchanger (not shown) may be interposed in the line 214.
Atmospheric air is drawn through a conduit 216, in which may be located a conventional dust filter (not shown), to the suction of a first stage air compressor 217, which delivers it at an elevated pressure through a connection 218 to a second stage air compressor 219, which delivers it hot and at a further increased pressure to a line 220. (Two-stage gas turbine compressors of some manufacturers may have an intercooler, and a drum in which to disengage condensate, interposed between first and second stages.)
Char slurry from the line 214 and air (oxidant) from the line 220 are intimately mixed in, or immediately following, the mixing device 215. The air may be divided among primary and secondary passages and the device 215 may contain swirl baffles and/or other dispersing and mixing means known to the arts of mixer, burner and/or spray drier design, including air and/or steam atomization. The air-slurry mixture discharges into the inlet zone of an elongated oxidation reactor 221, which may have internals (not shown) as described for FIG. 1 of U.S. Pat. No. 5,050,375, to induce recirculation of hot oxidation products to the inlet zone, for the purpose of quickly heating the fuel-air mixture to a temperature at which the reaction proceeds rapidly. Secondary or tertiary air may be added to the internal recycle as through the connection 222.
Part or all of the air in the line 220 may be diverted to an air separation unit to be enriched in oxygen. In particular, that part to be mixed with the char slurry as primary oxidant may be so enriched.
Gas evolved in the carbonization section 210 and shown to be exiting via the control device 211 may also be introduced to the mixer 215 or the inlet zone of the reactor 221 (by means of connections not shown).
The internal diameter of the reactor 221 is chosen to provide a relatively high velocity reaction zone such that solid particles remain entrained in and flow with the gaseous phase. Fuel particles react with oxygen to form carbon dioxide and water vapor, releasing the corresponding heat of reaction and causing the temperature of the mixture to rise. The maximum temperature is limited, however, by adjustment of the oxidant:slurry ratio.
Upon being discharged into an expanded diameter disengaging zone 223, kinetic energy of solid particles, together with the force of gravity, causes most of them to disengage from gaseous products and fall to a conical bottom section 224, from which they are withdrawn through a main standpipe 225. The conical bottom of the section 224 may contain aeration connections (not shown) through which air and/or steam is injected to maintain the solid particles in free-flowing condition.
While the principal control of oxidation temperature is by fuel slurry:oxidant ratio, this temperature is moderated by the injection of high pressure steam as through one or a plurality of connections symbolized by a line 226.
Although the flow direction of the reactor 221 illustrated in FIG. 2 is downward, entrained flow reactors for my invention may also be upflow or horizontal and the products recycle passage may be external, rather than internal. FIG. 3 of U.S. Pat. No. 5,050,375 illustrates a U-shaped reactor, permitting a relatively short external recycle passage. Reactors for the embodiment of FIG. 2 are not necessarily of entrained flow type but may be configured as circulating fluidized bed reactors, as illustrated in FIG. 5, including those which operate in "transport" phase.
Product gas, carrying some fine ash particles, discharges from the disengaging zone 223 to a cyclone separator 227. Utilizing centrifugal force, the separator 227 performs a further separation between the gas and entrained particles, which fall by gravity into a standpipe 228 which joins the main standpipe 225. Other cyclone configuration, including multi-stage, or other known gas-solids separation devices, may be substituted for the cyclone 227.
Product gas, still carrying fine dust particles unseparated in the cyclone 227, flow through a line 229 to the hot side of a reheat exchanger 230 in which they are cooled to a temperature approaching their dew point by indirect exchange with clean (scrubbed) gas. Cooled product gas then flow via a line 231 to a gas-liquid contactor 232 in which they are further cooled to their dew point and have entrained dust particles wetted by contact with fines slurry recirculated from the base of a scrubber vessel 233, by means of a suction line 234, a fines slurry pump 235 and a recirculation line 236.
The pump 235 also supplies the net production of fines slurry through a line 237 to an eductor 238, which receives the ash particles separated in the disengaging zone 223 and the cyclone 227 via the standpipes 225 and 228. In the eductor 238 the ash particles, accompanied by some gas, are cooled, wetted, slurried and discharged through a line 239 to a fluidizing gas separator 240. In the separator 240 fluidizing gas is disengaged from the ash slurry and separated for venting, along with an equilibrium amount of steam, via a line 241, into the scrubber 233. (The latent heat of steam accompanying the gas in the line 241 represents heat recovered from hot ash.) Ash slurry is withdrawn via a bottom connection into a line 242 from which it flows to the hot side of a ash slurry-feedwater heat exchanger 243 in which it is cooled to a temperature suitable for discharge, through a pressure control device 244, to conventional ash slurry disposal. In some cases the heat in ash slurry in the line 242 may be used to heat incoming char slurry instead of feedwater.
Treated boiler feedwater enters the apparatus, under pressure from an offsite pump, via a line 245, and is preheated by indirect heat exchange with ash slurry in the exchanger 243. From the exchanger 243 it flows via a line 246 to a boiler feedwater accumulator 247 (which may be a "deaerator" of proprietary design). Gases liberated by the heating in the exchanger 243 are vented to the atmosphere from the top of the accumulator 247 through a pressure control device 248. A boiler feedwater pump 249 takes suction from the accumulator 247 and discharges feedwater through a line 250 to a series of spray nozzles arrayed across the upper cross-section of the scrubber 233. Spray nozzles may be disposed on a plurality of levels. The purpose of the feedwater sprayed into the gas stream rising through the scrubber 233 is to cool it slightly below its dew point, condensing from it a small part of the steam it contains. Condensation of water on and around dust particles effectively wets them and removes them from the gaseous phase. In order to increase the liquid/gas ratio of the spray contact, spray water may be recirculated by means of an internal sump and circulation pump (not shown). Water from another suitable source may be substituted for boiler feedwater.
Clean product gas (containing a substantial content of steam) leaves the scrubber 233 through a mist extractor 251 and flows to the cold side of the reheat exchanger 230, in which it is heated by hot product gas to an approach to its temperature. The reheated clean product gas returns to the turbo-machinery via a line 252.
As an alternative to the scrubbing system comprising the reheat exchanger 230, the scrubber 233, the contactor 232, the mist extractor 251 and associated piping connections, another method of separating fine dust from hot gas-steam, such as a plurality of porous ceramic filter thimbles, may be employed.
The hot clean gas is partially expanded through a first-stage turbine 253, which delivers mechanical energy, in the form of shaft horsepower, to the second-stage air compressor 219. In order to maintain critical components of the turbine 253 within safe operating temperatures, high pressure steam, and/or air from the line 220, may be supplied to internal cooling passages (through connections not shown).
Having been cooled by giving up energy in the turbine 253, the partially expanded gas flows via a crossover 254 to be expanded further in a second-stage turbine 255, which delivers mechanical energy, in the form of shaft horsepower, to the first-stage air compressor 217. Having been further cooled by giving up energy in the turbine 255, the further expanded gas flows via a crossover 256 to be expanded again in a third-stage turbine 257. Supplementing the discharge of the turbine 255 in driving the turbine 257 is superheated intermediate pressure steam joining it by means of a line 258. The turbine 257 delivers mechanical energy, in the form of shaft horsepower, to a generator (or alternator) 259 which converts it into electricity. After diversion of a small amount to power internal services, such as lubricating oil pumps (through a conduit not shown), the net production of electricity is delivered from the apparatus through a conduit 260.
The injection of steam into the reactor via the line 226 and into the turbine 257 through the line 258 categorizes the gas turbine set as a "steam injected gas turbine" or "STIG".
The embodiment of FIG. 2 is structured to take advantage of gas turbines which are, or are expected to become, commercially available. The pressure of the reactor 221 is determined by the discharge pressure of the compressor 219. The discharge pressure of the turbine 253 is adjusted so that it produces only as much power as consumed by the compressor 219. Similarly, the discharge pressure of the turbine 255 is adjusted so that it produces only as much power as consumed by the compressor 217, excess potential energy in the gas being transferred to the turbine 257 in the form of pressurized exhaust.
Although illustrated by means of turbo-machinery supplied by a particular manufacturer, the embodiment of FIG. 2 can readily be adapted to turbo-machinery from other manufacturers having a different air discharge pressure and/or variations in the numbers of individual machines and their inter-relationships.
The turbine 257 discharges into an exhaust manifold 261 which conducts the fully expanded gas to a Heat Recovery Steam Generator (HRSG) 262. The HRSG 262 is a more-or-less standardized assembly of economizers, boilers and superheaters, designed for heat recovery from turbine exhaust and available from several manufacturers. As configured for this embodiment it comprises an economizer, low, intermediate and high pressure boilers and a superheater for intermediate pressure steam. A number of other configurations are feasible alternatives, particularly as regards steam pressures and disposition of economizer(s) and superheater(s).
Exhaust, from which economically useful heat has been recovered, is discharged to the atmosphere through a vent 263. Boiler feedwater is supplied to the HRSG 262 by the pump 249 by way of a line 264. Low pressure steam is delivered through a line 265 to offsite use, such as for sterilization of raw slurry (if needed), by means of the line 208, and for building heating during cold weather. Intermediate pressure steam is superheated and delivered through the line 258 to the inlet of the turbine 257. High pressure steam is delivered through the line 226 to the air-slurry mixer 215 and/or the reactor 221. Some of the intermediate pressure steam may be diverted to offsite use through a line 266. Although high pressure steam is nominally unsuperheated, in practice it is preferrable to impart to it a minor degree of superheat to minimize troublesome condensation in its piping. Blowdown is cascaded from high pressure boiler to intermediate to low pressure boiler and withdrawn from the HRSG 262 through a control device 267. Since the offsite demand for low pressure steam is expected to be intermittent, the HRSH 262 is equipped with feedwater piping connections and valving which permit heat transfer surface to be shifted from the low pressure boiler to the economizer coil and the intermediate pressure boiler.
The HRSG 262 may be equipped for firing with supplemental fuel (i.e., employ "duct burners") and can incorporate a coil in which to finish the heating of carbonaceous slurry to carbonization temperature.
If, in spite of the density separations performed in the unit 203 and the extractions performed in the unit 210, the char slurry being charged to the reactor 221 contains toxic metals such that its ash might be rated as hazardous, the amount of primary oxidant mixed with the slurry in the mixer 215, and/or its oxygen concentration, may be increased so that the temperature reached in the upper part of the reactor 221 exceeds the fusion point of a majority of ash ingredients. Suspended ash particles then become small globules of molten slag. The subsequent admission of steam through the line 226 and/or secondary or tertiary oxidant through the line 222 (besides completing the oxidation) quenches the mix temperature to a level below the ash fusion point so that the ash separated from product gas in the disengaging zone 223 and the cyclone 227 is in the form of roughly spherical, non-adherent particles.
It is also possible to perform part or all of the quenching of the hot gas-slag globules mixture with cooled clean product gas recycled from the top of the scrubber 233 by means of a line 268, a gas circulator 269 and a quench line 270. Alternatively, part or all of the quenching may be accomplished with water injected above the disengaging zone 223 (by means of a line not shown). Quenching by either, or a combination, of these other means decreases the amount of excess air needed to regulate the temperature of product gas in the zone 223, thereby making more available for oxidizing additional char slurry.
Quenching with recycled cleaned product gas may entail a substantial recycle through the disengaging zone 223, the cyclone 227, the hot side of the exchanger 230 and the scrubber 233. The thermal capacity of the net cleaned product gas on the cold side of the exchanger 230 may be inadequate for this duty. Up to a point additional cooling duty can be shifted to an exchanger (not shown but similar to the exchanger 545 of FIG. 5), preheating char slurry or boiler feedwater, interposed in the line 236. But, it may also be necessary to supplement such hot product gas cooling duty by means of an exchanger or waste heat boiler (not shown) in parallel or series with the exchanger 230, transferring part of it to, for example, boiler feedwater.
Although each are diagrammed as a single connection, steam, air, cooled gas and/or water may actually be injected into the reactor 221 through a plurality of connections around its circumference and located in more than one horizontal plane.
Not shown in FIG. 2 are auxiliary systems and equipment, such as those needed to bring the apparatus on stream from a cold start, back-up fuel and power, blowdown and pressure relief systems.
The embodiment of FIG. 3 incorporates the embodiment of FIG. 1 and the conversion of the high energy density char slurry to electricity, by means of thermal oxidation, separation of ash particles from the hot gas and conversion, by means of a gas turbine generator, of its heat and pressure energy to electricity. Heat remaining in turbine exhaust is converted to steam which, expanded through a condensing steam turbine generator, produces additional electricity.
The concentrated or re-slurried char slurry enters the apparatus, preferably at the temperature at which it was produced, through a line 301 and is pressurized by a reactor charge pump 302, which delivers it through a line 303 to a dispersing and mixing device 304. Should the char slurry in the line 303 be at a temperature near to its atmospheric boiling point, and it is economic to transfer to it process heat which would otherwise have been wasted, a heat exchanger (not shown) may be interposed in the line 303.
Atmospheric air is drawn through a conduit 305, in which may be located a conventional dust filter (not shown), to the suction of a first stage air compressor 306, which delivers it at an elevated pressure through a connection 307 to a second stage air compressor 308, which delivers it hot and at a further increased pressure to a line 309. (Two-stage gas turbine compressors of some manufacturers may have an intercooler, and a drum in which to disengage condensate, interposed between first and second stages.)
Char slurry from the line 303 and air from the line 309 are intimately mixed in, or immediately following, the mixing device 304. The air may be divided among primary and secondary passages and the device 304 may contain swirl baffles and/or other dispersing and mixing means known to the arts of mixer, burner and/or spray drier design, including air and/or steam atomization. The air-slurry mixture discharges into the inlet zone of an elongated oxidation reactor 310, which may have internals (not shown) as described for FIG. 1 of U.S. Pat. No. 5,050,375, to induce recirculation of hot oxidation products to the inlet zone, for the purpose of quickly heating the fuel-air mixture to a temperature at which the reaction proceeds rapidly. The air in the line 309 may be partially diverted as secondary or tertiary air to the reacting mixture downstream of the mixing device 304, as through connections 311 and 312.
Gas evolved in a carbonization section, such as that illustrated in FIG. 1, and shown to be exiting via the line 124, may also be introduced to the mixer 304 or the inlet zone of the reactor 310 (by means of connections not shown).
The internal diameter of the reactor 310 is chosen to provide a relatively high velocity reaction zone such that solid particles remain entrained in and flow with the gaseous phase. Char particles react with oxygen to form carbon dioxide and water vapor, releasing the corresponding heat of reaction and causing the temperature of the mixture to rise. The maximum temperature is limited, however, by adjustment of the air:slurry ratio.
Upon being discharged into an expanded diameter disengaging zone 313, kinetic energy of solid particles, together with the force of gravity, causes most of them to disengage from gaseous products and to fall to a conical bottom section 314, from which they are withdrawn through a main standpipe 315. The section 314 may contain aeration connections (not shown) through which air and/or steam is injected to maintain the solid particles in free-flowing condition.
Although the flow direction in the reactor 310 illustrated in FIG. 3 is downward, entrained flow reactors for my invention may also be upflow or horizontal and the products recycle passage may be external, rather than internal and axial. FIG. 3 of U.S. Pat. No. 5,050,375 illustrates a U-shaped reactor, permitting a relatively short external recycle passage. Reactors for the embodiment of FIG. 3 are not necessarily of entrained flow type but may be configured as circulating fluidized bed reactors, as illustrated in FIG. 5, including those which operate in "transport" phase.
Product gas, carrying some fine ash particles, discharges from the disengaging zone 313 to a cyclone separator 316. Utilizing centrifugal force, the separator 316 performs a further separation between gas and entrained particles, which fall by gravity into a standpipe 317 which joins the main standpipe 315. Other cyclone configurations, including multi-stage, or other known gas-solids separation devices, may be substituted for the cyclone 316.
Product gases, still carrying fine dust particles unseparated in the cyclone 316, flow through a line 318 to the hot side of a reheat exchanger 319, in which they are cooled to a temperature slightly above their dew point by indirect exchange with clean (scrubbed) product gas. Cooled product gas then flows via a line 320 to a contacting device 321 in which they are cooled to their dew point and have entrained dust particles wetted by contact with fines slurry recirculated from the base of a scrubber vessel 322, by means of a suction line 323, a fines slurry pump 324 and a recirculation line 325.
The pump 324 also supplies the net production of fines slurry through a line 326 to an eductor 327, which receives the ash particles separated in the disengaging zone 313 and the cyclone 316 via the standpipes 315 and 317. In the eductor 327 the ash particles, accompanied by some gas, are cooled, wetted, slurried and discharged through a line 328 to a fluidizing gas separator 329. In the separator 329 fluidizing gas is disengaged from the ash slurry and separated for venting, along with an equilibrium amount of steam, via a line 330, into the scrubber 322. (The latent heat of steam accompanying the gas in the line 330 represents heat recovered from hot ash.) The ash slurry is withdrawn via a bottom connection into a line 331 from which it flows to the hot side of an ash slurry-feedwater heat exchanger 332 in which it is cooled to a temperature suitable for discharge, through a pressure control device 333, to conventional ash slurry disposal. In some cases the heat in ash slurry from the separator 329 may be used to heat incoming char slurry instead of feedwater.
Treated boiler feedwater enters the apparatus, under pressure from an offsite pump, via a line 334, and is preheated by indirect heat exchange with ash slurry in the exchanger 332. From the exchanger 332 it flows via a line 335 to a boiler feedwater accumulator 336 (which may be a "deaerator" of proprietary design). Gases liberated by the heating in the exchanger 332 are vented to the atmosphere from the top of the accumulator 336 through a pressure control device 337. A boiler feedwater pump 338 takes suction from the accumulator 336 and discharges feedwater through a line 339 to a plurality of spray nozzles arrayed across the upper cross-section of the scrubber 322. Spray nozzles may be disposed on more than one level. The purpose of the feedwater sprayed into the gas stream rising through the scrubber 322 is to cool it slightly below its dew point, condensing from it a small part of the steam it contains. Condensation of water on and around dust particles effectively wets them and removes them from the gaseous phase. In order to increase the liquid/gas ratio of the spray contact, spray water may be recirculated by means of an internal sump and circulation pump (not shown). Water from another suitable source may be substituted for boiler feedwater.
Clean product gas leaves the scrubber 322 through a mist extractor 340 and flows to the cold side of the reheat exchanger 319, in which it is indirectly heated by hot product gas to an approach to its temperature. The reheated gas returns to the turbo-machinery via a line 341.
As an alternative to the scrubbing system comprising the reheat exchanger 319, the scrubber 322, the contactor 321, the mist extractor 340 and associated piping connections, another method of separating fine dust from hot gas-steam, such as a plurality of porous ceramic filter thimbles, may be employed.
The hot clean gas is partially expanded through a first-stage turbine 342, which delivers mechanical energy, in the form of shaft horsepower, to the second-stage air compressor 308. In order to maintain critical components of the turbine 342 within safe operating temperatures, high pressure steam, and/or air from the discharge of the compressor 308, may be supplied to internal cooling passages (through connections not shown).
Having been cooled by giving up energy in the turbine 342, the partially expanded gas flows via a crossover 343 to be expanded further in a second-stage turbine 344, which delivers mechanical energy, in the form of shaft horsepower, to the first-stage air compressor 306. Having been further cooled by giving up energy in the turbine 344, the further expanded gas flows via a crossover 345 to be expanded again in a third-stage turbine 346, which delivers mechanical energy, in the form of shaft horsepower, to a generator (or alternator) 347 which converts it into electricity and discharges it through a conduit 348.
The pressure of the reactor 310 is determined by the discharge pressure capability of the compressor 308. The discharge pressure of the turbine 342 is adjusted so that it produces only as much power as consumed by the compressor 308. Similarly, the discharge pressure of the turbine 344 is adjusted so that it produces only as much power as consumed by the compressor 306, excess potential energy in the gas-steam being transferred to the turbine 346 in the form of pressurized exhaust.
While FIG. 3 is illustrated by means of turbo-machinery supplied by a particular manufacturer, it can readily be adapted to turbo-machinery from other manufacturers having a different air discharge pressure and/or variations in the numbers of individual machines and their interrelationships.
The turbine 346 discharges into an exhaust manifold 349 which conducts the fully expanded product gas to a Heat Recovery Steam Generator (HRSG) 350. The HRSG 350 is a more-or-less standardized assembly of economizers, boilers and superheaters, designed for heat recovery from turbine exhaust and available from several manufacturers. As configured for this embodiment the HRSG 350 comprises economizer, low, intermediate and high pressure boilers and superheaters for high and intermediate pressure steam. A number of other configurations are feasible alternatives, particularly as regards steam pressures, reheat coils and arrangement of economizer(s) and superheater(s).
Exhaust, from which economically useful heat has been recovered, is discharged to the atmosphere through a vent 351. Boiler feedwater is supplied to the HRSG 350 by the pump 338 by way of a line 352. A high pressure feedwater booster pump (not shown) may be necessary to charge the high pressure boiler. Low pressure steam is delivered through a line 353 to offsite use, mainly for sterilization of raw slurry (if needed), and for building heating during cold weather. Superheated high pressure steam flows via a line 354 to the inlet of a condensing steam turbine 355. Superheated intermediate steam flows via a line 356 to an interstage of the turbine 355 appropriate for its pressure. The energy produced by the expansion of the high and intermediate pressure steam in the turbine 355 is transmitted, as shaft horsepower, to a generator (or alternator) 357 which converts it to electricity, which flows via a conduit 358 to join with that in the conduit 348. After diversion of a small amount to power internal services, such as lubricating oil pumps (through a conduit not shown), the net production of electricity is delivered from the apparatus through the conduit 359. If other installations at site have a need for saturated and/or superheated intermediate pressure steam a quantity may be diverted from the turbine 355 by means of a line or lines (not shown). Since the demand for low pressure steam is liable to be intermittent, a connection (not shown) may also be provided to convey excess low pressure steam to an appropriate stage of the turbine 355. Blowdown is cascaded from high pressure boiler to intermediate to low pressure boiler and withdrawn from the HRSG 350 through a control device 357. The HRSG 350 may be equipped for firing with supplemental fuel (i.e., employ "duct burners") and can incorporate a coil in which to finish the heating of carbonaceous slurry to carbonization temperature.
Fully expanded steam leaves the turbine 355 through a vacuum line 361 which conducts it to the hot side of a vacuum surface condenser 362. As shown, the heat necessary to condense the steam and create a vacuum is indirectly transferred to cooling water, supplied to the cold side of the condenser 362 by means of a line 363 and returned to an offsite cooling tower through a line 364. Alternatively, an air-cooled condenser could have been used in place of the water-cooled condenser 362. Steam condensate collects in the bottom of the condenser 362 from which it drains by gravity through a line 365 to a condensate receiver 366. An evacuation device 367, which may be a vacuum pump or steam jet ejector, is connected to the top of the receiver 366 in order to dispose to the atmosphere of any non-condensible gas entering the condenser 362, as with the steam exhausted from the turbine 355. From the receiver 366 steam condensate flows via a line 368 to a condensate pump 369, which gives it sufficient pressure to discharge into the accumulator 336.
If, in spite of the density separations and extractions performed during its preparation, the char slurry being charged to the reactor 310 contains toxic metals such that its ash might be rated as hazardous, the amount of primary oxidant mixed with the slurry in the mixer 304, and/or its oxygen concentration, may be increased so that the temperature reached in the upper part of the reactor 310 exceeds the fusion point of a majority of ash ingredients. Suspended ash particles then become small globules of molten slag. The subsequent admission of secondary or tertiary oxidant through the lines 311 and 312 (besides completing the oxidation) quenches the mix temperature to a level below the ash fusion point so that the ash separated from product gas in the disengaging zone 313 and the cyclone 316 is in the form of roughly spherical, non-adherent particles.
It is also possible to perform part or all of the quenching of the hot gas-slag globules mixture with cooled clean product gas recycled from the top of the scrubber 322 by means of a line 370, a gas circulator 371 and a quench line 372. Alternatively, the quenching may be accomplished with water injected above the disengaging zone 313 (by means of a line not shown). Quenching by either, or a combination, of these other means decreases the amount of excess air needed to regulate the temperature of product gas in the line 318, thereby making more available for oxidizing additional char slurry.
Quenching with recycled cleaned product gas may entail a substantial recycle through the disengaging zone 313, the cyclone 316, the hot side of the exchanger 319 and the scrubber 322. The thermal capacity of the net clean product gas on the cold side of the exchanger 319 may be inadequate for this duty. Up to a point additional cooling duty can be shifted to an exchanger (not shown but similar to the exchanger 545 of FIG. 5), preheating char slurry or boiler feedwater, interposed in the line 325. But, it may also be necessary to supplement such hot product gas cooling duty by means of an exchanger or waste heat boiler (not shown) in parallel or series with the exchanger 319, transferring part of it to, for example, boiler feedwater.
Although each are diagrammed as a single connection, air, cooled gas or water may actually be injected into the reactor 310 through a plurality of connections around its circumference and located in more than one horizontal plane.
Not shown in FIG. 3 are auxiliary systems and equipment, such as those needed to bring the apparatus on stream from a cold start, back-up fuel and power, blowdown and pressure relief systems.
The embodiment of FIG. 4 incorporates the embodiment of FIG. 1 and the conversion of the high energy density char slurry to electricity, by means of two-stage thermal oxidation, separation of ash particles from the first-stage gas and conversion, by means of a gas turbine generator, of its chemical, thermal and pressure energy to electricity. Heat remaining in turbine exhaust is converted to steam which, expanded through a condensing steam turbine generator, produces additional electricity.
The concentrated or re-slurried char slurry enters the apparatus, preferably at the temperature at which it was produced, through a line 401 and is pressurized by a reactor charge pump 402, which delivers it through a line 403 to a dispersing and mixing device 404. Should the char slurry in the line 403 be at a temperature near to its atmospheric boiling point, and it is economic to transfer to it process heat which would otherwise have been wasted, a heat exchanger (not shown) may be interposed in the line 403.
Atmospheric air is drawn through a conduit 405, in which may be located a conventional dust filter (not shown), to the suction of a first stage air compressor 406, which delivers it at an elevated pressure through a connection 407 to a second stage air compressor 408, which delivers a portion of the compressed air hot and at a further increased pressure to a line 409. (Two-stage gas turbine compressors of some manufacturers may have an intercooler, and a drum in which to disengage condensate, interposed between first and second stages.)
Part or all of the air in the line 409 may be diverted to an air separation unit (not shown) so that the oxidant going to the mixer 404 may have an oxygen concentration greater than that of normal air.
Char slurry from the line 403 and compressed oxidant from the line 409 are intimately mixed in, or immediately following, the mixing device 404. The oxidant may be divided among primary and secondary passages and the device 404 may contain swirl baffles and/or other dispersing and mixing means known to the arts of mixer, burner and/or spray drier design, including air and/or steam atomization. The oxidant-slurry mixture discharges into the inlet zone of an elongated oxidation reactor 410, which may have internals (not shown) as described for FIG. 1 of U.S. Pat. No. 5,050,375, to induce recirculation of hot oxidation products to the inlet zone, for the purpose of quickly heating the slurry-oxidant mixture to a temperature at which the reaction proceeds rapidly.
Gas evolved in a carbonization section, such as that illustrated in FIG. 1, and shown to be exiting via the line 124, may also be introduced to the mixer 404 or the inlet zone of the reactor 410 (by means of connections not shown).
The internal diameter of the reactor 410 is chosen to provide a relatively high velocity reaction zone such that solid particles remain entrained in and flow with the gaseous phase. Char particles react with oxygen to form carbon monoxide and dioxide and hydrogen, releasing the corresponding heat of reaction and causing the temperature of the mixture to rise, resulting in some light hydrocarbon gases as well being evolved from the char particles, and forming a fuel gas. The maximum temperature is, however, limited, by adjustment of the oxidant:slurry ratio.
Upon being discharged into an expanded diameter disengaging zone 413, kinetic energy of solid particles, together with the force of gravity, causes most of them to disengage from the fuel gas and to fall to a conical bottom section 414, from which they are withdrawn through a main standpipe 415. The section 414 may contain aeration connections (not shown) through which steam and/or cooled gas is injected to maintain the solid particles in free-flowing condition.
Although the flow direction in the reactor 410 illustrated in FIG. 4 is downward, entrained flow reactors for my invention may also be upflow or horizontal and the products recycle passage may be external, rather than internal and axial. FIG. 3 of U.S. Pat. No. 5,050,375 illustrates a U-shaped reactor, permitting a relatively short external recycle passage. Reactors for the embodiment of FIG. 4 are not necessarily of entrained flow type but may be configured as circulating fluidized bed reactors, such as illustrated in FIG. 5, including those which operate in "transport" phase, and which have provision for introducing the char slurry above the oxidant inlet, at a point that oxygen has been depleted.
Hot fuel gas, carrying some fine ash particles, discharges from the disengaging zone 413 to a cyclone separator 416. Utilizing centrifugal force, the separator 416 performs a further separation between gas and entrained particles, which fall by gravity into a standpipe 417 which joins the main standpipe 415. Other cyclone configurations, including multi-stage, or other known gas-solids separation devices, may be substituted for the separator 416.
Hot fuel gases, still carrying fine dust particles unseparated in the cyclone 416, flow through a line 418 to the hot side of a reheat exchanger 419 in which they are cooled to a temperature approaching their dew point by indirect exchange with scrubbed gas. Cooled fuel gases then flow via a line 420 to a contacting device 421 in which they are further cooled to their dew point and have entrained dust particles wetted by contact with fines slurry recirculated from the base of a scrubber vessel 422, by means of a suction line 423, a fines slurry pump 424 and a recirculation line 425.
The pump 424 also supplies the net production of fines slurry through a line 426 to an eductor 427, which receives the ash particles separated in the disengaging zone 413 and the cyclone 416 via the standpipes 415 and 417. In the eductor 427 the ash particles, accompanied by some gas, are cooled, wetted, slurried and discharged through a line 428 to a fluidizing gas separator 429. In the separator 429 fluidizing gas is disengaged from the ash slurry and separated for venting, along with an equilibrium amount of steam, via a line 430, into the scrubber 422. (The latent heat of steam accompanying the gas in the line 430 represents heat recovered from hot ash.) The ash slurry is withdrawn via a bottom connection into a line 431 from which it flows to the hot side of an ash slurry-feedwater heat exchanger 432 in which it is cooled to a temperature suitable for discharge, through a pressure control device 433, to conventional ash slurry disposal.
Treated boiler feedwater enters the apparatus, under pressure from an offsite pump, via a line 434, and is preheated by indirect heat exchange with ash slurry in the exchanger 432. From the exchanger 432 it flows through a line 435 to a boiler feedwater accumulator 436 (which may be a "deaerator" of proprietary design). Gases liberated by the heating in the exchanger 432 are vented to the atmosphere from the top of the accumulator 436 through a pressure control device 437. A boiler feedwater pump 438 takes suction from the accumulator 436 and discharges feedwater through a line 439 to a series of spray nozzles arrayed across the upper cross-section of the scrubber 422. Spray nozzles may be disposed on a plurality of levels. The purpose of the water sprayed into the gas stream rising through the scrubber 422 is to cool it slightly below its dew point, condensing from it a small part of the steam it contains. Condensation of water on and around dust particles effectively wets them and removes them from the gaseous phase. In order to increase the liquid/gas ratio of the spray contact, spray water may be recirculated by means of an internal sump and circulation pump (not shown). Water from another suitable source may be substituted for feedwater.
As an alternative to the scrubbing system comprising the reheat exchanger 419, the scrubber 422, the contactor 421, the feedwater spray line 439, the mist extractor 440 and associated piping connections, another method of separating fine dust from hot fuel gas, such as a plurality of porous ceramic filter thimbles, may be employed.
Clean fuel gas leaves the scrubber 422 through a mist extractor 440 and flows to the cold side of the reheat exchanger 419, in which it is indirectly heated by hot fuel gas to an approach to its temperature. The reheated gas flows via a line 441 to a second-stage oxidation reactor 442, in which it is joined and mixed with the balance of the air discharged, via a line 443, from the compressor 408. In the reactor 442, which may be a simple modification of the reactor supplied by the turbine manufacturer for natural gas fuel, oxidation is completed in the presence of sufficient excess air to limit the temperature to that allowable in turbine specifications. The hot clean product gas is then conducted by a conduit 444 to the inlet of a gas turbine 445.
Gas evolved in a carbonization section, such as that illustrated in FIG. 1, and shown to be exiting via the line 124, may bypass the mixer 404 and the reactor 410 to join the clean fuel gas going to the reactor 442 (by means of connections not shown).
The hot product gas is partially expanded through the first-stage turbine 445, which delivers mechanical energy, in the form of shaft horsepower, to the second-stage air compressor 408. In order to maintain critical components of the turbine 445 within safe operating temperatures, high pressure steam, and/or air from the discharge of the compressor 408, may be supplied to internal cooling passages (through connections not shown).
Having been cooled by giving up energy in the turbine 445, the partially expanded gas flows via a crossover 446 to be expanded further in a second-stage turbine 447, which delivers mechanical energy, in the form of shaft horsepower, to the first-stage air compressor 406. Having been further cooled by giving up energy in the turbine 447, the further expanded gas flows via a crossover 448 to be expanded again in a third-stage turbine 449, which delivers mechanical energy, in the form of shaft horsepower, to a generator (or alternator) 450 which converts it into electricity which is delivered via conduit 451.
The pressure of the reactor 410 is determined by the discharge pressure capability of the compressor 408. The discharge pressure of the turbine 445 is adjusted so that it produces only as much power as consumed by the compressor 408. Similarly, the discharge pressure of the turbine 447 is adjusted so that it produces only as much power as consumed by the compressor 406, excess potential energy in the gas being transferred to the turbine 449 in the form of pressurized exhaust.
While FIG. 4 is illustrated by means of turbo-machinery supplied by a particular manufacturer, it can readily be adapted to turbo-machinery from other manufacturers having a different air discharge pressure and/or variations in the numbers of individual machines and their interrelationships.
The turbine 449 discharges into an exhaust manifold 452 which conducts the fully expanded product gas to a Heat Recovery Steam Generator (HRSG) 453. The HRSG 453 is a more-or-less standardized assembly of economizers, boilers and superheaters, designed for heat recovery from turbine exhaust and available from several manufacturers. As configured for this embodiment, the HRSG 453 comprises economizer, low, intermediate and high pressure boilers and superheaters for high and intermediate pressure steam. A number of other configurations are feasible alternatives, particularly as regards steam pressures, reheat coils and arrangement of economizer(s) and superheater(s).
Exhaust, from which economically useful heat has been recovered, is discharged to the atmosphere through a vent 454. Boiler feedwater is supplied to the HRSG 453 by the pump 438 by way of a line 455. Low pressure steam is delivered through a line 456 to offsite use. Superheated high pressure steam flows via a line 457 to the inlet of a condensing steam turbine 458. Superheated intermediate steam flows via a line 459 to an interstage of the turbine 458 appropriate for its pressure. Since the demand for low pressure steam is liable to be intermittent, a connection (not shown) may also be provided to convey excess low pressure steam to an appropriate stage of the turbine 458. The energy produced by the expansion of the high and intermediate pressure steam in the turbine 458 is transmitted, as shaft horsepower, to a generator (or alternator) 460 which converts it to electricity, which flows via a conduit 461 to join with that in the conduit 451. After diversion of a small amount to power internal services, such as lubricating oil pumps (through a conduit not shown), the net production of electricity is delivered from the apparatus through the conduit 462.
Fully expanded steam leaves the turbine 458 through a vacuum line 463 which conducts it to the hot side of a vacuum surface condenser 464. As shown, the heat necessary to condense the steam and create a vacuum is indirectly transferred to cooling water, supplied to the cold side of the condenser 464 by means of a line 465 and returned to an offsite cooling tower through a line 466. Alternatively, an air-cooled condenser could have been used in place of the water-cooled condenser 464. Steam condensate collects in the bottom of the condenser 464 from which it drains by gravity through a line 467 to a condensate receiver 468. An evacuation device 469, which may be a vacuum pump or steam jet ejector, is connected to the top of the receiver 468 in order to dispose to the atmosphere any non-condensible gas entering the condenser 464 with the steam exhausted from the turbine 458. From the receiver 468 steam condensate flows via a line 470 to a condensate pump 471, which gives it sufficient pressure to discharge into the accumulator 436.
Blowdown is cascaded from high pressure boiler to intermediate to low pressure and withdrawn from the HRSG 453 through a control device 472. The HRSG 453 may be equipped for firing with supplemental fuel (i.e., employ "duct burners") and can incorporate a coil in which to finish the heating of carbonaceous slurry to carbonization temperature.
If, in spite of the density separations and extractions performed during its preparation, the char slurry being charged to the reactor 410 contains toxic metals such that its ash might be rated as hazardous, the amount of primary oxidant mixed with the slurry in the mixer 404, and/or its oxygen concentration, may be increased so that the temperature reached in the upper part of the reactor 410 exceeds the fusion point of a majority of ash ingredients. Suspended ash particles then become small globules of molten slag. The subsequent injection of cooled clean fuel gas from the top of the scrubber, 422 by means of a line 473, a circulator 474 and a quench line 475, quenches the mix temperature to a level below the ash solidification point so that the ash separated from gas in the disengaging zone 413 and the cyclone 416 is in the form of roughly spherical, non-adherent particles.
Since, in order that the tubes of exchanger 419 may be constructed of metal, rather than ceramic, it is necessary for the quench to cool the fuel gas appreciably more than required to solidify slag globules, generally below 1800° F., a substantial recycle of fuel gas through the disengaging zone 413, the cyclone 416, the hot side of the exchanger 419 and the scrubber 422 may be entailed. The thermal capacity of the net clean fuel gas on the cold side of the exchanger 419 may be inadequate for this duty. Up to a point additional cooling duty can be shifted to an exchanger (not shown but similar to the exchanger 545 of FIG. 5), preheating char slurry or boiler feedwater, interposed in the line 425. But, it may also be necessary to supplement such hot fuel gas cooling duty by means of an exchanger or waste heat boiler (not shown) in parallel or series with the exchanger 419, transferring part of it to, for example, boiler feedwater.
It is also possible to perform part or all of the quenching of the hot gas-slag globules mixture with water injected above the disengaging zone 413 (by means of a line not shown).
In the event that oxygen or enriched air is supplied to the mixer 404 from an air separation unit having its own charge air compressor, the line 409 may be omitted, all of the air discharged by the compressor 408 being delivered to the line 443 and the second'stage reactor 442.
Although diagrammed as a single connection, cooled gas (or water) may actually be injected into the reactor 410 through a plurality of connections around its circumference and located in more than one horizontal plane.
Not shown in FIG. 4 are auxiliary systems and equipment, such as those needed to bring the apparatus on stream from a cold start, back-up fuel and power, blowdown and pressure relief systems.
The embodiment of FIG. 5 also incorporates the embodiment of FIG. 1 and the conversion of the high energy density char slurry to high pressure superheated and medium pressure steam, which may be converted to electricity in an off-site conventional condensing turbo-generator and/or used for other site purposes. Slurry water is inherently distilled, becoming a useful byproduct. The concentrated or re-slurried char slurry enters the apparatus, preferably at the temperature at which it was produced, through a line 501. A reactor charge pump 502 gives it sufficient pressure to cause it to flow through a line 503 to the cold side of an ash slurry-char slurry heat exchanger 504 and through a line 505 to a circulating fluidized bed reactor 506.
Gas evolved in a carbonization section, such as that illustrated in FIG. 1, and shown to be exiting via the line 124, may also be introduced to the lower part of the reactor 506 (by means of connections not shown). Atmospheric air is drawn through a conduit 507, in which may be located a conventional dust filter (not shown), to the suction of a first stage air compressor 508, which delivers it hot and at an elevated pressure through a line 509 to the hot side of an intercooler 510, in which it is cooled by indirect exchange with high pressure boiler feedwater. Atmospheric air contains a variable amount of water vapor (humidity). Most of the water vapor carried by the air condenses to liquid water in the intercooler 510 and is discharged with the cooled air into a line 511. This water is separated from the air in a second stage compressor suction drum 512 and a mist extractor 513 and removed from the apparatus through a level control device 514.
From the mist extractor 513 the partially compressed air flows to the suction of a second-stage air compressor 516, which delivers it hot and at a further increased pressure to a line 517. The line 517 supplies primary air through a line 518 to the bottom of the reactor 506. Since staged air introduction is a known means of minimizing nitrogen oxides formation, primary air may be considerably less than theoretically required for complete oxidation of the char in the slurry charged, the remainder of the air discharged by the compressor 516 being added through reactor connections at successively higher elevations as illustrated by a line 519.
The temperature in the inlet zone of the reactor 506 is such that the fuel slurry water immediately vaporizes so that char and ash particles become entrained in the upflowing air and water vapor, along with a quantity of hot recycled solids. Oxidation of char particles is initiated and proceeds rapidly as the gas-solids mixture flows at relatively high, turbulent flow velocity through the reactor 506. Heat liberated by the oxidation causes the temperature to rise but heat indirectly transferred to boiling feedwater in a ring of vertical boiler tubes lining the inside circumference of the reactor 506, along with the heat capacity of circulated solids, limits the rise so that a predetermined maximum temperature is not exceeded.
The boiler tubes (not shown) are supplied with hot feedwater by a feedwater manifold 520 and discharge a mixture of feedwater and steam into an outlet manifold 521.
Upon reaching the top of the reactor, the gas-solids mixture, from which most of the carbon has been oxidized, exits through a crossover 522 to a hot cyclone separator 523. In the separator 523 centrifugal force causes most of the solid particles to separate from gaseous products and fall by gravity into a standpipe 524. Solids flow down the standpipe 524 in relatively dense phase, producing, by their weight, a pressure at the bottom somewhat above that existing at a similar level of the reactor 506. This pressure differential causes all or a major portion of the solid particles to flow, via a seal or trap 525, as a hot solids recycle, to the inlet zone of the reactor 506, where it mixes with and heats incoming air and char slurry. The standpipe 524 and the seal 525 may be equipped with aeration connections (not shown).
While not illustrated in this embodiment, solids circulation may be assisted by an eduction device, utilizing the kinetic energy of oxidation air and/or vaporizing slurry water, a version of which is illustrated in FIG. 2 of U.S. Pat. No. 4,714,032. Features of other variations of the circulating fluidized bed principle may also be used, including those extracting heat from the dense solids recirculated via the cyclone separator and the standpipe.
Some of the chars envisaged in this invention may contain insufficient ash to accumulate a solids recycle in the reactor 506, and/or the ash may be so fine, or attrit to an extent that insufficient is retained by the cyclone 523. It is quite permissible, in such case, to augment the circulated solids with extraneous inert particles of suitable size range and resistance to attrition. It may, in any case, be useful to provide an initial charge of such material so that there will be sufficient inventory of recycle for start-up.
High pressure steam and feedwater from the outlet manifold 521 flow to a high pressure steam drum 526 in which the water separates and flows by gravity through a downcomer 527 as recycle feedwater to the inlet manifold 520. The separated steam flows upward and exits the drum 526 through a mist extractor 528, continuing on to a steam superheat exchanger 529 in which it is superheated to the temperature at which it will be delivered from the apparatus through a line 530 as the main energy product.
Product gas, carrying fine solid particles unseparated by the cyclone 523, leaves the reaction system by means of a manifold 531, which may contain a second-stage cyclone, porous ceramic filters or other device (not shown) for separating fine solids from gases. The manifold 531 supplies the hot gas as heating media, via a line 532 to the steam superheat exchanger 529, and via a line 533 to a secondary first-stage flue gas reheat exchanger 535 and via a line 534 to a second-stage flue gas reheat exchanger 536. Having been partially cooled by indirect heat transfer in the exchangers 529, 535 and 536, product gases are recombined in a manifold 537 and flow to a primary first-stage flue gas reheat exchanger 538, in which they are cooled to a temperature approaching their dew point.
Depending upon individual heat balance, there may be more sensible heat in the hot product gases leaving the reaction system than required for the proper functioning of the exchangers 529, 535, 536 and 538. In such case, a trim waste heat boiler may be inserted in the line 531 or the manifold 537, supplementing the production of high or medium pressure steam.
Cooled product gas flows, via a line 539, to a contacting device 540 in which it is cooled to its dew point and has entrained dust particles wetted by contact with fines slurry recirculated from the base of a vent gas dehydrator tower 541, by means of a suction line 542, a fines slurry pump 543 a recirculation line 544, a fines slurry-feedwater exchanger 545 and a return line 546. The device 540 discharges into a flash zone 547 of the tower 541, in which a separation occurs between the product gas, which flows upward, and the slurry, which falls to the base of the tower 541.
The pump 543 also supplies the net production of fines slurry through a line 548 to an ash eductor 549, which receives the net production of ash particles from the reactor 506 via a bottom standpipe 550. In the eductor 549 the ash particles, accompanied by some gas, are cooled, wetted, slurried and discharged through a line 551 to a fluidizing gas separator 552. In the separator 552 fluidizing gas is disengaged from the ash slurry and separated for venting, along with an equilibrium amount of steam, via a line 553, into the tower 541. (The latent heat of steam accompanying the gas in the line 553 represents heat recovered from hot ash.) The ash slurry is withdrawn via a bottom connection into a line 554 from which it flows to the hot side of the ash slurry-char slurry heat exchanger 504, in which it is cooled to a temperature suitable for discharge, through a pressure control device 555, to conventional ash slurry disposal. In case the char slurry charged to the apparatus is too hot to adequately cool the ash slurry, the cooling may be supplemented by exchange with boiler feedwater in a heat exchanger (not shown).
The gas flowing upward from the flash zone 547 is washed to remove entrainment in one or more countercurrent vapor-liquid contacting elements 556 before rising through an axial passage in a hot water sump 557, which supplies wash water to the elements 556 through a flow control device 558, and hot water to a circulating pump 559, which discharges it through the hot side of a waste heat boiler 560, which indirectly cools it for return through a line 561 as circulating reflux to the uppermost of a plurality of countercurrent vapor-liquid contacting elements 562 in the mid-section of the tower 541. The partially cooled water flowing downward through the elements 562 cools upflowing gas and condense steam from it, becoming reheated in the process before collecting in the sump 557.
Heat transferred from the circulating hot water in the boiler 560 vaporizes part of the feedwater supplied to the cold side of the boiler 560 by a line 563. Steam and water exit the cold side of the boiler 560 via a line 564 and are separated into their respective phases in a medium pressure steam drum 565, from the bottom of which unvaporized feedwater recirculates through a line 566 to the inlet of the cold side of the boiler 560. Steam separated in the drum 565 exits through a mist extractor 567 and leaves the apparatus as a secondary energy product via a line 568.
Because of the steam condensed from the gas stream in the mid-section of the tower 541 there is a net production of water which is discharged through a level control device 569 into a similar circulating system in the upper section of the tower 541. Partially cooled and dehydrated by circulating water in the mid-section of the tower 541, the gas, still carrying an appreciable portion its former steam content, rises through an axial passage in an upper sump 570, which supplies warm water to a circulating pump 571, which discharges it through the hot side of a feedwater preheat exchanger 572, in which it is cooled for return through a line 573 as circulating reflux to the uppermost of a plurality of countercurrent vapor-liquid contacting elements 574, in the upper section of the tower 541. The cooled water flows downward through the elements 574, further cooling the upflowing gas and condensing from it most of the steam it contained when entering the section. The net water condensed in the mid and upper sections of the tower 541 are discharged through a level control device 575 as a product of the embodiment. Except for a minor content of dissolved gases it is high quality water, low in dissolved solids.
Heat transferred from the circulating warm water in the exchanger 572 preheats medium pressure boiler feedwater entering the apparatus from offsite via a line 576 and routes it through a line 577 to a medium pressure feedwater accumulator 578 (which may be a "deaerator" of proprietary design). Gases liberated by the heating in the exchanger 572 are separated in the accumulator 578 and discharged through a control device 579. From the accumulator 578 deaerated medium pressure feedwater flows via a line 580 to the suction of a medium pressure boiler feedwater pump 581 which discharges it as make-up into the circulating system of the boiler 560.
As illustrated, the vent gas dehydrator tower 541 has three sections. Depending upon individual heat balance and economic factors, one or more additional sections may be justified, with the result that recovered sensible and latent heat are made available with less loss of temperature. Heat in water circulating through additional sections would be used, for example, to generate steam at another pressure level or to increase the preheat of boiler feedwater.
High pressure boiler feedwater enters the apparatus under pressure of an offsite pump via a line 582, which conducts it to the cold side of the intercooler 510 in which it is indirectly heated by hot compressed air. Leaving the intercooler 510 through a line 583 the partially heated feedwater flows through the cold side of the fines slurry-feedwater exchanger 545, in which it is indirectly heated by hot fines slurry. The heated feedwater continues via a line 584 to a high pressure boiler feedwater accumulator 585 (which may be a "deaerator" of proprietary design). Gases liberated by the heating in the exchangers 510 and 545 are separated in the accumulator 585 and discharged through a control device 586. From the accumulator 585 deaerated high pressure feedwater flows via a line 587 to the suction of a high pressure boiler feedwater pump 588, which discharges it as make-up into the circulating system of the high pressure boiler loop.
Clean, dehydrated product gas leaves the tower 541 through a mist extractor 590 and is reheated indirectly by partially cooled product gas in the exchanger 538, then proceeds via a line 591 to the cold side of the exchanger 535 in which it is indirectly heated by, and to an approach to the temperature of, hot product gas. The fully reheated clean, dehydrated gas is then conducted via a line 592 to the inlet of a first-stage gas turbine 593, which delivers energy, in the form of shaft horsepower, to the second-stage air compressor 516. Having been cooled by giving up energy in the turbine 593, the partially expanded gas flows via a line 594 to the cold side of the exchanger 536, in which it is indirectly reheated by, and to an approach to the temperature of, a parallel stream of hot product gas from the line 534. The reheated clean gas then flows via a line 595 to be fully expanded through a second-stage turbine 596, which delivers mechanical energy, in the form of shaft horsepower, to the first-stage air compressor 508. Having been cooled by giving up energy in the turbine 596, the fully expanded gas is discharged to the atmosphere through a vent 597. In some cases the sensible heat remaining in the gas discharged from the turbine 596 may justify the inclusion of an economizer exchanger in the vent line 597, to preheat medium or high pressure feedwater.
FIG. 5 illustrates a limiting case in that dehydrated gas is reheated only to a temperature sufficient to provide, upon expansion, enough power to drive the air compressors, whereas FIGS. 2-4, incl. illustrate embodiments in which the gas being expanded is hot enough to produce excess horsepower, over that required to compress the air, which excess is converted to electricity. The embodiment of FIG. 5 could not produce as much excess gas turbine horsepower as the cited embodiments but it is feasible, in some cases, for one or both turbines of FIG. 5 to produce a modest excess, convertible into electricity.
As illustrated, the turbines and compressors of FIG. 5 are configured as separate, custom manufactured machines, which has the advantage that the pressure level of the reactor 506 may be chosen on the basis of overall process economics. Since such machines are not necesarily available for identical rotating speeds, it is permissible for the shafts between one or both sets of machines to be equipped with gearing for speed adjustment. In some cases, on the other hand, it may be more economical to adjust this pressure to the capabilities of catalog turbo-machinery and/or gas turbines.
Although FIG. 5 shows a first-stage turbine driving a first-stage compressor and a second-stage turbine driving a second-stage compressor, the services of first-and second-stage turbines could be reversed.
Not shown in FIG. 5 are auxiliary systems and equipment, such as those needed to bring the apparatus on stream from a cold start, back-up fuel and power, blowdown and pressure relief systems.
DESCRIPTION OF THE INVENTION
Physical separation of dense inorganic impurities from a low quality fuel will usually be accomplished by known methods. For example, there is extensive art concerning hydraulic coal cleaning and beneficiation, including froth flotation. In the case of MSW, U.S. Pat. No. 4,624,417 (Gangi) describes a suitable method of slurrying and of separating debris, iron, glass and nonferrous metals (wet Resource Recovery), including preliminary concentration of carbonaceous slurry to a suitable viscosity.
In a Technical Report to the Illinois Clean Coal Institute (ICCI) for the second quarter of 1983, "Behavior of Sulfur and Chlorine in Coal During Combustion and Boiler Corrosion", the authors report to the ICCI that, in a coal sample containing 0.42% on a dry basis, "most of the chlorine occurs as chloride ions adsorbed on inner walls of the pores" and, in "Characterization of Available Coals from Illinois Mines", only about 0.12% can be extracted with water, ammonia and sodium hydroxide. The structural rearrangement which occurs at the conditions claimed herewith for slurry carbonization is expected to free nearly all of the chlorine unavailable by atmospheric pressure extraction (as well as to increase the pumpable energy density and decrease the content of other soluble, or difficultly soluble, impurities).
Portions of a sample of wet-processed RDF, containing 0.41% chlorine (dry basis) from Reno, N.V., and MSW were ground through plates with 1/4 holes (Tests 1 and 2) and portions through 1/8-inch holes (Tests 3 and 4). Approximately 460 grams of each grind were slurried in approximately 2540 grams of water and subjected to carbonization at temperatures of 572° F. (Tests 1 and 3) and 617° (Tests 2 and 4) and saturation pressure. The yield of dry char solids was about 80% and contained (Tests 1-4, resp.) 0.05, 0.14, 0.02, and 0.07% chlorine. Thus, under the best of these conditions, 94% of the chlorine was removed. These tests were made without alkali addition, which is expected to improve chlorine extraction still further.
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Disclosed is a method and system for recovering energy from low-grade fuels such as industrial, municipal and agricultural waste, low-grade carbonaceous fuels such as lignite and similar solid fuels in which the fuel is comminuted into small particles and slurried in water. The alkali content of the slurry is adjusted to be at least about equal to the chemical equivalent of the halogen content of the slurry and, following pressurization of the slurry, it is heated sufficiently so that the substantial portion of chemically bound oxygen in the fuel separates therefrom as carbon dioxide, leaving a slurry including char particles and dissolved impurities such as halogen salts. The char particles are removed from the slurry and reslurried with just enough halogen-free water to provide the slurry with the needed viscosity to maximize the energy density thereof. The char particles are then reacted with air at a temperature below their ignition value to convert the fuel value of the low-grade fuel into thermal energy which is then further used, for example, to drive a turbine.
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BACKGROUND OF THE INVENTION
The invention relates generally to seat adjusters and more particularly to an adjustable hinge mount for seats having reclineable backrests, particularly motor vehicle seats, and including a fixed hinge part assigned to the seat proper and a tiltable hinge part assigned to the back rest, and connected by a pivot axle to the fixed hinge part whereby one of the two mount parts are arrestable in an adjusted position of the back rest by arresting means including a ratchet or serrated segment formed on the rotatable hinge part and cooperating with an arresting pawl which is pivotably mounted on the fixed hinge mount. The arresting pawl is controlled by a driven gear rotatably mounted on the fixed hinge part and supporting a cam slidably joining the arresting pawl. A manually controlled two-arm lever is provided with driving gear segments which is engageable with driven gear to rotate the same and thus the cam into an arresting position and into a releasing position of the arresting means.
In a known hinge mount of the above-described type, the hinge part secured to the reclineable back rest is provided with a disc which in the range below the pivot axle is formed with a gear segment. An arresting lever is pivotably mounted on the fixed hinge part assigned to the seat proper and is also formed with arresting gears engageable with the gear segment on the disc of the pivotable hinge part. The arresting lever is arranged so that due to its own weight the arresting gear normally moves out of engagement from the arresting segment of the disc. In order to maintain the desired adjusted inclined position of the back rest relative to the seat part, a setting lever is pivotably mounted on the fixed hinge part and is provided with a cam which urges the arresting arm to move with its arresting piece into or from the engagement with the arresting segment of the disc on the movable hinge part. For this purpose the arresting lever has in the range opposite its arresting piece a back surface which is slidably engaged by the cam attached to the setting lever when the latter is adjusted in the arresting position. At a distance from the back surface of the arresting lever there is provided a projection against which side surface of the cam abuts when the setting lever is moved into is releasing position. As a consequence the working angle of such known cam arrangement is limited and does not exceed the maximum value of about 30° . Since the angle of inclination of the camming surface of the cam has to be lower than that at which self-locking action occurs, the tensioning displacement of the cam at the above-mentioned relatively low inclination angle is also small and consequently it is insufficient both for its primary purpose, namely for securing the engagement of the arresting piece between the movable and fixed hinge parts, and for elimination of manufacturing tolerances between the mutually engaging loaded parts of the hinge mount.
SUMMARY OF THE INVENTION
It is therefore a general object of the present invention to overcome the aforementioned disadvantages.
More particularly, it is an object of the invention to provide an improved adjustable hinge mount of the aforedescribed type in which an increased path of the tensioning displacement is available for the cam which is sufficient for the elimination of manufacturing play or tolerances of respective component parts.
Another object of this invention is to provide such an improved hinge mount at which the locking cam can be reliably disengaged from its arresting position.
In keeping with these objects, and with others which will become apparent hereafter, one feature of the invention resides in the provision of arresting means including a serrated segment formed on the rotatable hinge part and a pawl pivotably mounted on the fixed hinge part opposite the threaded segment, a driven gear pivotably mounted on the fixed hinge part supporting for joint rotation a cam in the form of a spiral segment cooperating with the pawl, a spring arranged for rotating the driven gear together with the cam into an arresting position in which the cam urges the pawl into engagement with the serrated segment on the rotatable hinge part, and control means including a driving gear engageable with a driven gear to rotate the same and cam from the arresting position into a releasing position in which the pawl is disengaged from the serrated segment.
The radius of the cam segment is larger than that of the driven gear whereby the cam segment occupies approximately one third of the circumference of the driven gear. Due to this arrangement it is achieved that a relatively low inclination or pitch angle of the camming spiral segment is used which lies well below the self-locking limit of the cam and at the same time the camming surface is rotated about a relatively large central angle and consequently the cam has a relatively large adjustment pitch. For this reason, manufacturing tolerances which normally amount only to a fraction of the adjustment pitch of the cam are effectively neutralized whereas the major part of the pitch is used for compressing the arresting mechanism. Accordingly, during the manufacturing of individual parts of the hinge mount of this invention, no particularly high requirements are set for the accuracy of these parts and the play which always occurs during normal manufacturing methods can be very easily eliminated.
In the preferred embodiment of this invention, the camming surface has the form of an Archimedes spiral so that the height of the inclined camming surface increases proportionally to the increase of the central angle and therefore the pitch of the camming surface is uniform with respect to the crown circle of the driven gear. Due to the fact that the camming spiral segment extends about a central angle of 120°, and the radius of the spiral segment is larger than the radius of the driven gear, the peripheral length of the camming segment is larger than the peripheral segment of the driven gear and consequently the compressing stroke of the camming surface is considerably large while the inclination angle is below the limits of self-locking effects.
In order that the camming spiral segment upon the release of the setting lever return automatically in an arresting position in which the pawl is urged against the serrated segment, a spiral spring loads and rotates according to another feature of this invention the driven gear with the camming spiral segment in the arresting direction. One end of the biasing spring is connected to the fixed hinge part whereas the other end of the spiral spring is secured to the cam. Preferably, the setting lever is formed with a driving gear segment which during the arresting position of the cam is completely out of engagement with the driven gear and is dimensioned so as to rotate the driven gear about the entire length of the camming spiral surface.
According to still another feature of this invention, the driving gear segment controlled by the setting lever has a leading introduction tooth which at the beginning of the releasing movement of the setting lever adjusts the driving gear into a position in which the remaining teeth of the driving gear segment correctly mesh with the teeth of the driven gear. By means of this correction made by the introductory tooth it is prevented that the remaining teeth of the driving and driven gears be accidentally moved in a "tooth against tooth" mutual position when the setting lever is operated.
In order to prevent that the setting lever be positively driven during the entire length of travel of the arresting cam towards its releasing position, the setting lever is loaded by a tensioning spring in the direction in which the driving gear segment disengages the driven gear and automatically resumes a starting disengaged position.
The novel features which are considered as characteristic for the invention are set forth in particular in the appended claims. The invention itself, however, both as to its construction and its method of operation, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a side view of the adjustable hinge mount of this invention; and
FIG. 2 is a sectional top view of the hinge mount of FIG. 1, taken along the line II--II.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The hinge mount as illustrated in FIG. 1 includes a tiltable hinge part 10 connectable to a back rest of the seat and a fixed hinge part 11 connectable to the seat proper and being rotatably connected to the rotatable hinge part 10 by a pivot axle 12. In order to arrest the adjusted angular position of the rotatable hinge part 10 relative to the fixed hinge part 11, the hinge mount includes an arresting device 13 formed by a ratchet and pawl mechanism 14 and a control device 15. The ratchet and pawl mechanism 14 includes a serrated segment 16 formed on the rotatable hinge part and an arresting pawl 18 mounted for rotation about a pivot pin 17 secured to the fixed hinge part 11. The arresting pawl 18 has at one side thereof arresting teeth 19 for engaging the threaded segment 16 on the swingable hinge part 10 and a juxtaposed rear surface for engaging an actuation cam as will be explained below. The pawl is supported for rotation on the pivot pin 17 in such a manner that its arresting teeth 19 normally disengage by the force of gravity the segment 16 when the pawl is operated. As soon as the arresting pawl is disengaged from the serrated segment, the swingable hinge part 10 is ready to be adjusted to any desired angular position of the back rest.
The actuation or control device 15 cooperating with the ratchet and pawl device 14 includes a driven gear 24 supported for rotation on the fixed hinge part 11 and of a driving gear segment 32 formed on one arm of the control lever 22 which is supported for rotation on a pivot pin 21 projecting also from the fixed hinge part 11. The driven gear 24 is integrally connected with a cam 20 in the form of a spiral segment 23 which occupies approximately one-third of the root circle of the gear 24. The cam 20 together with the driven gear 24 are connected to a central pin 25 which is supported for rotation in the fixed hinge part 11. The periphery of the spiral segment 23 defines a camming surface 26 which slidably engages the rear surface 27 opposite the arresting teeth 19 of the pawl 18. Even if the curved camming surface 26 can be shaped as a section of an arbitrary spiral in the preferred embodiment of this invention this camming surface is formed as a section of an Archmides spiral. The pivot pin 25 of the cam 20 and of the driven gear 24 is secured against axial displacement in the fixed hinge part 11 whereby the central part of the side of the cam 20 opposite the bearing pin 25 is provided with a trunnion 28 having on its end face a diametric slot 29. This slot 29 receives a bent inner end of spiral spring 30 the outer end of which is secured to a trunnion 31 opposite the pivot axle 21 of the control lever 22. The spiral spring 30 is biased so that the cam 20 together with the driven gear segment 24 are rotated counterclockwise so that the camming peripheral surface section 36 urges via the rear surface 27 the arresting teeth 19 of the pawl 18 into an arresting engagement with the serrated segment 16 of the reclineable hinge part 10.
In order to release the pawl 18 from this arresting position (as illustrated in FIG. 1) and thus to enable the angular adjustment of the reclineable hinge part 10, the lower arm of the control lever 22 is formed with the aforementioned gear segment 32 which can be brought into engagement with the driven gear 24 and rotates the same clockwise so that camming surface 26 can disengage the rear surface 27 of the pawl 18 and allow the same to rotate by its own weight into the releasing position in which its teeth 19 are disengaged from the arresting teeth 16. The driving gear segment 32 is formed such that in the arrested position of the reclineable hinge part 10 in which the inclined surface 26 of cam 20 urges the pawl 18 against the serrated segment 16, the teeth of the driving gear segment 32 completely disengage the teeth of the driven gear 24. Tension spring 33 which at one end is attached to the fixed hinge part 11 and at the other end to the upper arm of the control lever 22, maintains the driving gear segment 22 in this disengaged position. As a result, the biasing spiral spring 30 now rotates the driven gear 24 together with the cam 20 counterclockwise into the arresting position as illustrated in FIG. 1 and the pawl 18 engages with its teeth 19 the serration 16 of the tiltable hinge part 10 thus arresting the same in the adjusted reclined position.
To release again the hinge part 10 from its arrested position, the control lever 22 is rotated counterclockwise against the force of the tension spring 33 and in doing so the driving segment 32 engages the teeth of the driven segment 24. To insure a proper gear mesh during the introduction of driving gear 32 into the driven gear segment 24, the leading tooth 34 of the driving gear is adjusted in shape in such a manner that its height is shorter than that of the remaining teeth and consequently at the beginning of the shifting operation the leading tooth 34 cannot abut against a tooth of the gear segment 24 but instead is always introduced into the gap between the teeth and adjusts the angular position of the driven gear segment 24 for proper meshing with the remaining driving teeth. In this manner upon turning of the control lever 22 counterclockwise this movement is always reliably transmitted to the cam 20 which is thus turned clockwise. During the clockwise movement of the cam 20 the converging part of the spiral section 26 is moved below the back surface 27 of the pawl 18 and the arresting teeth 19 of the pawl are disengaged from the serrated segment 16 of the recliner part. As soon as the arresting mechanism 14 is released, the back rest can be adjusted to any desired position. A spiral spring 35 is arranged between the rotatable hinge part 10 and the fixed hinge part 11 to counteract the weight of the back rest and to move the latter forwardly into its upright position. On the other hand, the back rest has to be loaded against the force of the counterbalancing spring 35 to rotate the back rest and the hinge part 10 rearwardly. Upon the adjustment of the desired position of the back rest, the control lever 23 is released and by the force of the tension spring 33 is automatically moved clockwise whereby the driving gear 32 rotates the driven gear segment 24 and the cam 20 counterclockwise into the arresting position as illustrated in FIG. 1. As it has been mentioned above, the gear segment 32 is dimensioned such as to completely disengage the driven gear segment 24 and the biasing spiral spring 30 takes over to arrange the cam 20 counterclockwise and to maintain the arresting position in which the diverging part of the spiral surface 26 abuts against the rear surface 27 of the pawl 18 so that the arresting teeth firmly engage the serrations of the segment 16. In this manner, the adjusted position of the back rest is locked.
It will be understood that each of the elements described above, or two or more together, may also find a useful application in other types of constructions differing from the types described above.
While the invention has been illustrated and described as embodied in a hinge mount using an Archimedes spiral for the camming surface in its control mechanism, it is not intended to be limited to the details shown, since various modifications and structural changes may be made without departing in any way from the spirit of the present invention.
For example, instead of the Archimedes spiral it is possible to employ another radially increasing camming surface 26. It is also possible to arrange the arresting pawl 18 in such a manner that upon its disengagement from the cam 20 an additional biasing spring is used instead of the force of gravity to disengage the pawl teeth 19 from the serrated segment 16 on the reclinable hinge part 10. Furthermore, instead to form the serrated segment 16 integrally on the hinge part 10, it is possible to use separate disc which is rigidly connected to the part 10.
Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can, by applying current knowledge, readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention.
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A hinge mount for seats having reclineable back rest includes two hinge parts pivotably connected one to another. The hinge part assigned to the back rest is formed with an arresting serration cooperating with an arresting pawl supported for rotation on the fixed hinge part; a control mechanism including a cam segment is rigidly connected to a driven gear supported for rotation on the fixed hinge part and controlled by a driving gear segment manually operated by a spring biased lever. The radius of the cam segment is larger than the radius of the driven gear and extends approximately about a central angle of 120°.
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FIELD OF THE INVENTION
This disclosure is directed to a lamp, and more importantly, a lamp utilizing a transformer which reduces the voltage from the typical line voltage of 110 V AC to a low voltage which is intrinsically safe to use and handle. This lamp construction takes advantage of the low voltage, to wit, it avoids the installation of cable conductors from the power cord up to the lamp bulb. The lamp construction thus permits the lamp to be deployed on a long thin support arm made of two parallel support members, the support members holding the lamp at a distance to permit it to be easily repositioned by the user. Repositioning is an advantage which cannot be otherwise provided should there be an electric cable extending to the lamp. Power distribution is thus accomplished by thin metal conductors affixed to the mounting arms. The power conductors would not otherwise be safe if they were conducting 110 V AC. However, at the low voltages contemplated, they are quite safe in that they operate at low voltages. Spark suppression is achieved by operation at low voltage. Ignition is not possible because the voltage is so low as to be deemed intrinsically safe.
Since the cable is omitted, a greater measure of flexibility is achieved. The lamp is suspended in a housing which in turn fastens between a pair of parallel arms, the arms extending from a base to some maneuverable elevated location.
The arms are lighter gauge than would be the case if a conductor cable system were incorporated. The arms are further deployed from one another so that they clamp the housing which supports the lamp. The housing connects with the arms by supports the lamp. The housing connects with the arms by conventional banana plugs which stab into the housing and thereby define an axis of rotation. This axis permits the housing for the lamp to rotate indefinitely without entanglement of conductors and moreover, provides current flow for operation of the lamp through a low resistance connection.
The present invention is thus summarized as a lamp construction having a base adapted to be rested on a table or fastened to a wall which supports a pair of extending arms. The two arms in turn are spaced from one another and are parallel to one another. The arms connect with the output secondary of a coupling transformer which steps down the voltage to something in the range of 12 V AC or less. This voltage is viewed as intrinsically safe in operation. The two arms extend to a pair of oppositely mounted banana plugs which connect with a housing supporting the lamp. This lamp construction is able to be rotated and pivoted. One or more pivots are arranged in the apparatus to permit proper rotation.
In one embodiment, first, second and third pivots are included to provide three degrees of freedom. Reduced flexibility can be obtained as for instance through the use of two pivots yielding two degrees of freedom. In both instances, the arms are extended through a pair of parallel members which support metal conductors of sufficiently low voltage that insulation is not required.
DESCRIPTION OF THE DRAWINGS
So that the manner in which the above recited features, advantages and objects of the present invention are attained and can be understood in detail, more particular description of the invention, briefly summarized above, may be had by reference to the embodiments thereof which are illustrated in the appended drawings.
It is to be noted, however, that the appended drawings illustrate only typical embodiments of this invention and are therefore not to be considered limiting of its scope, for the invention may admit to other equally effective embodiments.
FIG. 1 is a side view of a lamp constructed in accordance with the teachings of the present disclosure and having three degrees of freedom wherein a pair of spaced arms provide electrical conductors through two pivot points connected to a lamp in a housing at the end of the apparatus;
FIG. 2 is a sectional view along the line 2--2 of FIG. 1 showing details of construction of a lamp and lamp housing and illustrating a mechanism for connecting electrical power to the lamp;
FIG. 3 is an orthogonal view to FIG. 2 showing details of construction of the lamp housing and lamp;
FIG. 4 is a detailed view along the sectional line 4--4 of FIG. 1 showing details of construction through a pivotal connection so that power is provided along two separate and insulated paths;
FIG. 5 is a sectional view along the line 5--5 of FIG. 4 showing deployment of conductive material on an arm construction;
FIG. 6 is a sectional view along the line 6--6 of FIG. 4 showing additional details of construction of the opposite arm to that of FIG. 5 wherein the two arms are connected for rotation around the same axis and yet provide insulated electrical current paths;
FIG. 7 is a detailed sectional view through the bracket supported on a pair of arms which in turn support the lamp and housing shown in FIG. 1 wherein the sectional view illustrates conductive material thereon for providing the two conductor paths for the lamp;
FIG. 8 is a sectional view along the line 8--8 of the structure shown in FIG. 7 showing the conductive coating and illustrating connection to a mounting bracket supporting the lamp and housing;
FIG. 9 is a sectional view along the line 9--9 of FIG. 7 showing additional details of construction of the opposite side of the structure shown in FIG. 7 and further illustrating the second conducting path extending to the lamp and housing;
FIG. 10 is a side view of an alternate construction of the lamp of the present disclosure with a simplified support arm;
FIG. 11 is an orthogonal view of the structure shown in FIG. 10 showing the spaced parallel arms;
FIG. 12 is a schematic circuit diagram of a circuit which provides an adjustable reduced voltage current flow for lamp illumination; and
FIG. 13 is a sectional view through an alternate pivotal connection.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Attention is first directed to FIG. 1 of the drawings where the numeral 10 identifies a lamp constructed in accordance with the present invention. This lamp 10 will be described preceding from the base upwardly. It incorporates a bottom support plate 11 which is aligned on a center line axis for rotation of a turn table 12. The plate is received in a support receiving a power cord through a central vertical hole. A base housing 13 is supported by the turn table 12. The device includes circuitry enclosed in the housing 13. A convenient knob 14 is affixed to an adjustable potentiometer to adjust the lamp current by adjusting the lamp voltage. This changes the illumination. The structure preferably is constructed with relatively thick walls to provide some measure of weight to avoid wobbling and to enhance stability of the base. Also, air cooling is obtained through air holes in the housing 13.
The structure supports a pair of upstanding parallel arms 15 and 16. These arms are better shown in FIG. 4 which is a sectional view through the arms 15 and 16. In FIG. 1, one is obscured by the other.
Going back to FIG. 1, the arms extend upwardly to the pivotal connection which provides the second degree of freedom and is better illustrated in FIG. 4. At this location the structure includes a rotatable member which supports a counter balance weight 17 at one end, the lamp housing 20 being located at the opposite end. The relative length of the structure between the weight 17 and the housing 20 in conjunction with the relative weights achieves a balance so that the relative angular position is sustained when the lamp 10 is positioned in a particular angular position. The counter balance weight 17 is located in distance and sized in mass so that it serves as a proper counterbalance.
Continuing with FIG. 1 of the drawings, the numeral 18 identifies an upper frame member parallel to a lower frame member 19. They connect to the counter balance weight 17.
The frame members 18 and 19 are elongate rectangular members. They are preferably made of hollow stock. The upstanding arms 15 and 16 are of similar construction. A preferred material is a relatively good conducting material such as brass. Alternate materials include aluminum. Another alternate material is any plastic which is doped with a conductive material such as graphite to provide conductivity. The arms 15 and 16 are vertical while the arms 18 and 19 rotate and thus can be horizontal or extend at an angle as shown in FIG. 1. The arms 18 and 19 are spaced apart from one another by the counterweight at one end and the various brackets. The spaced pairs of arms are shown in FIG. 4. Since they are made of conductive material, they serve as conductors. Assume for purposes of description that the upstanding vertical arm 15 is positive while the return current path is through the arm 16. Assume further that the voltage applied thereon (to be discussed later) is up to about 12 V AC. The vertical arm 15 is thus made into a conductor. A bolt 22 is passed through appropriate drilled holes at the end of the arm 15. It is locked in place by a suitable locking nut 23 which contacts a friction washer 24. This assures a threaded connection which will not loosen. Electrical connection is enhanced by the use of a star lock washer 25. This lock washer 25 abuts a metal flat washer 26 to assure a good metal contact for current flow. The current flow path is through the arm 15 and into the bolt 22. The bolt 22 has a head which abuts a ply of conductive metal 28 on a bracket plate 30. The head of the bolt 22 is secured by a lock washer 25 followed by a hex nut 27 to the outside of bracket plate 30. The nut 27 assures clamping against the metal foil 28. The contact to the metal foil is sufficient to conduct current, and the nut 27 cooperating with the lock washer clamps the bolt head to obtain adequate loading to sustain contact. An option is adding a solder joint 29, if desired, to enhance contact. The current flow path is thus through the arm 15 and into the bolt 22. Because of the friction achieved by the use of the lock washers 25 and the tightness of the nut 23 on the bolt, current flow is assured along the bolt 22 to the head of bolt 22 and then to the metal ply 28.
The bracket plate 30 is made of non-conductive material such as sheet epoxy glass. One suitable arrangement is to use printed circuit board material (PCB hereinafter) so that the metal ply 28 is an isolated island on the PCB 30. In other words, the bracket 30 is cut to a particular profile and has the conductive metal on one face etched. This defines the location of the metal. The metal extends along the bracket 30 to contact the metal (conductive) member 19.
The foregoing description applies to the bolt on the left hand side of FIG. 4. The numeral 32 identifies the duplicate bolt on the right hand side. It is connected with the metal ply 33 which is on the bracket member 34. The brackets 30 and 34 are identical in shape or profile. They are both equipped with selected coating material having locations better shown in FIGS. 5 and 6. To summarize the current flow paths shown in FIG. 4, recall that one flow path is up through the arm 15. This flow path extends through the bolt 22, the metal film 28 and into the frame member 19. The other current flow path includes the upwardly extending arm 16, the bolt 32, and metal ply 33 and the frame member 18. These two current flow paths are spaced from one another and are held apart by insulating material (PCB) of the brackets 30 and 34. The structure shown in FIG. 4 further includes the screws 35 which join the brackets together.
In FIGS. 5 and 6, the conductive regions on the brackets are shown. FIG. 5 shows the bracket 30 supporting the conductive metal ply 28. FIG. 6 shows the bracket 34 which supports the conductive metal ply 33. As will be understood, both of these members are preferably made of PCB material which is patterned with a photoetch process which forms the metal islands shown in FIGS. 5 and 6.
Going now to FIG. 7 it will again be observed that the spaced metal frame members 18 and 19 are separated by opposing mounting brackets. In this instance, the brackets are identified by the numerals 36 and 37. Again, they are preferably made of PCB material. As shown in adjacent FIGS. 8 and 9, the bracket 36 has a metal layer 38 deployed in a particular region while the bracket 37 is provided with metal plating in a particular region identified at 39. Moreover, the metal layers 38 and 39 are deployed adjacent to the frame members 18 and 19 to be clamped thereagainst. To this end, the mounting brackets are joined by fastening screws 40 at the indicated locations. They are fastened into the frame members 18 and 19 to assure adequate connection.
The brackets 36 and 37 are perforated at suitable locations and conductive metal members extend therethrough. The conductive metal members incorporate upstanding tabs identified at 42 and 43 in FIGS. 8 and 9 which are in fact protrusions of the "L" shaped frame yokes 44 and 45. The tabs 42 and 43 are soldered at the opposite faces to define structures better shown in FIG. 3. In FIG. 3, an "L" shaped yoke member 44 is positioned on one side while the symmetrical yoke member 45 is on the opposite side. The two yoke members are soldered to axially aligned banana plugs 46 and 47 better shown in FIG. 2 of the drawings. The banana plugs 46 and 47 are received through insulated sockets 48 and 49. The sockets in turn have internal terminals which electrically connect with the banana plugs. In turn, they connect with electrical conductors shown in FIG. 2 which extend to a lamp base 50. The lamp base 50 is wired in the circuit and supports a bulb 51 for providing illumination. The bulb is integral to and centered in a reflector 52. The reflector directs light in the proper direction. The reflectorbulb 52 is a high intensity bulb which is mechanically protected by a transverse bar 53 supporting a cap or a protective shield 54 to assure physical security to the bulb and also to cut down on the bright spot which might otherwise blind a person momentarily. The reflector 52 directs the light out of the housing.
The lamp base 50 is supported by a transverse frame member 55. In turn, the frame member 55 is anchored in a rectangular housing having a back or end wall 56 adjacent to four side walls 57. Ideally, the several walls form a cube which is open at one face so that light may emerge from the cube. The frame members 44 and 45 are flexible sufficiently to enable the miniature banana plugs 46 and 47 to stab into the respective sockets. The housing can be dismounted. The housing is that structure generally shown in FIGS. 2 and 3. The housing encases the lamp and reflector so that light is controllably directed. The banana plugs are located along an axis approximately through the center of the cube defining the housing 20. This permits easy rotation. There is sufficient friction along the banana plugs to hold the balanced housing at any particular angle. As will be understood, the banana plugs define the third axis of rotation or the third degree of freedom for the lamp 10 shown in FIG. 1 of the drawings.
Going now to FIG. 10 of the drawings, an alternate embodiment is identified by the numeral 60. This embodiment incorporates a larger base 61 to assure adequate stability. It utilizes a similar turn table 62 for rotation about a first axis which is vertical to the base 61. A cabinet 63 encloses the circuitry which provides the output voltage. A pair of bent arms extend upwardly and are identified by the numerals 64 and 65. Again, the arms 64 and 65 terminate at banana plugs in the same fashion as shown in FIG. 2 and support the cube shaped housing 66 for rotation about a second axis of rotation. This yields two degrees of freedom for the embodiment 60.
In FIG. 12 of the drawings, a conventional voltage source is identified at 70. Typically, this is a commercial power system and connection is made by means of an extension cord or power cord to it. The numeral 71 identifies the primary of a transformer having a secondary 72. Current flow is through a triac 73. The triac is switched off and on by a signal applied to the gate thereof through a conductor 74. Switching current is controlled by a diac 75. Triggering of the diac is determined by an RC circuit. A grounded capacitor 76 connects with two series resistors 77 and 78. The resistor 78 is adjustable. Excursion of the resistance is limited by a parallel resistor 79. Thus, a suitable voltage is determined for the diac 75 which in turn triggers the triac 73. The triac is varied in operation to alter the current flow through the primary and hence through the secondary. The net effect is to provide a reduced primary voltage. The conductive cycle can be so reduced that current flow in the secondary is quite low depending on the control achieved. The variable resistor 78 can be used as a dimmer switch. It is infinitely adjustable from total darkness to full illumination. Full illumination is accomplished by adjustment to one extreme and the light is extinguished by adjustment to the other extreme. As will be understood in the operation of the diac, control voltage is achieved for each cycle of operation of the AC current applied to the system.
The current flow path should be traced; it begins at the secondary 72 and extends to the lamp 51. Thus, the secondary 72 is connected to the upstanding arms 15 and 16 shown in FIG. 1 of the drawings. The upstanding arms are provided with the intrinsically safe current flow and the current is directed along the arms up through the bracket shown in detail in FIG. 4. The current flow is then applied to the arms 18 and 19. The current flow is then directed along the arms 18 and 19 as shown in FIG. 1 to the frame members 44 and 45 in FIG. 3. Current flows through the banana plugs 46 and 47 to the lamp 51 for illumination.
Three degrees of mechanical freedom are achieved with the structure shown in FIG. 1. The provision of the counterbalance 17 enables the arms 18 and 19 to be extended horizontally so that substantial lateral reorientation is achieved.
FIG. 13 discloses an alternate pivot 100 to that of FIG. 4. A bolt 101 having a head 102 is threaded at 103 into the current conductor 18 (the frame member). The head 102 and threads 103 assure quality connection. The bolt supports four washers which are lock washers 104 and 107 while flat washers 105 and 106 are clamped therebetween. A lock washer 108 adjacent to a nut 109 assures firm metal to metal contact for a conductive path to the arm 16. The conductive path is assured by the pivotal connection 100.
While the foregoing is directed to the preferred embodiment, the scope is determined by the claims which follow.
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In a lamp, a construction is set forth including a low voltage power source including an adjustable supply to a transformer in a base wherein the transformer is connected with a pair of coextensive arms. The arms are preferably made of metal and are the conductors. The voltage level is intrinsically safe. The arms extend to remotely support a housing with a bulb therein. The housing has a pair of oppositely positioned sockets and the arm supports miniature banana plugs which stab into the sockets to provide electrical current for bulb operation and to also serve as a pivot for the housing. In addition, a greater measure of freedom is obtained by incorporating a pivot wherein the arms pivotally connect with a second pair of coextensive arms to provide an added degree of freedom.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention relates generally to poker-style games and methods, and more particularly to poker-style games and methods that provide opportunities for a player to make wagers on certain selected winning hands which will adjust the posted payout odds on the selected winning hand as well as other winning hands thereby increasing player excitement.
[0003] 2. Description of the Prior Art
[0004] The game of poker is widely played at peoples' homes and in a casino setting. At a casino, it is played both in a traditional format, with traditional playing cards, and in an electronic format. In the electronic version, typically known as “video poker”, a player makes a wager, pushes a button to start the game, and is then presented with five cards shown on the video display. A player can choose to either keep the cards or discard a specified number of cards and receive replacement cards. Whether or not the player's final hand qualifies for a payment is determined according to a pay table, which is generally displayed on the video poker machine itself.
[0005] The best hand that a player can achieve in classic five card poker of the type typically played on video poker machines is a royal flush. A royal flush consists of an Ace-high straight, where all of the cards have the same suit.
[0006] Many video poker players find that the basic video poker game has become somewhat stale and boring. In addition, many feel that the payouts associated with video poker are not high enough to make the game exciting. For instance, the chances of a player achieving a royal flush are generally about 1 in 35,000. However, since the player essentially wagers on all potential winning hands at once, the payout for a royal flush is typically no more than 800 credits or coins to every one credit or coin wagered. If the player were provided the opportunity to wager on any one selected hand(out of a large number of possible hands), in some instances, a player could stand to win at least one hundred times what the player would normally win by wagering in the typical manner and achieving the same winning hand.
[0007] Furthermore, if a player is able to wager on a specific winning hand, then the posted payout odds on other winning hands should also be adjusted. For example, if a player places a wager on a royal flush, then the payouts associated with other winning hands (i.e., straight, flush, 4 of a kind, etc) should also increase. The reason for this is that a player's strategy has a large effect on obtaining the specific winning hand. Thus, in the above example, if a player wagers heavily on a royal flush, the player will most likely play the optimum strategy for achieving a royal flush. As a result, the probability of the player achieving other winning hands (i.e., straight, flush, 4 of a kind, etc) will decrease. Thus the posted payout odds for the other winning hands should increase to encourage the player to wager on other hands as well.
[0008] Therefore a need existed to provide a video poker-style game and method that substantially increases payouts by providing additional wagering opportunities for the player to wager on selected winning hands. A need further existed to provide the highest possible payouts for the additional wagering opportunities by adjusting the posted payout odds based on the player's wager, or by restricting the player's wagering options.
SUMMARY OF THE INVENTION
[0009] In accordance with one embodiment of the present invention, it is an object of the present invention to provide a video poker-style game and method that substantially increases payouts by providing additional wagering opportunities for the player to wager on selected winning hands.
[0010] It is another object of the present invention to provide the highest possible payouts for the additional wagering opportunities by adjusting the posted payout odds based on the player's wager, or by restricting the player's wagering options.
BRIEF DESCRIPTION OF THE EMBODIMENTS
[0011] In accordance with one embodiment of the present invention, a method of playing a poker-style game comprising: making an opening wager by a player; permitting the player to make at least one wager to obtain at least one certain selected winning hand; adjusting payout odds on winning hands based on an amount of the opening wager and the at least one wager to obtain at least one certain selected winning hand; dealing a hand of cards to the player; allowing the player to hold desired cards of the hand; dealing replacement cards to the player; determining if a new hand of cards is a winning hand; and paying the player based on the adjusted payout odds.
[0012] In accordance with another embodiment of the present invention, a video poker-style game is disclosed. The video poker-style game has a video display adapted to display to a player a hand of cards for a poker-style game; means for permitting the player to make an opening wager by the player; means for permitting the player to make at least one wager to obtain at least one certain selected winning hand; means for permitting the player to hold a desired number of the hand of cards; means for permitting the player to receive replacement cards; means for displaying a payout table associated with probabilities of obtaining the at least one selected winning hand of said game; means for displaying the payout associated with each said at least one wager; means for determining if a winning hand has been achieved; and means for paying the player in accordance with the payout table.
[0013] The foregoing and other objects, features, and advantages of the invention will be apparent from the following, more particular, description of the preferred embodiments of the invention, as illustrated in the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] The novel features believed characteristic of the invention are set forth in the appended claims. The invention itself, as well as a preferred mode of use, and advantages thereof, will best be understood by reference to the following detailed description of illustrated embodiments when read in conjunction with the accompanying drawings.
[0015] FIG. 1 is a elevated front view of a video poker machine or terminal using the present invention.
[0016] FIG. 2 is a flow chart depicting a number of methods of play consistent with the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0017] Referring to FIG. 1 , a video poker machine terminal 10 is shown. Its main features include a video display 12 , a plurality of hold buttons 14 , a draw/deal button 16 , at least one bet button 18 , a pay table 20 , and a coin output 22 . The terminal 10 should also have a payment receiver (not shown), through which coins, cash, payment cards, paper credits or the like may be inserted for purposes of placing a wager.
[0018] Generally, in a prior art video poker game, play is initiated by the insertion of a payment into the payment receiver. A player will typically then depress the bet button 18 in order to receive a display of a hand of cards. (In some games, more than one bet button 18 is provided, with, for example, one bet button allowing a player to bet one amount, and another allowing a player to bet a larger or additional amount.) After a hand of cards is displayed in the video display 12 , the player then decides which cards he/she wants to hold and which cards are to be discard. A player indicates a hold selection for each card that is to be held by depressing the hold button 14 located directly below a card 24 that is to be held. (If a player changes his or her mind, the hold button 14 can be depressed a second time to cancel the selection.)
[0019] Once the player completes his or her hold selections, the player will depress the draw/deal button 16 a second time. This will cause the non-held cards 24 to be replaced with new cards. If the player has a winning hand according to the pay table 20 , a payment is made and can either be paid through the coin output 22 or simply indicated on a portion of the video display 12 as credits to be paid later.
[0020] The present invention concerns both the video poker-style game using, for example, the video poker machine on terminal 10 of FIG. 1 , and the wagering options provided to the player both before play is initiated and during the game. Referring to FIG. 2 , a method of playing and wagering options of one embodiment of the game of the present invention is illustrated. The video display 12 will display a pay table which relates the payouts (as a ratio of the amount paid per unit bet) associated with wagers placed on certain selected winning hands. The following table shows a preferred pay table to be used with one embodiment of the game and method of the present invention. Changes in the various ratios can be made, as desired, in keeping with the concepts of this invention.
TABLE 1 Royal Flush 20,000 to 1 Straight Flush 5,000 to 1 Four of a Kind 300 to 1 Full House 60 to 1 Flush 60 to 1 Straight 60 to 1 Three of a Kind 8 to 1 Two Pair 3 to 1 Jacks or Better 2 to 1
[0021] The player will then wager on the certain selected winning hand or hands of his or her choice. This can be done in any desired form, including for example having a touch-sensitive region on, for example, the video display 12 , or on the pay table 20 so that the player can touch the different section or sections of the pay table 20 to select the winning hand or hands on which he or she chooses to wager, as well as selecting how much to wager on each selected hand. Software in the terminal 10 is used to recognize that such wagers have been made and the amount of any payout due to the player depending on the amount wagered. As the player makes these wagers, for example, the video display 12 or the pay table 20 will display the potential payouts associated with each wager should the player obtain or achieve that certain selected winning hand. Play will then continue as described above in prior art games with the player receiving a hand of cards, deciding which cards to hold, and receiving replacements for the non-held cards. After play is completed, software in the terminal 10 will determine if a winning hand has been achieved (i.e. a pair of Jacks or better) and also if a wager was registered on the player obtaining the certain selected winning hand or hands that occurred. If such a wager was registered, a payment is made according to the payout odds in Table 1 , or according to other pre-set payout odds acceptable to the casino and any applicable gaming authority.
[0022] Still referring to FIG. 2 , a method of play of another embodiment of the game of the present invention is illustrated. There is a concern that some casino operators might not want to provide the wagering option of the present invention unless the player has also wagered in the traditional manner of prior art games as described above. To address this, optionally, a player can be required to register such a traditional wager prior to receiving the wagering option of the present invention (to pre-select a winning hand or hands). That this step is optional is illustrated by dashed-lines for this portion of the flow chart of FIG. 2 .
[0023] Referring to FIG. 3 , another method of an embodiment of the game of the present invention is illustrated. This method is similar to that described above. A player will wager in the traditional manner of prior art games as described above. Once, the player makes the traditional wager, the player will receive the wagering option to pre-select a winning hand or hands. There will be certain restrictions on what a player may wager on selected winning hands. For example, a player will generally not be allowed to place credits on a selected winning hand without first placing a certain minimum traditional wager. Larger traditional wagers will allow more credits to be placed on a selected winning hand.
[0024] Other restrictions may include, only allowing a player to place a single credit wager on a first select winning hand. The player may place another credit on the first selected winning hand only after placing another credit on a second select winning hand. For example, if a player makes a one credit wager on obtaining a royal flush, the player must wager another credit on a second winning hand (for example, a straight) prior to placing another credit wager on the royal flush. Another restriction may include, having the maximum allowable wager on a selected winning hand being a function of the total amount wagered on all other selected winning hands.
[0025] Once the traditional wager is made, the video display 12 will display a pay table which relates the payouts (as a ratio of the amount paid per unit bet) associated with wagers placed on certain selected winning hands. The player will then wager on the certain selected winning hand or hands of his or her choice. This can be done in any desired form, including for example having a touch-sensitive region on, for example, the video display 12 , or on the pay table 20 so that the player can touch the different section or sections of the pay table 20 to select the winning hand or hands on which he or she chooses to wager, as well as selecting how much to wager on each selected hand.
[0026] Software in the terminal 10 is used to recognize that wagers on select winning hands are made. Once this is done, the payout odds will be adjusted. The adjustment on the payout odds may be done in several different manners. First, the payout odds on the select winning hands may be adjusted. The adjustment on the certain select winning hands are adjusted by the software. The adjustment on the payout for select winning hands is based on the amount wagered in the traditional manner. Thus, larger wagers in a traditional manner will increase the payout odds on the select winning hands. For example, a player makes a traditional wager of 5 credits. The player then makes a wager of 1 credit on a select winning hand. The software will then produce a payout schedule for the traditional winning hands as well as the select winning hand. If the player had made a traditional wager of 8 credits, then the software would have produce a payout schedule for the traditional winning hands as well as the select winning hand wherein the payout schedule for the select winning hand would be higher. Thus, larger wagers in a traditional manner will increase the payout odds on the select winning hands.
[0027] Alternatively, the adjustment to the payout odds may be done to the non-selected winning hands. For example, a player makes a normal traditional wager of 5 credits. The player then makes another wager of 1 credit on a select winning hand (for example a royal flush). Since the player made a wager on a select winning hand, the posted payout odds on the non-selected winning hands will be adjusted. The reason for this is that a player's strategy has a large effect on the probability of winning the selected winning hand. In the above example, if a player bets on obtaining a royal flush, the player will most likely play the optimum strategy for achieving a royal flush. As a result, the probability of the player obtaining other winning hands that were not selected will decrease. Thus, the posted payout odds for the other winning hands that were not selected will increase to encourage the player to wager on additional hands, as well as provide the highest possible payouts.
[0028] While the invention has been particularly shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that the foregoing and other changes in form and details may be made therein without departing from the spirit and scope of the invention.
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A method and apparatus for playing a poker-style game has a player making an opening wager. The player is permitted to make at least one wager to obtain at least one certain selected winning hand. The payout odds are adjusted on winning hands based on an amount of the opening wager and the at least one wager to obtain at least one certain selected winning hand. A hand of cards are then dealt to the player. The player is allowed to hold desired cards of the hand. Replacement cards are dealt to the player. One determines if a new hand of cards is a winning hand. Paying the player is based on the adjusted payout odds.
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FIELD OF THE INVENTION
[0001] The present invention is directed to a folding apparatus having a cylinder whose circumference is adjustable. The cylinder is rotatably supported on the frame and has at least one hoop or ring supported on its shell surface.
BACKGROUND OF THE INVENTION
[0002] A prior folding apparatus is known from DE 38 21 442 C2, for example. A folding apparatus with a folding cylinder is described in this document as the prior art of this technology. A shell surface of the cylinder of this prior device is constructed of segments which are fixedly mounted on a frame of the cylinder, as well as of movable hoops, which bridge gaps between the segments. These hoops have two ends in the circumferential direction of the cylinder, one of which is fixedly mounted on one of the segments, while the other is adjustable with the aid of a strip which can be displaced parallel with the axis of the cylinder. A conversion of the axis-parallel adjustment movement of the strip, to a displacement of the end of the hoop, takes place with the aid of a pin, which pin is fixedly mounted on a sliding plate of the strip connected with the displaceable end of the hoop and which engages an elongated hole, that is oriented obliquely, in respect to the extension of the strip. By displacing the movable end of the hoop in the direction of the fixed end of the hoop, with the aid of this mechanism, arching of the hoop and therefore an increase of the circumference of the cylinder is achieved.
[0003] In connection with a folding apparatus described as the invention in DE 38 21 442 C2, the adjustment movement of the strip itself is driven with the aid of a planetary gear which, with the folding cylinder rotating, allows the rotation of two sun wheels which are coaxial with the folding cylinder. One of the sun wheels meshes with a plurality of intermediate wheels, which in turn mesh with pinion gears. The pinion gears are connected, fixed against relative rotation, with a helical spindle which engages a screw thread of the strip. The rotation of the spindles drives a translation of the strips.
[0004] With this construction, the hoops are compressed in the longitudinal direction if the circumference is to be increased. Since the hoops or bows must have a degree of stiffness, which is not negligible, in order not be deformed during contact with the material to be processed during the operation of the folding apparatus, a considerable force is required to accomplish this compression. In most cases, an adjustment movement requires a multitude of revolutions of the spindle.
[0005] DE 197 55 428 Al describes a device for displacing two cylinder bodies of a folding cylinder by the use of a harmonic drive mechanism.
SUMMARY OF THE INVENTION
[0006] The object of the present invention is directed to providing a folding apparatus including a cylinder whose circumference can be adjusted.
[0007] In accordance with the present invention, this object is attained by providing the cylinder, which is rotatably supported in a frame, with at least one hoop on its shell surface. The at least one hoop can be displaced by the operation of an adjusting gear assembly. That adjusting gear assembly is in the form of a flexible toothed sleeve, which is deformed by an out of round section of a shaft, and at least one internally geared wheel which meshes with the sleeve. The result is a harmonic drive gear.
[0008] The advantages which can be obtained by the present invention consist, in particular, in that the employment of a “harmonic drive” mechanism permits a very compact structure, along with a large load-bearing capacity.
[0009] By connecting the out-of-round section of the shaft of the “harmonic drive” mechanism with the drive mechanism for driving the displacement of the hoops, it is possible to achieve very low gear ratios for the transmission of the revolution of the drive mechanism to the hoops, and therefore to obtain and to accomplish a very sensitive regulation with a small outlay of force at the drive mechanism.
[0010] The “harmonic drive” mechanism is preferably designed with two stages. The internally geared wheel of one stage is coupled to the rotation of the cylinder, and the one of the other stage provides coupling to the movement of the hoops by way of a gear wheel which is rotatable around the axis of the cylinder relative to the latter.
[0011] In accordance with a first preferred embodiment of the present invention, a gear wheel, by the use of which the internally geared wheel coupled to the rotation of the cylinder is driven, can be rigidly connected with the cylinder. In other words, a drive train for the internally geared wheel can extend via the cylinder, or a common drive train for the internally geared wheel and the cylinder extends via this gear wheel. Alternatively, there is the option of providing an independent drive train for this internally geared wheel which is parallel with the one for the cylinder. Both drive trains can, in particular, originate from a common second driven cylinder.
[0012] The tooth numbers of the first and second tooth arrangement at the internally geared wheels of the “harmonic drive” mechanism, of the drive wheels which are coaxial to the cylinder, and of the flexible sleeves, are preferably selected in such a way that, with a stopped drive mechanism, the gear wheels rotate at the same number of revolutions. However, in this case, the tooth numbers of the first and second tooth arrangements, of the drive wheels which are coaxial to the cylinder, and of the flexible sleeves, must not all be identical in pairs.
[0013] Preferably, the tooth numbers of the flexible sleeves are selected to be identical, but those of the internally geared wheels are selected to be different. If then, the tooth numbers of the second tooth arrangements are identical, the tooth numbers of the coaxial gear wheels and of the second tooth arrangements should be in the same ratio.
[0014] In accordance with a first preferred embodiment of the present invention, the other gear wheel, which is coupled to the hoops, has an external tooth arrangement. In accordance with a further preferred development, however, this other gear wheel is embodied as a crown gear. This makes possible the placement of the “harmonic drive” gear near the shaft of the cylinder, and therefore results in a particularly compact construction of the folding apparatus.
[0015] One option of driving the displacement of the hoops is the use of an eccentric that is driven by the other gear wheel. A second option is the use of a displaceable strip with cam faces, which cam faces are engaged by the respective loops of the cylinder.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Preferred embodiments of the present invention are represented in the drawings and will be described in greater detail in what follows.
[0017] Shown are in:
[0018] FIG. 1 , a partial section through a cylinder in accordance with a first preferred embodiment of the present invention and taken transversely to its longitudinal axis, in
[0019] FIG. 2 , a partial section through the cylinder and taken parallel to the longitudinal axis of the cylinder, and showing the eccentric shaft, in
[0020] FIG. 3 , a simplified partial section, analogous to that shown in FIG. 1 through the cylinder, and taken in a first phase of the adjustment movement of the eccentric shaft, in
[0021] FIG. 4 , a partial section analogous to that in FIG. 3 taken in a second phase of the adjustment movement, in
[0022] FIG. 5 , a partial section through a first modification of the cylinder of the first preferred embodiment shown in FIG. 1 , in
[0023] FIG. 6 , a partial section through a second modification of the cylinder of the first preferred embodiment shown in FIG. 1 , in
[0024] FIG. 7 , a cross-section through an adjustment gear for rotating the eccentric shafts, in
[0025] FIG. 8 , a perspective plan view of a folding cylinder and of a blade cylinder of a folding apparatus in accordance with a second preferred embodiment of the present invention, in
[0026] FIG. 9 , a schematic representation of the gear of the folding apparatus in FIG. 8 , in
[0027] FIG. 10 , a first modification of the gear shown in FIG. 9 , in
[0028] FIG. 11 , a second modification of the gear shown in FIG. 9 , in
[0029] FIG. 12 , a third preferred embodiment of the present invention, in the form of a cross-section through the head area of a folding cylinder, in
[0030] FIG. 13 , a section through the folding cylinder in FIG. 12 at the level of the toothed belt, and in
[0031] FIG. 14 , a modification of the embodiment in FIG. 12 .
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0032] A schematic partial cross-sectional view through a cylinder 01 , for example a folding cylinder 01 , and in particular through a folding blade cylinder, in a plane perpendicularly to its longitudinal axis, is shown in FIG. 1 . A shell surface of the folding cylinder 01 is substantially composed of three segments 02 , two of which segments 02 are represented in FIG. 1 , and all three of which segments 02 are mounted fixedly on a frame of the folding cylinder 01 with cover disks, which are not specifically represented. The segments 02 are separated from each other by a cylinder gap 03 . The number of the segments 02 and of the gaps 03 of the folding cylinder 01 can, of course, also be other than three.
[0033] A folding blade is pivotably housed in each cylinder gap 03 . Since the folding blade in each cylinder gap 03 is not a part of the present invention, it is not represented in FIG. 1 and will not be further described here.
[0034] Each of the cylinder gaps 03 is bridged by a plurality of hoops 04 or hoop-like bands which are longitudinally extending in a circumferential direction of the folding cylinder 01 . In the axial direction the of the folding cylinder 01 , hoops 04 are separated from each other by spaces, through which spaces respective teeth of the folding blade can be extended out of the cylinder gap 03 . Each of two spaced linear ends 06 , 07 of each of the hoops 04 have an eye 08 , which eye 08 protrudes, or extends into an interior region of the folding cylinder 01 and each which eye 08 has a circular bore, in which an eccentric 09 is rotatably seated. As shown in FIG. 2 , the eccentric 09 is embodied as one part of a shaft 11 . On each of its ends, the shaft 11 is supported by a bearing 12 , for example by a roller bearing 12 , in a cover disk 13 , 14 , which cover disk 13 , 14 is a part of the frame of the folding cylinder 01 . A first gear wheel 16 is mounted at an end of the shaft 11 , which shaft end 11 extends past the adjacent cover disk 13 .
[0035] In the first preferred embodiment of the present invention, as shown in FIG. 1 , a shaft 11 is arranged on each of the two sides of each gap 03 . Since the folding cylinder 01 has a total of three gaps 03 , there is a total of six shafts 11 . The first gear wheels 16 of all of these six shafts 11 all mesh in the same way with a second gear wheel 17 , depicted here in the form of a crown gear 17 and provided with an external tooth arrangement, which crown gear 17 is arranged, concentrically rotatable around an axis of rotation A of the folding cylinder 01 , on the cover disk 13 , and whose pitch circle is indicated in the form of a dash-dotted line in FIG. 1 . Thus, by the effecting of a rotation of the second gear wheels 17 , all eccentrics 09 are rotated to the same extent, and the hoops 04 are moved. The way the second gear wheel 17 is rotationally driven will be discussed in more detail subsequently.
[0036] FIGS. 3 and 4 show two distinct phases of the movement of the hoops 04 which are caused by the rotation of the gear wheels 17 , 16 . FIG. 3 corresponds, in a simplified form, to the plan view of FIG. 1 . With respect to the centers M 11 of the shafts 11 , in FIG. 3 the centers M 09 of the eccentrics 09 are each offset radially in the direction toward the center M 01 of the folding cylinder 01 , i.e. an eccentricity vector E, extending respectively from the center M 11 of the shaft 11 to the center M 09 of the eccentric 09 , is oriented radially inward. The hoop 04 rests against the surfaces of the segments 02 at the spaced sides of the cylinder gap 03 .
[0037] The eccentricity vectors E of each of the two shafts 11 for each hoop 04 intersect at an angle corresponding to the angular distance of the shafts 11 in relation to the center M 01 of the folding cylinder 01 . This does not change, even with a rotation of the second gear wheel 17 with respect to the folding cylinder 01 .
[0038] In FIG. 4 , the shafts 11 are each rotated by 180° from their positions in FIG. 3 , and the centers M 09 of the eccentrics 09 are now displaced radially outward with respect to the centers M 11 of the shafts 11 , i.e. the eccentricity vector E is now directed radially oriented toward the outside. The hoop 04 is now spaced at a distance from the surface of the segments 02 corresponding to twice the eccentricity of each eccentric 09 with respect to its position shown in FIG. 3 .
[0039] During the transition of the hoops 04 from the inner position shown in FIG. 3 to the outer position shown in FIG. 4 , the two eyes 08 of the hoop 04 not only move away from the center M 01 of the folding cylinder 01 . They also move apart from each other. To make such a movement possible, the hoop 04 can be extended in the circumferential direction with the aid of a rail mechanism which is not specifically shown. For example, one of the hoop's eyes 08 , the one on the left in FIG. 4 , is connected, displaceable in the circumferential direction, with the associated linear end 07 of the hoop 04 by the use of a guide rail.
[0040] FIG. 5 shows a modified preferred embodiment of the folding cylinder 01 . In this second embodiment, the eccentricity vectors E of the two eccentrics 09 are always exactly parallel. This means that in the position of the eccentrics 09 represented in FIG. 5 , their centers M 09 are displaced in the vertical direction of FIG. 5 in respect to the centers M 11 of the shafts 11 . The parallel orientation of the eccentricities is maintained, even if the shafts 11 are rotated with the aid of the second gear wheel 17 , which is not specifically represented in FIG. 5 . During a complete revolution of each of the shafts 11 , each point on the hoop 04 travels in a circular track of a radius corresponding to the amount of eccentricity of the eccentrics 09 . No deformation of the hoop 04 occurs. The connection of the hoop 04 with the eyes 08 can also be rigid in this embodiment, since, in the course of a revolution of shafts 11 , the distance between the two eyes 08 does not change. With this embodiment, it is not possible that, in a “retracted” position of hoop 04 , corresponding to a minimal circumference of the folding cylinder 01 analogous to the position depicted in FIG. 3 , the hoop 04 simultaneously touches both segments 02 , which are partially covered by it. Instead, in the “retracted” position represented in FIG. 5 , and corresponding to a minimal circumference of the folding cylinder 01 , the hoop 04 is separated from both adjacent segments 02 by a respective gap 18 .
[0041] A third, preferred embodiment of the folding cylinder 01 of the present invention is represented, in a simplified manner, in FIG. 6 . Here, an eye 08 has been arranged on only one linear end 06 of the hoop 04 . The other linear end 07 of hoop 04 is fastened on a cylinder segment 02 , for example with the aid of a screw 19 which passes through an elongated hole 20 situated at the linear end of the hoop 04 not provided with eye 08 . If, with this embodiment, the shaft 11 is rotated, the linear end 06 , with the eye 08 , is lifted and lowered in the radial direction. At the same time, the linear end 07 without the eye 08 , is displaced in the circumferential direction of cylinder 01 in relation to the screw 19 . A deformation of the hoop 04 is practically not required for such a displacement of hoop 04 . Therefore the displacement of hoop 04 requires only a small outlay of force.
[0042] Such a construction of the end 07 of hoop 04 , without the eye 08 , can also constitute the rail mechanism mentioned above in relation to FIG. 4 .
[0043] There is also a possibility of fastening the linear end 07 immovably on the segment 02 . In this case, a rotation of the shaft 11 and a change of the circumference of the folding cylinder is also possible, but it is necessary, in order to accomplish this, that the hoop 04 have a greater elasticity than in the previously discussed preferred embodiments, since the change is connected with a compression of the hoop 04 .
[0044] Changing the circumference of the cylinder 01 means that an at least partial change of the radius of cylinder 01 also takes place.
[0045] FIG. 7 shows a mechanism which, in use with a rotating folding cylinder 01 , permits a turning of the second gear wheel, or crown gear, 17 , shown in FIG. 2 , relative to the folding cylinder 01 , and therefore accomplishes a change of the circumference of folding cylinder 01 . FIG. 7 is a partial section through a frame of a folding apparatus in a plane which is parallel to the longitudinal axis of the folding cylinder 01 . A hollow shaft 21 formed on one of the cover disks 13 is rotatably seated in a lateral plate 22 of the frame. A drive gear wheel 23 , which transfers the torque of a non-represented motor to the folding cylinder 01 , is wedged on an end of the hollow shaft 21 facing away from the cover disk 13 .
[0046] An adjusting gear assembly 26 , for example a “harmonic drive” gear 26 , is fixedly mounted on the frame of the folding apparatus. It comprises a shaft 27 , for example an adjusting shaft 27 , which is connected with a drive mechanism, which is not specifically represented in FIG. 7 , for example a motor or an arrestable crank. The adjusting shaft 27 has an out-of-round section 28 , or more exactly an elliptical cross section, also called rotor 28 , on which, separated by bearings 30 , for example ball bearings 30 of elliptical cross section corresponding to the shape of the rotor 28 , two flexible sleeves 29 , 31 have been pushed, each of which has exterior tooth arrangements. The two sleeves 29 , 31 are connected with each other, fixed against relative rotation, and mesh with respective tooth arrangements 32 or 33 , for example interior tooth arrangements 32 or 33 , of a internally geared wheel 41 or 42 of circular cross section surrounding them. The internally geared wheels 41 , 42 are connected with further gear wheels 45 , 50 . These gear wheels 45 , 50 are seated, rotatable around the adjusting shaft 27 , with the aid of bearings 34 , for example ball bearings 34 . Each of these further gear wheels 45 , 50 has a tooth arrangement 36 , 37 , for example an exterior tooth arrangement 36 , 37 , of which the one exterior tooth arrangement 36 meshes with a gear wheel 24 , which is arranged next to the drive gear wheel 23 and is wedged, the same as the latter, on the hollow shaft 21 . The other exterior tooth arrangement 37 meshes with a gear wheel 38 , which is rotatable around the axis A of the folding cylinder 01 and is connected with a rigid sleeve 39 extending through the interior of the hollow shaft 21 into the interior of the folding cylinder 01 and there supports the already mentioned second gear wheel 17 , which drives the displacement movement of the hoops 04 via the first gear wheels 16 .
[0047] If the folding cylinder 01 is driven at a circumferential speed n 01 , this results in the internally geared wheel 41 of the “harmonic drive” gear 26 also rotating at a speed of
n41 = n01 z24 z36
wherein the respective tooth numbers z 24 , z 36 are those of the gear wheel 24 or of the external tooth arrangement 36 . If the adjusting shaft 27 is at rest, this results in a rotation of the sleeves 29 , 31 at a rotational speed of
n29 = n41 z29 z32
wherein the respective tooth numbers z 29 , z 32 are those of the sleeve 29 or the interior tooth arrangement 32 of the internally geared wheel 41 . From this results a number of revolutions
n42 = n29 z31 z33
of the internally geared wheel 42 in turn, wherein the respective tooth numbers z 31 , z 33 are those of the sleeve 31 or of the interior tooth arrangement 33 of the internally geared wheel 42 . From this results a number of revolutions
n38 = n41 z37 z38
of the gear wheel 38 , wherein the respective tooth numbers z 37 , z 38 are those of the exterior tooth arrangement 37 or of the gear wheel 38 .
[0052] So that, with the adjusting shaft 27 stopped, the second gear wheel 17 will rotate at exactly the speed of the folding cylinder 01 , it is necessary that the requirement
z37 z31 z32 z24 z38 z33 z29 z36 = 1 ( 1 )
be met.
[0054] In order to cause a rotation of the second gear wheel 17 , in relation to the folding cylinder 01 , by the rotation of the adjusting shaft 27 , it is furthermore necessary that either the tooth numbers z 29 , z 31 , z 32 , z 33 of the two sleeves 29 , 31 , or of the crown gears 32 , 33 , or both, differ. If this were not the case, a rotation of the adjusting shaft 27 would not result in a rotation of the internally geared wheels 41 , 42 in relation to each other.
[0055] This means that the mechanism in FIG. 7 must fulfill the conditions of equation 1 and, at the same time
z 29 ≠z 31 V z 32 ≠z 33 (2)
must apply.
[0057] The two conditions can be met in general, because the gear wheels 24 , 38 have a considerably greater diameter than the internally geared wheels 41 , 42 and can have a large number of teeth z 24 , z 38 , which are only slightly different from each other.
[0058] Thus, it is possible, for example, to select the tooth numbers of the interior and of the exterior tooth arrangements of the internally geared wheels 41 , 42 to be identical in pairs, and to accept a slight difference between the tooth numbers z 29 , z 31 of the flexible sleeves 29 , 31 . In this case the equation 1 is reduced to
z31 z24 z38 z29 = 1 ( 3 )
i.e. the synchronous running of the gear wheel 17 with the folding cylinder 01 , while the adjusting shaft 27 is stopped, is assured if the tooth numbers z 29 , z 31 of the flexible sleeves 29 , 31 are at the same ratio to each other as those of the gear wheels 24 , 38 :
z29 z31 = z38 z24
[0060] It is therefore sufficient to select the tooth numbers z 24 , z 38 of the gear wheels 24 , 38 and of the flexible sleeves 29 , 31 to be identical in pairs.
[0061] The smaller the difference of the tooth numbers z 9 , z 31 of the flexible sleeves 29 , 31 , the more sensitively can the turning of the gear wheels 24 , 38 toward each other be performed by rotating the adjusting shaft 27 . Approximately n 31 /(n 31 −n 29 ) revolutions of the adjusting shaft 27 are required for rotating the gear wheels 24 , 38 by 360° in relation to each other.
[0062] Alternatively, it is possible, for example, to select the tooth numbers z 29 , z 31 , z 36 , z 37 of the flexible sleeves 29 , 31 and of the exterior tooth arrangements 36 , 37 , respectively identical in pairs, and to accept a slight difference between the tooth numbers z 32 , z 33 of the interior tooth arrangements 32 , 33 . In this case, Equation 1 is reduced to
z32 z24 z38 z33 = 1 ( 4 )
i.e. the synchronous running of the gear wheel 17 with the folding cylinder 01 , while the adjusting shaft 27 is stopped, is assured, if the tooth numbers z 29 , z 31 of the flexible sleeves 29 , 31 are at the same ratio to each other as are those of the gear wheels 24 , 38 :
z32 z33 = z38 z24
[0064] It is therefore sufficient to select the tooth numbers z 24 , z 38 , z 32 , z 33 of the gear wheels 24 , 38 and of the interior tooth arrangements 32 , 33 to be identical, in pairs, in order to assure, with the adjusting shaft 27 at a stop, the synchronous running of the gear wheel 38 with the folding cylinder 01 and, in this way, to prevent the unintentional displacement of the hoops 04 .
[0065] FIG. 8 shows a perspective view of a folding cylinder 01 and of a cooperating cylinder 44 , for example a blade cylinder 44 of a folding apparatus, in accordance with a second preferred embodiment of the present invention. The blade cylinder 44 is directly connected with a drive motor, which is not specifically represented. A drive train of the folding cylinder 01 extends from the motor via the blade cylinder 44 and a gear, also not specifically represented, and which is arranged between the cylinders 01 , 44 .
[0066] The blade cylinder 44 supports two blades, each extending over its entire axial width, for use in cutting an endless strand of material into individual products to be folded. These blades, as well as suitable grippers or pointed needles of the folding cylinder 01 , which are used for holding the separated product, are not represented in FIG. 8 , since they are generally known. Flexible hoops 04 on the surface of the cylinder 01 are maintained fixed on one of their ends and are displaceable in the circumferential direction of the folding cylinder 01 on the other one, as generally disclosed in the publication DE 38 21 442 C2, which was cited at the outset of the specification. Pins, which, starting at their displaceable ends, are oriented into the interior of the folding cylinder 01 , each engage oblique, axially displaceable slits of a strip 61 that is hidden in the interior of the cylinder 01 and which is shown schematically in FIG. 9 . In this way, the lateral flanks of the slits constitute cam surfaces, by the use of which the strips 61 drive a deformation of the hoops 04 . In the second preferred embodiment represented in FIGS. 8 and 9 , three groups of hoops 04 are provided, which three groups follow each other in the circumferential direction of the folding cylinder 01 . Three strips 61 are correspondingly provided. Each one of these strips 61 has an internal screw threaded bore on its end face, which internal screw threaded bore is engaged by a threaded shaft. Each threaded shaft, which is maintained rotatably, but axially fixed in the cylinder 01 , has a pinion 46 on one end, which pinion 46 is visible at the end face of the folding cylinder 01 . All three pinions 46 mesh with an exterior tooth arrangement of a crown gear 47 , which is rotatably arranged on the end of the folding cylinder 01 and which encircles a central opening 48 , as seen more clearly in FIG. 8 . A shaft 49 of a folding blade support or spider extends eccentrically through the opening 48 into the interior of the folding cylinder 01 . The spider supports folding blade shafts on diametrically oppositely located arms 51 , which are essentially hidden in FIG. 8 , and on each of which, a comb-like folding blade 52 is mounted. The folding blade 52 rotates around its respective folding blade shaft, coupled to the rotation of the spider around the shaft 49 . Tips of the comb-like folding blade 52 , and, extending out of slits between the gaps 04 , are represented in FIG. 8 .
[0067] A gear wheel 53 is furthermore arranged in the opening 48 and meshes with an interior tooth arrangement of the crown gear 47 . The gear wheel 53 is rigidly coupled via a shaft 54 with a “harmonic drive” or adjusting gear 26 . The internal structure of the adjusting gear 26 , and its relationship with an adjusting drive mechanism 56 and with the blade cylinder 44 can be best seen in FIG. 9 , which represents the structure shown in FIG. 8 in the form of a schematic sectional view. The structure of the “harmonic drive” gear 26 is the same as that described with respect to FIG. 7 and will not be explained again. In FIG. 7 and in FIG. 9 the same reference symbols have been used for identical components of the “harmonic drive” gear 26 . The gear wheel 53 , although separated from the internally geared wheel 42 by the shaft 54 , can be considered to be equivalent with the exterior tooth arrangement 37 represented in FIG. 7 .
[0068] The exterior tooth arrangement 36 of the internally geared wheel 41 meshes with a gear wheel 57 , for example a first intermediate gear wheel 57 , which is coupled via a further gear wheel 58 , for example a second intermediate gear wheel 58 , with a gear wheel 59 , which is rigidly fixed on the blade cylinder 44 . Thus, a drive train for the crown gear 47 extends from the blade cylinder 44 via the gear wheels 59 , 58 , 57 to the “harmonic drive” gear 26 , and via the shaft 54 on to the gear wheel 53 . The ratio of the numbers of revolutions of the blade cylinder 44 and of the folding cylinder 01 corresponds to the ratio of the groups of parallel hoops 04 on the folding cylinder 01 to the number of blades of the blade cylinder 44 , and in the case here considered is 3:2. The tooth numbers on the drive train of the crown gear 47 , such drive train consisting of the components 59 , 58 , 57 , 26 , 53 , has been fixed in such a way that the crown gear 47 rotates at the same speed as the cylinder 01 as long as the adjusting shaft is stopped. The strip 61 is not axially displaced, and the shape of the hoops 04 thus remains unchanged. Turning the adjusting shaft 27 causes turning of the crown gear 47 with respect to the folding cylinder 01 , and in this way axial movement of strip 61 is used for deforming the hoops 04 , which deformation of the hoops 04 changes the circumference of the folding cylinder 01 .
[0069] The schematic sectional view represented in FIG. 10 differs from that in FIG. 9 in that the exterior tooth arrangement 36 of the internally geared wheel 41 is not coupled to the blade cylinder 44 but, as in the preferred embodiment in FIG. 7 , meshes directly with a gear wheel 62 , which is rigidly connected with the folding cylinder 01 . In contrast to the gear wheel 38 in FIG. 7 , the gear wheel 62 is an internally geared wheel 62 . The tooth number formulas cited in connection with FIG. 7 can be analogously applied in order to determine tooth numbers which assure a synchronous running of the crown gear 47 with the folding cylinder 01 also for this gear.
[0070] As previously mentioned above, the folding cylinder 01 has holding devices, such as grippers or pointed needles which, in coordination with the rotation of the cylinder 01 , are movable in order to close over or engage a product conveyed to a fixed receiving point of the cylinder circumference and to hold the product for further conveyance and processing at the cylinder 01 , and to open again at a delivery point, so that the product can be passed over to a further cylinder or the like. The holding devices can be operated in a single or in a collection mode of operation. In the single mode of operation the holding devices open during each passage through the delivery point in order to release the product they are holding. In the collection mode of operation, such a holding device passes the delivery point once without opening, then receives a second product in the course of a second passage through the receiving point and then releases both products together in the course of a second passage through the delivery point. The movement of these holding devices is controlled in a generally known manner with the aid of a cam disk, which is not specifically depicted, and which is coaxial to the folding cylinder 01 and on which the pivot arms of the holding devices roll off. The cam disk has a recess at a location corresponding to the delivery point and into which a passing pivot arm dips, whereupon the corresponding holding device opens and releases the product held. In order to accomplish the holding device only opening during every second passage through the delivery point, during collecting operations, a so-called cover disk is employed. This cover disk is parallel with the cam disk and rotates coaxially with the cylinder 01 , but only at half the number of revolutions of the latter. The cover disk has a section of a large radius, which, in the course of every second passage through the delivery point, covers the recess on the cam disk and prevents the opening of the holding device. The cover disk also has a section of a lesser radius which, when it lies in front of the recess on the cam disk, permits the opening of the holding device. In the embodiment of the present invention represented in FIG. 11 , such a cover disk, identified by 63 , has been integrated into the drive train of the crown gear 47 . As depicted in the diagram of FIG. 9 , this drive train runs from the directly driven blade cylinder 44 , via the gear wheel 59 , which is rigidly coupled to the blade cylinder 44 and is aligned with the axis B of the latter, and two intermediate wheels 58 , 57 . The intermediate wheel 57 does not directly mesh with the exterior tooth arrangement 36 of the internally geared wheel 41 , but instead meshes with an exterior tooth arrangement 64 of the cover disk 63 , wherein the latter again has an interior tooth arrangement 66 , which meshes with the exterior tooth arrangement 36 . The tooth numbers of the gear elements 57 , 58 , 59 , 64 have been selected to be such that half of the number of revolutions of the folding cylinder 01 results for the cover disk 63 , i.e. with a ratio of the number of revolutions n 01 of the folding cylinder 01 to the number of revolutions n 44 of the blade cylinder 44 of n 01 /n 44 =⅔, the following must apply to the number of revolutions n 63 of the cover disk 63 : n 63 =n 44 /3. If the number of revolutions of the internally geared wheels 41 , 42 of the “harmonic drive” gear 26 are identical when the adjusting shaft 27 is stopped, the result for the tooth numbers n 66 , n 36 , n 53 and n 47 of the interior tooth arrangement 66 of the cover disk 63 , the exterior tooth arrangement 36 of the internally geared wheel 41 , of the gear wheel 53 and the interior tooth arrangement of the crown gear 47 is the requirement
z53 z47 · z66 z36 = 3
[0071] FIG. 12 shows a third preferred embodiment of the present invention, in the form of a cross-section through the head area of the folding cylinder 01 and of the adjoining portions of the lateral frame of a folding apparatus. Portions of two plates 68 , 69 of the lateral frame can be seen, one of which, 68 , supports a tapered shaft section 71 protruding from a front end of the folding cylinder 01 . The plate 69 supports a “harmonic drive” gear assembly 26 , whose structure, comprising the components 29 , 31 , 32 , 33 , 36 , 37 , 41 and 42 , has been described previously in connection with FIG. 7 and will thus not be again explained here. The exterior tooth arrangement 36 meshes with a gear wheel 24 that is rigidly fastened on the shaft section 71 . The exterior tooth arrangement 37 meshes with the exterior tooth arrangement of a crown gear 47 mounted rotatably around the end of the shaft section 71 . The shaft 27 is connected with an adjustment drive mechanism, which is not specifically represented.
[0072] A bore 72 extends in the longitudinal direction of the tapered shaft section 71 . A shaft 73 is rotatably maintained in the bore 72 and supports a pinion 67 on one end thereof, which pinion 67 is meshing with an interior tooth arrangement of the crown gear 47 . On its other end shaft 73 carries a pulley 74 . A toothed belt 76 is looped around the pulley 74 and around a plurality of pulleys 77 . These pulleys 77 are used, in the same way as the pinions 46 in FIG. 8 , for displacing the strips 61 which the hoops 04 engage in a displaceable manner and which displacement of the hoops 04 cause the circumferential change of the folding cylinder 01 .
[0073] FIG. 13 shows schematically a section through the folding cylinder 01 at the level of the pulleys 74 , 77 and the toothed belt 76 . Between two pulleys 77 , the toothed belt 76 loops around respective rollers 78 , at least one of which is displaceable in the radial direction for tightening the toothed belt 76 .
[0074] As long as the adjustment drive of the shaft 27 remains stopped, a rotation of the gear wheel 24 is transmitted to the crown gear 47 via the “harmonic drive” gear 26 at the same rotational speed. The shaft 73 does not rotate in its bore 72 , and the strips 71 are not axially displaced. When the adjustment drive is actuated and the shaft 27 rotates, this leads to a displacement of the crown gear 47 with respect to the gear wheel 24 . The result is a displacement of the strips 61 and a change of the circumference of the cylinder 01 .
[0075] Link chains can also be employed in place of the toothed belt 76 .
[0076] FIG. 14 shows a modification of the third embodiment of the invention. This modification differs from the embodiment shown in FIG. 12 by the attachment of the crown gear 47 , which in FIG. 14 is rotatably seated not on the shaft section 71 of the folding cylinder 01 , but instead coaxially with the folding cylinder 01 on the plate 69 that is located opposite to it. The mode of functioning of this modification does not differ from that of the embodiment in FIG. 12 .
[0077] While preferred embodiments of a folding apparatus comprising a cylinder with an adjustable circumference, in accordance with the present invention have been set forth fully and completely hereinabove, it will be apparent to one of skill in the art that various changes in, for example the overall configuration of the printing device with which this folding apparatus is utilized, the type of material being folded, and the like could be made without departing from the true spirit and scope of the present invention which is accordingly to be limited only by the appended claims.
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A folding gear comprises a cylinder mounted in a frame such as to rotate, with at least one clamp arranged on the outer surface thereof which may be positioned by means of an actuator, whereby the actuator comprises a flexible toothed shell, shaped by a non-circular section of a shaft and a hollow gear engaging with the shell, in other words a harmonic drive gear.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to the field of paper cutters and particularly to a device for cleanly shearing the guide edge from a computer paper manuscript.
2. Background Information
A standard type of computer paper (81/2×11 inches) for commercially available dot matrix and printwheel computer printers has a construction which includes the basic sheet and a guide edge. The guide edge runs parallel to the long dimension of the sheet on both sides and is connected to the sheet along a perforated line. Equispaced uniform holes are positioned down the center line of each guide edge and permit twin drive wheels to advance the sheet during printing, line feed, form feed, sheet ejection, and manual sheet advance. After the printing process has been completed, the guide edges are typically removed from the sheet by being torn or ripped by hand. Although the perforations are designed to permit clean separation, too often the printed sheet is torn. Of particular difficulty is the situation in which the printed manuscript is thicker than five sheets. Not only is the risk of tearing a printed sheet greater, but also the force necessary to achieve separation becomes too great for most people. At this time, the manuscript must be separated into smaller stacks, resulting in a time-consuming activity.
When using a machine having a cutting blade to cut through relatively large stacks of paper, the paper tends to twist and contort and becomes shredded at the edge being cut; therefore, when using a blade, extreme accurary must be exercised in order to cut the paper to the specific desired dimension.
It may be possible to use a blade to cut relatively large stacks of paper when a large amount of paper on each side of the cut is available; however, when a small amount of paper (approximately one-fourth inch) is to be trimmed off the paper sheets (as is done by the device of the present invention), a knife edge usually results in shredding of the larger side of the paper, resulting in a cumbersome and expensive operation.
The above-noted difficulties are overcome by the device of the present invention which uses the shearing edge of a shear plate to shear the computer paper along a perforated edge thereof.
Additionally, the shearing device of the present invention is safe to use in that no knife edges which may cut the operator's fingers are used. Also, a pressure plate is provided to retain the stack of papers in place for the shearing operation, thus keeping the operator's fingers away from the shearing mechanism.
SUMMARY OF THE INVENTION
In accordance with this invention, a computer paper guide edge trimming device is provided which will cleanly remove the guide edges of a manuscript having one or more pages. The removal is accomplished in a shearing action. The device includes a first frame having a support plate secured thereon for supporting the computer paper manuscript during the shearing operation. A shearing mechanism is supported by a second frame for vertical movement and includes a load member and a shear plate rigidly coupled together in spaced relation by coupling means. The load member and the coupling means are slidably supported in the second frame and coupled to the shear member for downward movement thereof responsive to a downward force being applied to the load member. The shear plate engages the paper for the shearing operation. A plurality of downwardly extending alignment guides on the shear plate seats the shear plate along the computer paper guide edge to assure a clean cut along the guide perforations of the paper. Return springs bias the load plate upwardly after the shearing operation. As a further feature, a tray is slidably carried in the first frame to collect the cuttings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a pictorial view of one embodiment of the computer paper guide edge shearer of the present invention.
FIG. 2 is a top view of the device of FIG. 1.
FIG. 3 is an elevational view of the device of FIG. 1.
FIG. 4 is a front view of the device of FIG. 1.
FIG. 5 is a sectional view taken along line 5--5 of FIG. 2.
FIG. 6 is an enlarged elevational sectional view of the shearing mechanism shown in FIG. 5. The view is enlarged to more clearly show the details of the shearing mechanism.
FIG. 7 is an elevational view, partially in section, of the load member and shear rods for connecting the load member to the shear plate of the device of the present invention. Alignment pin guides are shown extending downwardly from the shear plate.
FIG. 8 is an exploded pictorial view of the device of the present invention. The view is exploded to illustrate the manner in which the device is assembled.
FIG. 9 is a plan view of a sheet of computer paper which is sheared by the device of the present invention.
FIG. 10 is a pictorial view of another embodiment of the computer paper guide edge shearer of the present invention.
FIG. 11 is a top view of the device of FIG. 10.
FIG. 12 is an elevational view of the device of FIG. 10.
FIG. 13 is a front elevational view of the device of FIG. 10.
FIG. 14 is a sectional view taken along line 14--14 of FIG. 11.
FIG. 15 is an enlarged sectional view of the shearing mechanism shown in FIG. 14.
FIG. 16 is an elevational view, partially in section, of the load member and shear rods for connecting the load members to the shear plate. Alignment pin guides are shown extending downwardly from the shear plate.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
As seen in FIG. 1, the computer paper trimming device 10 of the present invention includes a first frame or formed base 12 having a bottom 14 provided with a pair of spaced, upwardly extending sides 16 having a support plate 18 secured thereto. Base plate 12 forms an opening 20 in which a cutting tray 22 is slidably carried. A second frame 24 is secured to the top of frame 12 and houses a shearing mechanism 26. Together, the base 12, including support plate 18, acts as a reaction mass during the shearing operation and as a support for the document being trimmed.
As more clearly seen in FIGS., 5, 6, and 8, frame 24 includes a face plate 28 and a back plate 30 disposed for secured relation. Face plate 28 includes upper and lower rearwardly extending surfaces 32 and 34 and sides 36 and 38, respectively. Back plate 30 includes upper and lower forwardly extending surfaces 40 and 42 and sides 44 and 46, respectively. An opening 35 is provided in surfaces 32 and 40. The sides and upper and lower surfaces of the face and back plates are disposed for mating relation responsive to assembly of the frame. Back plate 30 further includes a flanged section 48 for securing the frame assembly to base 12. Openings 47 are provided through surfaces 34 and 42.
A transverse opening 50 (FIG. 5) is formed between back plate 30 and the lower stop portion 52 thereof and the shearing edge 54 at the distal end of support plate 18 to allow the cuttings to fall into tray 22. Lower portion 52 of back plate 30 forms a stop against which the paper abuts when it is placed on plate 18 for a cutting operation.
FIG. 9 illustrates the computer paper 56 having guide edges 58 thereon and perforations 60 between the main section of computer paper 56 and guide edges 58. To remove the guide edges from the computer paper, the shearing mechanism 26 is disposed for vertical movement in frame 24 and for engaging the computer paper along perforations 60 to shear the guide edges at the perforations.
The shearing mechanism includes a main shear rod 62 (FIGS. 5, 6, and 8) which is coupled directly to and extends upwardly from a load plate 64 and out of the top of frame 24 through opening 35. A plurality of secondary shear rods 66 (four being shown in FIG. 7) extend downwardly from load plate 64. A shear plate 68 having a shearing edge 70 is secured to rods 66 at the ends thereof, and a plurality of guide pins 72 (four being shown) depend from plate 68. Shear plate 68 is positioned below surfaces 34 and 42 after assembly of plates 36 and 46 and shearing edge 70 is disposed in substantially parallel relation with shearing edge 54.
To apply the shearing force to the shear plate, a pull-down yoke 74 (FIGS. 1, 3, 5, and 7) is in engagement with main shear rod 62 for downward movement thereof. Yoke 74 includes an upper cap portion 76, an intermediate section 78, and a lower section 80. Cap portion 76 is in engagement with main shear rod 62, and lower section 80 includes a pair of inwardly extending lip portions 82.
To impart downward movement to the yoke, a lever 84 having a handle 86 thereon is pivotally secured at one end 88 to lower flanged portion 48 of frame 24. Lever 84 is provided with grooves 87 on opposite sides thereof in which lip portions 82 of yoke 74 are seated for slidable movement therein. The pull-down yoke allows for angular displacement at its pinned connection to the lever and its rounded capped mounting on the main shear rod at its upper end 76.
To retain the manuscript in secured relation for the shearing operation, a pressure flange 89 is mounted on frame 24 for movement up and down the frame on a track-roller assembly 90. A handle 92 is secured to the pressure flange. Pressure flange 89 includes a pair of upstanding sides 99 and 94 (FIG. 8) having a cut-out therein which forms the track 95 for the track-roller assembly 90. Rollers 96 are secured to the sides 36 and 38 of front plate 28 and extend into the track 95 to permit vertical movement of the pressure plate on the frame.
To return the shearing mechanism to its original position after a cutting operation, a plurality of return springs 98 are mounted on shearing mechanism 26 for biasing the shearing mechanism upwardly after a cutting operation. In one embodiment, return springs 98 are mounted around secondary shear rods 66, with the ends of the springs abutting the upper flanges 32 and 40 and lower flanges 34 and 42 of frame 24 (FIG. 6). If desired, return springs 98 may be positioned around a pair of rods 100 extending between load plate 64 and shear plate 68 as shown in phantom lines in FIG. 7.
In operation, the manuscript is mounted on plate 18 and accurately positioned by a guide strip 97. The manuscript is secured in place by pressure plate 89, with perforations substantially aligned along shearing edge 54 of plate 18. The operator then pushes down the lever 84, gripping it by the handle 86. The lever transmits the downward applied force to pull-down yoke 74, which in turn transmits the downward applied force to the main shear rod 62, load plate 64, secondary shear rods 66, and shear plate 68. The alignment guide pins 72 are seated in holes 100 of the computer paper and aligns the shearing edge of shear plate 68 along the perforations 66 of paper 56 (FIG. 9). All the transmitted force from the lever, less the force required to overcome return springs 98 and friction, is applied along the guide edge perforations 60, resulting in a clean separation of the computer paper guide edge at the perforation. The shearing mechanism is returned to the upstart position by return springs 98.
To prevent bottoming out of the pull-down yoke on the frame 24 of the shear mechanism, grommet 102 is positioned around main shear rod 62 on the top of frame 24 (FIG. 1). A secondary protection from bottoming out is provided by rubber grommets 104 mounted around the bottom of secondary shear rods 66 (FIG. 6) or rod 100 (FIG. 7).
Another embodiment of the present invention is shown in FIGS. 10-15 wherein like numerals refer to like parts. In this embodiment, the device is designed for shearing a smaller computer paper manuscript, that is, a manuscript comprised of fewer computer papers. The device includes a frame or base 12 having a bottom 14 with a pair of spaced, upwardly extending sides 16 and a support plate 18. Frame 12 forms an opening 20 in which a cutting tray 22 is slidably carried. A frame 24 is provided on the top of frame 12.
The shearing mechanism 26 includes a pair of load members 106 (FIGS. 14, 15, and 16), secondary shear rods 66, springs 98, shear plate 68, and guide pins 72, all assembled in the manner described above except for load members 106. In this embodiment, the shearing mechanism utilizes two secondary shear rods 66 which are engaged by a lever 108 through the load members 106 which are secured to and extend through openings 110 in the top of frame 24. Lever 108 is pivotally secured at its ends 112 to the top of frame 24 for upward and downward movement. The lever 108 includes a forwardly extending portion 114. In this embodiment, the frame includes a guide track 116 in which the shear rods 66 and springs 98 are movably mounted. Springs 98 are seated between the lower surface of load members 106 and a flanged portion 118 of the frame. Grommets 104 are positioned around the bottoms of the springs to prevent bottoming out.
The document is positioned by the use of guide strip 97. The lever is depressed by pushing down on portion 114 with the palm of the hand. The lever applies force directly to the load members 106 which transmit the force directly to the shear plate or strip 68 through members 106 and rods 66. Shear plate 68 transmits all of the force aplied to the lever, less the force required to overcome the springs 98 and friction, to the guide edge along the perforation line of the computer paper.
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A device for removing the perforated guide edges from computer paper by a shearing action. The computer paper is supported on a support plate of a first frame, with the line of perforations substantially aligned with a shearing edge provided on the distal end of the support plate. A shearing mechanism is slidably mounted for vertical movement in a second frame which is secured to the top of the first frame. The shearing mechanism includes a shear plate which is movable downward for engagement with the computer paper along the line of perforations where application of an additional force to the shear plate results in clearly shearing the perforated edges from the computer paper. Springs bias the shear plate upwardly for another shearing operation.
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FIELD OF THE INVENTION
[0001] The invention relates to a method of exfoliating clay into polyolefins. In particular, the invention relates to treating smectite clay with a Ziegler-Natta catalyst and polymerizing an olefin in the presence of an organoaluminum cocatalyst and the treated clay.
BACKGROUND OF THE INVENTION
[0002] Polyolefins are widely used because of their properties. Nevertheless, the applications for polyolefins could be extended if certain properties such as stiffness, strength and heat resistance were improved. While fillers can improve these properties, their use is limited because there does not exist a good method for dispersing the fillers and achieving the desired properties without concomitant loss of toughness. This is presumably due to the high levels of fillers needed and concomitant problems with dispersing the fillers in the polyolefin matrix. There is a need for an improved method to disperse clay filler into a polyolefin matrix.
[0003] U.S. Pat. Nos. 5,830,820; 5,906,955; 5,925,587; 6,034,187 and 6,110,858 provide supported catalysts for the polymerization of olefins. Low levels of these supported catalysts are then used to catalyze the polymerization of olefins and provide polyolefins with only low levels of the support material.
[0004] U.S. Pat. No. 6,252,020 provides for clay-filled compositions by bulk and suspension polymerization of vinyl monomers such as styrene in the presence of clay and catalysts such as peroxides. Neither the polymerization of olefins such as ethylene or propylene nor the use of transition metals as catalysts is described or suggested.
[0005] U.S. Pat. No. 4,473,672 describes a process for making polyolefin compositions with a variety of fillers such as graphite, carbon black, an aluminosilicate clay, mica, talc, vermiculite or glass fibers by pretreating the filler with an organic magnesium compound and then adding the resultant composition to a transition metal and subsequently initiating the polymerization with an organoaluminum compound.
[0006] U.S. Pat. No. 4,564,647 teaches a process for producing a filled polyethylene composition with a variety of fillers. The process is general with regard to fillers. Specifically mentioned are metals, metal oxides, metal carbonates, titanium dioxide, mica, glass beads, glass fibers, silica, alumina, silica aluminate and organic pigments among many others. The filler may take various forms, such as powder, granule, flake, foil, fiber and whisker. The catalyst component is a transition metal treated with either a magnesium or manganese compound or is a Group 4 cyclopentadienyl compound. Despite a very broad disclosure, there is no mention of clay and no indication of a method of exfoliating clay.
[0007] PCT Int. Appl. WO 01/30864 discloses a method for producing a nanocomposite polymer by use of an acid-treated, cation-exchanging layered silicate material. The reference teaches that the silicate material is acidified by contacting it with a Bronsted acid such as a mineral acid or an amine hydrochloride. This requires an extra step, which increases the cost and complexity of the process. We found that the acid can also a have deleterious effect on the yield of the polymerization process, particularly when a Ziegler-Natta catalyst is used instead of a metallocene complex.
[0008] It has been observed that the synthesis of polyolefin-silicate nanocomposites remains a synthetic challenge (Bergman et al., Chem. Commun . (1999) 2179). These workers attributed the difficulty to the sensitivity of the vast majority of olefin polymerization catalysts to Lewis bases and water. Therefore, they used late transition metal catalysts to attempt to polymerize ethylene in the presence of a synthetic fluorohectorite. The product formed was described as a rubbery polymer that was highly branched. Such a polymer is unsuitable for many applications because of difficulties in processing.
[0009] There is a need for a simple process for providing clay-filled compositions and, in particular, for polyolefin compositions containing exfoliated clay.
SUMMARY OF THE INVENTION
[0010] The invention is a process for incorporating clay into polyolefins. The process involves treating smectite clay with a hydrocarbon solution of a Ziegler-Natta catalyst and polymerizing the olefin in the presence of the treated clay and an organoaluminum cocatalyst.
[0011] This invention provides for a simple method to prepare polyolefin compositions that contain exfoliated clay platelets. The invention also includes clay-filled polyolefin compositions prepared by this method.
DETAILED DESCRIPTION OF THE INVENTION
[0012] The clays useful in the invention are non-acid-treated smectite clays. Smectite clays are well described in the literature (see Izumi, Y. et al., Zeolite. Clav and Heteropoly Acid in Organic Reactions , VCH Publishers Inc. (1992)). They are layered materials with exchangeable cations between the layers to compensate for the negative charge of the layers. Clays are classified according to their layer charge. Smectite clay minerals have cation exchange capacity in the range of 60-100 meq/100 g-clay.
[0013] Smectite clays can be synthesized from magnesium silicates. Synthetic smectite clays are available from ZEN-NOH UNICO America Corporation. More commonly, they are available from naturally occurring bentonite ore. Two common types of smectite clay are montmorillonite and hectorite. Montmorillonite is classified as magnesium aluminum silicate and hectorite as magnesium silicate. Montmorillonite is more available due to the vast naturally occurring deposits.
[0014] By “non-acid-treated,” we mean that the clay has not been treated with a Bronsted acid to exchange the cations with a proton. Bronsted acids are acids that can donate a proton. Examples include HCl, H 2 SO 4 , triethylammoniumchloride and N,N-diethylanilinium chloride.
[0015] The cations on the clay surface affect the organophilicity of the clay. If the cation is a metallic cation such as sodium or calcium, the clay is not very organophilic and will not dissolve in organic solvents such as toluene. These clays are useful in the invention. However, optionally, it may be preferred to use a more organophilic clay. If the cation is an organic cation such as an ammonium cation, then the clay becomes more organophilic. These are readily prepared by cation exchange of the sodium clay with an organic cation. Suitable organic cations include ammonium cations where the nitrogen has four non-hydrogen substituents, such as hexadecyloctadecyidimethyl ammonium, dimethyldioctadecyl ammonium, benzyl triethyl ammonium, methyltrioctylammonium and poly(oxypropylene)methyldiethyl ammonium. This increases the solubility and ease of dispersion in organic solvents. Dependent upon the amount of cation exchange and the particular organic cation used, the clay may be soluble in organic solvents such as toluene.
[0016] Optionally, the clay can be surface treated to react hydroxyl groups on the clay and to increase the organophilicity of the clay. By reacting the hydroxyl groups on the clay, the catalyst performance and hydrogen response is often improved. By “hydrogen response,” we mean the ability to incorporate hydrogen as a means of controlling polyolefin molecular weight. The surface treatment can be done with a silicon compound or with a monoalkyl metal compound. Preferably, the surface treatment is done with a silicon compound and preferably the silicon compound is an alkyl disilazane. Suitable alkyl disilazanes include hexaalkyl disilazanes having the formula R 1 3 SiNHSiR 1 3 where R 1 is a C 1 -C 20 hydrocarbyl. In particular, hexamethyidisilazane is preferred. Preferred monoalkyl metal compounds contain a single C 1 to C 8 alkyl group, as in ethyl aluminum dichloride, isobutyl aluminum dichloride or methyl magnesium chloride.
[0017] Optionally, the clay is dried. When the clay has an organic cation or has been treated with an organosilicon compound, it is less hydrophilic and has a tendency to retain less water. For these clays, the drying step is less important. When the clay has a metal cation, it is more hydrophilic and therefore it is preferable to dry the clay. If the clay has a metal cation, preferably the drying is done at a temperature of from about 50° C. to about 600° C., more preferably from about 100° C. to about 400° C. If the clay has an organic cation or has been treated with an organosilicon compound, preferably the drying is done at a temperature of from about 50° C. to about 250° C., more preferably from about 50° C. to about 150° C. All clays are preferably dried with vacuum or with a stream of dry nitrogen.
[0018] The clay is treated with a Ziegler-Natta catalyst. By “Ziegler-Natta catalyst,” we mean a transition metal compound that incorporates a Group 4-8 transition metal, preferably a Group 4-6 transition metal, and one or more ligands that satisfy the valence of the metal. The ligands are preferably halide, alkoxy, hydroxy, oxo, alkyl, and combinations thereof. Preferred Ziegler-Natta catalysts incorporate Ti, V, or Cr, most preferably Ti. Preferred Ziegler-Natta catalysts also have high thermal stability. They include titanium halides, titanium alkoxides, vanadium halides, and mixtures thereof, especially, TiCl 3 , TiCl 4 , mixtures of VOCl 3 with TiCl 4 , and mixtures of VCl 4 with TiCl 4 . Suitable Ziegler-Natta catalysts also include the transition metal compound admixed with various metal halides such as TiCl 3 with magnesium chloride or mixtures of VCl 4 and TiCl 4 with aluminum chloride. Other suitable Ziegler-Natta catalysts appear in U.S. Pat. No. 4,483,938, the teachings of which are incorporated herein by reference, and in Eur. Pat. 222,504.
[0019] The catalyst is dispersed, dissolved, or suspended in a compatible organic solvent such as heptane or toluene and added to the clay. The amount of organic solvent can be chosen so that the catalyst solution is just enough to wet the surface of the clay or more solvent can be used to create a slurry or solution of the clay. Optionally, the clay can be predispersed in the organic solvent and then the catalyst or a catalyst solution added. Dependent upon the organophilicity of the clay and the particular solvent chosen, the clay may appear as a damp solid or if sufficiently organophilic may appear to dissolve in the solvent.
[0020] When the clay is insoluble, the clay is preferably mixed to ensure good distribution. A convenient way of mixing is to put the treated clay in a bottle on a roll mill.
[0021] When a monoalkyl metal is used as a surface treatment, it is preferred to thoroughly mix the clay in an organic solvent prior to adding the monoalkyl metal and the catalyst. This can be done by stirring the clay in the solvent prior to the addition of the monoalkyl metal and the catalyst. The period of time necessary for thorough mixing will vary based upon the shear rate of the stirring.
[0022] The treated clay may be used as is with solvent present or optionally the solvent may be removed. If the clay is dissolved in the organic solvent, it is preferable to use the solution as is in the subsequent polymerization. If the clay is insoluble, it is preferable to remove the solvent with vacuum to form a more easily handled solid.
[0023] The organoaluminum cocatalyst is an alkyl aluminum or an alkyl aluminum halide. Preferred alkyl aluminums include trialkyl or triaryl aluminum compounds, which preferably have the formula AlR 5 R 6 R 7 where R 5 , R 6 and R 7 denote the same or different C 1 -C 20 hydrocarbyl. Particularly preferred alkyl aluminums are trimethylaluminum, triethylaluminum, tripropylaluminum, and triisobutylaluminum. Suitable alkyl aluminum halides include dialkyl aluminum halide and alkyl aluminum dihalide compounds, which preferably have the formula AlR 5 R 6 X or AlR 5 X 2 where X is Cl, Br, or I.
[0024] Exemplary alkyl aluminum halides are dimethylaluminum chloride, methylaluminum dichloride, diethylaluminum chloride, ethylaluminum dichloride, diisobutylaluminum chloride, isobutylaluminum dichloride, methylaluminum sesquichloride, ethylaluminum sesquichloride, and isobutylaluminum sesquichloride.
[0025] Optionally, silicon compounds may be used in the polymerization. These can offer certain improvements such as an improved sensitivity to hydrogen as a means of controlling molecular weight. Preferred silicon compounds are dialkyl dialkoxysilanes which have the formula R 1 R 2 Si(OR 3 )(OR 4 ) where R 1 , R 2 , R 3 , and R 4 denote the same or different C 1 -C 20 hydrocarbyl. Exemplary dialkyl dialkoxysilanes are cyclohexyl-methyldimethoxysilane, dimethyldimethoxysilane, dimethyldiethoxysilane and dicyclopentyidimethoxysilane.
[0026] Suitable olefins for the polymerization are C 2 -C 20 α-olefins, such as ethylene, propylene, 1-butene, 1-hexene, 1-octene and mixtures thereof. Preferred olefins are ethylene, propylene and mixtures thereof with α-olefins such as 1-butene, 1-hexene and 1-octene.
[0027] The treated clays can be used in a variety of well-known olefin-polymerization processes, including gas, high pressure liquid, slurry, solution, or suspension-phase techniques and combinations of these. The pressures used typically range from about 15 psig to about 15,000 psig. Polymerization temperatures range from about −100° C. to about 300° C., more preferably from about 20° C. to about 200° C., and most preferably from about 60° C. to about 150° C.
[0028] The clay imparts improved properties such as stiffness and barrier properties including a decreased rate of moisture vapor transmission. In the process of the invention, the clay becomes exfoliated, thereby improving the dispersion of the clay and enabling the improved properties without severe loss of other properties such as impact or toughness. Smectite clay has a multilayer structure. By “exfoliation,” we mean breaking the layered structure to improve the dispersion of the clay in the polyolefin. By analogy with a deck of playing cards, non-exfoliated playing cards would be present as groups of 52 stacked playing cards, while exfoliated playing cards would be more dispersed and principally present in groups of substantially fewer than 52 with some cards even being dispersed as single cards. The greater the exfoliation, the better the dispersion and the more effective a certain level of clay at improving the desired properties.
[0029] Dependent upon the application, the level of clay in the polymer can be varied. Preferably, the clay will be present at about 0.1% to about 15% by weight. More preferably, the clay will be present at about 1% to about 10% by weight, and most preferably at about 4% to about 6% by weight.
[0030] The following examples merely illustrate the invention. Those skilled in the art will recognize many variations that are within the spirit of the invention and scope of the claims.
EXAMPLE 1
Preparation of Treated Clay
[0031] Ten grams of montmorillonite clay with sodium cation was dried at 150° C. in a nitrogen stream and then treated with 4 mL of a solution of 0.8 mL of TiCl 4 in 100 mL of heptane. The treated clay was rolled for two hours and then vacuum dried.
EXAMPLE 2
Ethylene Polymerization
[0032] A polymerization reactor was pressure purged with dry nitrogen three times at 100° C. After completely venting the reactor, 1.5 mL of a 1.6 M solution of triethylaluminum and 800 mL of isobutane were charged to the reactor. To the reactor was added 0.74 grams of the treated clay from Example 1 and 200 mL of isobutane. Hydrogen (100 delta psig on a 300-mL vessel) was added to the reactor. The reactor was pressurized to 550 psig with ethylene and heated to 80° C. The pressure was maintained at 550 psig by addition of ethylene and the polymerization allowed to continue for 2 hours to obtain 4.8 grams of polymer composite containing 15% clay. X-ray diffractograms of the polymer powder and the absence of fines indicate that the clay was finely dispersed in the polymer matrix.
EXAMPLE 3
Preparation of Treated Clay
[0033] Ten grams of montmorillonite clay with sodium was dried at 300° C. in a nitrogen stream and then treated with 8 mL of a solution of 0.8 mL of TiCl 4 in 100 mL of heptane. The treated clay was rolled for two hours and then vacuum dried.
EXAMPLE 4
Ethylene Polymerization
[0034] In similar fashion as in Example 2, a polymerization reactor was charged with 1.5 mL of a 1.6 M solution of triethylaluminum, 1.0 mL of 0.1 M cyclohexylmethyldimethoxysilane and 800 mL of isobutane. To the reactor was added 0.74 grams of the treated clay from Example 3 and 200 mL of ethylene. Hydrogen (100 delta psig on a 300 mL vessel) was added to the reactor. The reactor was heated to 80° C. and the polymerization allowed to continue for 2 hours to obtain 23.8 grams of polymer composite containing 3.1% clay. X-ray diffractograms of the polymer powder and the absence of fines indicate that the clay was finely dispersed in the polymer matrix.
EXAMPLE 5
Preparation of Treated Clay
[0035] In a dry-box, 2.0 grams of Claytone HY (montmorillonite clay with ammonium cation from Southern Clay Products Inc., Gonzales, Tex.) was placed in a bottle with a stir-bar. Dry toluene (40.0 mL) was added and the slurry was mixed with a magnetic stir plate until all of the clay solids appeared to dissolve (about one hour). 1,1,1,3,3,3-hexamethyldisilazane (HMDS) was added at the loading of 0.14 grams per gram of Claytone. TiCl 4 was added as a 1.0 M heptane solution at the loading of 1.00 millimole Ti per gram of clay.
EXAMPLE 6
Ethylene Polymerization
[0036] A one-gallon autoclave reactor was pressure purged with dry nitrogen three times at 100° C. After completely venting the reactor, hydrogen was added as a 100-psi pressure drop from a 300-mL vessel. 1100 mL of isobutane was added to the reactor and the stirring was started. Triethyl aluminum (1.92 mL of 1.56 M solution in heptane) was added to the reactor with a flush of 200 mL of isobutane. Ethylene was added to the reactor to reach 410 psi, and 21.0 mL of catalyst solution from Example 5 (1.00 grams of clay) was added to the reactor with a flush of 200 mL of isobutane. Ethylene was fed into the reactor to maintain 450 psi. After one hour the reactor was vented and the polymer was collected and dried to yield 10.15 grams of polymer. A sample of this polymer was pressed into a plaque and cryogenically sliced. Transmission Electron Microscopy (TEM) showed the clay to be exfoliated.
EXAMPLE 7
Treated Clay
[0037] In a dry-box, 2.0 grams of Claytone HY was placed in a bottle with a stir-bar. Dry toluene (40.0 mL) was added and the slurry was mixed with a magnetic stir plate until all of the clay solids appeared to dissolve (about one hour). TiCl 4 was added as a 1.0 M heptane solution at the loading of 1.00 millimole Ti per gram of clay.
EXAMPLE 8
Ethylene Polymerization
[0038] The polymerization procedure of Example 6 was repeated using 21.0 mL of catalyst solution from Example 7 (1.00 grams of clay). The polymerization was conducted for two hours to yield 26.18 grams of polymer. TEM showed exfoliation of the clay.
EXAMPLE 9
Treated Clay
[0039] In a dry-box, 2.0 grams of Claytone HY was placed in a bottle with a stir-bar. Dry toluene (40.0 mL) was added and the slurry was mixed with a magnetic stir plate for about an hour until all of the clay solids appeared to dissolve. Ethylaluminumdichloride was added at the loading of 1.00 millimole Al per gram of Claytone. TiCl 4 was added as a 1.0 M heptane solution at the loading of 1.00 millimole Ti per gram of clay.
EXAMPLE 10
Ethylene Polymerization
[0040] The polymerization procedure of Example 6 was repeated using 21.6 mL of catalyst solution from Example 9 (1.00 grams of clay). The polymerization was conducted for twenty-two minutes to yield 55.38 grams of polymer. TEM showed little to no exfoliation of the clay.
EXAMPLE 11
Treated Clay
[0041] The conditions of Example 9 were repeated on a larger scale and using a longer mixing time. Fifteen grams of Claytone HY were placed in a three-neck flask fitted with an overhead paddle stirrer. The flask was connected to an oil bubbler and the flask was purged with nitrogen for three days. Dry toluene (400 mL) was added and the clay was mixed into the toluene until the clay solids appeared to dissolve. After four hours of mixing, ethylaluminumdichloride was added at the loading of 1.00 millimole Al per gram of clay. TiCl 4 was added as a 1.0 M heptane solution at the loading of 1.00 millimole Ti per gram of clay.
EXAMPLE 12
Ethylene Polymerization
[0042] The polymerization procedure of Example 6 was repeated using 7.0 mL of 1.56 M triethylaluminum and all of catalyst solution from Example 11 (15.0 grams of clay). The polymerization was conducted for seven hours to yield 93.08 grams of polymer. TEM showed some exfoliation of the clay.
EXAMPLE 13
Treated Clay
[0043] In a dry-box, 2.0 grams of synthetic smectite clay containing methyltrioctylammonium cation (Lucentite STN available from Co-Op Chemical Co., LTD. Tokyo, Japan) was placed in a bottle with a stir-bar. Dry toluene (60.0 mL) was added and the slurry was mixed for 48 hours with a magnetic stir plate. 1,1,1,3,3,3-hexamethyldisilazane (HMDS) was added at the loading of 0.14 grams per gram of clay. TiCl 4 was added as a 1.0 M heptane solution at the loading of 1.00 millimole Ti per gram of clay.
EXAMPLE 14
Ethylene Polymerization
[0044] The polymerization procedure of Example 6 was repeated using 31.0 mL of catalyst solution from Example 13 (1.0 grams of clay). The polymerization was conducted for 171 minutes to yield 35.52 grams of polymer. TEM showed exfoliation of the clay.
EXAMPLE 15
Treated Clay
[0045] In a dry-box, 2.0 grams of Lucentite STN clay was placed in a bottle with a stir-bar. Dry toluene (60.0 mL) was added and the slurry was mixed for 48 hours with a magnetic stir plate. TiCl 4 was added as a 1.0 M heptane solution at the loading of 1.00 millimole Ti per gram of clay.
EXAMPLE 16
Ethylene Polymerization
[0046] The polymerization procedure of Example 6 was repeated using 31.0 mL of catalyst solution from Example 15 (1.0 grams of clay). The polymerization was conducted for 35 minutes to yield 34.76 grams of polymer. TEM showed exfoliation of the clay.
EXAMPLE 17
Treated Clay
[0047] In a dry-box, 2.0 grams of Lucentite STN clay was placed in a bottle with a stir-bar. Dry toluene (60.0 mL) was added and the slurry was mixed for 48 hours with a magnetic stir plate. Ethylaluminumdichloride was added at the loading of 1.00 millimole Al per gram of clay. TiCl 4 was added as a 1.0 M heptane solution at the loading of 1.00 millimole Ti per gram of clay.
EXAMPLE 18
Ethylene Polymerization
[0048] The polymerization procedure of Example 6 was repeated using 31.0 mL of catalyst solution from Example 17 (1.0 grams of clay). The polymerization was conducted for five hours to yield 9.52 grams of polymer. TEM showed exfoliation of the clay. (Compared to previous preparations with shorter mixing times, this sample shows more exfoliation.)
EXAMPLE 19
Treated Clay
[0049] The treatment procedure of Example 15 was repeated on a larger scale and using a lower loading of TiCl 4 . Twenty-five grams of Lucentite STN were dissolved in 600 mL of dry toluene and were stirred for 48 hours using a magnetic stir bar. Eighty mL of this clay solution was treated with 2.0 mL of a 1.00 M TiCl 4 solution for a loading of 0.60 millimole Ti per gram of clay.
EXAMPLE 20
Ethylene Polymerization
[0050] The polymerization procedure of Example 6 described above was repeated using 3.84 mL of 1.56 M triethylaluminum and all of catalyst solution (3.33 grams of clay) of Example 19. The polymerization was conducted for one hour to yield 70.33 grams of polymer. TEM showed exfoliation of the clay.
COMPARATIVE EXAMPLES 21-26
[0051] These examples show the deleterious impact of pretreating the clay with an acid prior to combining the clay with a Ziegler-Natta catalyst.
COMPARATIVE EXAMPLE 21
Clay Pretreated with Acid
[0052] Ten grams of montmorillonite clay with sodium cation (as used in Example 1) was placed in a 250-mL flask and 100 mL of a 1.0 M HCl solution was added. After stirring for one hour at room temperature, the contents of the flask were filtered, reslurried in 20 to 25 mL of a 0.5 M solution of HCl and filtered again. The clay was slurried in 0.5 M HCl a second time, filtered and then washed twice with 20-30 mL of deionized water. Water was removed from the clay by drying in a flowing nitrogen atmosphere overnight at a 150° C. The resultant acid-treated clay was then treated as in Example 1 with 4 mL of a solution of 0.8 mL of TiCl 4 in 100 mL of heptane. The treated clay was rolled for two hours and then vacuum dried.
COMPARATIVE EXAMPLE 22
Polymerization Using Clay Pretreated with Acid
[0053] The polymerization process of Example 2 was generally followed, except that the clay pretreated with acid from Comparative Example 21 was used in place of the clay from Example 1. No measurable polymer was obtained.
COMPARATIVE EXAMPLE 23
Polymerization Using Clay Pretreated with Acid
[0054] The polymerization process of Example 22 was generally followed, except that 1.5 mL of 0.1 M cyclohexylmethyidimethoxysilane was also added to the polymerization reaction. Again, no measurable polymer was obtained.
COMPARATIVE EXAMPLE 24
Clay Pretreated with Acid
[0055] The procedure of Comparative Example 21 was repeated except that sulfuric acid was used in place of hydrochloric acid.
COMPARATIVE EXAMPLE 25
Polymerization Using Clay Pretreated with Acid
[0056] The polymerization process of Example 2 was generally followed, except that the clay pretreated with acid from Comparative Example 24 was used in place of the clay from Example 1. No measurable polymer was obtained.
COMPARATIVE EXAMPLE 26
Polymerization Using Clay Pretreated with Acid
[0057] The polymerization process of Example 25 was generally followed, except that 1.5 mL of 0.1 M cyclohexylmethyidimethoxysilane was also added to the polymerization reaction. Again, no measurable polymer was obtained.
[0058] The preceding examples are meant only as illustrations. The following claims define the invention.
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A clay-filled polyolefin composition and process for making it are disclosed. The process involves treatment of a non-acid-treated smectite clay with a Ziegler-Natta catalyst in the presence of a hydrocarbon and subsequent polymerization of an olefin in the presence of the treated clay and an organoaluminum cocatalyst. Results indicate that filled compositions produced by this process contain exfoliated clay.
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CROSS REFERENCE TO OTHER PATENT APPLICATION
This is a division of applicant's U.S. patent application Ser. No. 10/291,220, filed Nov. 7, 2002 now U.S. Pat. No. 6,910,232.
FIELD OF THE INVENTION
A closure for a fast-discharge, small volume toilet tank flush system.
BACKGROUND OF THE INVENTION
The advent of indoor plumbing and flush toilets, and decades of use and gradual improvement started with simple plug and flapper tank valves that were levered open, to remain open while a full tank emptied, and a ballcock valve which was open whenever the water level in the tank was below a storage level. While the ballcock valve was open, part of its total flow was diverted to refill the bowl at the same time the tank was being refilled. That procedure remains the same to this day for systems which use stored water to flush the toilet.
Nearly every year there has been an improvement in some part of the conventional systems. Tank-valves have evolved into many forms of pivoted plates and floats. Ballcock valves have evolved from simple floats on a lever that pressed on a valve plate, to differential pressure actuated valves that require movement by the float of only a pin to open or close a very small bleed orifice for their control.
The floats themselves have evolved from copper spheres to foam bodies, to inverted cups of various shapes. Some were on lever arms. Others embraced an upright post. The ultimate limit on the water level was overflow into the bowl, through the same passage as was provided for the bowl refill.
The industry was greatly assisted by the development of plastic materials of construction. These materials need to resist pressure-for a long time and also resist chemicals which would show up in the water from time to time. They enable the production of shapes and parts which could not economically be produced by metal casting and machinery processes.
As a disadvantage these new shapes and materials also enabled the production of sophisticated products in low-cost countries, to the disadvantage of domestic production. As a consequence, there has been significant incentive to invent and market even more sophisticated products hopefully made as inexpensively and perhaps better in the United States.
If it were merely a matter of making a same thing cheaper, there would be no merit in making changes. However, as the availability of these products (in part because of their low cost) improved, and along with population growth, the effluent from their systems also has increased to the extent that sewage systems designed for lesser loads are being overwhelmed.
The response to this problem has been to redefine how much water a toilet is permitted to discharge per flush. Low volume flush systems are now routinely required. Whereas in the past a large flush which depended on a sustained and relatively slow flow of water was the norm, now a much lesser amount of water is permitted for each flush cycle to do the same job. In order for this to happen a quick, high rate of flow of a low total volume of water is needed to wash away the waste.
Systems using direct flow from a pressure valve can often attend to this, but systems favored in less commercial places such as residences tend to use water tanks. It is an object of this invention to provide a water tank system with the capability of a sufficient and very rapid discharge of stored water.
As it happens, such improved systems involve related problems of their own. While each problem is relatively small, together they add up to a significant challenge. For example, to discharge a large volume quickly requires a large area discharge port and an equally large closure for it. The force required to lift the closure off of the discharge port valve seat is proportionally increased to the extent that it is difficult for an average person to operate.
Here, the ultimate problem is in the inefficiency of the trip lever used to lift the valve. The lever is inherently inefficient because the outside handle or knob available to the user is short, and the inside lever it turns is long. In itself it magnifies the force necessary to turn the handle, thereby compounding the problem.
It is an object of this invention to reduce the force needed to open the tank valve. In fact, without the improvements of this invention it may take as much as 10 pounds force on a 3 inch handle to open the valve. With the improvements of this invention, the required force to open a 3 inch diameter plug valve is only about 3 pounds. 10 pounds is too much force for many people, while 3 pounds is tolerable by almost everybody.
Another problem arises from the-variations of dimensions of installed systems. To compensate for these, trip levers have often lifted a valve closure with flexible links such as chains or cables. This invention provides a lifting lever with a profile suitable for a wide range of dimensions for actuating the valve closure, and which does not require a flexible link. This is a savings in cost and, as will be seen, is also an improvement in function.
Conventional tank valves often rely on a pivoted valve closure which is costly and subject to later malfunction. It is an object of this invention to provide a single piece valve closure of surprisingly simple design—a unibody with a distinctive exterior, a passage entirely through the closure, with a lower guide and an upper end receptive of refill water, and which when open is a freely floating body without restraint to the tank structure. It can readily be opened by a tilting, rather than an axial movement, requiring less physical force to open the valve.
BRIEF DESCRIPTION OF THE INVENTION
This invention is adapted for use in a tank having a bottom and a peripheral sidewall to receive, store and discharge water to flush a toilet. A discharge port is formed through the bottom. A tank valve having a tank valve seal is fitted in the discharge port. This seal is horizontally disposed.
A tank valve closure is a hollow circularly-shaped body having an upper opening and a lower opening. It includes a reduced dimension lower guide loosely to guide the closure in the discharge port. A flared-out portion above the guide has a lower valving surface disposed and arranged to rest upon the valve seat to close it. A reduced-diameter neck rises from the flared-out portion, and carries an engagement means to be engaged by a lifting lever, eccentrically from the central axis of the closure.
A ballcock valve receives water which on demand supplies the tank with stored water and supplies the bowl with refill water. The ballcock valve is responsive to the water level in the tank. It is closed when the tank is filled to a desired storage level and open when the tank is to be refilled. Its bowl refill tube discharges into the neck of the tank valve closure.
Low profile installations frequently require that all of the mechanisms be in the tank, located above its bottom. For such installations, an optional riser may be fitted into the tank's discharge port and the valve seat is placed well above the bottom of the tank. This enables all parts of the system to be placed in the tank above the bottom, or within a spud just beneath the bottom.
The system is actuated by turning a handle which is journaled to the sidewall. When turned it rotates a lever linked to the closure. According to a preferred but optional feature of this invention, the lever is connected to the closure laterally off of its axis so that when it lifts the closure it first tilts it with little effort, which promptly reduces the differential pressure across the closure and thereby reduces the ultimate force needed to open the valve by further lifting the closure.
According to a preferred but optional feature of the invention the upper edge of the lifting lever is serrated along part of its length so that it can engage the closure reliably over a wide range of dimensions, and with the closure in a wide range of angular portions around its axis. This enables considerable freedom of movement and adaptability to dimensions of different installations.
As another preferred but optional feature of the invention, the handle is attached to the lift lever by a joinder which allows for universal adjustment of the angle between the two.
The above and other features of this invention will be fully understood from the following detailed description and the accompanying drawings, in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevation of a toilet tank installation, partly in cutaway cross-section, showing the invention;
FIGS. 2 and 2A are cross-sections taken at line 2 — 2 in FIG. 1 , showing the tank valve closed and first being opened, respectively;
FIG. 3 is an exploded schematic view showing the lift lever and tank valve;
FIG. 4 is an enlarged fragment of the lift lever;
FIG. 5 is an axial cross-section of the tank valve; and
FIG. 6 is a side elevation-similar to FIG. 1 , showing the system open to flow.
DETAILED DESCRIPTION OF THE INVENTION
A toilet tank 10 has a bottom 11 , a peripheral sidewall 12 and an open top 12 a , which in use is covered by a removable lid (not shown). A central water discharge aperture 13 and an inlet aperture 14 are formed in the bottom of the tank.
A ballcock valve 20 is fitted in the inlet aperture by means of a typical spud 21 and nut 22 . Any type of ballcock valve is suitable that provides the necessary functions of opening to flow when the water level 23 in the tank is below a predetermined elevation. At that time the valve workings 25 will supply water to the tank via a discharge tube 26 , and to the toilet bowl through a bowl refill tube 27 .
The illustrated valve is fully described in Antunez U.S. Pat. No. 6,244,292 which is incorporated herein in its entirety and made a part hereof by reference for its showing of the construction and operation of the valve workings.
A float 28 is wrapped partially around riser 29 . Water under pressure is conveyed through the riser to the valve workings. The float follows the water level to actuate the workings via a linkage 30 .
A tank valve 31 is fitted in water discharge aperture 13 . A circular riser 32 is fitted to the tank bottom and held to it by a nut 33 . The riser has a height H for a reason to be described below.
A tank valve seat 35 is formed atop riser 32 . If the height of the riser were not necessary, the seat could be formed closer to the bottom.
A flexible washer 36 can be provided loosely, or can instead be attached to a closure 40 or to the valve seat so as in effect to form a valve seat, as preferred. A centering guide 41 comprises a group of axially and inwardly extending blades 42 . Their innermost edges form a centering path. Guide 41 is fixed in the riser below the seat.
Closure 40 is a hollow structure with a substantially constant wall thickness throughout. It has a dimension of axial length with an upper neck 43 , a bottom guide 44 , and an enlargement 45 between them. Although it is not immediately apparent, this closure will float when its upper end and lower end are vented at the same time and the closure is not seated on the seal.
As best seen in FIG. 5 , the neck, guide, and enlargement forming a continuous passage open from the upper end of the closure to its lower end.
The enlargement has a lower surface 46 which can abut and close on the seal (or washer). When it is seated, the lower end will be exposed to atmosphere in the outlet port (which leads to the toilet bowl), and the upper end will be above the water line and thereby also exposed to atmosphere. At this time there is a substantial net downward force on the closure which will keep it closed.
Here it will be observed that the bowl refill line discharges into the upper end of the closure, and water from it will flow directly through the closure to the bowl to refill it.
The closure is conveniently made by a blow-molding process. Ears 50 , 51 are formed on the outside of the neck wall, to one side of the central axis 52 of the closure. Alternatively, the ears may be formed on a separate collar to be fitted around the neck. Actuation of the system begins with a full tank and the closure against the tank valve seal to close the tank valve.
A lift lever 60 has a free end 61 , and a pivot end 62 . The pivot end is attached to flush handle 63 through the peripheral wall, to both of which they are mounted. In order that the lever and handle can be adjusted relative to one another, the lever makes a press fit in a socket (not shown) in the lever. If desired, axial striations and grooves in the handle can be provide for a greater range of angular relationship between them. Alternatively the lever and socket may have smooth enlarging surface to permit universal adjustments between them.
A plurality of holes 64 are provided near the free end of the lever. A circlet 65 can be fitted into one of them after the free end has been inserted through one of the ears of the closure. The circlet will prevent the lever from separating from the closure. The plurality of holes 64 provides for different distances between the location of the ears and the pivot of the handle.
A plurality of serrations 66 are formed along the top of the lever where contact is to be made with the ears. In the course of use, the closure may turn around its axis for a few degrees, and also the distance from the ears to the handle may differ among installations. There will always be a serration in which the upper reach of an ear will lodge.
The advantage of the off-center lift on the closure will be appreciated from an examination of FIGS. 2 and 2A . In FIG. 2 , the closure is firmly seated on the seat, and is held by the pressure derived from the differential pressure on the top surface 70 of the closure which is exposed to water pressure, and the lower surface 46 which is exposed to atmosphere. This is a net heavy load to be lifted by an inefficient lever.
FIG. 2A shows the closure being lifted by the ear. Its first effect is to tilt, rather than axially to lift, the closure. This requires a markedly lesser force than a straight lift. “Cracking” the abutment as shown in FIG. 2A immediately releases the downward net force, and the closure can easily be raised the rest of the way.
After this is done, the float remains buoyant so long as water is flowing through the outlet port so as to expose the lower surface to atmospheric pressure. When flow stops, the closure will drop and close the outlet, and the net closure force is again exerted. The ballcock valve while still open will provide water directly to the tank and, through the closure to the bowl.
Attention is called to the stabilizing effect of the bottom guide 44 and the group of spaced apart blades 42 . While permitting some tilting and sideward movement of the closure, they still keep the closure in line for operation.
In the embodiment shown in the drawings, there will always be water in the tank up to the level of the top of riser 32 . This enables the mechanism to be contained entirely inside the tank and that portion of the riser which must extend below the bottom of the tank in any arrangement.
It will be noted that many of the advantages of this invention can be obtained by connecting the lever to the ears with a chain. This is another “operative engagement” of the lever and the closure. Therefore the use of a direct connection of the lever and the ears is not a limitation on the invention, but instead is a considerable advantage
This invention is not to be limited by the embodiment shown in the drawings and described in the description, which is given by way of example and not of limitation, but only in accordance with the scope of the appended claims.
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A hollow, open-ended closure for the tank valve which enables a large cross-section area of discharge port to be used, and which can pass bowl-refill water during the flushing sequence. It is especially useful as part of a valve in which it can be tilted to open the tank valve with reduced physical effort.
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CROSS REFERENCE TO RELATED APPLICATION
This application claims the benefit of priority to Provisional Application 60/280,586 filed on Mar. 30, 2001.
FIELD OF THE INVENTION
The invention relates to twisting bulk continuous fiber or synthetic yarn to create torque in the yarn to give a highly textured effect to rugs and carpets created from the yarn.
BACKGROUND OF THE INVENTION
The following disclosures may be relevant to various aspects of the present invention and may be briefly summarized as follows:
U.S. Pat. No. 3,950,932 to Durling discloses a multicolored, cabled, stuffer box crimped yarn containing filaments of respectively at least two non-contrasting colors and a contrasting color, the filaments of the at least two non-contrasting colors imparting a heather appearance to the yarn and the filaments of the contrasting color imparting color accents to the yarn, is produced by cabling together at least three stuffer box crimped multifilament ends, each of the three ends containing filaments of at least two non-contrasting colors and one of the three ends containing filaments of the contrasting color in a discrete grouping and in a proportion greater than the proportion in the same end of filaments of any individual non-contrasting color and, prior to being twisted together with the other ends, containing a twist in the same sense as the twist to be imparted in the step of twisting together all the ends and, after being twisted together with the other ends, preferably containing a twist of a higher degree than the twist contained in the other ends.
U.S. Pat. No. 4,206,589 to Markey et al. discloses a method of forming a self-twisted fibrous structure comprises twisting two strand of similar count such that each has repeated along its length alternating zones of opposite twist, converging the strands at a convergence point such that they partly untwist around one another to form a self-twisted structure and acting on the strands at or downstream of the convergence point by applying further alternating zones of opposite twist so as to modify the strand to ply twist ratio of the structure. The further twist is applied at a point not greater than one-half cycle length from the first twist point and at a phase difference 20° to 60° following.
Presently cotton flooring articles are commonly used for flooring articles such as bath carpets and rugs and other residential uses. Flooring articles made from cotton have a tendency to mat, are not readily dyeable to a desired shade, particularly for dark colors, difficult to clean and have a tendency to develop pills or fuzziness from use. These problems are further accented for textured flooring articles.
It is desirable to have a carpet or flooring article that has a textured design without the above indicated problems. It is also desirable to have a flooring article that requires no heat setting to maintain the textured design of the flooring article. It is further desirable to have a textured loop styling of synthetic yarns for bath and residential end uses.
SUMMARY OF THE INVENTION
Briefly stated, and in accordance with one aspect of the present invention, there is provided a method for forming a textured loop style flooring article comprising: twisting a first yarn end with a second yarn end using a first twist forming a third yarn end; cabling two third yarn ends in a same direction as the first twist of the first yarn end and the second yarn end using a cable twist forming a final yarn, wherein a differential twist occurs between the first twist and the cable twist imparting a torque to the final yarn creating a textured effect in the final yarn; and tufting the final yarn in a loop pile construction of a flooring article having the textured effect.
Pursuant to another aspect of the present invention, there is provided a method for forming a textured loop style flooring article comprising: twisting at least one feed yarn end with a second feed yarn end using a first twist forming a third yarn end; twisting a fourth feed yarn end with a fifth feed yarn end using the first twist forming a sixth yarn end; cabling the third yarn end and the sixth yarn end together in a same direction as the twisting of the yarn ends in forming the third yarn end and the sixth yarn end using a cable twist forming a final yarn, wherein a differential twist occurs between the first twist and the cable twist imparting a torque to the final yarn creating a textured effect in the final yarn; and tufting the final yarn in a loop pile construction of a flooring article having the textured effect.
Pursuant to another aspect of the present invention, there is provided a flooring article having a textured effect comprising: at least two first yarn ends twisted together with a first twist forming a third yarn end, said third yard end and another at least two-ply yarn end twisted together with a cable twist in the same direction as the first twist creating a final yarn; a differential twist occurring between the first twist and the cable twist imparts a torque to said final yarn for a textured effect; and said final yarn being tufted into a loop pile construction.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be more fully understood from the following detailed description, taken in connection with the accompanying drawing, in which:
FIG. 1 is a schematic illustration of the process described in Example 1.
FIG. 2 is a schematic illustration of the process described in Example 2.
FIG. 3 is a photographic illustration of a textured effect.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
The following definitions are provided as reference for interpretation of these terms used in the context of this specification and the accompanying claims.
1. Cable: to twist together two or more folded yarns.
2. Cabled yarn: is two or more folded yarns twisted together in one or more operations. Combinations of single yarn(s) may be described as cabled yarns, e.g. a single yarn twisted together with two folded yarns to build yarn size and impart texture to the resulting yarn.
3. Conventional Twister: A system of producing a folded yarn by twisting together two or more single yarns simultaneously.
4. Dpf: denier per filament.
5. End: An individual strand or filament for twisting.
6. Folded yarn or Plied yarn: A yarn in which two or more single yarns are twisted together in one operation, e.g., two-folded yarn, three-fold yarn, etc. (In some sections of the textile industry these yarns are sometimes referred to as two-ply three-ply, etc.)
7. Loop pile: The pile of a carpet consisting of loops. (e.g. uncut pile)
8. Pile: a surface effect on a fabric formed by tufts or loops of yarn that stand up from the body of the fabric. In carpet, pile is the part of the carpet consisting of textile yarns or fibers, cut or looped, projecting from the substrate and acting as the use-surface.
9. Textured pile: A pile in which the surface character is varied e.g., by having areas of different characteristics or by combinations of different yarn or pile types, (e.g., soft and hard twist.)
10. Tpi: turns per inch (e.g. tpi defines a degree of twist which is the number of turns or twist per unit length)
10: Twist direction: is described as “s” or “z” according to which of these letters has its center inclined in the same direction as the surface elements of a given twisted yarn, when the yarn is viewed vertically (e.g. twisting in the s-direction is clockwise and the z-direction is counter-clockwise)
In the present invention, BCF (bulk continuous fiber) or synthetic yarn such as nylon or other polyamides are used to create a textured loop pile construction for rugs/carpets. Unlike cotton, which has a tendency to mat and pill, is difficult to clean, and is difficult to dye dark colors, synthetic fiber such as nylon 6, 6 is durable, has easy care, colorfast, quick drying and resistant to fuzzing/pilling. Using a conventional twister (such as Volkman, Verdol, ICBT & Hammel), the feed fiber or yarn is plied or twisted with another (i.e. a second) fiber or yarn of the same or different deniers forming a third yarn. This initial twisting (i.e. or first twist) of the yarn to form a third yarn as indicated above is preferably about 1.0 to about 10.0 twists per inch. The feed yarn is preferably at least two-ply and, most preferably two-plied or three-plied. The feed yarns can be colored or white dyeable.
Then, at least two of the plied or twisted third yarns are then cabled together forming a final yarn. The third yarns cabled together can be either of the same denier, or of different deniers. (For example, a first third yarn can be comprised of two 2250 denier/11.5 dpf and a second third yarn can be comprised of two 1400 denier/10 dpf. Then the first third yarn and second third yarn of different deniers can be cable twisted forming a final yarn. The dpf effects the hand or softness of the finished yarn.) The total denier of the final yarn preferably ranges from about 2,000 to about 20,000. The yarns that are cabled together preferably have a cable twist of about 0.5 to about 10 twists per inch.
In the present invention, a twist differential must occur between the initial twisting of the feed yarn and the cable twisting to provide a torque to the final yarn for the textured look desired. The torque causing the textured effect is a novel element of the present invention. The twist differential is a delta between the degree of twist at the initial twist and the cable twist. (For example, if the initial twist is 3.0 tpi and the cable twist is 2.0 then the twist differential is (3.0 tpi −2.0 tpi) =1.0 tpi.). Furthermore, the twisting and the cable twisting must be twisted in the same direction (e.g. s-direction or the z-direction). That is, if the initial twist is in the s-direction then the cable twist for the final yarn must be in the s-direction not the z-direction. Similarly if the initial twist is in the z-direction then the cable twist for the final yarn must also be in the z-direction. In order to maximize the torque/textured effect, the yarn should not be heatset.
There can be additional twisting of the yarns with the same or different deniers after the initial twisting and prior to cabling into the final yarn.
Referring now to the drawings, where the showing is for the purpose of describing an embodiment of the invention and not for limiting same. The twisting operations may be conducted on any conventional twisters such as Volkman, Verdol, ICBT & Hammel. The examples below were twisted using a Volkman twister.
Examples of the present invention are illustrated in FIGS. 1 and 2 and will be briefly described below. The feed yarn, end-A in FIG. 1, is the starting point. A variety of samples of different denier were made using the following yarns as end-A:
1400-denier/10-dpf
2250-denier/11.5 dpf
995×2/12.5 dpf
1800-denier/8-dpf
The same process as described in Example 1 below was used for each of these samples which also yielded the textured loop pile of the present invention.
EXAMPLES
Example 1
One end of 2200-denier/8-dpf (end-A in FIG. 1) was plied with another end of 2200-denier/-8-dpf (end-A in FIG. 1) at 4.0 twist per inch in “s” direction to form a 4400-denier (end-B in FIG. 1) Then, two ends of 4400-denier (end-B in FIG. 1) are cabled together at 3.0 twists per inch in the “s” direction to form a 8800-denier (end-C in FIG. 1) The differential twist (i.e. 4.0 twist per inch -3.0 twist per inch =1.0 twist per inch) of 1.0 twist per inch is imparted as torque to the final yarn. End-C in FIG. 1, was tufted into a rug or carpet in a loop pile construction on a backing using a conventional tufting machine to achieve a textured loop aesthetics. The yarn was not heatset in order to maximize the torque/textured effect.
Example 2
One end of 2200-denier/8-dpf (end-A in FIG. 2) was plied with another end of 2200-denier/-8-dpf (end-A in FIG. 2) at 4.0 twists per inch in “s” direction to form a 4400-denier (end-B in FIG. 2 ). One end of 1400-denier/10-dpf (end-C in FIG. 2) was plied with another end of 1400-denier/10-dpf (end-C in FIG. 2) at 4.0 twists per inch in the “s” direction to form a 2800-denier yarn (end-D in FIG. 2 ). Then one end-B was cabled with one end-D at 3.0 twist per inch in “s” direction to form a 7200-denier (end-E in FIG. 2 ). The differential twist of 1.0 twist per inch imparted the torque to the final yarn. Then the end-E, shown in FIG. 2, was tufted into a rug or carpet in a loop pile construction on a backing on a conventional tufting machine to give a textured loop aesthetics. To maximize the torque/textured effect, the yarn was not heatset.
Reference is now made to FIG. 3, which shows the textured effect of the yarn in a loop pile construction. The yarn, as shown, has been twisted and cabled to impart the torque to the BCF or synthetic yarn and tufted.
It is therefore, apparent that there has been provided in accordance with the present invention, twisting then cabling BCF yarns to impart torque for a textured loop pile construction that fully satisfies the aims and advantages hereinbefore set forth. While this invention has been described in conjunction with a specific embodiment thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.
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A method for forming a highly textured loop pile rug and/or carpet using the torque created by twisting then cabling bulk continuous yarns. A flooring article having a textured effect by creating torque in the yarn through the twisting and cabling of bulk continuous fiber.
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FIELD OF THE INVENTION
[0001] The present invention relates to a fuel injection system for a two-stroke engine. In particular, the present invention concerns a fuel injection system for a two-stroke engine with crankcase scavenging, with at least one transfer duct. The transfer port to the transfer duct, which opens into the cylinder, is controlled by the engine piston. A fuel injector is positioned in the transfer duct, the injection jet from the injector being directed onto the side of the piston crown that is proximate to the combustion chamber, the axis of the injection jet subtending an angle of less than 90° with the axis of the piston. The injection jet is directed, for the most part at least, onto that half of the piston crown that is opposite the exhaust port.
BACKGROUND OF THE INVENTION
[0002] European Patent No. 302 045 B2 describes a two-stroke engine in which the injector is configured as a multi-orifice injector, and in which the injection process for the range of higher engine speeds begins before the transfer port of the transfer duct is uncovered by the piston, so that some of the fuel can be pre-vaporized in the transfer duct. This is necessary, in particular, if the amount of time required for injection exceeds the amount of time for which the transfer ducts are open, as may be the case at very high engine speeds. In such a case, however, one disadvantage is that essentially injection takes place radially to the cylinder wall, and in the direction of the scavenging gas flowing into the cylinder by way of the transfer ducts. When this happens, it is scarcely possible to avoid unburned fuel flowing out of the combustion chamber into the exhaust, and this in its turn results in a loss of fuel and increased hydrocarbon emissions.
[0003] In order to prevent or reduce the fuel-air mixture from flowing through the combustion chamber into the exhaust to the maximum possible extent, in a modified version of the two-stroke engine described heretofore, European Patent No. 302 045 B2 proposes that the piston be configured as a deflector-crown piston that has a rounded, concave deflector surface on the same side as the transfer port. The jet from the injector is directed, at least in part, onto said deflector surface. (See also Austrian Patent No. 3 394 U1).
[0004] U.S. Pat. No. 4,779,581 describes another two-stroke engine, in which fuel is injected in the same direction as the scavenging gas that is flowing into the cylinder. In this engine, the fuel is injected in the direction of the spark plug, away from the top surface of the piston.
[0005] It is also known that low-pressure injectors can be used. Low pressure injectors introduce the fuel directly into the combustion chamber when the piston has uncovered the exhaust duct or transfer ducts. (See, e.g., U.S. Pat. No. 5,762,040, German Patent No. 39 13 629 C2, and German Patent No. 37 44 609 A1.) However, according to these publications, because the fuel is injected not into the transfer duct but rather directly into the cylinder through a separate port, injection can only take place once the piston has uncovered the injection port. Otherwise, the fuel mixture would be injected directly onto the piston skirt, which, on the one hand, would result in inadequate preparation of the mixture and, on the other, would result in the film of lubricating oil being washed off the piston and this, in turn, would increase the danger of damage being done to the engine.
[0006] The same difficulty arises with European Patent No. 302 045 B2 and Austrian Patent No. 3 394 U1. In both engine designs, the injector nozzles open out into the transfer ducts. Although the injectors are almost perpendicular to the piston skirt, namely, the side of the piston skirt that is most greatly stressed (the cyclic pressure and back-pressure side), in the case of advanced injection of fuel before the edge of the transfer port is uncovered by the piston, the film of lubricating oil is washed off the piston, thereby curtailing the service life of the engine.
[0007] In addition, German Patent No. 37 44 609 describes the use of at least two injectors, each injector having its own, dedicated fuel-supply. In this engine, it is possible to activate each injector separately as a function of the operating parameters of the engine.
[0008] According to U.S. Pat. No. 5,762,040, two direct-injection low-pressure injectors can be provided for each cylinder. These injectors inject fuel directly into the cylinder and are connected to a common fuel-supply system. As before, the injectors are directed essentially towards the exhaust duct, so that a not insignificant loss of fuel, and the concomitant escape of unburned gasoline, have to be taken into account.
[0009] As indicated, in each of the prior art two-stroke engine designs, the fuel injection systems do not provide reduced emissions across a wide range of engine operating speeds.
[0010] In addition, the prior art engines also experience a decrease in performance across a range of operating parameters in addition to experiencing an increase in unwanted exhaust emissions.
SUMMARY OF THE INVENTION
[0011] Therefore, it is an object of the present invention to provide a fuel injection system for a two-stroke engine that maintains or increases performance of the engine across a range of operating parameters while also reducing exhaust emissions from the engine by solving the problems of the prior art listed above.
[0012] Accordingly, one aspect of the present invention is the provision of at least two fuel injectors, disposed so as to be essentially parallel to each other and so as to subtend an angle of 20° to 50°, preferably 35°, with the axis of the cylinder, the injector being directed towards the side of the piston crown that is proximate to the combustion chamber. The fuel injectors open out into the side transfer ducts, preferably one injector into one side transfer duct on the left-hand side and one on the right-hand side, adjacent to a rear boost port. The arrangement of the fuel injectors in the side transfer ducts means that the fuel that is added to the gas (air or a combination of air, vaporized fuel, and/or oil (among other components)) is always injected almost perpendicularly (i.e., across and partly against) to the gas flowing into the combustion chamber. This results in the greatest possible flow differential between the inflowing gas and the fuel that is injected, and results in superior, favourable mixing conditions. Arrangement of the fuel injectors in this manner also permits the complete (or nearly complete) vaporization of the fuel and also prevents unburned hydrocarbons from being exhausted from the cylinder, since no unvaporized fuel can be sprayed into the exhaust.
[0013] According to the present invention, it is preferred that the injectors be configured as multi-orifice injectors, since these generally provide for finer vaporization as compared to single-orifice nozzles, given identical injection parameters (i.e., pressure, flow, etc.).
[0014] During development of the present invention, the inventors realized that, primarily in the range of greater engine speeds and loads when the amount of time available for injecting the fuel is very small, the fuel can be injected before the transfer port to the side transfer duct is uncovered. This means that some of the fuel can be pre-vaporized in the transfer duct. This ensures that sufficient fuel can be introduced into the cylinder, even at high engine speeds.
[0015] To be able to match the quantity of fuel that is introduced into the cylinder to particular demands, such as load and engine speed, the injectors may be activated independently of each other. Thus, in the partial-load range, only one of the two injectors may be active and, in contrast to this, when the engine is under full load, both the injectors may supply fuel to the cylinder. With such an arrangement, it also may be possible to have the injectors work in alternation when the engine is operating under partial load, so as to avoid localized overheating of the engine. To this end, one injector is activated for one cycle, and the other injector is activated for the subsequent cycle.
[0016] Another way of matching the quantity of fuel injected to the load on the engine is to use two injection valves of different sizes, which is to say, valves with different flow characteristics. The smaller of the two is designed to deliver fuel mainly when the engine is idling or running under partial load. The other is activated only when the engine is operating under a specific load or at a specific speed, so that the demand for fuel can be satisfied, especially when the engine is operating under full load.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] An example of the objects of the present invention is shown in the drawings appended hereto, like reference numbers indicating like parts throughout. In the drawings:
[0018] [0018]FIG. 1 is a partial cross-section of one embodiment of an injection system according to the present invention, as viewed from above;
[0019] [0019]FIG. 2 illustrates the injection system in cross-section, taken on the line II-II shown in FIG. 1;
[0020] [0020]FIG. 3 shows the injection system in cross-section, taken on the line III-III shown in FIG. 1; and
[0021] [0021]FIG. 4 depicts the injection system shown in FIG. 1, together with crankcase, in partial cross-section, as viewed from the side.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0022] As shown in the accompanying figures and as is conventionally known, a two-stroke engine includes a cylinder 1 having an exhaust port 2 , side transfer ports 3 , and a rear boost port 4 . The cylinder 1 is mounted to a crankcase 9 and a cylinder head 8 is mounted to the cylinder 1 to close the cylinder 1 . A reed valve 5 is mounted in the intake path of the cylinder 1 and allows air to pass from the atmosphere to the crankcase 9 . In other known embodiments, the reed valves can be mounted in the crankcase 9 itself.
[0023] In a conventional carbureted two-stroke engine, an air and fuel mixture is sucked into the crankcase 9 through the reed valve 5 as a piston 10 moves upward in the cylinder 1 . When the piston 10 reaches the top of its stroke and begins moving downward in the cylinder, it compresses the air and fuel charge in the crankcase 9 , thereby closing the reed valve 5 . (See FIG. 4.) When the piston has moved downward in the cylinder sufficiently to open the transfer ports 3 a, 3 b and rear boost port 4 , the compressed air and fuel charge is pushed upward through these ports into the cylinder 1 . (See, e.g., FIGS. 1 and 3.) This charge also serves to push the spent exhaust gases from the previous combustion out of the cylinder through the exhaust port 2 . However, considering all of the operating parameters of the engine, it is difficult to do this without either having incomplete scavenging of the exhaust gases from the cylinder or pushing some of the air and fuel charge into the exhaust port. Both occurrences affect the performance of the engine but the latter also increases hydrocarbon emissions from the engine since unburned fuel is being exhausted into the atmosphere.
[0024] In the present invention, two fuel injectors 6 are mounted beside the rear boost port 4 . They are also mounted to have a downward angle of injection into the cylinder, with the angle preferably being approximately 35° from a plane normal to an axis of the cylinder. As would be appreciated by those skilled in the art, however, the angle can be varied, as appropriate, to achieve desired operating conditions of the engine. It has been shown, however, that the angle preferably should be within the range of 20° to 50° in order to achieve satisfactory results with respect to engine performance and emissions. FIG. 2 illustrates the range of the complementary angles between 40° and 70°. The fuel is not injected radially, towards the center of the cylinder, as in the prior art. Instead, it is injected tangentially to the cylinder 1 . As shown, the fuel is injected in a direction substantially parallel to a plane bisecting the cylinder 1 through its center point.
[0025] It is preferred that the two injectors 6 be disposed so as to be parallel to each other. So arranged, the two injectors 6 can be supplied with fuel very simply by way of a common fuel rail 7 ; this is particularly so when a number of cylinders are disposed in a row. Each injector 6 opens out into one of the side transfer ducts 3 a that are located alongside the rear boost port 4 . The injectors 6 thus inject the fuel almost perpendicularly (i.e., across and partly against) to the gas 13 that is flowing into the cylinder through the side transfer ducts 3 a (the flow patterns of the gas that enters the cylinder through the various ports are indicated by the arrows shown in the drawings). This results in the best possible vaporization of the fuel 12 and the best possible mixing with the gas 13 that enters the cylinder by way of the transfer ducts. Furthermore, injection takes place at the upper edge 14 of the side transfer ports 3 a, where the flow velocity is greatest when the gas 13 flows into the cylinder 1 , so that the fuel and air are mixed even more thoroughly. The gas 13 flowing into the cylinder 1 transversely to the injection jet 12 also acts as a barrier, because it prevents the fuel that is injected from flowing across the cylinder 1 into the exhaust port 2 .
[0026] The flow of gas 13 that emerges from the rear boost port 4 and which is directed upward (see FIG. 3) does not interact directly with the injected fuel 12 . However, because the flow of gas 13 causes the flows of gas emerging from the transfer ports 3 a, 3 b to flow upward (i.e., it deflects them towards the cylinder head), it ensures that the injected fuel 12 is also deflected in this direction, so that all of the fuel is burned.
[0027] In addition, injection takes place in the direction of the maximum width W of the side transfer ducts 3 a, 3 b and not across the low height of the transfer port 3 a. Accordingly, injections taken place from the upper edge 14 of the transfer port towards the lower edge of the transfer port, as was usually the case in the prior art.
[0028] Even though the major portion of the fuel 12 that is injected is directed onto the half of the piston that is remote from the exhaust port 2 , some of the injected fuel can nevertheless interact with the gas emerging from the transfer ducts 3 b that are more remote from the point of injection. This is further facilitated in that the flow of gas from the side transfer ducts 3 b is not oriented radially inward, but rather in the direction toward the rear boost port 4 , so that at least a considerable component of the gas flow is directed against the injection jet 12 . In this way, mixing is improved to an even greater extent, and it is ensured that the fuel 12 that is injected cannot enter the exhaust port 2 .
[0029] Because of the fact that the injectors 6 are inclined slightly towards the side of the piston 10 that is proximate to the combustion chamber, a certain amount of fuel 12 can reach the crown of the piston, vaporize on this, and thus cool the piston as ;a result of the heat loss caused by this vaporization.
[0030] As indicated above, it is preferred that fuel be supplied to the fuel injectors 6 through a common fuel rail 7 . However, as would be appreciated by those skilled in the art, the fuel injectors 6 may be supplied with fuel from separate fuel lines.
[0031] Under partial load conditions, the timing of the injection of the fuel from the fuel injectors into the cylinder will preferably be delayed until later in the scavenging phase (but prior to closing of the scavenging ports 3 a, 3 b and 4 by the piston 10 ). This delay in injecting fuel into the cylinder reduces or eliminates unburned fuel from escaping out of the exhaust port to the atmosphere during operation of the engine. The operating conditions of the engine, such as throttle opening, engine speed (“rpm”), etc., will dictate the amount of fuel injected by the injectors during each injection cycle.
[0032] The amount of fuel injected during each injection cycle is generally controlled by the length of the injection cycle. Therefore, at operating conditions requiring higher amounts of fuel, e.g. under full load condition, the duration of the injection cycle will be longer. This may require that the injection cycle starts sooner (as compared with lower fuel requiring conditions) to provide sufficient time for the injection cycle prior to closing of the scavenging ports. When the engine is running under full load, injection can take place before the piston 10 begins to uncover the transfer ducts. (See FIG. 4.) In this case, a large part of the fuel 12 that is injected strikes the hot piston skirt, where it is prevaporized and is carried into the cylinder 1 by the flow of gas, once the transfer duct 3 a has been uncovered.
[0033] This earlier injection of the fuel into the cylinder 1 is still less likely to result in unburned fuel escaping out of the exhaust port as compared with a carbureted engine, since the expansion chamber will generally be tuned for such operating conditions to prevent the escape of unburned fuel into the atmosphere.
[0034] The use of multiple fuel injectors increases the fuel delivery capacity of the injection system and provides for shorter injection cycles. This is especially important at high rpm and full throttle (i.e., throttle opened to a great extent) conditions where the time available for injection is smaller (due to the high rpm) but the amount of fuel required is larger. Alternatively, three or more fuel injectors can be used per cylinder in more demanding applications, as can one fuel injector per cylinder in less demanding applications. Furthermore, the use of multiple fuel injectors can be staged such that one fuel injector operates at less demanding operating conditions and a second (or further) injector begins operation at more demanding conditions to supplement the fuel delivery by the first fuel injector. Moreover the fuel injectors do not necessarily need to be of the same size or type. Quite contrary to this one fuel injector could be designed to be smaller than the other one and be operated only under idle speed and under part load to provide better sensibility and reproducibility under these operating conditions where small quantities of fuel are demanded.
[0035] In the preferred embodiment, the control of the fuel injectors is by an Electronic Control Unit, (“ECU”). The ECU takes into account one or more operating conditions, such as throttle opening, rpm, engine temperature, atmospheric temperature, barometric pressure, etc., determines the appropriate fuel delivery for such conditions, and controls the fuel injectors to deliver the desired amount of fuel.
[0036] The reduction of emissions due to the present fuel injection system can be complemented by the use of a catalytic converter in the exhaust system and reductions of oil supplied to the engine for lubrication, for instance, due to more precise metering and spot delivery.
[0037] The present invention was developed preferably to meet the operating requirements of a snowmobile. As would be appreciated by those skilled in the art, snowmobiles operate at high engine speeds and loads. As discussed, the fuel injection system of the present invention improves performance across a range of operating parameters, including high speed (and/or high load) operation. While designed with the requirement of a snowmobile in mind, however, the present invention could be applied to an engine designed for any type of vehicle including a personal watercraft, ATV, or the like.
[0038] The present invention is not meant to be limited solely to the embodiments described. To the contrary, the embodiments described may be modified in various ways without departing from the scope and, content of the present invention. Modifications that may be apparent (or will become apparent) to those skilled in the art are also intended to fall within the scope of the present invention.
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An internal combustion, two stroke engine is disclosed. The engine includes a crankcase with a cylinder adapted to house a piston. At least one transfer duct communicates the crankcase to the cylinder. At least one fuel injector is disposed through a wall of the transfer duct. The fuel injector is positioned to inject fuel tangentially to the cylinder.
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This application claims the benefit of U.S. Provisional application No. 60/052,752, filed Jun. 30, 1997.
FIELD OF THE INVENTION
The present invention relates to a generally elongated tampon for insertion into a mammalian body cavity. These tampons have smooth, apertured polymeric formed film covers to provide for smooth gentle insertion into and removal from a body cavity.
BACKGROUND OF THE INVENTION
Catamenial tampons are used by women to absorb the flow of menstrual fluids to prevent leakage and staining of undergarments, and other clothing. Therefore, it is desirable for tampons to demonstrate good absorbency and to be able to absorb fluid quickly. Unfortunately, tampons are not without disadvantages and inconveniences. For example, tampons may unexpectedly leak if they do not expand quickly enough or fully enough to fill the vaginal canal. Tampons are also sometimes difficult or uncomfortable to insert into or remove from the vaginal canal. These insertion and removal difficulties may be especially apparent when the menstrual flow is light.
There have been many attempts to remedy these problems by altering the absorbent material or the outer cover of the tampon. Greener et al., U.S. Pat. No. 2,710,007, and Burgeni, U.S. Pat. No. 3,340,874, are examples of the use of low density material in portions of a tampon to promote rapid fluid absorption.
Gellert, U.S. Pat. No. 4,475,911, describes a tampon made up of an unbonded array of nonabsorbent, hydrophilic, resilient fibers completely enclosed within a porous overwrap of apertured formed film.
Thompson, U.S. Pat. No. 3,929,135, describes a topsheet useful in disposable absorptive devices, including catamenial tampons. The topsheet is an apertured formed film having tapered capillaries. The Examples in this reference describe a topsheet having a top surface which is more than about 90% open area.
Lloyd et al., U.S. Pat. No. 5,374,258, describes a tampon with a cover comprising lengthwise ribs. The ribs on the cover are parallel to the tampon's axis and are separated from one another by multiple transverse ribs. Howarth, U.S. Pat. No. 5,403,300, describes a tampon with a polymer net outer cover. The net comprises two intersecting sets of parallel ribs which are aligned obliquely with respect to the main axis of the tampon and to each other. The orientation of the ribs allegedly aids in the smooth insertion and removal of the tampon.
Commonly assigned, copending patent application to Foley et al., U.S. patent application Ser. No. 08/789,747 (also published as EP 685 215) describes a tampon which demonstrates low capillary suction pressure on the vaginal epithelium. The contents of this application are hereby incorporated herein by reference.
It is an object of this invention to provide a novel tampon with good absorbency and leakage protection, ease of insertion into and removal from a body cavity, and a relatively clean dry surface after use.
SUMMARY OF THE INVENTION
The tampons of this invention provide good absorbency and protection from leakage while providing a smooth surface for easy, gentle insertion into and removal from the vaginal canal. They accomplish this by providing a generally elongated absorbent core made from absorbent materials, and an outer cover made from an apertured formed film. The apertured polymeric formed film comprises a land region having a multiplicity of openings therein. Each of these openings is defined by a first aperture and sidewalls extending in a uniform direction from the first aperture. The side walls terminate in a second aperture. The open area formed cumulatively by the second apertures comprises less than about 35% of the surface area of the apertured polymeric formed film. The outer cover is oriented on the tampon such that the second apertures are adjacent the absorbent core.
The apertured formed film provides a generally smooth land area on the outermost surface of the tampon for gentle, nondrying passage along the vaginal walls. The apertures in the film allow fluid to pass through the cover and into the absorbent core, where the fluid is held to prevent leakage.
The tampon of the invention may be made by forming a generally elongated blank of absorbent material, attaching a length of apertured polymeric formed film so that it covers at least the generally elongated surface of the blank, and then compressing the covered blank to form a tampon. A withdrawal cord or string may be attached to the blank or the covered blank to aid a user in withdrawing the tampon from a body cavity after use.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 illustrates a perspective view of a preferred embodiment of a tampon of the invention.
FIG. 1A illustrates an exploded cross-sectional view of the apertured film of FIG. 1 .
FIG. 2 is a side view of a tampon of the prior art with fibers protruding through the cover.
FIG. 3 is a side view of a tampon of this invention.
FIG. 4 is a graph illustrating the frequency of the distances of “Nearest Neighbor” apertures (“NNDIST”) in a preferred embodiment of an outer cover for the tampon of the invention.
FIG. 5 is a graph illustrating the frequency of the distances of “Nearest Neighbor” apertures (“NNDIST”) in a fibrous cover for a commercially available o.b.® tampon.
FIG. 6 is a diagrammatic view of a preferred type of apparatus for producing apertured formed film for use on the tampon of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
As shown in FIGS. 1 and 1A, a preferred embodiment of the tampon 10 of the invention has a generally elongated absorbent core 12 of absorbent materials and an outer cover 14 of apertured formed film. The apertured formed film of the cover 14 , when arranged in a substantially planar orientation, comprises a land region 16 having multiple openings 18 therein. Each opening 18 has a first aperture 20 in the land region 16 and side walls 22 extending therefrom in a substantially uniform direction and terminating in second apertures 24 . It is not necessary that all of the second apertures 24 lie within the same plane.
Some of the second apertures 24 may be split by bridging fibrils 26 or thread-like extensions of the sidewalls across the second apertures 24 . These fibrils 26 are created by incomplete aperturing of the starting film. An unexpected advantage of the fibrils 26 is that they provide the outer cover with additional capability for preventing absorbent core materials from protruding through the openings in the film.
This apertured formed film is placed on the tampon 10 so that the second apertures 24 are generally adjacent the absorbent core 12 . An advantage of the apertured film cover is that it minimizes the presence of the absorbent materials on the surface of the tampon. The land region 16 has a projected land area which results from projecting the land region 16 onto a plane substantially parallel to it.
The size and number of the apertures in the film are chosen to minimize the penetration of absorbent core materials through the film. The presence of absorbent core materials on the surface of the tampon both increases friction against the vaginal wall upon insertion and contributes to desiccation of the vaginal wall during use, leading to removal discomfort. The absence of absorbent core materials on the surface of the tampon helps to maintain the ease of insertion and removal
The length of the sidewalls connecting the first and second apertures may play a role in providing the tampon with improved insertion characteristics. The presence of the sidewalls between the first and second apertures imparts a generally three-dimensional quality to the film. This three-dimensional quality is in contrast to the generally two-dimensional quality of reticulated films such as that described in U.S. Pat. No. 4,710,186, the disclosure of which is herein incorporated by reference. Two-dimensional reticulated films more readily allow portions of the absorbent materials of the absorbent core to protrude through to the surface of the tampon.
The three-dimensional quality provided by the sidewalls helps to separate the absorbent materials of the absorbent core from the surface of the tampon. The longer the sidewalls, the greater the separation of the absorbent core materials from the tampon surface, and the less likely it is that the absorbent core materials will protrude through the openings in the apertured film to contact the vaginal tissues during insertion.
The optimum length of the sidewalls is dependent upon the type of absorbent material which is used for the absorbent core. Some types of absorbent materials may protrude more easily through the openings in the apertured film, and thus longer sidewalls may be required to prevent protrusion. It will be recognized by those familiar with the manufacture of tampons that tampons are often compressed during the manufacturing process. Such compression causes the sidewalls of the apertured film to fold over. Such folding, however, does not detract from the ability of the sidewalls to prevent protrusion of the absorbent materials through the openings in the apertured film.
FIG. 2 illustrates a side view of a prior art tampon 100 with a fiber cover 102 . The surface 104 of the prior art tampon 100 has a “fuzzy” appearance caused both by absorbent core fibers protruding through the fiber cover 102 and by loose fibers from the cover 102 .
FIG. 3 shows a side view of a tampon 10 of the invention with an apertured film cover 14 . The surface of the tampon 10 is smooth with the fibers substantially all contained by the cover 14 . The apertured formed film cover 14 helps to hold the absorbent core fibers away from the surface of the tampon 10 . Since the apertured formed film cover 14 does not comprise fibers, there are no loose cover fibers to interfere with insertion and removal comfort.
This smoothness may be measured by average surface roughness as measured by the Kawabata Surface Tester according to the method described in the Examples. Preferably, the average surface roughness is less than that of conventional fibrous tampon cover material. More preferably, the average surface roughness is less than about 3 microns.
The absorbent core of the tampon may comprise any absorbent material, including but not limited to cellulosic fibers such as rayon and cotton, other natural or synthetic absorbent fibers, superabsorbent fibers, absorbent foams, absorbent gelling agents, and the like. In a preferred embodiment, the absorbent core of the tampon comprises a blend of rayon and cotton.
The apertured formed film of the invention may comprise any polymeric film-forming material including but not limited to polyethylene, polypropylene, other polyolefins, ethylene vinyl acetate, polyesters, polystyrene, polyamides, polyethers, copolymers of these, and blends of these. In a preferred embodiment, the apertured formed film of the invention comprises a blend of ethylene vinyl acetate and polypropylene. In another preferred embodiment, the apertured formed film comprises a blend of polypropylene and low density polyethylene.
The generally elongated absorbent core has a generally elongated surface and two end surfaces. Preferably, the apertured formed film substantially covers at least the generally elongated surface of the absorbent core to form an outer cover on the tampon. The outer cover is oriented and configured such that the second apertures are adjacent to the absorbent core. One or both of the ends of the absorbent core may also be covered, but this is not necessary to obtain the insertion and removal advantages of the invention.
The land region of the apertured formed film is chosen such that it provides the outer body-contacting exterior of the tampon with a gliding surface which allows for smooth and easy insertion of the tampon into a body cavity. The smoothness of the surface allows the tampon to slide easily over the vaginal tissues, thereby reducing the frictional drag which may occur when fibrous or absorbent or less smooth tampon surfaces rub along the sensitive vaginal tissues. The projected land area, projected side wall area, and open area of a given area of apertured formed film are equal to unity. Of these three areas, the easiest to determine is the open area. It has been found that apertured formed films with open area of less than about 35% function effectively to provide this smooth surface on tampons. However, apertured films with open area of as little as 2% are also effective on such tampons.
Open area may be determined by using image analysis to measure the relative percentages of apertured and unapertured, or land, areas. Essentially image analysis converts an optical image from a light microscope into an electronic signal suitable for processing. An electronic beam scans the image, line-by-line. As each line is scanned, an output signal changes according to illumination. White areas produce a relatively high voltage and black areas a relatively low voltage. An image of the apertured formed film is produced and, in that image, the holes are white, while the solid areas of thermoplastic material are at various levels of gray.
The more dense the solid area, the darker the gray area produced. Each line of the image that is measured is divided into sampling points or pixels. The following equipment can be used to carry out the analysis described above: a Quantimet Q520 Image Analyzer (with v. 5.02B software and Grey Store Option), sold by LEICA/Cambridge Instruments Ltd., in conjunction with an Olympus SZH Microscope with a transmitted light base, a plan 1.0× objective, and a 2.50× eyepiece. The image can be produced with a DAGE MTI CCD72 video camera.
A representative piece of each material to be analyzed is placed on the microscope stage and sharply imaged on the video screen at a microscope zoom setting of 10×. The open area is determined from field measurements of representative areas. The Quantimet program output reports mean value and standard deviation for each sample.
In addition to open area, the apertured formed film of the tampon of the invention is characterized by a distribution of the distances of nearest neighbor apertures. Nearest neighbor distance may be determined by a variety of means including the use of image analysis for the calculation of the “nearest neighbor” in an array of apertures. The nearest neighbor distance is the distance between an aperture and the aperture which is its nearest neighbor in an apertured formed film, measured from the centroid of the first aperture to the centroid of its nearest neighbor. This distance, when plotted against the frequency of such distances, provides a frequency distribution of nearest neighbors for the apertures in the film. Such a nearest neighbor distribution may be observed in FIGS. 4 (an apertured formed film according to the present invention) and 5 (a thermobonded fibrous web). It can be noted from FIG. 4 that the distribution for this apertured formed film sample is binodal; that is, there is a first distribution of nearest neighbor distances in the 0.5 to 1.1 mm range and a second distribution in the 1.1 to 2.5 mm range. This binodal distribution is attributed to the presence of fibrils across about 60% of the second apertures in this sample of apertured formed film. In contrast, as shown in FIG. 5, the nearest neighbor distribution for a fibrous nonwoven cover similar to that formed on a commercially available o.b.® tampon shows a very narrow distribution of nearest neighbor distances. Additionally, the nearest neighbor distances for the fibrous cover are much smaller than for the film cover. This illustrates that the apertures in the fibrous cover are much closer together than the apertures in the film.
The apertured formed film may be applied as an outer cover to an absorbent core to form a tampon by any of a number of known methods. Preferred methods of applying the cover are disclosed in U.S. Pat. No. 4,863,450 (Friese), in which a length of cover is attached to one end of a length of absorbent material and the assembly is rolled up into a cylinder such that the cover forms the outside surface of the cylinder, and U.S. Pat. No. 5,004,467 (Hinzmann et al.), in which one end of an absorbent cylinder is placed in the center of a rectangle of cover, and the cover is folded up and around the sides of the cylinder.
The contents of these two patents are hereby incorporated herein by reference.
After the cover is applied to the absorbent core, the covered core is radially compressed,to form a tampon pledget. A preferred compressed tampon and method for making it are described in commonly assigned, co-pending U.S. patent application Ser. No. 07/596,456 (Friese et al.), the contents of which are hereby incorporated herein by reference. The tampon of Friese et al. has a generally cylindrical shape formed by multiple longitudinal, relatively low-density ribs surrounding a more highly compressed core. The term “generally elongated” as used herein is intended to include the generally cylindrical tampon of Friese et al. as well as other tampons with a generally elongated shape.
The compressed pledget may be inserted into a user's body cavity with the user's fingers (digitally) or by means of an applicator.
Apertured polymeric formed films are known and may be made by a number of methods which are known to those in the art, including hot air aperturing and water aperturing. A preferred apertured formed film for this invention is made using an apparatus as described in U.S. Pat. No. 5,567,376, the contents of which are hereby incorporated herein by reference. FIG. 6 illustrates a method of making an embodiment of an apertured film for use in this invention. A continuous starting film 200 is unwound from an unwind station 210 and supported on a three-dimensional apertured forming member 220 . Situated above the starting film 200 is a manifold 230 for applying multiple fine streams of hot water to the upper surface of the starting film 200 as the film, supported on the forming member 220 , passes under the manifold 230 . The water may be applied at varying pressures. High pressures (i.e., 900 pounds per square inch) or low pressures (i.e., 165 pounds per square inch) may be used, as may combinations of high and low pressures. Disposed beneath the forming member 220 is a vacuum manifold 240 for removing water which is directed onto the upper surface of the starting film 200 as it passes under the manifold 230 .
The pressurized streams of hot water cause the film to conform to the topography of the apertured forming member 220 and to rupture in the areas where the film overlies the apertures in the forming member 220 . The resulting apertured formed film has a top surface corresponding to the surface contacted by the water streams, and a bottom surface corresponding to the surface supported by the forming member 220 . The apertured film is then passed through one pair or dewatering rolls, 250 A and 250 B, and one pair of backing rolls, 260 and 270 , to remove excess water and to dry the film. Surfactant is then applied to the top surface of the apertured film, the film is slit, e.g., by a cutting knife 280 , into appropriate widths for tampon converting lines, and the narrow widths of film are wound onto standard cores 290 .
The narrow widths of apertured formed film are then cut into strips of predetermined lengths. The cut edge of each strip of the apertured film is heat-welded to the outside of the rear end of a section of a cotton/rayon nonwoven ribbon. The blend of cotton and rayon in the nonwoven ribbon may range from 100% cotton and 0% rayon to 0% cotton and 100% rayon. Preferably, the blend of cotton to rayon ranges from 25:75 to 0:100. The nonwoven ribbon is provided with a withdrawal cord and rolled up on itself to form a tampon blank so that the apertured film length extends over the circumference of the tampon blank with the top surface of the apertured film facing away from the nonwoven ribbon. The free end of the apertured film length is heat-sealed onto the outer apertured film-covered surface of the blank. The blank is subsequently radially compressed to produce the final form of the tampon.
EXAMPLES 1A, B, C, D
Tampons 1 A and 1 C are made by applying the apertured film cover according to the method above. Tampons 1 B and 1 D are made by first rolling up a section of a cotton/rayon nonwoven ribbon to form a generally cylindrical tampon blank. One end of the blank is placed on the center of a length of apertured film. The apertured film is folded up and around the sides, or generally cylindrical surface, of the tampon blank. The covered blank is then radially compressed to form a tampon.
Tampons 1 A, 1 B, 1 C, and 1 D are tested for absorbency by a standard Syngina test, as described in the Federal Register, Part III, Department of Health and Human Services, Food and Drug Administration (21 CFR Part 801, pp. 37263-4, Sep. 23, 1988). It can be seen from Table 1 below that tampons made with films of small open area (high land area) demonstrate Syngina capacities which are comparable with tampons made with higher open area (lower land area) films and fibrous covers.
TABLE 1
Apertured Film
Syngina
Open Area
Capacity
Product
(%)
(g)
Tampon 1A with apertured
2.3
9.2
film cover
Tampon 1B with apertured
3.0
9.5
film cover
Tampon 1C with apertured
3.6
9.3
film cover
Tampon 1D with apertured
22.7
9.7
film cover
Commercial o.b. ® with
—
9.2
fibrous cover
EXAMPLE 2
A comparison was made of the perceived insertion and removal comfort of two control products, (1) a super absorbency commercial digital tampon with a fiber cover (o.b.® Brand), and (2) a digital tampon made with a two-dimensional reticulated film, such as that described in U.S. Pat. No. 4,710,186, and an experimental tampon made by substituting an apertured film cover with an open area of 3% for the fiber cover on a super absorbency commercial o.b.® tampon. The test tampon (Example 2) was made according to the same method used to made Tampons 1 A and 1 C above. Fifty-five panelists were each given one each of the control product and the test tampon. Each participant was instructed to insert the tampons digitally during nonmenstrual days only to simulate light flow days. Each tampon was to be worn for 3 to 4 hours before being removed, and there was to be a minimum of 20 hours between the testing of each tampon. The panelists completed questionnaires immediately after the insertion process of each tampon and then again immediately after the withdrawal process of each tampon. The panelists were asked to rate each tampon from 0, extreme negative, to 10, extreme positive, on their perceptions of various attributes of the tampons. The results of the test are shown below in Table 2.
TABLE 2
Reticulated
o.b. ® Super
Film of
Example 2
Attribute
absorbency
U.S. Pat. No. 4,710,186
Tampon
Overall insertion
6.9*
7.4
7.7
performance
Easy to position
7.1*
7.7
7.9
for insertion
Comfortable
7.1*
7.6*
8.1
during insertion
Easy glide
6.4*
7.3
7.7
Overall removal
6.7*
7.2
7.4
*Indicates that the number shown is significantly less at a 95% confidence level as measured by the Paired T-test.
It can be seen from the results in Table 2 that the tampon with the apertured formed film cover (Example 2 tampon) was rated higher than the commercial tampon for overall insertion, ease and comfort of insertion, easy glide, and overall removal.
These cover materials were also tested for Coefficient of Friction on polished steel and surface roughness. The surface roughness was measured using the Kawabata Surface Tester KES-FB-4, available from Kato Tekko (Kyoto, Japan).
The Kawabata Surface Tester allows the measurement of surface roughness of films and nonwoven fabrics. In performing this test, the mean deviation of surface roughness, SMD, is measured over a distance of 2 cm. The contactor for measurement of surface roughness is a steel piano wire (0.5 mm diameter, 5 mm length) placed on the material surface with a contact force of 10 gf (gram force). The contactor is specially designed to simulate the human finger surface. The specimen is moved between a 2 cm interval both backwards and forwards at a constant velocity of 0.1 cm/sec on a horizontal smooth steel plate. The tension of the specimen is kept constant at 20 gf/cm and the contactor stays in place during the measurement. The electrical signal related to the vertical displacement of the piano wire is then translated into a digital readout.
The results of the Kawabata Surface Tester and Coefficient of Friction on Steel are shown below in Table 3.
TABLE 3
Surface
Surf. Rough.
Coefficient
Roughness
Std. Dev.
of
Product
(microns)
(microns)
Friction
Reticulated Film of
3.5
0.24
0.11
U.S. Pat. No. 4,710,186
Fibrous cover of
3.2
0.20
0.16
Commercial o.b. ®
Apertured Formed
1.5
0.87
0.22
Film as in Ex. 2
It can be seen from the surface roughness test results that the three-dimensional apertured formed film of the invention has a lower average surface roughness than either the fibrous cover from a commercial o.b.® tampon or a two-dimensional reticulated film. In the Kawabata Surface Roughness Test, lower measurements indicate lower surface roughness.
However, as Table 3 shows, the lower surface roughness does not result in a lower coefficient of friction. The apertured formed film has a higher coefficient of friction on polished steel than either the reticulated film or the fibrous cover. Surprisingly, a tampon surface that provides greater frictional drag demonstrates greater comfort upon actual insertion into and removal from a woman's vagina than a tampon having a cover with less frictional drag.
The specification and examples above are presented to aid in the complete and non-limiting understanding of the invention disclosed herein. Since many variations and embodiments of the invention can be made without departing from its spirit and scope, the invention resides in the claims hereinafter appended.
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An absorbent tampon has improved ease of insertion into and removal from a body cavity. This is accomplished by covering at least a portion of the outer surface of the tampon with an apertured polymeric formed film. The apertured formed film provides a smooth land area on the outermost surface of the tampon for gentle, nondrying passage along the vaginal walls. The apertures in the film allow fluid to pass through the cover and into the absorbent core, where the fluid is held to prevent leakage.
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1. FIELD OF THE INVENTION
[0001] This invention relates in general to production of oil and gas wells, and in particular to a wellhead system having a flow line for venting an annulus in the wellhead system that is heated by a production flow line also within the wellhead system.
2. DESCRIPTION OF RELATED ART
[0002] Wellheads used in the production of hydrocarbons extracted from subterranean formations typically comprise a wellhead assembly attached at the upper end of a wellbore formed into a hydrocarbon producing formation. Wellhead assemblies usually provide support hangers for suspending production tubing and casing into the wellbore. The casing lines the wellbore, thereby isolating the wellbore from the surrounding formation. The tubing typically lies concentric within the casing and provides a conduit therein for producing the hydrocarbons entrained within the formation.
[0003] Wellhead assemblies also typically include a wellhead housing adjacent where the casing and tubing enter the wellbore, and a production tree atop the wellhead housing. The production tree is commonly used to control and distribute the fluids produced from the wellbore and selectively provide fluid communication or access to the tubing, casing, and/or annuluses between the tubing and casing. Valves assemblies are typically provided within wellhead production trees for controlling fluid flow across a wellhead, such as production flow from the borehole or circulating fluid flow in and out of a wellhead.
[0004] In FIG. 1 , one example of a prior art wellhead assembly 10 is shown in a side sectional view. The wellhead assembly 10 is mounted on a wellbore 12 that intersects a subterranean formation 14 . As is typical, the wellhead assembly 10 includes a main bore 16 that registers with the wellbore 12 and extends vertically upwards through the wellhead assembly 10 . Swab valves 18 are generally set within the main bore 16 for isolating the main bore 16 and wellbore 12 from ambient conditions above the wellhead assembly 10 . Production from the wellbore 12 is generally accomplished via a production line 20 shown intersecting the main bore 16 and extending laterally through a production tree 21 . A production wing valve 22 is shown within the production line 20 for selectively regulating flow through the production flow line 20 . Often, wellhead assemblies 10 also include an annulus line 24 mounted on the production tree 21 and which usually includes an annulus wing valve 25 for controlling flow therein.
[0005] Generally, production tubing 26 is the inner most tubular within a wellhead assembly 10 , thus the inner surface of the production tubing 26 defines the production bore 16 . Circumscribing the production tubing 28 is casing 28 that generally extends down from the tree 21 and into the wellbore 28 to form a wellhead housing. An annulus 30 is defined between the tubing 26 and casing 28 which typically is in communication with the annulus line 24 . Often, for access or for venting of the annulus 30 , an annulus bleed line 32 , which is schematically illustrated in FIG. 1 , has one end connected to the annulus 30 and often is routed to above sea surface in the case of sub sea wells. A bleed valve 34 is shown included within the bleed line 32 and is generally implemented for regulating flow through the bleed line 32 .
[0006] Fluids produced from within the wellbore 12 can include components that form hydrates when subjected to certain temperatures and pressures. When formed, hydrates are ice like solids made up of gases enclosed within a cage of hydrogen bonded water molecules. Because hydrate formation can occur when cooling a fluid having hydrate components, flow circuits that experience a sudden pressure drop, such as through a throttling valve, may induce hydrate formation. The ice like nature of hydrates typically impedes fluid flow through lines and valves of a flow circuit. Chemical injections can be useful for avoiding hydrate formation, but performing and maintaining the injections introduces added complexity to production of hydrocarbons.
SUMMARY OF THE INVENTION
[0007] Disclosed herein is an example of a wellhead assembly equipped with an annulus bleed line designed to prevent hydrate formation. In an example embodiment the wellhead assembly includes a wellhead housing mounted on a wellbore with a production tree connected on top of the wellhead housing. A production flow path is formed through the wellhead housing and production tree, where the production flow path is in fluid communication with the wellbore. Concentric tubulars are included with the wellhead assembly, both of which are registered with the wellbore. The concentric tubulars define an annulus therebetween. The annulus bleed line has an end in fluid communication with the annulus and has a portion routed so that it is in thermal communication with the production flow path. Thus when production fluid from the wellbore flows through the production flow path, and annulus fluid is in the bleed line, thermal energy from the production fluid transferred to bleed line heats the annulus fluid in the bleed line. Heating the annulus fluid that is in the bleed line prevents hydrate formation in the bleed line, even when the annulus fluid is throttled across a valve. In an example embodiment, the wellhead assembly further includes a cross over line for selectively providing fluid communication between the annulus and the production flow path; in this embodiment the bleed line has an end connected to the cross over line. In an example embodiment, the portion of the production tree having the production flow path defines a production wing block, and the bleed line is provided in the production wing block. In an example embodiment, a portion of the bleed line is adjacent a portion of the production flow path. In an example embodiment, a portion of the bleed line contacts a portion of the production flow path. In an example embodiment, a portion of the bleed line circumscribes a portion of the production flow path. In an example embodiment, the portion of the bleed line circumscribing the portion of the production flow path can be one or both of a helical line or a jacket. In an example embodiment the wellbore is subsea.
[0008] Also disclosed herein is a method of preventing hydrate formation in fluid produced from a wellbore. In an example embodiment, the method includes providing a wellhead assembly: where the wellhead assembly is made up of a wellhead housing mounted on the wellbore, a production tree connected on top of the wellhead housing, a production flow path formed through the wellhead housing and production tree and in fluid communication with the wellbore. An annulus is formed between concentric tubulars that are registered with the wellbore. Further included with the wellhead assembly is a bleed line having an end in fluid communication with the annulus and having a portion routed in thermal communication with the production flow path. The method further includes flowing production fluid from the wellbore through the production flow path, flowing annulus fluid from the annulus through the bleed line, and heating the annulus fluid by transferring heat from the production fluid to the annulus fluid so that the annulus fluid is at a temperature above that which hydrates are formed. In an example embodiment, after heating the annulus fluid, the annulus fluid is transferred to above sea surface while retaining sufficient thermal energy to remain above a hydrate forming temperature.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 is a side partial sectional view of a prior art wellhead assembly.
[0010] FIG. 2 is a side sectional view of an example embodiment of a wellhead assembly in accordance with the present invention.
[0011] FIG. 3 is a side sectional view of an alternate embodiment of a wellhead assembly in accordance with the present invention.
[0012] FIG. 4 is a side sectional view of an alternate embodiment of a wellhead assembly in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0013] The apparatus and method of the present disclosure will now be described more fully hereinafter with reference to the accompanying drawings in which embodiments are shown. This subject of the present disclosure may, however, be embodied in many different forms and should not be construed as limited to the illustrated embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Like numbers refer to like elements throughout. For the convenience in referring to the accompanying figures, directional terms are used for reference and illustration only. For example, the directional terms such as “upper”, “lower”, “above”, “below”, and the like are being used to illustrate a relational location.
[0014] It is to be understood that the subject of the present disclosure is not limited to the exact details of construction, operation, exact materials, or embodiments shown and described, as modifications and equivalents will be apparent to one skilled in the art. In the drawings and specification, there have been disclosed illustrative embodiments of the subject disclosure and, although specific terms are employed, they are used in a generic and descriptive sense only and not for the purpose of limitation. Accordingly, the subject disclosure is therefore to be limited only by the scope of the appended claims.
[0015] Referring now to FIG. 2 , one example of a wellbore assembly 40 is shown in a side sectional view; where the wellbore assembly 40 is shown mounted above a wellbore 42 that is formed within a subterranean formation 44 . In the example embodiment of FIG. 2 , the wellhead assembly 40 includes a production tree 46 that mounts over a wellhead housing 48 . In the example of FIG. 2 , the wellhead housing 48 includes an outer tubular 50 shown depending into the wellbore 42 . The outer tubular 50 can be a string of casing, such as conductor pipe or production casing. Also depending into the wellbore 42 is production tubing 52 illustrated as concentrically disposed within the casing 50 and registering with the wellbore 42 . A main bore 54 is shown above an upper end of the production tubing 52 that extends upward within the production tree 46 and includes a swab valve 56 in its upper portion. A production flow line 58 is shown formed laterally through the production tree 46 having an end in communication with the main bore 54 . The combination of the main bore 54 and production line 58 defines a production flow path for flowing production fluids from the wellbore 42 to a production facility (not shown). Set within the production line 58 is a wing valve 60 used for regulating flow through the production line 58 .
[0016] An annulus 62 is defined between the concentric production tubing 52 and casing 50 . An annulus passage 64 is illustrated in FIG. 2 that extends within the production tree 46 and into communication with an annulus flow line 66 . The annulus flow line 66 may be used for providing access to the annulus 62 as well as introducing fluids from the surface into the annulus 62 , or for venting of fluids within the annulus 62 to surface or another designated location. An annulus wing valve 68 provided within the annulus flow line 66 can be used for selectively allowing flow through the annulus flow line 66 .
[0017] Still referring to FIG. 2 , a crossover line 70 extends from the annulus flow line 66 , at a location upstream of the wing valve 68 and connects to the production flow line 58 upstream of the wing valve 60 . A crossover valve 72 is shown set within the crossover line 70 for controlling flow through the crossover line 70 . A bleed line 74 connects to the crossover line 70 in the portion between the crossover valve 72 and where the crossover line 70 contacts the annulus flow line 66 . A selectively opened and closed bleed valve 76 is provided within the bleed line 74 for venting fluid within the annulus 62 to a location away from the wellhead assembly 40 . Further illustrated in the embodiment of FIG. 2 is how the bleed line 74 is disposed in thermal communication with the production line 58 . As the production fluid within the production flow line 58 is typically heated above that of the fluid in the annulus 62 , thermal energy (represented as Q) will be transferred from the production flow line 58 and into the bleed line 74 . As such, the fluid within the bleed line 74 may be maintained at a temperature sufficient such that hydrates will be prevented from forming within the fluid. Moreover, embodiments exist wherein the amount of heat Q transferred is sufficient to prevent hydrate formation even downstream of the valve 76 where the annulus fluid is let down to a much lower pressure. As is known, the throttling effect across a valve, especially in instances of relatively large pressure drop, can in turn produce a temperature reduction in which hydrate formation production is enhanced. Thus by heating the fluid in the bleed line 74 , especially prior to any pressure letdown such as provided in the bleed valve 76 , hydration formation may be prevented thereby enhancing fluid flow of the annulus fluid.
[0018] FIG. 3 illustrates in a side sectional view an example embodiment of a wellhead assembly 40 A that is configured for avoiding hydrate formation in the annulus fluid. More specifically, in the example of FIG. 3 , fluid from the annulus 62 is routed through a bleed line 74 A that connects directly to the annulus 62 and is piped similar to the embodiment of FIG. 2 so that thermal communication is maintained with the production flow line 58 . As such, the need for the crossover line or spool of FIG. 2 is unnecessary for the venting of fluid within the annulus 62 to a surface location.
[0019] FIG. 4 illustrates yet another embodiment of a wellhead assembly 40 B that allows fluid from the annulus 62 to be conveyed above surface without formation of hydrates. More specifically, the embodiment of FIG. 4 includes a bleed line 74 B that connects to the annulus 62 on one end and to a jacket 78 on an opposite end. The jacket 78 is shown circumscribing the production flow line 58 so that the fluid within the bleed line 74 B flows over and contacts with the outer surface of the production flow line 58 thereby receiving thermal energy from production fluid in the production flow line 58 . Dashed lines illustrate the portion of the production flow line 58 surrounded by the jacket 78 . On a discharge side of the jacket 78 , a bleed line 80 is provided for transferring the annulus fluid to a site away from the wellhead assembly 40 B. The bleed valve 76 is shown integrally provided within the bleed line 80 .
[0020] While the invention has been shown or described in only some of its forms, it should be apparent to those skilled in the art that it is not so limited, but is susceptible to various changes without departing from the scope of the invention.
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A wellhead system for producing hydrocarbons from a subterranean formation that includes concentric tubulars that form an annulus. The annulus is vented by flowing fluid from the annulus through a bleed line having a valve that is selectively opened and closed. Upstream of the bleed line valve, the bleed line is routed adjacent a production flow line. The temperature of the fluid in the production flow line is greater than annulus temperature and warms the bleed line. Hydrate formation in the bleed line is thereby inhibited by the thermal energy it receives from the production flow line.
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BACKGROUND OF THE INVENTION
[0001] The present invention relates to limb protection devices for amputees and, in particular, to a multi-piece, padded, fabric and fleece lined assembly for below-knee amputees, wherein a leg or thigh piece, a stump contact piece, a distal end cap cover piece and a knee or patella cover piece contain resilient contoured inserts and/or foam cushion pieces that support/brace and cushion the thigh, knee and stump end and wherein hook and loop fasteners and stabilizing straps organize and secure the pieces to each other and to the amputee's limb.
[0002] A variety of appliances have been developed for amputees for use during post-operative recovery, therapy and long term maintenance. The devices are typically constructed for particular use with the arms and legs. Some devices serve as dressings during recovery. Some devices mount to the limb to stabilize the stump end and support or cushion a prosthesis mounted to the limb. Some devices include active linkages that cooperate with and stabilize limb movement. U.S. Pat. Nos. 5 , 302 , 169 ; 5 , 529 , 575 ; 5 , 571 , 206 and 5,651,792 disclose devices having active, hinged linkage pieces adapted for use by below-knee amputees.
[0003] Some appliances are used daily after removal of a prosthesis to cover, warm and/or protect the limb and stump, such as during periods of relative inactivity (e.g. when at home or asleep). It is to the latter category that the subject invention belongs. The assembly of the present invention is intended to mount to and warm an amputated limb to promote vasodilatation, maintain blood circulation and prevent ulceration or other physical degradation of the stump. That is, by keeping the limb and stump end warm, the blood vessels don't constrict and healthy blood flow is maintained. The device also physically cushions and warms the limb with minimal skin trauma (e.g. ulcerations, cracking and/or abrasions).
[0004] The present below-knee limb protector assembly was developed to provide a multi-piece light weight assembly that warms, cushions and stabilizes the extremity. The assembly includes a thigh piece having a longitudinal support portion containing a rigid channel member constructed from a resilient and malleable material and several laterally extending cloth covered wings having fasteners that overlap to encase the limb and cooperate with associated strap fasteners. A stump contact piece, end cap piece and knee or patella cover piece contain foam pads to cushion the stump end and knee. Strips of hook and loop fastener material are arrayed about the protector pieces and judiciously overlap to contain the protector pieces to each other and the limb. Buckled straps further support the protector to the limb.
SUMMARY OF THE INVENTION
[0005] It is accordingly a primary object of the invention to provide a thermally insulated protection assembly for below-knee amputees to stabilize, cushion and warm the limb to stimulate blood circulation.
[0006] It is a further object of the invention to provide a below-knee protective assembly comprising several sewn fabric and fleece pieces having a number of hook and loop fasteners fitted to overlapping surfaces of the assembly pieces and associated straps to collectively wrap and fasten to configure and encase the protective device about the thigh.
[0007] It is a further object of the invention to provide a protective device having a thigh piece that contains a longitudinal, foam covered, contoured, resilient channel member shaped to contain and support the thigh.
[0008] It is a further object of the invention to provide a thigh support piece wherein overlapping fleece lined fabric wings contain multiple separated lines of stitching that segregate the wings to accommodate tailor fitting the assembly; presently the stitching is positioned to accommodate differing circumferential limb sizes and wherein the stitching transversely bisects each wing piece and is displaced sufficiently (e.g. 1 to 4 inches) to segment each wing and permit shortening the wing pieces adjacent the stitching without fraying to tailor the length of the wing pieces to fit the circumference of the amputee's limb.
[0009] It is a further object of the invention to provide stump contact cushions, spacers and adjoining end cap pieces that provide cloth/fleece covered foam cushions that directly contact the stump end and/or fill a space between the contact piece and an end cap piece to conform to and cushion the stump end and fasten to a limb encasing thigh piece.
[0010] It is a further object of the invention to provide a knee or patella cover support piece that contains a foam cushion and mounts to a limb encasing thigh piece.
[0011] The foregoing objects, advantages and distinctions of the invention are obtained in a presently preferred fabric covered limb protector assembly of the invention that is lined with fleece. One or more pieces can also contain a thermal insulation. Several overlapping tabs of hook and loop fastener material are arrayed about the surfaces of several wing pieces at a thigh cover piece and detachable knee and end cap fabric cover pieces and mate with other associated fastener pieces and straps. The fasteners at the wings of the thigh piece and detachable knee and end cap pieces align to define and selectively control the fitting of the protective assembly to the amputee's thigh and stump.
[0012] The thigh piece contains a longitudinal foam covered, rigid channel member constructed from a resilient and malleable material having a contoured channel that supports the posterior surface of the thigh and knee. Laterally extending wing portions extend such that the thigh piece exhibits a general “H” shape. The wing pieces include displaced lines of transverse stitching organized and arranged to permit cutting and shortening the wing pieces to fit different thigh circumferences. The length of at least one wing piece can thereby be tailored to assure a proper fit about the circumference of an amputee's thigh upon wrapping and overlapping the wing pieces onto each other.
[0013] Hook and loop fasteners are secured to external fabric and internal fleece surfaces of the assemblies' pieces and are aligned to overlap and secure the protective assembly to the amputee's thigh. Other accessory, extension pieces having tabs of hook and loop fastener material can be mounted to the thigh piece wings to extend the wings to fit amputees with large diameter thighs.
[0014] A stump cover or end cap piece contains a foam cushion and provides a fleece liner and mates to the stump end. Associated fabric/fleece covered foam spacers can be added to fill the longitudinal space of the thigh piece.
[0015] An end cap piece contains a foam cushion and wing pieces that support tabs of hook and loop fastener material and mount to the thigh piece to contain the stump cover and filler pieces to the thigh cover piece.
[0016] A fabric and fleece covered knee or patella cover piece contains a foam cushion and supporting sewn strips and straps of hook and loop fastener material that overlap and mount to the thigh piece to cover the knee.
[0017] Still other objects, advantages, distinctions and constructions of the invention will become more apparent from the following description with respect to the appended drawings. Similar components and assemblies are referred to in the various drawings with similar alphanumeric reference characters. The components can be combined in various combinations and with other limb protection assemblies. The description should therefore not be literally construed in limitation of the invention. Rather, the invention should be interpreted within the broad scope of the further appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 is a perspective drawing of the leg protector assembly removed from an amputee's leg and wrapped and buckled to a closed condition with the knee and end cap pieces mounted to the leg or thigh cover piece.
[0019] FIG. 2 is a perspective drawing of the leg protector assembly folded open and showing the relative positioning of a portion of an amputee's leg to the leg or thigh cover, the knee cover, stump cover, and end cap pieces and an accessory foam filler pad that mounts between the stump cover and end cap pieces and wherein a cutaway view is shown to an internal foam cushioning and/or a possible thermal insulation/cushioning material.
[0020] FIG. 3 is a rear perspective drawing of the leg protector assembly folded open with the knee and end cap cover pieces detached, along with a detached thigh wing extension piece and wherein cutaway views depict an elongated rigid thigh channel support member and foam cushioning liners mounted in the thigh cover piece and several foam pads mounted in the knee cover, stump cover and end cap pieces.
[0021] FIG. 4 is a rear perspective drawing of the leg protector assembly folded open with the knee and end cap cover pieces attached to the thigh cover piece and wherein stump cover end cap and spacer pieces are shown removed from the assembly.
[0022] Similar structure throughout the drawings is referred to with the same alphanumeric reference numerals and/or characters.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0023] Referring to FIGS. 1-4 several perspective views are shown in various stages of assembly to the present invention of a therapeutic leg protector assembly 2 for partial leg (e.g. below-knee) amputees. The leg protector assembly 2 is constructed of several sections or pieces that assemble to form the protector 2 shown removed from a wearer's leg in a fully assembled condition in FIG. 1 . The several pieces of the protector 2 are constructed from an air permeable fabric cover material 4 . The cover material 4 is presently sewn from a durable velour cloth. Other materials such as a heavyweight cotton fabric, CORDURA® or other fabrics or laminated/layered fabric and insulation combinations might also be used.
[0024] The interior surface of the cover material 4 is lined with a fleece material 6 . A thermal insulation material 8 shown in partial cutaway at FIG. 2 , if desired, can also be mounted between the cover material 4 and the interior fleece lining 6 . A suitable thermal insulation material 8 can for example comprise THINSULATE® or any of a variety of other cushioning and insulating materials. The fleece 6 and any provided insulation material 8 collectively provide a thermal barrier to maintain the temperature of a covered limb 9 to promote dilation of the blood vessels and blood flow through the covered extremity.
[0025] The leg protector 2 when fitted to an amputated limb, such as the leg or thigh, is assembled from a number of separate pieces that are positioned to the limb and sequentially overlapped and fastened or attached to each other. When fully assembled the protector 2 covers, warms and protects the amputee's limb.
[0026] With attention to FIG. 2 and during fitting, an elongated, “H-shaped” leg or thigh piece 10 is typically laid out and the wearer's limb 9 is aligned to lie in a longitudinal center portion that defines a channel or trough space 11 . The trough space 11 exhibits a contoured curvature (e.g. arcuate) when viewed end on. The curvature is defined by a resiliently rigid, generally “U-shaped” channel or trough member 12 contained in the longitudinal center portion of the thigh piece 10 , see FIG. 3 . Prior to mounting the protector assembly 2 , the limb 9 can be wrapped with a gauze material or other suitable cover or sock 7 can be mounted to the limb.
[0027] The channel member 12 extends substantially the length of the thigh piece 10 . The channel member 12 is presently constructed of a resilient plastic material. The material is generally rigid but can flex laterally and torsionally without breaking. A variety of different plastics, KEVLAR®, polymers, compositions or metal materials can be used to form the channel member 12 . The contour of the channel shape might also be adjusted depending upon the limb and for example might be molded or formed into a preferred shape prior to or after mounting in the thigh piece 10 . Depending upon the material, heat or other external energy sources can be used to tailor contour the channel space 11 .
[0028] One or both of the posterior and anterior surfaces of the channel member 12 can be covered with a layer of foam 14 . The channel member 12 mounts in a longitudinal pocket defined by lines of stitching formed between the cover and fleece liner materials 4 and 6 . The limb 9 (e.g. leg or thigh) of an amputee when fitted to the thigh piece 10 nests in the curvature of the channel space 11 and the internal fleece lining 6 and underlying foam layer 14 conform about the limb 9 . The thigh and knee are simultaneously supported in coaxial alignment with the channel space 11 and the knee is generally immobilized.
[0029] Once the thigh and knee are fitted into the thigh piece 10 a space can exist at the end of the amputee's stump. A stump contact cover piece 20 is then positioned in the space to contact the distal or stump end of the limb. The stump cover piece 20 provides a fabric cover 22 and fleece liner 24 that are sewn together to contain a generally cylindrical foam pad 26 . The fleece end 24 is mounted to contact the stump end. Depending upon the length of the limb relative to the thigh piece 10 , one or more cloth covered foam filler pieces 26 can be mounted distal to the stump contact cover piece 20 , see FIG. 4 .
[0030] An end cap piece 30 having a fabric cover 32 and fleece lining 34 and containing a foam pad 36 is next fastened to the thigh cover piece 10 . Tabs of hook and loop fastener material 38 and 40 that are adhered or affixed such as by sewing to the fleece lining 34 and fabric cover material 4 of the thigh piece 8 are overlapped and fastened together to hinge the end cap piece 30 to the thigh piece 10 . The end cap piece 30 can thereby pivot relative to the distal end of the thigh piece 10 to align the foam pad 36 of the end cap 30 with the stump cover piece 20 and any filler pieces 26 .
[0031] A tongue portion 42 extends from the end cap piece 30 and independently folds to mount over the anterior surface of the contained limb 9 and stump cover piece 20 . Wings or straps 43 of hook fastener material 38 laterally extend from the end cap piece 30 and separately attach to longitudinal tabs of loop fastener material 40 attached to external sides of the thigh piece 10 . Upon folding the tongue 42 over the stump end and stump cover 20 and securing the fastener straps 43 to the thigh piece 10 , the stump contact piece 20 and filler pieces 26 are held in place.
[0032] The remainder of the limb protector pieces are next arranged and secured to each other to fully secure the protector assembly 2 to the amputee's limb. The thigh piece 10 is secured to the limb and end cap piece 30 with upper and lower wing or arm portions 50 and 52 and 54 and 56 that extend from longitudinal sides of the thigh piece 10 . The relatively short side arm portions 52 and 56 extend approximately 1 to 2-inches and contain tabs of appropriate hook/loop fastener material 38 or 40 sewn to the fleece lining 6 .
[0033] The relatively longer upper arm portions 50 and 54 are constructed to lengths on the order of 8 to 14-inches to accommodate thighs of differing circumference. The arm portions 50 and 54 include displaced lines of sewn stitching 60 that segment and define a series of tabs 62 at each arm portion 50 and 54 . A tab 62 can be severed from the thigh piece 12 by cutting between the lines of stitching 60 or in other fashions without producing fraying at the severed edges. The paired lines of stitching 60 separate the wing arms 50 and 54 into several tabs 62 and each tab sized in a range of approximately 2 to 4 inches in length. Depending upon the amputee, one or more tabs 62 can be severed to tailor fit the length of the wings 50 and 54 to the circumference of the bound limb. The extraneous tabs 62 are severed at or between the stitching lines 60 without fraying or separation of the fabric and fleece layers 4 and 6 . It is to be appreciated single lines of stitching 60 might also be used to accommodate tailor fitting.
[0034] Upon wrapping the wing arms 52 and 56 over the limb and overlapping the arms 52 and 56 with the arms 50 and 54 , tabs of appropriate hook/loop fastener material 38 or 40 sewn to the fabric cover material 4 and fleece lining 6 at the arms 52 and 56 mate with the fastener tabs at the arms 50 and 54 to secure the thigh piece 8 to the limb 9 . The overlapped arms 52 and 56 also bind the tongue portion 42 of the end cap piece 30 to the limb.
[0035] One or more fabric 4 and fleece 6 covered wing extension pieces 64 (one of which is shown at FIG. 3 ) can be fastened to the arms 50 - 56 to appropriately extend the length of the overlapping combined arm pieces 50 , 52 and 54 , 56 to fit amputees having thighs of large circumferences.
[0036] The protector assembly 2 is further secured to an amputee's limb by additionally wrapping buckled straps 70 sewn to the cover material 4 at the wing arms 50 - 56 to independently overlap the fastened wing arms 50 - 56 . Mating buckles 72 and 74 sewn to the ends of the straps 70 are then fastened to securely attach the thigh piece 10 to the amputee's limb, see FIG. 1 . A variety of different types of mating buckles and fasteners can be used to secure the ends of the straps 70 .
[0037] A knee or patella cover piece 80 is next affixed to the thigh piece 10 . The knee cover piece 80 comprises an envelope of fabric 4 and fleece 6 material that contain a foam cushion piece 82 . Straps 84 extend from the fabric cover material 4 and support tabs of hook/loop fastener material 38 and/or 40 . The knee cover piece 80 is mounted over the wrapped thigh cover 10 to cover the amputee's knee and the straps 84 are secured to the longitudinal tabs of hook/loop fastener material 38 and/or 40 that extend along the sides of the thigh piece 10 .
[0038] While the invention has been described with respect to a number of preferred constructions and considered improvements or alternatives thereto, still other constructions may be suggested to those skilled in the art. It is also to be appreciated that selected ones of the foregoing features can also be used singularly or be arranged in different combinations to provide a variety of improved therapeutic limb wear. The foregoing description should therefore be construed to include all those embodiments within the spirit and scope of the following claims.
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A multi-piece therapeutic cover that assembles to warm, cushion and stabilize the thigh of a below-knee amputee. A thigh piece contains a resiliently rigid channel piece and several laterally extending, wings including sizing tabs that overlap and cooperate with associated straps. A stump contact piece, end cap piece and knee cover piece contain foam pads to cushion the stump end and knee. Strips of hook and loop fastener material arrayed about the surfaces of the protector pieces judiciously overlap to contain the protector pieces to each other and the limb. Buckled straps further support the protector assembly to the limb.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Pat. No. 9,284,019 filed on May 16, 2014 and issued on Mar. 15, 2016 and claims priority to U.S. Provisional Application Ser. No. 61/824,339 filed on May 16, 2013, the contents of which are hereby incorporated in their entirety.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable.
NAMES OF PARTIES TO A JOINT RESEARCH AGREEMENT
[0003] Not Applicable
REFERENCE TO SEQUENCE LISTING, A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED ON A COMPACT DISC AND INCORPORATION-BY-REFERENCE OF THE MATERIAL
[0004] Not Applicable.
COPYRIGHT NOTICE
[0005] A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. 37 CFR 1.71(d).
BACKGROUND OF THE INVENTION
[0006] 1. Field of Endeavor
[0007] The present invention relates to apparatuses, systems and methods for improved boat of both mono-hull and multi-hull designs. More particularly, the invention relates to boat hulls modified to provide better fuel economy, maneuverability, a smoother ride at both high and low speeds, less side to side rolling motion when stationary in waves and greater weight carrying capacity.
[0008] 2. Background Information
[0009] Boat hull design has been a constantly evolving field of art for thousands of years. In particular, the development of non-wind propulsion systems, material science and other technologies, has contributed to many advances in hull design over the past two hundred years.
[0010] Flat-bottom boats have a large, substantially flat hull bottom, making them very stable in calm weather. Characteristically, however, the flat, broad bow area creates a rough ride. These boats are usually limited to low horsepower motors because they do not generally handle well at high speed. Flat-bottom boats are also well suited for shallow water.
[0011] Early in nautical history, boats were powered by wind or by hand-stroked oars. Early boat designers found that boats went faster, and were easier to steer, if the bow was pointed. They also soon discovered that by lowering the center of gravity, the sailing boats had better stability, and usually kept the boat upright even in bad weather.
[0012] With the advent of mechanical power came boats with “planing” hulls, which lift the boat partially out of the water to skim on the surface allowing the boat to be operated at higher speeds for the same power. “Displacement” hulls push through or cruise through the water instead of skimming on the surface and are not able to operate at the higher speeds of a planing hull.
[0013] “Semi Displacement” hulls act in a manner part way between Displacement hulls and Planing hulls. At slow speeds they are more efficient than Planing hulls but not as efficient as Displacement hulls, while at medium speed they are more efficient than both Displacement and Planing hulls. Semi Displacement hulls are not usually able to operate at the high speeds typical of Planing hulls but are able to operate efficiently at higher speeds than a Displacement hull.
[0014] The V bottom boat is probably the most common hull design for planing hulls. Most manufacturers of performance boats built today use variations of this design. This design offers a reasonable ride in rough water as the pointed bow slices through the water forward and the V-shaped bottom softens the slamming of the boat in waves. The angle of the V is called “deadrise”. A sharper V has more deadrise. Some “V”-bottom boats have a small, local flat surface at the very bottom of the aft end called a “pad.” This pad creates a little more lift which increases top speed but at the sacrifice of a little softness in the ride.
[0015] A chine in V bottom planing or semi-displacement power boat hull forms refers to the hard corner or edge at the intersection between the hull bottom and the hull side.
[0016] With sailboats, it is common to have a rounded hull with no strakes or chines. A keel is often employed. However, the keel of a sailboat generally is generally deep vertically in proportion to the overall depth of the hull. On modern designs, it does not typically run the length of the boat.
[0017] Boats having a flatbottom, are stable at low speed while also being maneuverable and provide a large displaced volume for a given draft, thus accommodating more weight.
[0018] A deep V hull provides a relatively smooth ride at high speed. However, at low speed a deep V hull is very inefficient. Furthermore, at low speeds, a deep V hull is less stable, less maneuverable and tends to roll side to side to a high degree when side on to the waves.
[0019] Many attempts have been made to design hulls that combine features of flatbottom, round and/or deep V hulls in an effort to design hulls exhibiting the advantages of each.
[0020] In view of the foregoing, there is a need to provide a hull design that performs well at both high and low speeds. It is therefore desirable to provide a hull combining improved performance and ride comfort of any of the existing hulls at speed and in waves and improved comfort of any of the existing hulls at slow speed in waves and when stationary in waves.
BRIEF SUMMARY OF THE INVENTION
[0021] Accordingly, the primary object of the present invention is to provide a boat hull that provides a smooth ride at both high and low speeds with good fuel economy and maneuverability.
[0022] A high and moderate speed boat hull incorporates a keel running the center line of the hull starting 20 to 25% aft of the bow continuing aft 75 to 80% from the bow. The hull has a larger V shaped forward section twisting and flattening out running aft to a much lesser of a V with combinations of flat keel pad and ellipsoidal shaped areas. The keel provides both lift and lessens impact in rough water. The keel has a convex shape vertically and is shallow compared to any other keel. the keel starts thin and is narrow widening aft and tapers gently back to a point with an angel rising aft and up to the hull. This aft shape of the keel directs or allows the water to flow naturally back together over the flat keel pad to create solid water to feed to the engine propeller or propellers. The flat keel pad has two purposes: 1. a dedicated support for the vessel's riding or planning angle. 2. Is it is actually a step and allows the vessel to pivot at high speed and at all speeds giving the vessel greater maneuverability. The V port and starboard of the keel is the area feeding the lifting strakes. The lifting strakes works with the keel to provides positive lift and continues to create the softness of the ride these areas provide. The lifting strakes are shaped in a triangular manner pointing downward and has a radios inside of the lifting strake helping to create the curl of the natural shape of waves both providing lift and softness of the ride in a choppy or rough sea. Outside the lifting stakes continues the genital ellipsoidal shape of the hull and feeds the water out and aft. The spoilers also provide lift both forward in the lager V area and moving aft to the chine flats.
[0023] The spoilers also provide softer looser water or soiled water to the chine flats aft relieving friction of wetted surface of the hull. The chine flats are wider than most of any hull designs. The chine flats provide stability at rest and on plane at high speed and in a side rougher sea. The chine flats also provide a positive buoyancy giving and assisting the keel and the lifting strakes and the hull a direct attitude from rest to a full plane without squatting, digging or typically raising the bow high out of the water which also allows the vessel to reach a plane and high speed in very shallow water. The chine flat has a step 5 to 10% forward of the transom relieving friction of the wetted surface of the hull. The chine flats are assisted by the bracket or extension which is also a step. The bracket has a large flat bottom angling downward aft of the transom creating more assist in planning as a large trim tab.
[0024] The bracket adds buoyancy to support the weight of engine or engines. The bracket provides positive lift in a following sea lifting up on the inside of the wave and moving the vessel forward decreasing or eliminating the sea engulfing the engine or engines and or sinking the vessel. The bracket's large flat area adds additional stability supporting the chine flats in the side to side motion laying to in large seas preventing violent rocking motion of this vessel. the bracket is also a step allowing this vessel design to pivot over the water aft of the transom and as the bracket dose not touch the water at speed or plane it does not create drag at speed.
[0025] These and other objects and advantages of the present invention will become apparent from a reading of the attached specification and appended claims. There has thus been outlined, rather broadly, the more important features of the invention in order that the detailed description thereof that follows may be better understood, and in order that the present contribution to the art may be better appreciated. There are features of the invention that will be described hereinafter and which will form the subject matter of the claims appended hereto.
BRIEF DESCRIPTION OF THE DRAWINGS
[0026] A more complete understanding of the present invention, and the attendant advantages and features thereof, will be more readily understood by reference to the following detailed description when considered in conjunction with the accompanying drawings wherein:
[0027] FIG. 1 is a forward perspective view of a boat hull in accordance with the principles of the invention;
[0028] FIG. 2 is a bottom perspective view of a boat hull in accordance with the principles of the invention;
[0029] FIG. 3 is a side perspective view of a boat hull in accordance with the principles of the invention;
[0030] FIG. 4 is another perspective view of a boat hull in accordance with the principles of the invention;
[0031] FIG. 5 is another bottom perspective view of a boat hull in accordance with the principles of the invention;
[0032] FIG. 6 is bottom plan view of a boat hull in accordance with the principles of the invention;
[0033] FIG. 7 is a diagram of a chine of a boat hull having a bulge in accordance with the principles of the invention;
[0034] FIG. 8 is a cross-section of a lifting strake or spoiler of a boat hull in accordance with the principles of the invention;
[0035] FIG. 9 is a side view showing sections of a boat hull in accordance with the principles of the invention;
[0036] FIG. 10 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0037] FIG. 11 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0038] FIG. 12 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0039] FIG. 13 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0040] FIG. 14 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0041] FIG. 15 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0042] FIG. 16 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0043] FIG. 17 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0044] FIG. 18 is a cross-sectional view of a boat hull in accordance with the principles of the invention;
[0045] FIG. 19 is another perspective bottom view of a boat hull in accordance with principles of the invention;
[0046] FIG. 20 is a bottom perspective view of a keel of a boat hull in accordance with the principles of the invention;
[0047] FIG. 21 is a side elevation will view of a keel of a boat hull in accordance with the principles of the invention;
[0048] FIG. 22 is a bottom plan view of a keel of a boat hull in accordance with the principles of the invention;
[0049] FIG. 23 is a cross-sectional view of a keel of a boat hull in accordance with principles of the invention;
[0050] FIG. 24 is a side elevation oh view of a bracket of a boat hull in accordance with the principles of the invention;
[0051] FIG. 25 is a rear perspective view of a bracket of a boat hull in accordance with the principles of the invention.
DETAILED DESCRIPTION
[0052] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.
[0053] Disclosed is a hull design that improves the stability of a boat at low speed and efficiency at high speed. The forward region of the hull may have a bulbous, i.e. ellipsiodal, area that may be centered around the chine within the impact zone of the boat. The impact zone is the area or region of the hull impacted by water projecting upward due to the hull moving through water and is generally in a region extending from about 15% to about 35% down the length of the bottom of the hull. Modified chines and strakes may by combined to reduce drag at lower speeds typical of a flatbottom boat while also having the stability of a deep hull boat at higher speeds. Lifting strakes, or spoilers, may also contribute to reduce drag. An aft centerline pad may also be incorporated into the hull design.
[0054] The hull may also have a mid and aft ellipsoidal fullness aft of the forefoot and forward ellipsiodal fullness. The ellipsoidal fullness may continue to a lesser extent all the way to the transom. Without being bound by theory, the inventor believes that the mid and aft ellipsiodal fullness may work synergistically with the forefoot and forward ellipsiodal fullness to allow for a more natural water flow and makes for a smoother ride in large chop conditions.
[0055] The chine near the bow may be of a conventional design, but may include a bulge or fullness in the impact zone. Aft of the bow, in the area at the aft end of the forefoot and forward ellipsiodal fullness, the chine flat may become wider and may sweep around the mid and aft ellipsoidal fullness. The dead rise angle of the hull in this area may gradually flatten until it becomes a continuation of the chine flat as one wide surface on each side of the hull. This wide chine flat may continue aft with a slight negative dead rise angle. The wide chine flat may vary in dead rise and width, and may be stepped. The hull and chine flat in accordance with the invention may create extremely high levels of stability both at speed and when stationary in wave and cross wave conditions.
[0056] A keel may begin at a point aligned with the impact zone and extend aft along the centerline to a point near the hull's center of gravity. The keel may be shallow keel and extend aft widening along a convex path and having concave sides. The keel may blend into the hull with a large radius. The keel may have a tear drop shape similar to an airfoil, but in a direction opposite to a NACA keel. The aft end of the keel may taper to a fine section to promote clean water flow. The keel may promote natural water flow, and may enhance slow speed and at rest stability especially in cross waves, and works together with the forward ellipsiodal fullness and the mid and aft ellipsoidal fullness to create a smoother ride in large chop conditions. A flat centerline pad may provide lift at speed and is also used to control planing attitude in extreme conditions.
[0057] On each side of the hull there may be one or more lifting strakes also to be known as spoilers. The outboard edges of the spoilers may be lower than the inboard edges (negative deadrise) and the inboard and outboard edges may be blended into the hull with a radius on each edge. Without being bound by theory, the spoilers may create lift and may simultaneously interact synergistically with the keel and with the wide aft chine flat to create a smoother, more stable ride in large chop conditions and in slow speed or when stationary in cross wave conditions.
[0058] FIGS. 1-6 show one exemplary embodiment a boat hull 100 in accordance with the principles of the present invention. The boat hull 100 may be generally described as having a modified V-hull. The hull 100 includes a keel 120 , a spoiler 170 and a lifting strake 140 . The lifting strake 140 runs parallel to and equidistant from both the keel 120 and the spoiler 170 . The hull 100 has a V-shaped forward region, and the hull bottom twists down the length of the hull and the lateral region 184 flattens out as it travels down the length of the hull 100 so that it becomes a chine flat 180 which extends to the stern.
[0059] The boat hull 100 has a bow 112 and stem 114 . Those skilled in the art will appreciate that the term stem is used to refer to the leading edge of a boat hull. The hull 100 has a total length defined by the bow 112 and the transom 116 . The bottom 118 of the boat hull 100 is generally defined as the portion of the hull 100 below the chine 182 . The length of the bottom 118 is generally defined as the distance between the transom and the point 115 where the stem 114 intersects the chine 182 . Generally, when identifying a position on the hull 100 by the approximate percentage of the distance along the hull length, it is in reference to the length of the hull bottom 118 below the chine.
[0060] The keel 120 is aligned with the centerline 122 of the hull 100 . In this embodiment, the keel begins at a point on the hull bottom 118 about 20-25% aft of the bow and continues aft to a terminal end 124 to a point about 75-80% from the bow 110 . Without being bound by theory, the inventor believes that the keel 120 provides both lift and lessens impact in rough water.
[0061] The bottom 118 of the hull 100 , for clarity in defining certain aspects of the invention, may be characterized as having regions. The regions of the bottom 118 between the keel 120 and the lifting strake 140 is referred to herein generally as the medial region 130 . The region of the bottom 118 between the lifting strake 140 and the spoiler 170 is referred to herein as the intermediate region 160 . The region of the bottom 118 between the spoiler 170 and the chine 182 is referred to herein as the lateral region 184 . The lateral region 184 has almost the same dead rise angle and is almost parallel to the medial 130 in the intermediate 160 regions of the hull in the forward region 110 of the hull 100 . As the lateral region 184 extends aft, it twists from the forward configuration into a substantially horizontal configuration, thereby forming the chine flat 180 .
[0062] Referring to FIGS. 3 and 4 , the boat hull 100 has an “impact zone” 104 located within a region 15-35% down the length of the hull bottom 118 . This is the region where water impacting the forward region 110 of the hull 100 is projected into the air by the force of the impact with the hull 100 as it travels through the water.
[0063] Referring to FIGS. 5 and 6 , the region 174 of the hull bottom 118 located aft of the spoilers 170 is radiused, i.e. is curved rather than having a pointed angle. This facilitates the movement of water and a more natural manner. The spoilers 170 typically have a terminating end 178 located at substantially the same point along the length of the hull 100 as the widest point 126 of the keel 120 . For clarity, the lifting strakes 140 are not shown in FIGS. 7-13 . However, in the other figures it may be seen that the lifting strakes 140 has terminating ends 148 closer to the bow than the terminating ends 178 of the spoilers 170 . FIG. 6 also shows a pad 217 extending from a step 215 . In some embodiments, the pad 217 may be referred to as a trimtab. Generally, the step 215 is relatively small, only an inch or two. This additional step 215 and pad 217 improve maneuverability of the vessel.
[0064] The region 186 of the chine 182 , in accordance with the principles of the invention, has a slight bulge 185 as shown in FIG. 7 . V-hull boat designs typically include components that are substantially parallel to one another. It is common for the chine, strakes and other components to follow the lines of the hull itself and run parallel. A hull 100 of the present invention, however, includes a region 186 within the impact zone 104 more or less centered around the chine 182 having a bulge 185 that is not parallel with the other components of the hull 100 and extends outward from line 187 which illustrates a normal curve of a chine parallel to the hull bottom 118 . Without being bound by theory, the inventor believes that the bulge 185 engages water projected upward in the impact zone and uses the force of the water to stabilize the hull 100 to provide a smoother ride and/or facilitate planing of the hull and/or improve maneuverability of the boat.
[0065] Both the lifting strake 140 and the spoiler 170 may have a substantially triangular cross-section similar to common strakes. Optionally, the lifting strake 40 and the spoiler 170 may have a modified design with a convex lateral side 142 and a concave medial side 144 as shown in FIG. 8 . Without being bound by theory, the inventor believes that the medial curvature along the strakes and spoilers facilitates a natural water flow, thereby improving efficiency of the design and providing a smoother ride of the boat itself.
[0066] FIGS. 9-18 show section profiles A-I of the hull 100 along the lateral, or transverse, planes identified in FIG. 9 . Section A is 15% down the length of the hull bottom 118 . Section B is 21% down the length. Section C is 26% down the length. Section D is 35% down the length. Section E is 44% down the length. Section F is 59% down the length. Section G is 71% down the length. Section 8 is 77% down the length. Section I is 97% down the length.
[0067] FIG. 10 shows section A which is located near the forward edge of the impact zone 114 , and shows the bulge 185 . The dead rise of the hull bottom 118 is greatest here. The lateral region 184 has a slightly smaller dead rise angle, due in part to the bulge 185 . FIG. 11 shows section B which is located just aft of the bulge 185 . Here, the lateral region 184 still has a dead rise angle slightly less than the dead rise angle of the medial and intermediate regions 130 and 160 , respectively. FIGS. 12 and 13 , showing lateral sections C and D, respectively, also show the lateral region 184 having a dead rise angle almost equal to the dead rise angle of the other regions of the bottom 118 . This is due more to the flattening and decreasing dead rise angle of the medial and intermediate regions 130 and 160 as they move down the length of the hull bottom 118 than it is to a change in the dead rise angle of the lateral region 184 . The bulge 185 in this embodiment is positioned in the forward region of the impact zone. The bulge may optionally be located at a different place within the impact zone or throughout the entire impact zone 114 . Those skilled in the art will appreciate that the bulge 185 does not greatly diverge from a line 187 parallel to the other regions of the hull 100 . The bulge 185 may optionally be larger or more pronounced. However, this is not necessary in order to obtain the beneficial results provided by the present invention.
[0068] The spoiler 170 can be seen in sections A-G as positioned within the crux formed at the medial end of the lateral region 184 . The keel 120 begins near section C shown in FIG. 12 and is first noticeable in section D shown in FIG. 13 . The keel 120 reaches its highest and widest point near section G shown in FIG. 16 . Section H, shown in FIG. 17 is aft of the keel. FIGS. 17 and 18 show sections H and I, respectively, where the keel pad 150 can be seen. Sections F-I show the lateral region 184 where it has become a chine flat 180 having a dead rise angle of about zero. The dead rise angle of the chine flat may preferably be between 5° and −5°. Referring to FIGS. 17 and 18 , it may be seen that the aft region of the hull bottom 118 includes three flat regions, the two chine flats 184 and the pad 150 . In addition, the medial region 130 and intermediate region 160 , while not flat, have a relatively small dead rise angle.
[0069] FIGS. 19-23 show the keel 120 in more detail. The keel 120 has a rounded edge 125 and the sides 121 of the keel 120 are radiused, with a concave transverse profile. The keel 120 is shallower than most keels. The keel 120 is narrow at its front 124 and widens as it moves aft. The keel's widest point 126 is proximal to the center of gravity of the hull 100 . Aft of point 126 , the keel 120 tapers downward along a curved aft end 127 and intersects the bottom 118 of the hull 100 at the forward end 152 of the keel pad 150 . Without being bound by theory, the inventor believes that the aft shape of the keel 120 directs or allows the water to flow naturally back together over the flat keel pad 150 to create solid water to be feed to the engine propeller or propellers.
[0070] The spoilers 170 have terminal ends 178 approximately aligned with the end of the keel 120 . The terminal ends 148 do not extend as far aft as the spoiler terminal ends 178 or the keel 120 . Without being bound by theory, the inventor believes that by having the spoilers 170 and the keel 120 longer than the lifting strakes 140 , water flowing over the hull 100 flows more naturally, creating less friction and more stability at both low and moderate speeds.
[0071] The keel 120 itself, referring now to FIGS. 20-23 , has a configuration similar to an airfoil, such as those promoted by NACA and considered fairly standard in hull design, but is inverted in accordance with the principles of the present invention. A typical NACA keel design has a relatively short and blunt forward end with a long, very gently sloping trailing end similar to an airfoil on an airplane. Keel 120 may be referred to as an inverted foil design.
[0072] The keel 120 of the present invention is similar to a NACA keel, but in reverse. The front of the keel 124 has a relatively sharp point. Leading edges 129 of the keel 120 provide a very gradual increase in width of the keel 120 along the length of the hull bottom 118 . Leading edges 129 may be slightly convex. The sides 121 of the keel are themselves concave, as shown in FIG. 23 . The keel 120 expands as it travels down the hull until it reaches its widest point 126 . The keel 120 begins along the centerline at its front end 124 which is located in the same region as the impact zone. That is, the keel 120 typically begins between 15% and 30% down the length of the hull bottom 118 . The widest point 126 is aligned with or very close to the center of gravity of the vessel. The aft end 127 of the keel 120 is located just aft of the widest point 126 and curves down in a concave manner and joined the hull bottom 118 at or near the forward end 152 of the centerline pad 150 . In this embodiment, the keel 124 begins at about 22% down the length of the hull bottom 118 , has a widest point at about 70% down the length of the bottom 118 and ends at about 75% of the length of the bottom. The leading portion of the keel, measured from the front 124 to the widest point 126 , is therefore about 5 times the length of the trailing portion 127 of the keel, measured from the widest point 126 to the end 131 where it meets the bottom 118 proximal to the leading edge 152 of the centerline pad 150 . That is, may be in the aft ⅔ of the keel, and may preferably about ⅚ aft of the total length of the keel. Generally, the leading portion of the keel is longer than the trailing portion of the keel. The trailing portion 127 is concave, but the trailing edges 133 around the trailing side 127 , where the keel meets the bottom 118 , may have a convex figuration, resembling the blunt end of a foil, or may optionally be straight.
[0073] The flat centerline pad, or keel pad, 150 is positioned aft of the keel 120 and extends to stern of the hull bottom 118 . The function of the keel pad 150 is to keep the aft end on centerline from digging in at low speeds and in turns, which allows the boat to pivot within its own length on a point at the end of the keel at any speed. It also assists in bringing an early onset to planing during acceleration. Without being bound by theory, the inventor believes that the flat keel pad 150 serves two purposes. First, it is a dedicated support for the vessel's riding or planning angle. Second, it acts as a step and allows the vessel to pivot at high speed and at all speeds giving the vessel greater maneuverability.
[0074] The medial region 130 of the hull bottom 118 , defined as the area of the hull bottom on both the port and starboard sides of the keel 120 between the lifting strakes 140 . The medial region 130 extends from the bow all the way aft to the transom 116 . In this embodiment, it has a deadrise angle of about 40-45 degrees at the bow 112 , which twists and flattens, to about 17-20 degrees at the transom 116 . This medial region 130 is bounded by the keel 120 inboard and the lifting strake 140 outboard. The medial region 130 is believed to function to dynamically lift the boat at speed and to provide the primary buoyancy area of the hull when planing.
[0075] The intermediate region 160 is the strip of bottom 118 outboard of the lifting strakes 140 and inboard of the spoiler 170 . The intermediate region extends from the stem 114 all the way aft to the transom 116 . It has a deadrise angle identical to the medial region 130 . The inventor believes that the intermediate regions 160 function to provide dynamic lift at moderate speeds as the boat gets up on plane.
[0076] The lateral region 184 is the strip of bottom 118 outboard of the spoiler 170 and inboard of the chine 182 , which extends from the stem 114 to the transom 116 . The portion of the intermediate region 160 located past the terminal end 178 of the spoiler 170 transitions into the lateral region 174 by a fillet, or radiused area, 174 running from the terminal end 178 of the spoiler 170 to the transom 116 . The fillet 174 is believed to allow the water to flow smoothly without abrupt changes of direction from the deadrise below to the much flatter deadrise of the chine flat 180 . The intermediate region 160 has a deadrise angle of about 50-52 degrees at the bow, which twists and flattens into the chine flat which has between a 5 and −5 degree deadrise. The function of Area 4 is to provide dynamic lift at sub-planing speeds in order to start the boat up on plane. Trim tab pockets are set in the aft end of Area 4 to mount adjustable trim tabs should they be needed.
[0077] When in motion, the keel 120 and the lifting strakes 140 feed water flowing through the lifting strakes 140 . The keel 120 is a vertical appendage to the hull on centerline, which adds longitudinal running stability to improve yaw control while planing. This structure tapers from thin at the bottom to thicker at the top, and has a small fillet at the transition to medial region 130 . The purpose of this is to provide a gentle turning of the water flow from horizontal up and over onto the deadrise angle of region 130 without abrupt changes that cause hydrodynamic drag. The keel 120 may run aft from about 20-25% aft of the bow, to 75-80% of the length from the bow where it terminates with a radiused end to aid in developing a combination of flow separation and smooth rejoining of the water as it flows from the rear end.
[0078] The lifting strakes 140 works with the keel to provides positive lift and continues to create the softness of the ride these areas provide. The lifting strakes 140 are shaped in a triangular manner pointing downward and has a radios inside of the lifting strake 140 helping to create the curl of the natural shape of waves both providing lift and softness of the ride in a choppy or rough sea. Outside the lifting stakes 160 continues the genital ellipsoidal shape of the hull 100 and feeds the water out and aft. The spoilers 170 also provide lift both forward in the lager V area and moving aft to the chine flats 180 . The Lifting Strakes 140 run from the bow aft to approximately 75% of the length of the hull. These strakes run approximately parallel to the chine, instead of tracing a waterline or buttock. In the midsection the lifting strakes flatten to horizontal, which causes the boat to run at a low bow trim angle near 0 degrees. These strakes also separate water flow from the area 2 strip, reducing friction and thus provide dynamic lift when the boat is fully planing.
[0079] The spoilers 170 also provide softer looser water or soiled water to the chine flats 180 aft relieving friction of wetted surface of the hull 100 . The chine flats 180 are wider than most of any hull designs. The chine flats 180 provide stability at rest and on plane at high speed and in a side rougher sea. The chine flats 180 also provide a positive buoyancy giving and assisting the keel 120 and the lifting strakes 140 and the hull 100 a direct attitude from rest to a full plane without squatting, digging or typically raising the bow high out of the water which also allows the vessel to reach a plane and high speed in very shallow water. The chine flat 180 has a step 215 5 to 10% forward of the transom 116 relieving friction of the wetted surface of the hull 100 . The chine flats 180 are assisted by the bracket or 210 which is also a step.
[0080] FIGS. 24-25 show the bracket 210 extending aft from the transom 116 . The bracket 210 is defined by two sides 230 , a back wall 232 , an angled bottom 234 and two beveled corners 236 . The bracket 210 has a large flat bottom 234 angling downward aft of the transom 116 creating more assist in planning as a large trim tab. The bracket 210 adds buoyancy to support the weight of engine or engines. The bracket 210 provides positive lift in a following sea lifting up on the inside of the wave and moving the vessel forward decreasing or eliminating the sea engulfing the engine or engines and or sinking the vessel. The bracket 210 's large flat area adds additional stability supporting the chine flats 180 in the side to side motion laying to in large seas preventing violent rocking motion of this vessel. the bracket is also a step allowing this vessel design to pivot over the water aft of the transom 200 and as the bracket dose not touch the water at speed or plane it does not create drag at speed. The bottom 234 of the bracket 210 also smooths the water as it moves aft toward a propeller of a motor mounted on the bracket 210 . This action reduces cavitation of water being fed to the propeller.
[0081] Whereas, the present invention has been described in relation to the drawings attached hereto, it should be understood that other and further modifications, apart from those shown or suggested herein, may be made within the spirit and scope of this invention. Descriptions of the embodiments shown in the drawings should not be construed as limiting or defining the ordinary and plain meanings of the terms of the claims unless such is explicitly indicated.
[0082] As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.
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A modified V-hull boat has a keel starting at about 20% from the bow ending 75 to 80% aft of the bow and has an inverted airfoil shape. A flat pad blends in aft of the keel assisting planning and attitude at speed. A bracket having a bottom shape and size to float a designated amount of weight and a downard angle facing down at the aft on the bottom to act as a positive planning fixed trim tape that ride's above the water at speed or on plane, and adds stability and positive buoyancy for weight of engines at rest or low speed.
Chine's are the outside corner of the boat joining the bottom to the side's. The chine's taper slightly inboard aft to relieve friction and drag. Although they do not come together the chine is no way a straight line the outer edges are slightly more ellipsoidal hence the name.
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FIELD OF THE INVENTION
[0001] This invention related to design of integrated circuits (ICs), and particularly to designing base platforms for integrated circuit design, and particularly to ASIC design.
BACKGROUND OF THE INVENTION
[0002] While the present invention will be described with particular reference to application specific integrated circuits (ASICs), the concepts are applicable to field programmable gate arrays (FPGAs) and to configurable logic blocks (CLBs) therein.
[0003] Integrated circuits are used in a wide range electronic devices produced by a large number of device manufacturers. In practice, ICs are seldom manufactured (fabricated) by the electronic device manufacturer. Instead, ICs are manufactured by an IC foundry to the specifications of the electronic device manufacturer. More particularly, the IC foundry supplies the technology to fabricate the IC and the device manufacturer supplies the intellectual property incorporated in the circuit of the IC being fabricated. Thus the IC design is often the result of corroboration between the device manufacturer and the IC foundry.
[0004] To reduce the time and cost of development of ASICs, IC foundries have developed base IC platforms using semiconductor wafers, sometimes called “slices,” containing layers of semiconductor, such as silicon layers, but without metal interconnection layers. Hardmacs are diffused into the semiconductor layers by permanently embedding transistors and other electronic elements into the wafer layers to achieve specific functions for the ICs. Examples of diffused elements include memories, transceivers, processors, etc. The diffused elements are optimally arranged in groups on the platform that, when properly configured, operate together to perform a particular function, as defined by a macro. The grouping of diffused elements is usually governed by prescribed macro placement rules, with each macro being defined by a plurality of gates and one or more diffused elements. The platform also includes an array composed of pre-diffused transistors, sometimes called the “transistor fabric,” arranged in a grid pattern.
[0005] The user selects a platform containing required groups of gates and elements that, when configured to macros, meet the user's requirements for an ASIC. Using tools supplied by the IC manufacturer, the user defines one or more metalization layers that interconnect the diffused elements and associated transistors, thereby creating required macros. These metalization layers also interconnect the transistors to configure them into logical gates. Hence, the user creates the custom ASIC, sometimes called a structured ASIC, by designing the metal interconnect layers to interconnect and configure the macros and gates. The macros do not actually exist on the platform until selected by the user and configured by the metalization layer(s).
[0006] There is a wide range of types of ICs. Consequently, foundries provide families of base platforms to perform various functions, with members of the families providing specific sets and arrangements of diffused elements. The user selects a base platform to configure into a custom ASIC best meeting the user's needs. Each platform contains diffused elements at locations so that macros can be created to accommodate the designs for a large number of customers and a large number of different ASICs. The user, using tools supplied by the IC foundry, designs one or more metalization layers for the base platform to interconnect the transistors and diffused elements to create the custom ASIC. In doing so, the user selects groups of diffused elements and associated transistors that form specific macros, creates those macros with the metalization layer, and couples the macros to other logic functions and macros through the metalization layers. Examples of such configurable base platforms are the RapidChip® slices available from LSI Logic Corporation of Milpitas, Calif. The RapidChip slices permit the development of complex, high-density ASICs in minimal time with significantly reduced design and manufacturing risks and costs.
[0007] In practice, the user selects a platform that contains the needed elements for necessary macros and whose physical layout is similar to an ideal ASIC for the user's requirements. The user designs the metalization layers to select and create macros and logic gates for the circuit.
[0008] Usually, the selected platform also contains elements and gates for macros that are not usable in the completed ASIC design. For example, if the platform contains processor and arithmetic elements and an associated memory element arranged as a potential macro, but the user only requires the memory, the macro was selected for the memory but the arithmetic and processor elements were not used in the completed ASIC. In such a case, the arithmetic and processor elements, along with the associated transistors, remained unused on the chip. Thus the transistor fabric for the macro also was not available for use in the ASIC. As another example, if an ASIC required two macros, such as different processors requiring similar diffused elements, such as similar memories, both groups of elements representing both macros were configured, so that each processor had its own memory.
[0009] It is desirable to reduce the number of base platforms in a given family. Each base platform represents a considerable expenditure to design and support. Proliferation of base platforms to meet user requirements adds to the expense of the entire family and the tools to support it. Therefore, it is desirable to design base platforms as generic as practical to reach the requirements of a greater number of users and ASIC designs.
SUMMARY OF THE INVENTION
[0010] One embodiment of the present invention is a process of designing base IC platforms that are customizable into integrated circuits, such as ASICs or FPGAs. A plurality of macros are identified for placement on an IC platform. Each macro represents a sub-circuit for placement on the ASIC or FPGA, and each has elements, such as diffused elements in ASICs or CLB in FPGAs. Identical elements in a plurality of macros are identified. An identical element is placed on the platform as a common element for at least two macros. The placement is at a location on the platform suitable for inclusion of the macros. All other elements of the macros are placed at locations relative to the common element as to satisfy macro placement rules for each of the macros.
[0011] In some embodiments, the identical elements are identified by identifying similar elements in a plurality of macros, and creating common elements generic to at least some of the similar elements.
[0012] Another embodiment of the invention is a platform configurable to an integrated circuit having a plurality of gates and elements, at least some of the elements being common elements to plural macros. Connection points are coupled to the gates and elements so that a metalization layer can be added to configure common elements to specific elements for a selected macro and to configure the macros and circuit.
[0013] Yet another embodiment of the invention is a process of designing an integrated circuit by selecting an IC platform containing a plurality of gates and elements, at least one of the elements being a common element to at least two macros. Macros are selected for inclusion in the integrated circuit, and a metalization layer is designed to connect gates and elements into the selected macros, to selectively configure common elements for a selected macro, and to selectively include gates in the integrated circuit that are outside the selected macros and in regions on the platform that would otherwise be included in unselected macros that would contain an element common to a selected macro.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a flowchart of the process of designing base platform according to the present invention.
[0015] FIGS. 2 and 3 are illustrations useful in explaining portions of the process of FIG. 1 .
[0016] FIGS. 4 and 5 are plan diagrams illustrating portions of a base platform according to the present invention and useful in explaining portions of the process of FIG. 1 .
[0017] FIG. 6 is a flowchart of the process of using the base platform according to the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0018] Prior to the present invention, it has not been possible to employ a common diffused element that can be selectively applied to a plurality of macros so that upon selection of one of the macros, the common element is configurable for that macro. One aspect of the present invention is directed to designing a base platform in which elements are placed on the platform so that a common element is configurable to one of a plural macros while the position of all elements within each macro are defined in accordance with applicable macro placement rules. User selection of one of the plural macros into the design configures the common element to the selected macro and permits use of gates that would be otherwise dedicated to other macros so that such gates can be used for other purposes in the ASIC.
[0019] FIG. 1 is a flowchart of a process of designing base platforms for customization to ASICs by the user. The base platform under design in FIG. 1 is a base platform that is user-configurable to a custom ASIC. More particularly, the user can design metal interconnection layers to connect transistors of the base platform and selectively utilize macros based on diffused elements imbedded into the base platform, some of which are common to plural macros, to thereby design the custom ASIC. Using the base platform according to the present invention, the user is able to flexibly create macros using common diffused elements to efficiently meet the user's needs and to recover use of gates in the ASIC that would have otherwise been assigned to unused macros sharing a common diffused element.
[0020] The process begins at step 10 with the conduct of market surveys or otherwise gather market information as to the requirements of users in custom ASICs. The specific manner of gathering market data is not material to the invention, as different organizations employ different techniques, both formal and informal, to gather such data. While the data gathered might not identify specific types of macros required by a given user, the data will reflect circuit requirements and specifications from which the base platform designer can identify specific types of macros required by various customers, as well as the use of such macros. Based on the use for the completed ASIC, the platform designer is able to identify needed macros and identify locations for macros on the platform under design.
[0021] The macros themselves are ordinarily designed by separate teams of macro designers. Prior to the present invention, macros were designed with a complete complement of diffused elements and assigned gates so that the macro, and its diffused elements and gates, could be used in the ASIC to meet the specific requirements of the user.
[0022] In the present invention, the macros are examined on a broader scale. More particularly, at step 12 macros are identified that require at least one diffused element that is identical to a diffused element in another macro.
[0023] At step 14 macros are identified that require at least one diffused element that is similar, but not identical, to a diffused element in another macro. The commonalities of the similar diffused elements are identified and examined to identify the extent to which the similar diffused elements are the same, and the extent that they are different. This relationship is diagrammatically illustrated in FIG. 2 where circles 100 and 102 represent different, but related, diffused elements having a low degree of commonality, represented by the common region 104 . This is referred to as the union of diffused elements 100 and 102 . It will be appreciated that a given platform contains numerous groups of diffused elements and transistors, each group being configurable to a macro. Consequently, the unions of plural diffused elements may be numerous.
[0024] At step 16 the goal is to increase the union 104 to 104 a between any given two similar diffused elements, and to increase the number of unions (commonality) between diffused elements, as diagrammatically illustrated in FIG. 3 .
[0025] At step 16 , the macro teams negotiate to refine the diffused elements. Here, the goal is to enlarge individual unions, bring additional macros into a given union and increase the number of unions. In carrying out step 16 , the extent that the similar diffused elements are different is examined with the view that diffused elements might be genericized by adding size or function, coupled with ports so that they might by configured by metal interconnections at a metalization layer to configure the diffused element for use in one or another macro.
[0026] At step 16 , a common element is created that is generic to plural similar elements. Connections are made to the common element allowing it to be configured into one or another of the similar elements, based on the user selection of macros.
[0027] Step 16 considers several possible actions to enlarge unions, some listed at block 18 in FIG. 1 . One is to find the identical diffused elements amongst plural macros. The genericization of diffused elements might be increased by adding gates and/or size to the element for given applications and by adding connection points, such as to meet a largest similar element, for connection to metal traces at the top level metalization layer.
[0028] At step 20 , different elements, including identical and genericized diffused elements, are placed into proximity in accordance with macro placement rules for plural macros, with overlapping regions containing one or more common diffused elements. The common diffused element is a diffused element that has been identified at step 12 as an identical diffused element to the plural macros, or genericized at step 16 from similar diffused elements in the plural macros. In some cases, a first macro might be placeable within the region of a second, larger macro so that the common diffused element might serve one purpose to the first macro and a different purpose to the second macro. Various cases of overlapping macro regions and regions within regions are illustrated in FIG. 4 . Suffice it to say, at step 20 the goal is to maximize the use of diffused elements and minimize the occurrence of unused diffused elements when the platform is customized for various uses.
[0029] As shown in FIG. 1 , the negotiations to enlarge unions in numbers and in size (step 16 and block 18 ) and the placement into overlapping macro regions (step 20 ) is an iterative process, repeated until the teams and platform designer are satisfied that the platform is likely to meet the needs of a largest possible number of users and uses based on the market data. At step 22 the diffused elements are embedded in the platform at locations useful for the macros that share the common diffused elements. The placement of diffused elements of a given macro is governed by the applicable macro placement rules. A common diffused element, therefore, must satisfy the macro placement rules for all macros to which it is common. As explained in conjunction with FIG. 5 , the diffused elements are placed with reference to a specific point in each macro. When the user selects (places) a macro on the platform by connecting the elements and gates of the macro with the custom metalization layer, the placement of the macros are defined with reference to a point on a grid array for the platform.
[0030] FIG. 4 illustrates a base platform layout 200 having a core 202 that contains gates and macros arranged in a grid array, and input/output channels 204 . The grid array, shown partially in FIG. 5 , defines x-y coordinates for each location on the grid. In the design of platform 200 , macros 210 , 212 , 214 , and 216 are selectively placeable at positions 210 a , 212 b , etc. on the platform identified by x-y coordinates on the array, as illustrated by positioning arrow 206 in relation to macro 210 a.
[0031] Diffused elements A, C and D are arranged in a group to define macro 210 . In practice, there may be any number of diffused elements for a given macro, but for purposes of explanation only three are illustrated in macro 210 . Diffused elements D, E and G are in a group that defines macro 212 . In this example, element D is common to macros 210 and 212 . Thus, element D either was found to be identical to macros 210 and 212 at step 12 ( FIG. 1 ) or it was genericized for similar elements at step 16 . For example, diffused element D might be a processor which is configurable to operate in macro 210 with diffused elements A and C, or it may be configurable to operate in macro 212 with diffused elements E and G.
[0032] It will be appreciated to those skilled in the art that the macros are not actually embedded in the platform and do not exist until they are created by the top metalization layer, to be added by the user design. Instead, only the diffused elements exist, and are placed in respect to each other in accordance with the macro placement rules for macros 210 and 212 . Thus, the configuration of diffused element D to macro 210 or 212 is performed at the top metalization layer during customization by the user.
[0033] The common diffused element D is ordinarily configurable to only one macro. Thus, if the top level metalization layer configures diffused element D to macro 212 , macro 210 does not exist, and diffused elements A and C might not be used in the customized ASIC. In some cases, diffused elements A and/or C might be used for other purposes, but not in macro 210 . Moreover, some macros might employ several common diffused elements. For example, if elements A and G are similar memories, diffused elements A or G might be genericized and placed on the platform as a single memory configurable to both macros 210 and 212 .
[0034] Another example of a common diffused element is diffused element G which is common to macros 212 and 214 . Macro 214 may be a test wrapper for the memory element G as a stand-alone memory. In this case, element G may be configured as a stand-alone memory with test wrapper in macro 214 (in which case macro 212 would not be available in the ASIC) or it may be configured as a memory for macro 212 , in which case the test wrapper of macro 214 is not available. Element G might also be a memory for macro 210 if configurable to macro 210 and placed in a common area with macros 210 and 212 according to the placement rules for both macros.
[0035] The placement of diffused elements in a macro is established in accordance with placement rules for each macro, and to meet placement requirements for common diffused elements. Placement of the macros is established to meet the macro requirements using the common diffused elements.
[0036] FIG. 5 illustrates the placement of macro 210 at position 210 a . The grid array is represented by horizontal and vertical lines, the intersections of which represent unique x and y coordinates that designate the position of macros, elements and gates on platform 200 . Because macro 210 extends over several grid lines, the position of the macro is identified by the x-y coordinates of a predetermined point on the macro, such as point 220 at the bottom left corner of the macro. Ordinarily, the positions of other macros are identified by similar predetermined points on the respective macros. The locations of diffused elements A, C and D are placed in accordance with macro placement rule in relation to a predetermined point on the macro, such as point 220 , as shown by arrows 222 , 224 and 226 , respectively.
[0037] In a similar manner, the position of the other macros are established on the grid array and the position of those macro's diffused elements are established in accordance with the macro placement rules.
[0038] FIG. 6 is a flowchart of a process of using the platform shown in FIG. 4 to create a custom ASIC. At step 300 a base platform according to the present invention is selected that meets, usually in excess, the requirements for the ASIC under design. Using the same considerations in selecting present base platforms, a platform is selected that, when customized according to the present invention, will meet the requirements of the user. At step 302 , the macros are selected, and at step 304 an initial design of the metalization layer is created.
[0039] More particularly, at step 304 , connections to the common diffused elements, such as element D in FIG. 4 , are interconnected at the metalization layer so that the common element D is configured to the requirements of the selected one of macros 210 or 212 ( FIG. 4 ). Additionally at the step 304 , the elements and gates are interconnected to form the sub-circuit of the selected macro in a manner well known in the art.
[0040] At step 306 , the ASIC is completed by connecting gates outside of selected macros, including in the area of unselected macros, such as macro 212 , that otherwise would contain common elements selected for a different macro. In preferred embodiments, this is performed by simple exclusion of macro 212 from use, allowing gates otherwise designed for macro 212 to be used for other purposes as well known in the art.
[0041] One feature of the invention is that the gates within macros not selected for use in the customized ASIC are available for other uses within the ASIC, as if the unused macros were not present. In the example of FIG. 5 where macro 210 is configured into the ASIC by top level metalization, macro 212 could not be selected. Consequently, resources otherwise devoted to unused macros, such as macro 212 , are available for use within the ASIC.
[0042] Another feature of the invention is the ability to create new macros after the base platform is created by re-configuring one or more common diffused elements and/or configuring a common diffused element to a different macro.
[0043] The present invention is also useful for management of macros in platforms having nesting areas into which pre-designed or custom processors may be placed, as describe in U.S. patent application Ser. No. 10/713,492 filed Nov. 14, 2003 for “Flexible Design for Memory Use in Integrated Circuits” by Douglas J. McKenney and Steven M. Emerson and assigned to the same assignee as the present invention, the content of which is hereby incorporated by reference in its entirety. Using the techniques of the present invention with those specifically taught in the McKenney application, flexibility of platforms is greatly increased, adding to the efficiency of the IC.
[0044] While the invention has been described in connection with using diffused elements in an array, the concepts described herein may be extended to CLBs in FPGAs with special elements.
[0045] Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.
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Base platforms customizable into ICs are designed by identifying a plurality of macros for placement on the platform, each macro being defined in part by a plurality of elements that perform respective functions of the macro. Identical elements in a plurality of macros are identified, and a common element is placed on the platform for an identical element of at least two macros. All other elements of the macros are placed at locations on the platform relative to the common element as to satisfy macro placement rules for each macro. Identical elements can be identified by identifying similar elements in a plurality of macros, and creating a common element generic to the similar elements. The user designs a metalization layer to select macros and configure common elements to the selected macros.
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TECHNICAL FIELD
This invention relates to the flooring art and more particularly to a portable floor section having a built-in post anchor for use with portable sectionalized flooring suitable for a volleyball court or other flooring requiring post support.
BACKGROUND OF THE INVENTION
Special flooring systems for indoor and outdoor sports activities, dancing and other like uses have been proposed in the prior art. Among the drawbacks of many prior art floors are their high initial cost, permanency of installation and the fact that they must be made and installed at the flooring site rather than being fabricated and carried to the desired assembly location.
Furthermore, there are many environments and applications where permanent installation of a sports activity type of floor is not dictated or justified. Some locations may require that the sports activity type flooring be removable such that the locations is susceptible to utilization for purposes other than sports activities or for a variety of sports activities. Portable sectionalized flooring such as that disclosed in U.S. Pat. No. 4,538,392 have been used to provide this adaptability.
However, floors suitable for sports activities such as volleyball or the like present special problems in requiring post anchors to firmly support posts which in turn support a net. The post anchors should be capable of countering the moment developed by the net through each post so that the vertically upright position of each post remains true.
The problems in meeting these flooring anchor requirements are exacerbated when attempts have been made to associate such anchors with floors in a portable and/or sectionalized form of construction. Prior art attempts to achieve anchor stability require securing an anchor base to the permanent flooring beneath the portable sectionalized flooring system. A further problem is that the anchor base must be aligned with the volleyball center line. Consequently, the prior art installation requires laying portable floor panels after drilling anchor base holes into the permanent subflooring so that the anchor base can be aligned with the volleyball center line of the portable sectionalized flooring. Such a prior art system also calls for building a dummy panel to fit over the installed anchor base to assist in the designing of a sectionalized flooring panel so that the volleyball net post may pass through the sectionalized flooring panel and into the anchor base. Among the drawbacks of such a prior art system are high installation costs, increased set up time, necessary fabrication at the flooring site and difficulty in repositioning the volleyball net since new holes would have to be drilled into the subflooring. Furthermore, where these prior art sectionalized floors must be repeatedly put down and taken up before and after successive sports activities, the separate parts required for the assembly of such volleyball post anchor systems may be easily lost or misplaced while the floor sections are in their disassembled state of non-use or in storage.
SUMMARY OF THE INVENTION
In view of the above and other deficiencies of the known prior art, it is the aim of this invention to provide a prefabricated floor section having a post anchor built therein for use with portable sectionalized flooring suitable for a volleyball court or the like which can be quickly assembled and installed in a variety of environments, and which does not require connection of the post or its support base to the subfloor.
Thus, the invention involves a first floor section having a post anchor base built therein and secured to the undersurface thereof. Floor sections to be installed adjacent to the first floor section have stabilizing base extensions, in the form of pairs of hollow tubes, secured to their respective undersurfaces. The anchor base and base extensions have securing mechanisms, in the form of an elongated rigid member passing through aligned hollow tubes, for coupling the base extensions on adjacent floor sections to one another. When these floor sections are assembled, the base extends well beyond the first floor section thereby providing the requisite post anchor stability without securing the post anchor to the flooring beneath the portable sectionalized flooring.
It is an object of the present invention to provide portable sectionalized flooring suitable for a volleyball court or the like with pre-fabricated post anchors built therein to enable fast set up time for any game.
It is another object of the present invention to provide a fully portable volleyball floor with built in post anchors to enable quick and simple disassembly and storage.
It is a further object of the present invention to provide a fully portable volleyball floor with post anchors not requiring any permanent anchor structure in the subfloor or drilling of post anchor holes in the subfloor, thereby reducing installation costs.
It is yet another object of this invention to provide portable sectionalized flooring having panels with built in post anchors thereby eliminating the problems of aligning the panel post hole with the anchor base hole or aligning the anchor base post hole with the volleyball court center line.
It is still a further object of the present invention to provide a volleyball post anchor base assembly and post therefore in an apparatus or kit form, for readily converting or adapting an existing portable sectionalized flooring for use as a volleyball court or the like with all of the advantages enumerated above.
Other important features and advantages of the invention will be apparent from the following description and the accompanying drawings, wherein for purposes of illustration only, a specific form of the invention is set forth in detail.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a plan view of an assembled sectionalized flooring system in accordance with the invention displaying appropriate markings for a basketball court and the post anchor base in phantom along the court center line;
FIG. 2 is an enlarged plan view of the post anchor assembly secured to the undersurface of sectionalized flooring panels;
FIG. 3 is an enlarged plan view of the post anchor assembly and post hole cover therefore from the upper surface of a panel;
FIG. 4 is a cross-sectional view of the post anchor assembly secured to the undersurface of a floor panel taken along line 4--4 of FIG. 3;
FIG. 5 is a cross-sectional view of a portion of the post anchor assembly taken along line 5--5 of FIG. 4 and further including the post ready to be inserted;
FIG. 6 is a cross-sectional view of the post anchor assembly of FIG. 5 with a further post embodiment having a second portion shown in phantom connected to the post anchor;
FIG. 7 is an enlarged view of the base of the post with a cross-sectional view of the abutment flange.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 depicts an overall plan view of a completed sectionalized flooring system 100 and with two post anchor base assemblies 200 shown in phantom. Each post anchor base assembly and post support 204 thereof is aligned along center line 120. As shown in FIG. 1, planar flooring system 100 is appropriately marked to provide the playing surface for a basketball court. However, it should be understood that post anchor base assembly 200 may be used with any portable sectionalized flooring suitable for volleyball or the like, and that such use is not limited, for example, to the playing surface or sectionalized flooring construction of FIG. 1.
Sectionalized flooring system 100 is assembled from a plurality of separate floor sections or panels falling into either of two size groups having respectively different lengths. The first group consists of large panels or sections 102 while the second group is made up of small panels or sections 104. For purposes of panel fabrication and subsequent floor assembly at the site, the large sections 102 are preferably 4 feet ×8 feet while the small sections are preferably 4 feet ×4 feet. As may be easily appreciated from the plan view of the panels shown in FIG. 1, by appropriately positioning large and small sections 102 and 104 in the rows of the flooring area 100, the joints between the ends of the longitudinally aligned sections can effectively be staggered between adjacent rows. Such flooring construction including panel-to-panel connectors, is described in detail in U.S. Pat. No. 4,538,392 to which the description therein is hereby incorporated herein. Obviously, anchor assembly 200 may be used with portable sectionalized flooring having different dimensions, markings, construction or other different structural characteristics than the flooring described above.
FIG. 4 illustrates anchor assembly 200 secured to a post receiving panel 170. The basic construction of each panel includes an upper flooring layer 108 and a lower flooring layer or layer of underlayment 110 which together form a substantially planar member. Upper flooring 108 defines a flooring surface 106, while underlayment 110 defines the panel undersurface (not designate). Each panel also includes a plurality of spaced elevation members 112 which extend transversely along and attached to the panel undersurface for supporting layers 108 and 110 above a base surface.
Post receiving panel 170 further includes post receiving hole 172 and cover plate 210 therefore. In the closed position, cover plate 210 is flush with floor surface 106. FIGS. 3 and 4 may be referred to as illustrating cover plate 210 closed from a top planar and cross-sectional view, respectively. FIGS. 5 and 6 show cover plate 210 in an open position from a cross-sectional view. Referring to FIG. 3, cover plate 210 includes lid 216 pivotally mounted to flat ring 214 by hinge 212. Flat ring 214 is received in a ring shape groove in upper surface 106 and secured to panel 170 by fasteners F.
Returning to FIG. 4, post anchor base assembly 200 includes a support plate 202 having a hole therethrough, a hollow tubular post support 204 inserted in the plate hole and secured to plate 202 by weld W or other suitable means, and two pieces of hollow rectangular tubing 206 each extending along the entire width of panel 170. Hollow rectangular tubing 206 is fixedly secured to support plate 202 along opposite edges thereof by suitable means. Tubing 206 is further secured to the undersurface of panel 170 by fasteners F, such as screws, so that the axis of tubular support plate 204 and the center of post panel post hole 172 are substantially aligned. As seen in FIG. 1, support plate 202 also is preferably secured to the undersurface of panel 170 by fasteners F. Referring to FIGS. 4 and 5, it can be seen that diametrically disposed pins P which extend radially into the bore of post support tube 204 are intended to engage with detents D provided in diametrically disposed bayonet type slots 308 of volleyball net post 300 and thereby connect post 300 to post anchor base assembly 200.
FIG. 2 shows the full span or anchor base assembly 200 fixedly secured to the underside of five floor panels arranged in three rows. The interlocking finger joint between the ends of panels 150 and 160, which are provided with projecting fingers 114, is aligned with the corresponding joint between panels 180 and 190. Obviously, the panel ends may be joined by other suitable means. These joints are staggered with respect to the ends of post receiving panel 170. Therefore, both rectangular tubing members 206 are fixedly secured to post receiving panel 170 while only one rectangular tubing extension 220 is fixedly secured to each remaining panel 150, 160, 180 and 190. After the rectangular tubing is fastened to respective panels by fasteners F, the panels are operatively associated, tubing members 206 for a first pair of tubes which aligns with second and third pairs of tubes formed by tubing extensions 220. A solid or hollow rectangular stiffening tube 208, having a length corresponding to approximately three panels widths, is inserted into each channel defined by rectangular tube 206 and one extension tube 220 at each end thereof. Thus, tube 208 not only connects or coupled, but stiffens, each group of three tubes which extend over three panel widths, thereby further stabilizing the orientation of tubular post support 204. Such construction enables the post when inserted into the post anchor base assembly to remain substantially in the upright position without the necessity of inserting or otherwise anchoring the post to the subfloor. That is, the construction of anchor assembly 200 results in a support base that extends over an area of three panel widths, and in the preferred embodiment, is connected to five panels. Such as anchor assembly readily absorbs moments placed on the post by a net.
The association between the post and anchor base is best understood from FIGS. 5-7. Referring to FIG. 5, volleyball net post 300 has an annular flange 302 and diametrically disposed bayonet type slots 308. Flange 302 abuts with shelf 205 defined by an end surface of tubular post support 204 and thereby provides a vertical stop and support mechanism. Post receiving hole 172 thus has a first diameter and hollow cylinder 204 has a smaller inner diameter. Alternatively, flange 302 could abut with ring 214 if desired and appropriate dimensional changes made. Slot 308 cooperate with pines P to provide a bayonet fastening mechanism between the post and anchor assembly.
FIG. 7 shows the basic construction of flange 302. Substantially inelastic core 306 provides the necessary rigidity for supporting post 300. Resilient casing 304 which may be made from elastomeric materials encapsulates core 306 and develops a spring bias between pin P and detent D.
FIG. 6 depicts a further embodiment of the volleyball post. Posts 303 and 305 form post assembly 301. Post 305 is essentially the same as post 300 but substantially shorter. Securement means for fixing post 303 to post 305 may be advanced through opening 307.
The parts of post anchor base assembly 200 also form an apparatus or system for converting a existing portable sectionalized flooring system into a flooring system for use as a volleyball court or another type of floor requiring posts. The apparatus would include support plate 202, post support 204, and tubes 206, 220 and 208.
Obviously, the sizes and materials used in the components making up the post anchor base assembly may be selected from a wide variety of sizes and/or materials. Merely to exemplify a preferred makeup of these components the following example may be recited. Support plate 202 can be 9 inches by 22 inches with a 5/8 inch thickness. Rectangular tube 206 and tube extension 220 have similar dimensions. These tubes can be 2 inches ×4 inches with a 1/8 inch wall thickness and have an approximately 47 inch length. Each stiffening tube 208 would have approximately a 12 foot length to extend across three panel widths. Post support tube 204 should be appropriately dimensioned to receive and support a post 1 or a post adapter having a 3 to 5 inch outer diameter, depending on the type of post used. Support plate 202, tubes 206, 208 and 220, and post support tube 204 may be aluminum, a relatively lightweight metal, to improve portability. Post anchor hole cover 210 should be brass.
Having described a preferred embodiment in detail, it will be recognized that the foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction, materials, assembly, etc. shown and described. Accordingly, all suitable modifications and equivalents may be resorted to the extent that they fall within the scope of the invention and claims appended hereto.
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A floor section assembly having a post anchor built into one of the floor panels for use with portable sectionalized flooring suitable for a volleyball court or the like is disclosed. The post anchor includes a base assembly attached to the undersurface of one of the panels and is coupled to a plurality of adjacent panels by tubes attached to the undersurface of the panels and coupled together by a rigid member extending through aligned tubes. This structure provides a broad base of support for the post carrying a volleyball net which can absorb moments placed on the post without the need for connecting the post to the base on which the flooring is assembled.
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This application is a continuation of application Ser. No. 492,841, filed Mar. 13, 1990, now abandoned.
BACKGROUND OF THE INVENTION
1. FIELD OF THE INVENTION
The invention relates to the construction of an inflatable packing element for use in inflatable packers or bridge plugs employed in subterranean wells.
2. SUMMARY OF THE PRIOR ART
Inflatable packers (or bridge plugs) have long been utilized in subterranean wells. Such inflatable tools normally comprise an elastomeric sleeve element mounted in surrounding relationship to a tubular body portion. Pressured fluid is communicated from the surface of the well to the bore of the tubular body and then through radial passages to the interior of the elastomeric sleeve. To protect the elastomeric sleeve, it is customary to completely surround the elastomeric sleeve with a plurality of peripherally overlapping, resilient, reinforcing slats or ribs. The medial portions of the reinforcing ribs are surrounded and may be bonded to an outer annular elastomeric packing element or cover of substantial wall thickness. Upper and lower securing assemblies respectively engage the ends of the elastomeric sleeve and the reinforcing ribs and is fixedly and sealably secured relative to a central tubular body. A lower securing assembly is secured to a sealing sub which is mounted for slidable and sealable movement on the exterior of the central tubular body, in response to the inflation forces. A structure of this general type is shown in U.S. Pat. No. 3,160,211 to MALONE.
With inflatable packers of this type, very substantial tensile forces are exerted on the reinforcing slats or ribs during the inflation of the elastomeric sleeve. It has been customary to clamp the ends of the ribs to the upper and lower securing assemblies, but such clamping arrangements are subject to failure if the inflatable packer is repeatedly inflated for engagement with different portions of the well casing or conduit in which it is inserted.
More recently, the ends of the flexible ribs have been welded to an internal surface of a securing sleeve, in the manner indicated in FIG. 1 of the drawings. If the welding operation is properly accomplished, this provides a secure anchoring of the ends of the flexible ribs to the mounting sleeve, but those skilled in the art will recognize the difficulty of making consistently good welds within the relatively small bore of a mounting sleeve for the inflatable packing element of an inflatable packer. If one or more of the ribs is not properly welded, such ribs will break loose under the tensile forces imposed by the inflation of the elastomeric sleeve packer or element which is inserted within the ribs and, because there is thus created a weak area in the cylindrical cage of the reinforcing ribs, the substantial fluid pressure applied to the inflatable elastomeric sleeve can well push such rib out of alignment with the other ribs and thus produce a potential area of breakage of the inflatable elastomeric sleeve because it will follow the outward displacement of the unanchored rib and form a thin walled bubble.
There is a need therefore for an anchoring system for the peripherally stacked cage of flexible reinforcing ribs which normally surround the inflatable elastomeric sleeve of an inflatable packer or bridge plug which effects a reliable rigid connection of the ends of the ribs to the mounting sleeves for the expansible packing element.
SUMMARY OF THE INVENTION
In accordance with this invention, the ends of the cylindrical cage of peripherally overlapped slats or ribs surrounding an inflatable elastomeric sleeve of an inflatable packing element are respectively welded to an external surface of a force transmitting sleeve. Such force transmitting sleeve is further provided with an external shoulder which is disposed in abutting relationship with an internal shoulder provided on the respective mounting sleeve for securing the entire inflatable assemblage to the body of the inflatable packer or bridge plug. Additionally, the location of the abutting shoulders is deliberately selected so as to provide an axial length of the circumferential array of resilient slats or ribs in frictional contact with the internal bore of the mounting sleeve. Such frictional forces, which are greatly increased through the application of the inflation pressures to the apparatus, significantly reduce the tensile forces applied to the welds, hence minimizing the opportunity for any individual rib to break at its weld.
Further advantages of the invention will be readily apparent to those skilled in the art from the following detailed description, taken in conjunction with the annexed sheets of drawings, on which is shown a preferred embodiment of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a combination perspective and sectional view illustrating a prior art method of welding the ends of the reinforcing ribs to the mounting sleeve of an inflatable packer.
FIG. 2 is a vertical quarter sectional view of the mounting sleeve portion of an inflatable packer wherein the reinforcing ribs are secured by utilization of the construction of this invention.
FIG. 3 is a view similar to FIG. 2 but illustrating the effects of application of inflation pressures to the elastomeric sleeve of the mounting construction of FIG. 1.
FIG. 4 is an enlarged scale sectional view taken on the plane 4--4 of FIG. 2.
DESCRIPTION OF PREFERRED EMBODIMENT
Referring to FIG. 1, a prior art construction for securing the reinforcing ribs of an inflatable element for an inflatable packer or bridge plug is shown. The ends of each rib is welded to an interior surface of a mounting sleeve. After the welding operation, a sleeve of elastomeric material (not shown) is inserted within the rib cage and the end secured in conventional fashion. It should be noted, however, that the welding has to be accomplished in a small internal bore surface and this is recognized to be a difficult procedure to consistently produce good welds for each of the multitude of reinforcing ribs.
Referring now to FIG. 2, only the upper securing portion of the inflatable element of an inflatable packer or bridge plug is shown. All other elements of the inflatable packer or bridge plug, including the valving apparatus for supplying inflation pressures are well known in the art. See for example, U.S. patent application Ser. No. 138,197, filed on Dec. 28, 1987; U.S. Pat. No. 4,708,208; and U.S. Pat. No. 4,805,699, and the disclosures of such patents are hereby incorporated by reference.
Inflatable element 10 comprises a cylindrical cage of peripherally overlapping flexible slats or ribs 12, the configuration of which is best shown in the enlarged sectional view of FIG. 4. The ends 12a of such ribs are welded to a force transmitting sleeve 14 by a weld W which is accomplished after the insertion of the ribs through a mounting sleeve 20. The force transmitting sleeve 14 is provided with an external shoulder 14a which cooperates with an internal shoulder 20a provided on mounting sleeve 20 for transmitting tensile forces exerted on the ribs 12 to the mounting sleeve 20.
An inflatable tube or sleeve 30 of elastomeric material is inserted within the bore of the rib cage 12 and passes through the bore 14b of the force transmitting sleeve 14. Tube retainer 1a is installed inside the mounting sleeve 20 radially forcing the inflatable tube or sleeve 30 of elastomeric material to extrude and engage in appropriate circumferential grooves 20c formed in a mounting sleeve 20. Anchor portion 1 is further provided with external threads 1b for threadably engaging the upper end of the mounting sleeve 20. Such threads are sealed by an O-ring 1e.
A cover portion 35 of elastomeric material is bonded to the medial portions of the rib cage 12 to provide a sealing contact with the bore of a well or well conduit, as is customary.
As is customary in inflatable packers, the internal surface of anchor body 1 cooperates with an internal body tube 2 to define an annular passage 1c and radial ports 1d for application of fluid pressure to the interior of the elastomeric sleeve 30. The application and maintenance of fluid pressure on the interior of the elastomeric sleeve 30 is accomplished in a manner well known in the art and fully disclosed in the aforementioned patents, hence further description is deemed unnecessary. Thus, when such fluid pressure is applied through the fluid passage 1c, the inflatable packing element 10 is expanded to assume the configuration illustrated in FIG. 3. The tensile forces developed in the ribs 12 by such expansion are transmitted by the welds W to the force transmitting sleeve 14 and by the peripheral shoulder 14a to the mounting sleeve 20 and the anchor body 1.
As best shown in FIG. 3, the location of the force transmitting sleeve 14 relative to the length of the mounting sleeve 20 is an important feature of this invention. The force transmitting sleeve is preferably located above the central or medial portion of the mounting sleeve 20 so that a substantial length of the ribs 12 are disposed in frictional engagement with the bore 20b of the mounting sleeve 20. These frictional forces are substantially increased by the fluid pressure forces illustrated by the arrows shown in FIG. 3 and result from the application of the inflation pressure.
It will be therefore be readily apparent to those skilled in the art that a very substantial frictional force may be developed to resist the tensile forces exerted on the reinforcing ribs 12 by the inflation of the elastomeric sleeve 30. Such frictional forces substantially diminish the tensile forces exerted on the welds W and thus provide further insurance against the separation of any of the welds W.
While only the mounting structure for one end of the inflatable packing element 10 has been shown, those skilled in the art will recognize that the other end of the element is of identical construction. Thus, the other ends of the reinforcing ribs 12 are secured by external welds W to a source transmitting sleeve which is identical to sleeve 14 except that it will be disposed in a vertically reversed relationship.
The aforedescribed construction resolves a troublesome constructural defect of inflatable packers or bridge plugs through not only the substantial elimination of welding defects caused by performing rib welds in an internal bore, but also significantly reduces the tensile forces applied to the welds through the utilization of an extended longitudinal bore area of the mounting sleeve in frictional contact with the reinforcing ribs 12 when such ribs are expanded by inflation pressure.
Although the invention has been described in terms of specified embodiments which are set forth in detail, it should be understood that this is by illustration only and that the invention is not necessarily limited thereto, since alternative embodiments and operating techniques will become apparent to those skilled in the art in view of the disclosure. Accordingly, modifications are contemplated which can be made without departing from the spirit of the described invention.
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An inflatable packing element for an inflatable packer or bridge plug utilized in subterranean wells comprises a tubular elastomeric sleeve which is surrounded by a plurality of circumferentially overlapping flexible metal ribs. The opposite ends of the ribs are respectively welded to an external surface provided on a force transmitting sleeve. The sleeve is provided with a shoulder having an abutting relationship with an internally projecting shoulder provided on the tubular mounting structure for the inflatable element.
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BACKGROUND
[0001] 1. Technical Field
[0002] One or more embodiments of the present invention generally relate to systems and processes for cooling a feed gas stream with a single closed-loop mixed refrigerant cycle.
[0003] 2. Description of Related Art
[0004] In recent years, natural gas has become a widely used source of fuel. In addition to its clean burning qualities and convenience, advances in exploration and production technology have permitted previously unreachable gas reserves to become accessible. Because many of these previously unreachable sources of natural gas are remote and are not connected to commercial markets or infrastructure by pipeline, cryogenic liquefaction of natural gas for transportation and storage has become increasingly important. In addition, liquefaction permits long term storage of natural gas, which can help balance out periodic fluctuations in supply and demand.
[0005] Several methods for liquefying natural gas are currently in practice. Although the specific configuration and/or operation of each facility may vary depending on, for example, the type of refrigeration system used, the rate and composition of feed gas, and other factors, most commercial facilities generally include similar basic components. For example, most facilities typically include a pretreatment area for removing one or more impurities from the incoming gas stream, a liquefaction zone for liquefying the gas stream, a refrigeration system for providing refrigeration to the liquefaction zone, and a storage and/or loading area for receiving, storing, and transporting the final liquefied product. Overall, the cost to construct and operate these facilities can vary widely, but in general, the cost of the refrigeration portion of the plant can account for up to 30 percent or more of the overall cost of the facility.
[0006] Thus, a need exists for an optimized refrigeration system capable of efficiently producing a liquefied gas product at a desired capacity, but with minimum amount of equipment. Ideally, the refrigeration system would be both robust and operationally flexible in order to handle variations in feed gas composition and flow rate, while still requiring minimal capital outlay and operating at the lowest possible cost.
SUMMARY
[0007] One embodiment of the present invention concerns a process for producing liquefied natural gas (LNG). The process comprises the following steps: (a) cooling a natural gas stream in a first heat exchanger to provide a cooled natural gas stream; (b) compressing a mixed refrigerant stream to provide a compressed refrigerant stream; (c) cooling and at least partially condensing the compressed refrigerant stream to provide a two-phase refrigerant stream; (d) separating the two-phase refrigerant stream into a first refrigerant vapor stream and a first refrigerant liquid stream in a first vapor-liquid separator; (e) combining at least a portion of the first refrigerant vapor stream withdrawn from the first vapor-liquid separator with at least a portion of the first refrigerant liquid stream to provide a combined refrigerant stream; (f) cooling at least a portion of the combined refrigerant stream to provide a cooled combined refrigerant stream; (g) separating the cooled combined refrigerant stream into a second refrigerant vapor stream and a second refrigerant liquid stream in a second vapor-liquid separator; (h) dividing the second refrigerant liquid stream into a first refrigerant liquid fraction and a second refrigerant liquid fraction; (i) cooling at least a portion of the first and second refrigerant liquid fractions to provide respective first and second cooled liquid refrigerant fractions; and (j) introducing the first and second cooled liquid refrigerant fractions into separate inlets of the first heat exchanger, wherein the first and second cooled liquid refrigerant fractions are used to carry out at least a portion of the cooling of step (a).
[0008] Another embodiment of the present invention concerns a process for producing a liquefied gas stream. The process comprises the following steps: (a) compressing a stream of mixed refrigerant in a first compression stage of a compressor to provide a first compressed refrigerant stream; (b) cooling and at least partially condensing the first compressed refrigerant stream to provide a cooled, compressed refrigerant stream; (c) separating the cooled, compressed refrigerant stream into a first refrigerant vapor stream and a first refrigerant liquid stream; (d) compressing the first refrigerant vapor stream in a second compression stage of the compressor to provide a second compressed refrigerant stream; (e) cooling and at least partially condensing at least a portion of the second compressed refrigerant stream to provide a partially condensed refrigerant stream; (f) separating the partially condensed refrigerant into a second refrigerant vapor stream, a second refrigerant liquid stream, and a third refrigerant liquid stream; (g) cooling the second and third refrigerant liquid streams to provide respective cooled second and third refrigerant liquid streams; (h) expanding at least one of the cooled second and cooled third refrigerant liquid streams to provide at least one cooled, expanded refrigerant stream; (i) cooling a feed gas stream via indirect heat exchange with the at least one cooled, expanded refrigerant stream to provide a cooled feed gas stream and at least one warmed refrigerant stream.
[0009] Yet another embodiment of the present invention concerns a system for cooling a natural gas stream. The system comprises a first heat exchanger for cooling a natural gas feed stream. The first heat exchanger comprises a first cooling pass having a feed gas inlet and a cool natural gas outlet, a second cooling pass for receiving and cooling a first stream of refrigerant liquid, wherein the second cooling pass has a first warm refrigerant inlet and a first cool refrigerant outlet; a third cooling pass for receiving and cooling a second stream of refrigerant liquid, wherein the third cooling pass has a second warm refrigerant inlet and a second cool refrigerant outlet; a first warming pass for receiving and warming a first stream of cooled refrigerant, wherein the first warming pass has a first cool refrigerant inlet and a first warm refrigerant outlet; and a second warming pass for receiving and warming a second stream of cooled refrigerant liquid, wherein the second warming pass has a second cool refrigerant inlet and a second warm refrigerant outlet. The first cool refrigerant outlet of the second cooling pass is in fluid flow communication with the first cool refrigerant inlet of the first warming pass, and the second cool refrigerant outlet of the third cooling pass is in fluid flow communication with the second cool refrigerant inlet of the second warming pass. The system also comprises at least one compressor for receiving and pressurizing a stream of mixed refrigerant. The compressor has a low pressure inlet and a high pressure outlet and the low pressure inlet is in fluid flow communication with at least one of the first warm refrigerant outlet of the first warming pass and the second warm refrigerant outlet of the second warming pass. The system also comprises a first cooler for cooling the pressurized stream of mixed refrigerant. The first cooler has a first warm fluid inlet and a first cool fluid outlet and the first warm fluid inlet is in fluid flow communication with the high pressure outlet of the compressor. The system also comprises a first vapor-liquid separator for separating a portion of the cooled refrigerant stream. The vapor-liquid separator comprises a first fluid inlet, a first vapor outlet, and a first liquid outlet and the first fluid inlet of the first vapor-liquid separator is in fluid flow communication with the first cool fluid outlet of the first cooler. The system also comprises a first liquid conduit for transporting at least a portion of the liquid exiting the first vapor-liquid separator. The first liquid conduit has a refrigerant liquid inlet and a pair of refrigerant liquid outlets. The refrigerant liquid inlet is in fluid flow communication with the first liquid outlet of the first vapor-liquid separator. One of the pair of refrigerant liquid outlets is in fluid flow communication with the first warm refrigerant inlet of the second cooling pass and the other of the pair of refrigerant liquid outlets is in fluid flow communication with the second warm refrigerant inlet of the third cooling pass.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] Various embodiments of the present invention are described in detail below with reference to the attached Figures, wherein:
[0011] FIG. 1 provides a schematic depiction of a liquefied natural gas (LNG) facility configured according to one embodiment of the present invention, particularly illustrating an optimized mixed refrigerant system;
[0012] FIG. 2 provides a schematic depiction of a liquefied natural gas (LNG) facility configured according to another embodiment of the present invention, similar to the embodiment depicted in FIG. 1 , but including a method for recycling refrigerant liquids; and
[0013] FIG. 3 provides a schematic depiction of a liquefied natural gas (LNG) facility configured according to another embodiment of the present invention, similar to the embodiment depicted in FIG. 1 , but including another method for recycling refrigerant liquids.
DETAILED DESCRIPTION
[0014] The following detailed description of embodiments of the invention references the accompanying drawings. The embodiments are intended to describe aspects of the invention in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments can be utilized and changes can be made without departing from the scope of the claims. The following detailed description is, therefore, not to be taken in a limiting sense. The scope of the present invention is defined only by the appended claims, along with the full scope of equivalents to which such claims are entitled.
[0015] The present invention generally relates to processes and systems for liquefying a natural gas feed stream to thereby provide a liquefied natural gas (LNG) product. In particular, the present invention relates to optimized refrigeration processes and systems for cooling the incoming gas. As described in further detail below, the incoming feed gas stream can be cooled and at least partially condensed with a closed-loop refrigeration system employing a single mixed refrigerant. According to various embodiments of the present invention, the refrigeration system may be optimized to provide efficient cooling for the feed gas stream, while minimizing the expenses associated with the equipment and operating costs of the facility.
[0016] Referring initially to FIG. 1 , one embodiment of an LNG production facility 10 is illustrated as comprising a closed-loop, mixed refrigerant refrigeration system 12 and a gas separation zone 14 . As shown in FIG. 1 , the incoming feed gas stream in conduit 110 can be cooled and at least partially condensed in a primary heat exchanger 16 of refrigeration cycle 12 before being separated and further cooled in gas separation zone 14 to provide the LNG product. Additional details regarding the configuration and operation of LNG facility 10 , according to various embodiments of the present invention, are described below with reference to FIG. 1 .
[0017] As shown in FIG. 1 , a feed gas stream can be introduced into LNG facility 10 via conduit 110 . The incoming gas stream in conduit 110 can be any gas stream requiring cooling and, in some embodiments, can be a natural gas feed stream originating from one or more gas sources (not shown). Examples of suitable gas sources can include, but are not limited to, natural sources such as, subterranean formations and petroleum production wells, and/or refining units such as fluidized catalytic crackers, petroleum cokers, or heavy oil processing units, such as oil sands upgraders. Depending on the origin and composition of the feed gas stream, LNG facility 10 can include one or more additional processing units or zones (not shown) upstream of primary heat exchanger 16 for removing unwanted components such as water, sulfur, mercury, nitrogen, and heavy (C 6 + ) hydrocarbon materials from the feed gas stream prior to its liquefaction.
[0018] According to one embodiment, the feed gas stream in conduit 110 can comprise at least about 65, at least about 75, at least about 85, at least about 95, at least 99 weight percent methane, based on the total weight of the stream. Typically, heavier components such as C 2 , C 3 , and heavier hydrocarbons, and trace amounts of components such as hydrogen and nitrogen, can make up the balance of the composition fo the feed gas stream. As discussed previously, the stream in conduit 110 may have undergone one or more pretreatment steps to reduce the amount of or remove one or more components other than methane from the feed gas stream. In one embodiment, the feed gas stream in conduit 110 comprises less than about 25, less than about 20, less than about 15, less than about 10, or less than about 5 percent of components other than methane. Depending on the source and composition of the feed gas stream, the undesired components removed in the pretreatment steps can include, but are not limited to, water, mercury, sulfur compounds, and other materials.
[0019] As shown in FIG. 1 , the feed gas stream in conduit 110 can be introduced into a first cooling pass 18 of a primary heat exchanger 16 , wherein the stream may be cooled and at least partially condensed via indirect heat exchange with at least one yet-to-be-discussed stream of mixed refrigerant. Terms such as “first,” “second,” and “third,” are used herein and in the appended claims to describe various elements of systems and processes of the present invention, and such elements should not be limited to by these terms. These terms are only used to distinguish one element from another and do not necessarily imply a specific order or even a specific element. For example, an element may be regarded as a “first” element in the description and a “second element” in the claims without departing from the scope of the present invention. Consistency is maintained within the description and each independent claim, but such nomenclature is not necessarily intended to be consistent therebetween.
[0020] Primary heat exchanger 16 shown in FIG. 1 can be any type of heat exchanger, or a series of heat exchangers, operable to cool and at least partially condense the feed gas stream in conduit 110 . For example, in some embodiments, primary heat exchanger 16 can be a brazed aluminum heat exchanger comprising a plurality of warming and cooling passes (e.g., cores) disposed within the exchanger configured to facilitate indirect heat exchange between one or more process streams and one or more refrigerant streams. In some embodiments, one or more of the warming and/or cooling passes may be alternately defined between a plurality of plates disposed within the external “shell” of exchanger 16 . It should be understood that, although generally illustrated in FIG. 1 as comprising a single shell, primary heat exchanger 16 may, in some embodiments, comprise two or more separate shells optionally encompassed by a “cold box” to minimize heat loss to the surrounding environment. Other types or configurations of primary heat exchanger 16 may also be suitable and are contemplated to be within the scope of the present invention.
[0021] Referring back to FIG. 1 , the cooled, two-phase stream withdrawn from cooling pass 18 of primary heat exchanger 16 via conduit 112 may subsequently be introduced into a vapor-liquid separator 20 . Separator 20 can be any suitable type of vapor-liquid separation vessel and may include any number of actual or theoretical separation stages. In one embodiment, vapor-liquid separation vessel may comprise a single separation stage, while, in other embodiments, separation vessel 20 can include at least about 2, at least about 5, at least about 10 and/or not more than about 50, not more than about 40, not more than about 25 actual or theoretical separation stages. Separator 20 may include any suitable type of column internals, including, for example, mist eliminators, mesh pads, vapor-liquid contacting trays, random packing, and/or structured packing in order to facilitate heat and/or mass transfer between the vapor and liquid streams. In some embodiments, when separator 20 comprises a single-stage separation vessel, few or no column internals may be employed. Additionally, gas separation zone 14 may include one or more other separation vessels (not shown) arranged in parallel or in series with separator 20 . When gas separation zone 14 includes one or more additional vapor-liquid separators, each of the additional separators may configured similarly to or different than separator 20 .
[0022] As shown in FIG. 1 , separator 20 can separate the two-phase fluid stream in conduit 112 into an overhead vapor stream in conduit 114 and a bottoms liquid stream in conduit 116 . Typically, the overhead vapor stream withdrawn from separator 20 via conduit 114 may be enriched in methane and lighter components, while the bottoms liquid stream in conduit 116 may be a methane-depleted stream enriched one or more heavier components, such as ethane, propane, and others. In some embodiments, the bottoms liquid stream in conduit 116 may be recovered as a separate natural gas liquids (NGL) product stream and may be subjected to further downstream processing and/or separation (not shown).
[0023] As shown in one embodiment depicted in FIG. 1 , the overhead vapor stream withdrawn from separator 20 via conduit 114 may be routed into a second natural gas cooling pass 22 of primary heat exchanger 16 . In cooling pass 22 , the cooled gas stream may be further cooled, condensed, and optionally sub-cooled, via indirect heat exchange with one or more yet-to-be-discussed refrigerant streams. As shown in FIG. 1 , the resulting sub-cooled LNG product stream may be withdrawn from primary heat exchanger 16 via conduit 118 . In some embodiments, the LNG product stream in conduit 118 may have a temperature in the range of from about −200° F. to about −290° F., about −220° F. to about −280° F., or about −240° F. to about −275° F. and/or a pressure of less than about 50 psia, less than about 40 psia, less than about 30 psia, or less than about 20 psia. Although not illustrated in FIG. 1 , LNG facility 10 may also include additional processing units and/or storage facilities downstream of primary heat exchanger 16 to further process, separate, and/or store the LNG product stream in conduit 118 . In some embodiments, at least a portion of the LNG product may be transported from LNG facility 10 to one or more separate facilities (not shown) for subsequent storage, processing, and/or use.
[0024] Turning now the embodiment of refrigeration system 12 of LNG facility 10 depicted in FIG. 1 , refrigeration cycle 12 illustrated as generally including a refrigerant suction drum 28 , a multi-stage refrigerant compressor 30 , an interstage cooler 32 , an interstage accumulator 34 , an interstage refrigerant pump 36 , a refrigerant condenser 38 , a refrigerant accumulator 40 , and a refrigerant pump 42 . Additionally, refrigeration system 12 includes a pair of refrigerant cooling passes 52 and 58 and a pair of refrigerant warming passes 56 and 62 , each having an expansion device 54 and 60 , respectively disposed between cooling pass 52 and warming pass 56 and cooling pass 58 and warming pass 62 .
[0025] According to one embodiment of the present invention, the refrigerant utilized in closed-loop refrigeration cycle 12 may be a mixed refrigerant. As used herein, the term “mixed refrigerant” refers to a refrigerant composition comprising two or more constituents. In one embodiment, the mixed refrigerant utilized by refrigeration cycle 12 may be a single mixed refrigerant and can comprise two or more components selected from the group consisting of methane, ethylene, ethane, propylene, propane, isobutane, n-butane, isopentane, n-pentane, and combinations thereof. In some embodiments, the refrigerant composition can comprise methane, ethane, propane, normal butane, and isopentane and can exclude certain components, including, for example, nitrogen or halogenated hydrocarbons. Various specific refrigerant compositions are contemplated according to embodiments of the present invention. Table 1, below, summarizes broad, intermediate, and narrow ranges for several exemplary components that may be employed in refrigerant mixtures suitable for use in refrigerant cycle 12 , according to various embodiments of the present invention.
[0000]
TABLE 1
Exemplary Mixed Refrigerant Compositions
Broad
Intermediate
Narrow
Range,
Range,
Range,
Component
mole %
mole %
mole %
methane
0 to 50
5 to 40
10 to 30
ethylene
0 to 50
5 to 40
10 to 30
ethane
0 to 50
5 to 40
10 to 30
propylene
0 to 50
5 to 40
5 to 30
propane
0 to 50
5 to 40
5 to 30
i-butane
0 to 10
0 to 5
0 to 2
n-butane
0 to 25
1 to 20
5 to 15
i-pentane
0 to 30
1 to 20
2 to 15
n-pentane
0 to 10
0 to 5
0 to 2
nitrogen
0 to 30
0 to 25
0 to 20
[0026] In some embodiments of the present invention, it may be desirable to adjust the composition of the mixed refrigerant to thereby alter its cooling curve and, therefore, its refrigeration potential. Such a modification may be utilized to accommodate, for example, changes in composition and/or flow rate of the feed gas stream introduced into LNG facility 10 . In one embodiment, the composition of the mixed refrigerant can be adjusted such that the heating curve of the vaporizing refrigerant more closely matches the cooling curve of the feed gas stream. One method for such curve matching is described in detail in U.S. Pat. No. 4,033,735, the disclosure of which is incorporated herein by reference in its entirety and to the extent not inconsistent with the present disclosure. In some embodiments, ability to alter the composition and, consequently, the heating curve of the refrigerant provides increased flexibility and operability to the facility, enabling it to receive and efficiently process feed streams having a wider variety of gas compositions.
[0027] Referring again to refrigeration cycle 12 shown in the embodiment of facility 10 in FIG. 1 , a stream of mixed refrigerant in conduit 120 may be introduced into a fluid inlet of refrigerant suction drum 28 , wherein any liquid present may be separated from the vapor phase. When present, the liquids may then be withdrawn from a lower liquid outlet of suction drum 28 and can be returned to the circulating system (not shown). As shown in FIG. 1 , a vapor phase stream of mixed refrigerant can be withdrawn from an upper vapor outlet of suction drum 28 and routed to a low pressure inlet of a low pressure compression stage 44 of multi-stage compressor 30 . Multi-stage compressor 30 may be any type of compressor suitable to increase the pressure of the mixed refrigerant in closed-loop mixed refrigeration cycle 12 . Although illustrated in FIG. 1 as generally comprising two compression stages, multi-stage compressor 30 may include three or more stages, in accordance with other embodiments of the present invention.
[0028] As shown in FIG. 1 , the compressed refrigerant stream withdrawn from the intermediate pressure outlet of low pressure compression stage 44 of refrigerant compressor 30 via conduit 126 can be routed to the warm fluid inlet of interstage cooler 32 , wherein the stream can be cooled and at least partially condensed via indirect heat exchange with at least one coolant stream (e.g., air or cooling water). The resulting two-phase refrigerant stream in conduit 128 can then be routed to an interstage accumulator 34 , wherein the vapor and liquid phases may be separated. As shown in FIG. 1 , the vapor stream withdrawn from interstage accumulator 34 via conduit 132 can be introduced into an intermediate pressure inlet of a high pressure compression stage 46 of multi-stage compressor, which can be connected to low pressure compression stage 44 via shaft 48 . In high pressure compression stage 46 , the mixed refrigerant stream may be further compressed before being discharged from a high-pressure outlet of high pressure compression stage 46 into conduit 134 . Additionally, as depicted in the embodiment shown in FIG. 1 , the liquid portion of the refrigerant stream withdrawn from interstage accumulator 34 via conduit 130 may be pumped to a higher pressure via refrigerant pump 36 , before being combined with the compressed refrigerant stream in conduit 134 . In one embodiment, the pressure of the liquid stream discharged from refrigerant pump 36 in conduit 136 can be within about 100, within about 50, within about 20, within about 10, or within about 5 psi of the pressure of the vapor stream in conduit 134 prior to combination of the two streams.
[0029] The combined refrigerant stream in conduit 138 can then be introduced into a refrigerant condenser 38 , wherein the stream may be cooled and at least partially condensed via indirect heat exchange with a coolant stream (e.g., cooling water). The resulting cooled, at least partially condensed refrigerant stream in conduit 140 may then be introduced into a refrigerant accumulator 40 , wherein the vapor and liquid phases may be separated. As shown in FIG. 1 , the vapor phase refrigerant stream in conduit 142 may be withdrawn and combined with a yet-to-be-discussed liquid refrigerant stream before being introduced into primary heat exchanger 16 .
[0030] According to one embodiment of the present invention, the liquid refrigerant stream withdrawn from refrigerant accumulator 40 via conduit 144 can be pressurized via refrigerant pump 40 and the resulting stream discharged into conduit 146 may be passed through a dividing device 50 , which can be configured to divide the pressurized liquid refrigerant into two separate portions in conduits 148 and 150 . As shown in FIG. 1 , dividing device 50 is not a vapor-liquid separator, but, instead, can be any device configured to divide the liquid stream in conduit 146 into two streams of similar composition and state. The flow rates of the individual streams in conduits 148 and 150 may be similar or different. For example, in some embodiments, the ratio of the mass flow rate of the stream in conduit 148 to the mass flow rate of the stream in conduit 150 can be at least about 0.5:1, at least about 0.75:1, at least about 0.95:1 and/or not more than about 2:1, not more than about 1.75:1, not more than about 1.5:1, not more than about 1.25:1. In the same or other embodiments, the ratio of the mass flow rate of the stream in conduit 148 to the mass flow rate of the stream in conduit 150 can be approximately 1:1.
[0031] As shown in FIG. 1 , the first portion of the liquid refrigerant stream in conduit 148 may be combined with the vapor phase refrigerant stream withdrawn from refrigerant accumulator 40 in conduit 142 . The amount of vapor and/or liquid introduced into conduits 142 and/or 148 may be controlled to achieve a desired ratio of vapor to liquid introduced into a refrigerant cooling pass 58 disposed within primary heat exchanger 16 . In one embodiment, the combined stream introduced into cooling pass 58 can have a vapor fraction of at least about 0.45, at least about 0.55, at least about 0.65 and/or not more than about 0.95, not more than about 0.90, not more than about 0.85. Although illustrated as being combined just prior to introduction into cooling pass 58 , it should be understood that the liquid stream in conduit 148 and the vapor phase refrigerant stream in conduit 142 may be alternatively be combined within primary heat exchanger 16 or may be combined at a different location further upstream of heat exchanger 16 , so that the combined stream may be introduced into cooling pass 58 via a common conduit external to primary heat exchanger 16 (embodiment not shown in FIG. 1 ).
[0032] As shown in FIG. 1 , the combined refrigerant stream introduced into primary heat exchanger 16 decends vertically downward through cooling pass 58 , wherein it can be cooled and condensed via indirect heat exchange with one or more refrigerant streams. The resulting condensed and subcooled liquid stream can be withdrawn from the lower portion of primary heat exchanger 16 via conduit 158 . As shown in FIG. 1 , the liquid refrigerant stream in conduit 158 may then be passed through an expansion device 60 , wherein the pressure of the stream can be reduced to thereby flash a portion thereof. The resulting cooled, two-phase stream in conduit 160 can then be introduced into refrigerant warming pass 62 , wherein the stream may be warmed as it ascends vertically upwardly through primary heat exchanger 16 . As the ascending refrigerant stream is warmed, it can provide refrigeration to one or more of the streams being cooled, as described previously.
[0033] According to one embodiment of the present invention, the second portion of the liquid refrigerant stream withdrawn from refrigerant accumulator 40 via conduit 150 can be separately introduced into a second refrigerant cooling pass 52 disposed within primary heat exchanger 16 . As the liquid stream travels vertically downward through cooling pass 52 , it is cooled and condensed via indirect heat exchange with one or more refrigerant streams. The resulting liquid refrigerant stream exiting cooling pass 52 in conduit 152 can then be passed through expansion device 54 , wherein the pressure of the stream can be reduced to thereby flash a portion of the stream. Although generally depicted as being an expansion valve or Joule-Thompson (JT) valve in FIG. 1 , it should also be understood that expansion device 54 may comprise any suitable type of expander, including, for example, a JT orifice or a turboexpander (not shown). Similarly, expansion device 54 may include, in some embodiments, two or more expansion devices, arranged in parallel or in series, configured to reduce the pressure of the liquid refrigerant stream in conduit 152 .
[0034] The resulting cooled, two-phase refrigerant stream in conduit 154 may then be reintroduced into another refrigerant warming pass 56 of primary heat exchanger 16 , wherein the stream can be warmed to thereby providing refrigeration to one or more other fluid streams being cooled in primary heat exchanger 16 , including the refrigerant streams in conduits 150 and 158 in respective cooling passes 52 and 58 , the natural gas feed stream in conduit 110 in cooling pass 18 , and/or the overhead vapor stream in conduit 114 in cooling pass 22 .
[0035] According to one embodiment depicted in FIG. 1 , the overall length of refrigerant cooling pass 52 can be less than the overall length of refrigerant cooling pass 58 . Consequently, the cooled refrigerant stream exiting refrigerant cooling pass 52 via conduit 152 may be withdrawn from a higher vertical elevation along the height of primary heat exchanger 16 than the cooled refrigerant stream withdrawn from refrigerant cooling pass 58 . For example, in one embodiment depicted in FIG. 1 , the cooled refrigerant stream exiting refrigerant cooling pass 52 may be withdrawn from a vertical mid-point of primary exchanger 16 , while the cooled refrigerant stream exiting refrigerant cooling pass 58 may be withdrawn from an outlet positioned near the lower vertical end of primary exchanger 16 . According to one embodiment, the ratio of the total length of refrigerant cooling pass 52 to the total length of refrigerant cooling pass 58 can be at least about 0.15:1, at least about 0.25:1, at least about 0.35:1 and/or not more than about 0.75:1, not more than about 0.65:1, not more than about 0.50:1, or in the range of from about 0.15:1 to about 0.75:1, about 0.25:1 to about 0.65:1, or about 0.25:1 to about 0.50:1. In the same or other embodiments, the ratio of the total length of refrigerant cooling pass 52 to the overall height (i.e., vertical dimension) of primary heat exchanger 16 can be at least about 0.15:1, at least about 0.25:1, at least about 0.35:1 and/or not more than about 0.75:1, not more than about 0.65:1, not more than about 0.55:1, while the ratio of the total length of cooling pass 58 to the overall height of primary heat exchanger 16 can be about 1:1.
[0036] As shown in FIG. 1 , a first warmed mixed refrigerant stream, which may have a vapor fraction of at least about 0.85, at least about 0.90, at least about 0.95, can be withdrawn from warming pass 62 via conduit 162 and a second warmed refrigerant stream having a similar vapor fraction may be withdrawn from warming pass 58 via conduit 156 . According to one embodiment depicted in FIG. 1 , the two streams of warmed refrigerant stream may then be combined and the resulting stream in conduit 120 may thereafter be recirculated to the inlet of refrigerant suction drum 28 , as described in detail previously.
[0037] Turning now to FIG. 2 , another embodiment of LNG facility 10 is illustrated. The embodiment of LNG facility 10 shown in FIG. 2 is similar to the embodiment depicted in FIG. 1 , but includes a different configuration of various components of refrigeration system 12 . The main components of LNG facility 10 shown in FIG. 2 are numbered the same as those depicted in FIG. 1 . The operation of LNG facility 10 illustrated in FIG. 2 , as it differs from that previously discussed with respect to FIG. 1 , will now be described in detail below.
[0038] As shown in FIG. 2 , the stream of mixed refrigerant in conduit 120 introduced into refrigerant suction drum 28 can be separated into an overhead vapor stream in conduit 124 and a bottoms liquid stream in conduit 122 . According to the embodiment depicted in FIG. 2 , the bottoms liquid stream in conduit 122 withdrawn from refrigerant suction drum 28 can be pressurized via a refrigerant pump 64 and the resulting stream in conduit 123 may then be combined with the two-phase refrigerant stream in conduit 138 . Thereafter, the combined refrigerant stream in conduit 138 can be introduced into refrigerant condenser 38 and the resulting cooled stream can then pass through the remainder of refrigeration cycle 12 , as discussed in detail previously with respect to FIG. 1 . In one embodiment (not shown in FIG. 2 ), it may be possible to combine the pressurized liquid bottoms stream in conduit 123 with the compressed vapor refrigerant stream exiting the high pressure compression stage 46 in conduit 134 to produce a combined stream, which can subsequently be combined with the pressurized liquid phase refrigerant stream discharged from interstage pump 36 in conduit 136 .
[0039] According to one embodiment, the addition of refrigerant pump 64 to the lower liquid conduit 122 of refrigeration suction drum 28 may permit refrigeration cycle 12 to utilize refrigerants having different compositions than those suitable for use in the embodiment of LNG facility 10 shown in FIG. 1 . In particular, the employment of a refrigeration liquid recycle conduit 123 as shown in the embodiment of LNG facility 10 depicted in FIG. 2 , may allow refrigeration cycle 12 to employ a mixed refrigerant that includes a higher concentration of heavy hydrocarbons than the mixed refrigerant utilized in LNG facility 10 shown in FIG. 1 . As described previously, it may be desirable to alter the composition of the mixed refrigerant employed in refrigeration cycle 12 to, for example, accommodate changes in composition of the feed gas stream and more closely match the heating curve of the mixed refrigerant with the cooling curve of the natural gas stream. In some embodiments, the option to utilize mixed refrigerants of varying composition, including those refrigerant compositions including a higher amount of heavier components, may impart even more operating flexibility to LNG facilities configured according to embodiments of the present invention.
[0040] Turning now to FIG. 3 , yet another embodiment of LNG facility 10 is illustrated. The embodiment of LNG facility 10 shown in FIG. 3 is similar to the embodiment depicted in FIG. 1 , but includes a different configuration of various components of refrigeration system 12 . The main components of LNG facility 10 shown in FIG. 3 are numbered the same as those depicted in FIG. 1 . The operation of LNG facility 10 illustrated in FIG. 3 , as it differs from that previously discussed with respect to FIG. 1 , will now be described.
[0041] As shown in FIG. 3 , two streams of warmed mixed refrigerant can be withdrawn from refrigerant warming pass 56 and refrigerant warming pass 62 via respective conduits 156 and 162 . Rather than being combined, as shown in the embodiment depicted in FIG. 1 , the warmed refrigerant streams in conduits 156 and 162 remain separate as shown in the embodiment of LNG facility 10 shown in FIG. 3 . As shown in FIG. 3 , the warmed refrigerant vapor stream in conduit 156 , which may have a temperature that is at least about 25° F., at least about 50° F., at least about 75° F. and/or not more than about 150° F., not more than about 125° F., not more than about 100° F. warmer than the warmed refrigerant vapor stream in conduit 162 , may be routed to a fluid inlet of a refrigerant separator 68 , wherein the vapor and liquid portions may be separated from each other. Refrigerant separator 68 may be any suitable type of vapor-liquid separator and can optionally include one or more tower internals described in detail previously with respect to separator 20 .
[0042] As shown in FIG. 3 , the liquid portion of the warmed refrigerant stream introduced into refrigerant separator 68 may be withdrawn from separator 68 via conduit 166 and pumped to a higher pressure via a refrigerant pump 70 . The resulting, pressurized stream of liquid refrigerant in conduit 168 may then be combined with the previously-discussed two-phase pressurized refrigerant stream in conduit 138 . The resulting combined refrigerant stream in conduit 139 may then be introduced into refrigerant condenser 38 , wherein the stream can be cooled and at least partially condensed before continuing through the remaining portions of refrigeration cycle 12 as described previously with respect to FIG. 1 .
[0043] Referring again to FIG. 3 , the vapor portion of the warmed refrigerant stream introduced into refrigerant separator 68 may be withdrawn from the upper portion of separator 68 via conduit 164 and combined with the second warmed refrigerant stream withdrawn from refrigerant warming pass 62 in conduit 162 . The resulting combined vapor-phase refrigerant stream in conduit 120 can then be routed to the inlet of refrigerant suction drum 28 , wherein the stream may be separated into vapor and liquid portions withdrawn from drum 28 via respective conduits 124 and 122 , as shown in FIG. 3 . Thereafter, each of the vapor and liquid portions may continue through the remainder of refrigeration cycle 12 as discussed in detail previously with respect to FIG. 1 .
[0044] Although described herein with respect to liquefying a natural gas stream, it should it should also be understood that processes and systems of the present invention may also be suitable for use in other gas processing and separation applications, including, but not limited to, ethane recovery and liquefaction, recovery of natural gas liquids (NGL), syngas separation and methane recovery, and cooling and separation of nitrogen and/or oxygen from various hydrocarbon-containing gas streams.
[0045] The preferred forms of the invention described above are to be used as illustration only, and should not be used in a limiting sense to interpret the scope of the present invention. Obvious modifications to the exemplary one embodiment, set forth above, could be readily made by those skilled in the art without departing from the spirit of the present invention. The inventors hereby state their intent to rely on the Doctrine of Equivalents to determine and assess the reasonably fair scope of the present invention as pertains to any apparatus not materially departing from but outside the literal scope of the invention as set forth in the following claims.
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Processes and systems for producing liquefied natural gas (LNG) with a single mixed refrigerant, closed-loop refrigeration cycle are provided. Liquefied natural gas facilities configured according to embodiments of the present invention include refrigeration cycles optimized to provide increased efficiency and enhanced operability, with minimal additional equipment or expense.
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BACKGROUND OF THE INVENTION
This application relates to disposable glucose test strips for use in electrochemical determinations of blood glucose, and to methods and compositions for use in making such strips.
Glucose monitoring is a fact of everyday life for diabetic individuals, and the accuracy of such monitoring can literally mean the difference between life and death. To accommodate a normal life style to the need for frequent monitoring of glucose levels, a number of glucose meters are now available which permit the individual to test the glucose level in a small amount of blood.
Many of these meters detect glucose in a blood sample electrochemically, by detecting the oxidation of blood glucose using an enzyme such as glucose oxidase provided as part of a disposable, single use electrode system. Examples of devices of this type are disclosed in European Patent No. 0 127 958, and U.S. Pat. Nos. 5,141,868, 5,286,362, 5,288,636, and 5,437,999 which are incorporated herein by reference.
In general, existing glucose test strips for use in electrochemical meters comprise a substrate, working and reference electrodes formed on the surface of the substrate, and a means for making connection between the electrodes and the meter. The working electrode is coated with an enzyme capable of oxidizing glucose, and a mediator compound which transfers electrons from the enzyme to the electrode resulting in a measurable current when glucose is present. Representative mediator compounds include ferricyanide, metallocene compounds such as ferrocene, quinones, phenazinium salts, redox indicator DCPIP, and imidazole-substituted osmium compounds.
Working electrodes of this type have been formulated in a number of ways. For example, mixtures of conductive carbon, glucose oxidase and a mediator have been formulated into a paste or ink and applied to a substrate. EP 0 127 958 and U.S. Pat. No. 5,286,362. In the case of disposable glucose strips, this application is done by screen printing in order to obtain the thin layers suitable for a small flat test strip. The use of screen printing, however, introduces problems to the operation of the electrode.
Unlike a thicker carbon paste electrode which remains fairly intact during the measurement, screen printed electrodes formed from carbon pastes or inks are prone to break up on contact with the sample. The consequences of this breakup are two-fold. Firstly, the components of the electrode formulation are released into solution. Once these components drift more than a diffusion length away from the underlying conductive layer, they no longer contribute toward the measurement, but in fact diminish the response by depleting inwardly-diffusing analyte. Secondly, the breakup of the screen printed electrode means that the effective electrode area is falling over time.
The combination of these two effects results in current transients which fall rapidly from an initial peak over the period of the measurement, and a high sensitivity to oxygen which quickly competes with the mediator for the enzyme. This fact is clearly demonstrated by the much lower currents measured in blood samples than in plasma samples or other aqueous media, and can result in erroneous readings. A further consequence is that the transients are often "lumpy" as the electrode breaks up in a chaotic manner. Lumpy transients either give rise to erroneous readings or rejected strips, neither of which are acceptable.
In addition to the potential for electrode breakup of screen-printed carbon-based electrodes, known electrodes used in disposable glucose test strips have been kinetically-controlled, i.e., the current depends on the rate of conversion of glucose by the enzyme. Because the response measured by the instrument represents a balance between the reaction of enzyme and mediator, enzyme and glucose and enzyme and oxygen, and because each of these reactions has its own dependence on temperature, the response of a kinetically-controlled test strip is very sensitive to the temperature of the sample. Substantial variation in the measured glucose value can therefore occur as a result of variations in sample handling.
Because of the importance of obtaining accurate glucose readings to the well-being of a patient using the meter and disposable test strips, it would be highly desirable to have a glucose test strip which did not suffer from these drawbacks, and which therefore provided a more consistent and reliable indication of actual blood glucose values, regardless of actual conditions. It is therefore an object of the present invention to provide disposable glucose test strips which are not prone to electrode breakup on contact with a sample.
It is a further object of this invention to provide glucose test strips which provide a glucose reading that is essentially independent of the hematocrit of the sample.
It is a further object of the present invention to provide glucose test strips which are substantially independent of temperature over a range between normal body temperature and room temperature.
It is a further object of the invention to provide test strips which provide a substantially flat current transient, without significant decay for periods of at least 10 seconds after the peak current level is obtained.
SUMMARY OF THE INVENTION
The present invention provides an improved disposable glucose test strip for use in a test meter of the type which receives a disposable test strip and a sample of blood from a patient and performs an electrochemical analysis of the amount of glucose in the sample. The test strip comprises:
(a) a substrate;
(b) a reference electrode;
(c) a working electrode; and
(d) means for making an electrical connection between the reference and working electrode and a glucose test meter. The working electrode comprises a conductive base layer disposed on the substrate and a non-conductive coating disposed over the conductive base layer. The non-conductive coating comprises a filler which has both hydrophobic and hydrophilic surface regions, an enzyme effective to oxidize glucose, e.g., glucose oxidase, and a mediator effective to transfer electrons from the enzyme to the conductive base layer. The filler is selected to have a balance of hydrophobicity and hydrophilicity such that on drying it forms a two-dimensional network on the surface of the conductive base layer. Preferred filler are non-conductive silica fillers. The response of this test strip is dependent on the diffusion rate of glucose, not on the rate at which the enzyme can oxidize glucose, such that the performance of the test strip is essentially temperature independent over relevant temperature ranges. Further, the silica appears to form a two-dimensional network which excludes red blood cells, thus rendering the test strip substantially insensitive to the hematocrit of the patient.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A and 1B shows an electrode structure useful in a disposable test strip in accordance with the invention;
FIG. 2 shows a test strip in accordance with the invention;
FIGS. 3A-3C show the current measured as a function of glucose concentration for three different hematocrit levels;
FIG. 4 shows the relationship of the glucose-concentration dependence of the measured current as a function of hematocrit;
FIGS. 5A-5C show the current measured as a function of glucose in blood and a control solution for three different variations of the conductive base layer;
FIG. 6A and 6B show the current measured as a function of glucose at two different temperatures;
FIG. 7 shows a further embodiment of a glucose test strip according to the invention; and
FIGS. 8A and 8B show a current transients observed using a test strip according to the invention and a commercial carbon-based test strip.
DETAILED DESCRIPTION OF THE INVENTION
FIGS. 1A and 1B show electrodes useful in a disposable test strip in accordance with the invention. As shown, the electrodes are formed on a substrate 10. On the substrate 10 are placed a conductive base layer 16, a working electrode track 14, a reference electrode track 15, and conductive contacts 11, 12, and 13. An insulating mask 18 is then formed, leaving a portion of the conductive base layer 16, and the contacts 11, 12 and 13 exposed. A region of a working coating 17 is then applied over the insulating mask 18 to make contact with conductive base layer 16.
The assembly shown in FIG. 1 provides a fully functional assembly for the measurement of blood glucose when connected to a meter. Advantageously, however, the electrode strips of the invention are finished by applying a polyester mesh 21 over the region of the working coating 17 of the electrode assembly 22, and then a top cover 23 to prevent splashing of the blood sample. (FIG. 2) The polyester mesh acts to guide the sample to the reference electrode, thereby triggering the device and initiating the test.
The substrate 10 used in making the test strips of the invention can be any non-conducting, dimensionally stable material suitable for insertion into a glucose test meter. Suitable materials include polyester films, for example a 330 micron polyester film, and other insulating substrate materials.
The working electrode track 15, the reference electrode track 14, and conductive contacts 11, and 12 can be formed from essentially any conductive material including silver, Ag/AgC1, gold, or platinum/carbon.
The conductive base layer 16 is preferably formed from conductive carbon. Preferred conductive carbon are ERCON ERC1, ERCON ERC2 and Acheson Carbon Electrodag 423. Carbon with these specifications is available from Ercon Inc. (Waltham, Mass., USA), or Acheson Colloids, (Princes Rock, Plymouth, England). The conductive base layer 16 makes contact with working electrode track 15, and is close too but not contacting the end of reference electrode track 15.
The insulating layer 18 can be formed from polyester-based printable dielectric materials such as ERCON R488-B(HV)-B2 Blue.
The key to the performance achieved using the present invention is in the nature of the coating 17. This coating contains a filler which has both hydrophobic and hydrophilic surface regions, an enzyme which can oxidize glucose, and a mediator which can transfer electrons from the enzyme to the underlying conductive base layer 16.
A preferred filler for use in the coating 17 is silica. Silica is available in a variety of grades and with a variety of surface modifications. While all silica compounds tested resulted in a product which could measure glucose under some conditions, the superior performance characteristics of glucose test strip of the invention are obtained when a silica having a surface modification to render it partially hydrophobic is used. Materials of this type include Cab-O-Sil TS610, a silica which is modified by partial surface treatment with methyl dichlorosilane; Cab-o-Sil 530, a silica which is modified by full surface treatment with hexamethyl disilazane; Spherisorb C4 silica, which is surface modified with 4 carbon chains; and other similarly modified by silicas, or combinations thereof. Silica with a surface modification which is too hydrophobic should be avoided, however, since it has been observed that C18-modified silica is too hydrophobic to form a printable ink.
During the process of manufacturing the ink of the invention, the particles are broken down by homogenization to expose hydrophilic inner portions of the silica particles. The actual particles present in the ink therefore have both hydrophilic and hydrophobic regions. The hydrophilic regions form hydrogen bonds with each other and with water.
When this material is formulated into an ink as described below in Example 1, and screen printed onto the conductive base layer 16, the dual nature of the material causes it to form layers of two-dimensional networks which take form as a kind of honeycomb. On rehydration, this layer does not break up, but swells forming a gelled reaction zone in the vicinity of the underlying conductive base layer 16. Enzyme, mediator and glucose move freely within this zone, but interfering species such as red blood cells containing oxygenated hemoglobin are excluded. This results in a device in which the amount of current generated in response to a given amount of glucose varies by less than 10 percent over a hematocrit range of 40 to 60%, and which is thus substantially insensitive to the hematocrit of the sample, and in fact performs substantially the same in blood as in a cell-free control solution. (FIGS. 3A-C, FIG. 4 and FIG. 5A-5C)
Furthermore, the gelled reaction zone presents a greater barrier to entry of glucose which makes the device diffusion, rather than kinetically limited. This leads to a device in which the measured current varies by less than 10 percent over a temperature range from 20° C. to 37° C. and which is thus essentially temperature independent. (FIGS. 6A and 6B)
The working layer is advantageously formed from an aqueous composition containing 2 to 10% by weight, preferably 4 to 10% and more preferably about 4.5% of a binder such as hydroxyethylcellulose or mixtures of hydroxyethylcellulose with alginate or other thickeners; 3 to 10% by weight, preferably 3 to 5% and more preferably about 4% silica; 8 to 20% by weight, preferably 14 to 18% and more preferably about 16% of a mediator such as ferricyanide; and 0.4 to 2% by weight, preferably 1 to 2% and more preferably about 1.6% of an enzyme such as glucose oxidase, assuming a specific activity of about 250 units/mg, or about 1000 to 5000 units per gram of ink formulation.
The working layer may also include additional ingredients without departing from the scope of the invention. For example, the nonconducting layer may include an antifoam. In addition, the nonconducting layer may be formulated with a buffering agent to control the pH of the reaction zone. The pH may be maintained at a level within the range from about pH 3 to pH 10. It is of particular utility to maintain the pH of the device at a level above 8 because at this pH oxygen bound to hemoglobin is not released. Further, at this pH, the reaction rate of glucose oxidase with oxygen is very low. Thus, selection of an appropriate pH can further stabilize the performance of the test strip against the effects of varying hematocrit.
FIG. 7 shows an alternative embodiment of the invention. In this embodiment, a second working layer 71 is disposed over the first working layer 17. This layer is formed from a composition which is identical to the first working layer except that the enzyme or both the enzyme and the mediator are omitted. This layer further isolates the conductive base layer from contact with oxygen-carrying red blood cells, thus reducing the effects of oxygen. Furthermore, to the extent that enzyme may tend to diffuse away from the surface of the electrode during the course of the measurement, this layer provides an increased region in which it will have mediator available for the transfer of electrons.
EXAMPLE 1
A non-conducting formulation for preparation of the working layer 17 was made as follows. 100 ml of 20 mM aqueous trisodium citrate was adjusted to pH 6 by the addition of 0.1M citric acid. To this 6 g of hydroxyethyl cellulose (HEC) was added and mixed by homogenization. The mixture was allowed to stand overnight to allow air bubbles to disperse and then used as a stock solution for the formulation of the coating composition.
2 grams Cab-o-Sil TS610 silica and 0.1 grams of Dow Corning antifoam compound was gradually added by hand to 50 grams of the HEC solution until about 4/5 of the total amount has been added. The remainder is added with mixing by homogenization. The mixture is then cooled for ten minutes in a refrigerator. 8 g of potassium hexacyanoferrate (III) is then added and mixed until completely dissolved. Finally, 0.8 g of glucose oxidase enzyme preparation (250 Units/mg) is added and the thoroughly mixed into the solution. The resulting formulation is ready for printing, or can be stored with refrigeration.
EXAMPLE 2
To prepare glucose test strips using the ink formulation of Example 1, a series of patterns are used to screen print layers onto a 330 micron polyester substrate (Melinex 329). The first step is the printing of carbon pads. An array of 10×50 pads of carbon is formed on the surface of the polyester substrate by printing with EC2 carbon. (Ercon) The printed substrate is then passed through a heated dryer, and optionally cured at elevated temperature (e.g. 70° C.) for a period of 1 to 3 weeks.
Next, an array of silver/silver chloride connecting tracks and contacts is printed onto the substrate using ERCON R-414 (DPM-68)1.25 bioelectrode sensor coating material and dried. One working track which makes contact with the carbon pad and one reference track is printed for each carbon pad in the array.
A dielectric layer is then printed using ERCON R488-B(HV)-B2 Blue and dried. The dielectric layer is printed in a pattern which covers substantially all of each devices, leaving only the contacts, the tip of the reference electrode and the carbon pads uncovered.
On top of the dielectric layer the ink of Example 1 is used to form a working layer overlaid on top of each conductive carbon pad.
Polyester mesh strips (Scrynel PET230 HC) are then laid down across the substrate in lines, covering the reactions areas exposed by the windows in the dielectric. A 5 mm wide polyester strip (50 microns thick) is then applied over the top of the mesh strips, and the edges of the electrodes are heat sealed. Finally, the substrate is cut up to provide 50 individual electrodes, for example having a size of 5.5 mm wide and 30 mm long.
EXAMPLE 3
Test strips manufactured using the ink formulation of Example 1 in the manner described in Example 2 were placed in a test meter with an applied voltage of 500 mV and used to test blood samples having varying glucose concentrations and hematocrits ranging from 40% to 60%. FIGS. 3A-3C show the current measured 25 seconds after applying the voltage as a function of the glucose concentration, and FIG. 4 plots the slope of the glucose response as a function of hematocrit. As can be seen, the indicators produce highly reproducible current levels which are essentially independent of hematocrit.
EXAMPLE 4
Glucose test strips in accordance with the invention were made in accordance with Example 2, except the non-conductive layer was formed with 7 g Spherisorb C4 and 1 g Cab-o-Sil TS610. This formulation was laid down on two three different types of carbon-containing conductive base layers as follows:
A: Ercon EC1
B: Ercon EC2
C: Ercon EC2 on top of Acheson Carbon, Electrodag 423 SS.
These test strips were used to measure varying levels of glucose in either a control solution (One Touch Control Solution, Lifescan Inc.) containing glucose in an inert solution or in blood at an applied voltage of 425 mV. The current observed 25 seconds after the voltage was applied was measured. FIGS. 5A-5C show the results obtained for the three formulations, A, B, and C, respectively. In all cases, the slope of the line showing the response of the meter to different glucose concentrations was essentially the same whether the measurement were made in blood or the control solution. Thus, this further demonstrates the independence of the test strips of the invention from the oxygen content and hematocrit of the sample, as well as the ability to use varied material as the conductive base layer.
EXAMPLE 5
Test strips prepared in accordance with Example 2 were tested at two different sample temperatures, namely 37° C. and 20° C. using an applied voltage of 425 mV. FIGS. 6A and 6B show the current measured 25 seconds after applying the voltage as a function of glucose concentration. As can be seen, the slopes of the two lines are essentially identical (0.1068 at 20° C. versus 0.1009 at 37° C.), thus demonstrating that the test strips provide essentially temperature-independent behavior over a temperature range from ambient to physiological temperatures.
EXAMPLE 6
The current transient was measured for a test strip prepared in accordance with Example 2 and for a commercial test strip made with a carbon-containing ink. The results are shown in FIGS. 8A and 8B. As shown, the test strip of the invention (FIG. 8A) provides a very flat transient which maintains more than 50% of the peak current for a period of more than 25 seconds after the initial response from the test strip. In contrast, the carbon-based electrode exhibited an almost immediate decay in the current, having lost 50% of the peak current in a period of the first 1 to 2 seconds after the initial response from the test strip. This makes timing of the measurement difficult if peak current values are to be captured, or reduces the dynamic range of the meter is currents must be measrured after substantial decay has occurred. Thus, the test strips of the invention are advantageous in that they provide test strips in which the amount of current generated in response to a given amount of glucose decays by less than 50% in the 5 seconds following peak current generation.
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An improved disposable glucose test strip for use in a test meter of the type which receives a disposable test strip and a sample of blood from a patient and performs an electrochemical analysis is made using a working formulation containing a filler, an enzyme effective to oxidize glucose, e.g., glucose oxidase, and a mediator effective to transfer electrons from the enzyme. The working formulation is printed over a conductive carbon base layer to form a working electrode. The filler, for example a silica filler, is selected to have a balance of hydrophobicity and hydrophilicity such that one drying it forms a two-dimensional network on the surface of the conductive base layer. The response of this test strip is essentially temperature independent over relevant temperature ranges and is substantially insensitive to the hematocrit of the patient.
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TECHNICAL FIELD
[0001] This invention relates generally to floor tiles, and more particularly to modular floor systems with a protective top layer.
BACKGROUND OF THE INVENTION
[0002] Floor tiles have traditionally been used for many different purposes, including both aesthetic and utilitarian purposes. For example, floor tiles of a particular color may be used to accentuate an object displayed on top of the tiles. Alternatively, floor tiles may be used to simply protect the surface beneath the tiles from various forms of damage. Floor tiles typically comprise individual panels that are placed on the ground either permanently or temporarily depending on the application. A permanent application may involve adhering the tiles to the floor in some way, whereas a temporary application would simply involve setting the tiles on the floor. Some floor tiles can be interconnected to one another to cover large floor areas such as a garage, an office, or a show floor.
[0003] Various interconnection systems have been utilized to connect floor tiles horizontally with one another to maintain structural integrity and provide a desirable, unified appearance. In addition, floor tiles can be manufactured in many shapes, colors, and patterns. Some floor tiles contain holes such that fluid and small debris is able to pass through the floor tiles and onto a surface below. Tiles can also be equipped with special surface patterns or structures to provide various superficial or useful characteristics. For example, a diamond steel pattern may be used to provide increased surface traction on the tiles and to provide a desirable aesthetic appearance.
[0004] One method of making plastic floor tiles utilizes an injection molding process. Injection molding involves injecting heated liquid plastic into a mold. The mold is shaped to provide an enclosed space to form the desired shaped floor tile. The liquid plastic is allowed to cool and solidify, and the plastic floor tile is removed from the mold.
[0005] A top surface of typical modular tile floors generally comprises the same material as the rest of the tile. However, the top surface is often scuffed, scratched, or otherwise damaged and dulled as the modular floor is used. Some have added paint coatings to modular tile floors in the past, but the paint coatings are not durable. Paint coatings are easily scratched and damaged. There is a need for a protective layer that better protects modular flooring systems.
[0006] The present invention is directed to overcoming, or at least reducing the effect of, one or more of the problems presented above.
SUMMARY OF EMBODIMENTS OF THE INVENTION
[0007] In one of many possible aspects, the present invention provides a method of making modular floor panels. The method comprises providing a mold, opening the mold, inserting a protective sheet into the mold, closing the mold, and injecting a liquid polymer into the mold. The method may include holding the protective sheet adjacent to a top plate of the mold prior to closing the mold. The protective sheet may be held by electrically charging it prior to inserting it into the mold. The method may also include bonding the protective sheet across a top surface of the liquid polymer or forming the protective sheet across the top surface of the liquid polymer in a pattern of the mold. According to some aspects of the invention, the protective sheet is a high gloss polymer sheet, which may be approximately 3-5 mm thick. The inserting of the protective sheet into the mold may be done robotically. The method may also include ejecting the modular floor panel and protective sheet from the mold as a single piece.
[0008] Another aspect of the invention also provides a method of making modular floor panels. The method includes providing a substantially transparent co-polymer sheet, picking up the transparent co-polymer sheet with a robotic arm, inserting the transparent co-polymer sheet into a floor panel mold, closing the floor panel mold, injecting a second co-polymer material into the mold, and melding the transparent co-polymer sheet to the second co-polymer material. The method may include electrically charging the transparent co-polymer sheet. The transparent co-polymer sheet may be approximately 3-5 mm thick. Moreover, a top surface of the second co-polymer and the co-polymer sheet may be formed into a surface pattern.
[0009] Another aspect of the invention provides a modular floor tile. The modular floor tile comprises an injection molded panel including a top surface and a plurality of lateral edge connectors, and a protective polymer layer disposed across the top surface. According to some embodiments the protective polymer layer is not paint, nor is it a sprayable or spreadable coating. Instead, the protective polymer layer is preferably a sheet of material. The modular floor tile and the protective polymer layer may comprise co-polymers. The top surface and the protective polymer layer may be molded into a single top surface pattern. The protective polymer layer may be a high gloss, substantially clear layer.
[0010] The foregoing features and advantages, together with other features and advantages of the present invention, will become more apparent when referring to the following specification, claims and accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The accompanying drawings illustrate various embodiments of the present invention and are a part of the specification. The illustrated embodiments are merely examples of the present invention and do not limit the scope of the invention:
[0012] FIG. 1 is a perspective assembly view of a modular floor panel and a protective sheet according to one embodiment of the present invention;
[0013] FIG. 2A is a perspective view of a modular floor panel mold and an associated robotic arm inserting the protective sheet into the mold according to one embodiment of the present invention;
[0014] FIG. 2B is a perspective view of the modular floor panel mold of FIG. 2A after injection molding the floor panel and bonding the protective sheet to the floor panel.
[0015] FIG. 3A is a perspective view, partly in section, of a completed modular floor panel with a protective layer made according to one aspect of the present invention.
[0016] FIG. 3B is a magnified view of a portion of the illustration shown in FIG. 3A .
[0017] FIG. 4A is a side view of the completed modular floor panel of FIG. 3A .
[0018] FIG. 4B is a magnified view of a portion of the side view shown in FIG. 4A .
[0019] Throughout the drawings, identical reference numbers designate similar, but not necessarily identical, elements.
DETAILED DESCRIPTION OF THE INVENTION
[0020] As mentioned above, typical modular flooring is easily damaged by scratches and scuffs. The look and life of modular flooring are often significantly compromised due to the direct exposure of the top surface to the elements, pedestrian and other traffic, and any objects that may be placed thereon. The present invention describes methods and apparatus that provide a protective layer over a top surface of a modular floor panel. Consequently, modular flooring made according to principles of the present invention may be more durable and aesthetically pleasing than prior modular flooring systems. The methods and systems shown and described below include specific modular flooring embodiments which including a protective layer. However, the application of the principles described herein is not limited to the specific devices shown. The principles described herein may be used with any flooring system. Therefore, while the description below is directed primarily to interlocking plastic modular floors, the methods and apparatus are only limited by the appended claims.
[0021] As used throughout the claims and specification, the term “modular” refers to objects of regular or standardized units or dimensions, as to provide multiple components for assembly of flexible arrangements and uses. The words “including” and “having,” as used in the specification, including the claims, have the same meaning as the word “comprising.”
[0022] Referring now to the drawings, and in particular to FIG. 1 , an assembly view of a modular floor panel 100 according to principles of the present invention is shown. The modular floor panel 100 shown in FIG. 1 includes an injection molded tile or panel 102 with a top surface 104 and a protective sheet of material such a co-polymer layer 106 adapted to be disposed across the top surface 104 . The injection molded tile 102 comprises a plurality of lateral edge connecting members. According to the embodiment of FIG. 1 , the plurality lateral edge connecting members comprise a plurality of female tabs 108 arranged on two adjacent sides 112 , 114 of the rectangular injection molded tile 102 , and a plurality of male tabs 110 arranged on another two adjacent sides 116 , 118 of the molded tile 102 . The female tabs 108 are receptive of male tabs of another injection molded tile 102 to modularly create a floor.
[0023] The male tabs 110 include a generally vertical component which, according to the embodiment of FIG. 1 , comprises a semi-circular post 120 . The male tabs 110 also comprise generally horizontal components which, according to the embodiment of FIG. 1 , comprise semi-circular discs 122 . A curved portion 124 of the semi-circular discs 122 face the floor or ground. The semi-circular discs 122 are received through the looping female tabs 108 , and extend at least partially under an adjacent injection molded tile to removably secure multiple tiles to one another. The semi-circular posts 120 and the semi-circular disc 122 are rigid, but compressible toward one another. When inserted into the female tabs 108 , the semi-circular posts 120 and the semi-circular discs 122 maintain a constant pressure against the female tabs 108 , thereby securing a connection between desired components (e.g. between two or more adjacent injection molded tiles 102 ). The connection members engage one another such that the different components are joined tightly to one another and provide a consistent upper surface. The injection molded tile 102 is preferably made of a co-polymer material.
[0024] The co-polymer layer 106 is also preferably made of a polymer or co-polymer, which may be a high gloss, substantially clear or transparent sheet. The co-polymer layer 106 is a separate component from the injection molded tile 102 , and is not a spray coating such as paint. The co-polymer layer 106 is substantially the same size as the top surface 104 of the injection molded tile 102 as shown in FIG. 1 . The co-polymer layer 106 is preferably substantially flat as shown in FIG. 1 , prior to being formed or melded across the top surface 104 .
[0025] The modular floor panel 100 is preferably made with the use of a mold. Referring to FIG. 2A , a mold 126 is shown in accordance with one embodiment of the present invention. The mold 126 is shown open and includes an injection cavity 128 and a top plate such as a lid 130 . The lid 130 includes an internal pattern 131 that will be formed into the top surface 104 ( FIG. 1 ) of the molded tile 102 and the co-polymer layer 106 .
[0026] According to some embodiments, the co-polymer layer 106 is electrically or statically charged, for example by a charger 132 . Alternatively, the co-polymer layer 106 could be mechanically placed in the mold 126 by arm 132 , and mechanically coupled to the lid 130 . A robotic arm 132 places the charged co-polymer layer in the mold 126 . The co-polymer layer is attracted to the lid 130 , which holds the co-polymer layer 126 adjacent thereto when the mold 126 is open. The lid 130 of the mold 126 is then closed, and a volume of liquid plastic, preferably a second co-polymer, is injected into the cavity 128 . The injected co-polymer is preferably opaque, as opposed to the clear co-polymer layer 106 . The injected co-polymer conforms to the shape of the cavity 128 and the inner surface pattern 131 of the lid 130 . In addition, the high temperature of the injected co-polymer or the lid 130 softens or melts the co-polymer layer 106 , which also conforms to the shape of the inner surface of the lid 130 . The co-polymer layer 106 bonds or melds to the liquid plastic of the molded tile 102 ( FIG. 1 ), and the liquid plastic is allowed to cool and solidify. As the liquid plastic solidifies, the copolymer layer 106 and molded tile 102 ( FIG. 1 ) form a single piece, which is ejected from the mold 126 .
[0027] The completed modular floor panel 100 is shown in FIGS. 3A-3B following ejection from the mold 126 . The modular floor panel 100 is thus layered with the co-polymer layer 106 disposed across the molded tile 102 . The co-polymer layer 106 may be approximately 1-7 mm thick, preferably about 3-5 mm thick. The partial sectional view of the completed modular floor panel 100 in FIGS. 3A-3B illustrates the co-polymer layer 106 conforming to the same shape as the top surface 104 of the molded tile 102 . In addition, as shown in FIGS. 4A-4B , the co-polymer layer 106 preferably extends along the entire top surface 104 ( FIG. 3A ). Many modular floor panels 100 may be made according to the same or similar processes, and each modular floor panel 100 may be interconnected with one or more other modular floor panels to create a floor of any size and shape. Thus, a modular floor with a protective, high gloss coating may be made according to principles of the present invention.
[0028] The preceding description has been presented only to illustrate and describe exemplary embodiments of invention. It is not intended to be exhaustive or to limit the invention to any precise form disclosed. Many modifications and variations are possible in light of the above teaching. It is intended that the scope of the invention be defined by the following claims.
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The present invention provides a method of making modular floor tiles. The method includes adding a protective layer to a modular floor tile, which may provide surface protection, a high gloss finish, or other advantageous features. The protective layer may comprise a polymer sheet that is melded to a top surface of the modular floor tile.
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SUMMARY OF THE INVENTION
The present invention is directed to a furniture structure having several component parts which are quickly and easily disassembled to facilitate shipping and storage. More specifically the present invention is directed to a furniture structure, such as a chair, which is readily disassembled into several component parts having more compact dimensions than the assembled chair itself and which can be readily assembled by simply joining the component parts together with an interlocking attachment means.
BACKGROUND OF THE INVENTION
Because of their necessary configuration, typical items of furniture such as chairs are one of the most awkward and bulky items for shipment. A typical chair for example, occupies a much larger volume for shipping purposes then its size would otherwise seem to require, largely due to the number of projecting surfaces which typify chairs and other such furniture. For example, a typical rocking chair is provided with a relatively high back which extends in one direction and a pair of rockers extending roughly at right angles to the back of the chair, in addition to the actual seating structure and any arms which may be present on the chair. Accordingly, the size of container, or even just the space that is necessary to accommodate such a chair during shipment, is considerable and contributes significantly to the cost and effort of shipping these items.
It is accordingly, an object of the present invention to provide a furniture structure, such as a chair, which can readily be disassembled into several convenient parts in order to significantly minimize the volume required to ship or otherwise transport the furniture structure either by itself or in a container such as a large box.
It is a further object of the present invention to provide a chair structure having attachment means for the various components parts of the structure which provide a convenient, easy to assemble, interlocking system.
Yet a further object of the invention is to provide a system for assembly of the component parts of a furniture structure which is both simple and inexpensive and does not diminish the strength of the assembled unit.
DETAILED DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the seat structure of a chair in accordance with the present invention.
FIG. 2 illustrates the disassembled arms of the chair structure of the invention.
FIG. 3 illustrates the back structure of the chair of the present invention.
FIG. 4 illustrates the pair of rockers which can be used on the chair of the present invention.
FIG. 5 is a perspective illustration of the assembled chair structure of the invention showing the various components interlocked in place.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention a furniture structure is provided which essentially consists of a seat which horizontally engages a leg structure consisting of four vertical legs arranged in a quadrangular configuration and mutually interconnected by a plurality of horizontal cross pieces which connect adjacent legs of the leg structure. A rectangular, generally flat back structure, which can have numerous ornamental and other configurations, slidably engages the tops of two of four vertical legs to form the back of the chair. The two vertical legs at the front of the chair extend to a somewhat greater height above the seat of the chair than the two legs at the rear. These two forward legs are provided also with means for connecting with a pair of horizontal arms which extend backward to engage the sides of the back of the chair. Optionally, a pair of rockers, which are slightly curved elongated members, are attached to the bottoms of the legs of the chair.
Of particular significance in the present invention is the manner in which the component elements described above are actually joined together to quickly and easily provide a rigid durable chair structure and to permit disassembly thereof for transport. In the preferred embodiment of the invention, interlocking members are provided which are elongated male members such as dowel rods which slidably engage into complementary slots in the adjacent interlocking furniture structure. Thus, the tops of the four legs of the structure are each provided with a vertical dowel rod or pin which extends upward a short distance to engage complementary slots which are provided in the back structure of the chair and in the arm rests. Additional reinforcement may be provided at particular points of stress such as where the arm rests engage the front posts or legs of the chair.
The invention will however, be more fully appreciated and comprehended by having reference to the drawings which depict a preferred embodiment thereof.
FIG. 1 of the drawings illustrates the leg and seat structure of the present invention as well as the provision made for attachment of the remaining components of the entire chair. Seat structure 1 is shown consisting of a generally flat seat 2 which, as shown, may be made of slats or any other conventional material commonly used for the seats of chairs and similar structures. The leg structure, which supports the seat 2, consists of two pairs of vertical legs 4, 5, 3, and 7 which are interconnected by a series of horizontal cross pieces 8 connecting adjacent legs to form a square or rectangular array. It will be noted that two adjacent legs 4 and 5, which are at a forward edge of the chair, extend a greater height above the plane of the seat than legs 3 and 7 which are at the rear of the chair. At the upper end of each of the four legs is a pin or dowel which projects upward to engage a complementary slot in the adjoining back and arm structures.
FIG. 3 of the drawings illustrates the back structure of the chair 17 which consists of a pair of spaced vertical posts 18 and 19 connected by two horizontal members 20. It will be appreciated that the actual configuration of the back structure can vary considerably in accordance with design preferences. The lower ends of post 18 and 19 are provided respectfully with vertical slots 22 of appropriate dimensions to accommodate vertical attachment pins 6 in the chair's seat and leg structure, illustrated in FIG. 1 of the drawings. Similar holes or slots are provided in post 18 and 19 at 21 to accommodate horizontal pins 15 and 16 of arm rests 14 and 13, respectively, illustrated in FIG. 2 of the drawings. These am rests are also provided with holes or slots 24 to accommodate the corresponding attachment dowels 9 on legs 4 and 5.
The lower ends of the leg structure may also be provided at 11 with vertical attachment pins or dowels to engage corresponding slots or holes 12 in the pair of rockers 10 that are attached, on assembly, to the bottom of the chair. It will be appreciated however, that the present invention is not restricted in scope to rocking chair structures only.
As illustrated in FIG. 5 of the drawings, when the leg and seat structure is assembled together with the back, armrest and rockers, an attractive, comfortable and sturdy rocking chair results. As can further be appreciated however, the assembled rocking chair is of such configuration and dimensions as would necessitate an extremely large and awkward container or volume of space for transportation whereas the disassembled components illustrated in FIGS. 1 through 4 of the drawings can easily be transported in a much more compressed volume or container. Assembly of the furniture structure of the invention, requires no particular skills or equipment and can be preformed in a matter of minutes by simply engaging the component parts as illustrated. In the event that a permanent structure is desired rather than one which can be disassembled for future transportation, appropriate adhesives or other binders can be employed to lock the attachment pins into there respective slots.
It will also be appreciated that the illustrated structure of the invention can further be strengthened by the addition of suitable brackets such as those shown in the drawings at 2 3. These brackets attach to the forward legs 4 and 5 of the chair structure at approximately the upper terminus of the legs and engage the underside of the respective arm rests shown in FIG. 2. Attachment to the arm rests is conventionally by means of screws which pass through small holes in the arm brackets.
It will further be appreciated that the present invention, is not limited to the particular chair structure shown by way of illustration herein, but rather encompasses numerous furniture structures which can be provided with the attachment provisions described to facilite disassembly, transportation, and reassembly of the structure. It will further be appreciated that the present invention includes numerous materials which can be employed and other modifications which will be apparent to those of ordinary skill in the art.
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A furniture structure is described in which the component parts of the structure are disassembled to facilitate storage and shipment, Assembly of the unit is facilitated by convenient attachment pins or dowels and complementary slots in the respective components.
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This is a continuation of application Ser. No. 143,897, filed Apr. 28, 1980 now abandoned.
BACKGROUND OF THE INVENTION
This invention relates to a process for preparing a sizing agent for paper in the form of an aqueous dispersion with a high free rosin content, from resins based upon reinforced and/or non-fortified rosins and water, with the use of an anionic dispersing agent. This invention also relates to aqueous dispersions useful as paper sizing agents, and to their use in the sizing of paper.
Paper sizing agents based upon fortified rosin in the form of aqueous dispersions with a high free resin content have been known for a long period of time. For example, German Patent No. 1,131,438 describes aqueous dispersions containing fortified rosins, such as adducts of rosin and α,β-unsaturated carbonyl compounds, such as fumaric acid, maleic acid, and the like. However, in order to achieve a certain stability in such dispersions, it has been necessary to add fatty acids and/or naphthenic acids in addition to the fortified rosin. Furthermore, the presence of a protective colloid, such as casein, is required as well. However, the concomitant use of casein is accompanied by several disadvantages. Primarily, casein is a valuable, expensive albumin product, and secondarily, dispersions made with the use of casein have only limited stability in storage and tend to show a precipitate after a certain storage time. Furthermore, the use of casein is accompanied by troublesome odors.
Various possibilities for the preparation of dispersions from free casein have been previously explored. In this respect, one may refer to German Pat. No. 1,958,965 which describes a process for the preparation of a fortified rosin sizing in accordance with which a solution is first made of the rosin based material and an organic solvent immiscible with water, which solution is then emulsified in water. After homogenizing, the organic solvent immiscible with water is, in essence, completely removed. The process is relatively complex and furthermore, working with organic solvents may pose potential health or environmental problems. Reclamation of the organic solvent is difficult and waste water contaminated with the organic solvents give rise to considerable ecological problems.
It has also been attempted to obtain stable dispersions of fortified rosin by using many various dispersing agents, such as salts of alkylaryl sulfonic acids, sulfonated higher fatty alcohols, sulfonated castor oil, resin soaps, and the like. Frequently, the use of these dispersing agents requires the concomitant use of additional protective colloids, such as casein, and special processing methods are often required to obtain a dispersion with a fine distribution. In addition, the resulting dispersions often have a stability of short duration and cannot be stored for any length of time. Besides numerous compounds with the sulfo substituents derived from succinic acid, German Pat. No. 2,627,943 also discloses compounds with are ethylene oxide adducts. Thus, the compound which is used to form the dispersion is obtained when a maleate is used as an initial material that has been esterified with an ethylene oxide adduct of an alkanol with at least 6 carbon atoms.
Although a large number of paper sizing agents in the form of aqueous dispersions containing high free resin content derived from rosin based material are already known, there still exists a need for a paper sizing agent of this type with improved characteristics which can be obtained through simple processing, while demonstrating suitable economic benefits.
An object of the present invention is therefore to make available a process, according to which the economic preparation of such dispersions will be possible in a simple manner, which process will also lead to dispersions having excellent stability, suitable for surface sizing, as well as internal sizing.
It is also an object of the present invention to make available a process by which dispersions may be prepared that can be stored for an extended period of time and that contain a high concentration of solid substances based upon rosin, leading to paper with a high degree of sizing that can be processed without difficulty.
A further object of the present invention is to make available sizing agents for paper that are compatible with the usual additives employed in the sizing of paper.
SUMMARY OF THE INVENTION
The foregoing objects and others are solved by providing an improved inversion process for the preparation of a paper sizing agent which is an aqueous dispersion containing a high content of free rosin in the form of fortified rosin and/or non-fortified rosin, water, and an anionic dispersing agent. The improved process comprises using as the dispersing agent a polyethoxylated, sulfated resin, or a derivative thereof.
The present invention also provides an aqueous dispersion useful as a paper sizing agent comprising from about 10 to about 60% of fortified and/or non-fortified rosin, from about 1 to about 10% of a dispersing agent which is a polyethoxylated, sulfated rosin, or a derivative thereof, based on the total weight of all solids in the dispersion, and a sufficient amount of water to form a dispersion.
If desired, other additives such as extenders may be included in the aqueous dispersions.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the practice of the present invention either fortified or non-fortified rosin may be utilized. It is preferable to utilize rosin which has been fortified with maleic acid, maleic anhydride, fumaric acid, or itaconic acid.
The rosin based material, which is utilized either fortified or non-fortified, is any commercial rosin, such as wood rosin, gum rosin, tall oil rosin, and the like, as well as partly or substantially completely hydrated rosin, and polymerized, as well as disproportionated rosin. Within the frame-work of the present invention rosin based material also refers to rosin material which has been obtained chemically, as by the transformatin of formaldehyde, acetic anhydride, and the like.
The dispersing agents which are useful for the preparation of the dispersions of the instant invention are polyethoxylated, sulfated rosin. The dispersing agents may also be present in the form of derivatives such as their salts, having, for example alkali metal ions, ammonium, or amines functioning as the cation. Also the rosins may have been fortified with any known fortified agent.
The dispersions of the present invention may be prepared according to the inversion method. However, the dispersant may also be added directly to the fortified or non-fortified rosin, or to the rosin mixture, without prior dilution.
As indicated, the paper sizing agent of the present invention comprises from about 10 to about 60%, preferably from about 20 to about 40%, by weight, of fortified and/or non-fortified rosin, water, and from about 1 to about 10%, preferably from about 3 to about 6%, by weight, of a polyethoxylated, sulfated material derived from rosin. Optionally, other additives such as extenders may be present. The sizing agents pursuant to the present invention are especially well suited for the sizing of paper.
As utilized herein, the expression high free rosin content designates that at least about 80%, preferably at least about 90%, of the rosin material is present as free rosin. For the preparation of the fortified rosin, use may be made of α,β-unsaturated aliphatic carboxylic acids and their anhydrides, such as fumaric acid, maleic acid, acrylic acid, itaconic acid, citraconic acid, maleic anhydride, itaconic anhydride, and citraconic anhydride. It is also possible to use acid mixtures of the aforementioned compounds for the preparation of the fortified rosin. If desired, it is also possible to use mixtures of different fortified rosins.
The extenders which are useful in the present invention include any customary extender, such as waxes, petroleum rosins, terpene rosins, and the like.
The dispersing agents which are useful in the practice of the present invention may be prepared in the following manner. First, an adduct is prepared in a typical manner as by adding ethylene oxide to a normal rosin, may be fortified or non-fortified. Depending upon the reaction conditions and the chosen initial compound, a product having a varying degree of ethoxylation may result. Preferably, the degree of ethoxylation will be such that the final sulfated dispersing agent contains from about 35 to about 70%, by weight, of ethylene oxide, based on the total weight of the dispersing agent. The preparation of the rosin adducts is described in N. Schoenfeldt, Surface active Ethylene Oxide Adducts, page 77.
To convert the ethylene oxide adduct to a corresponding sulfate, the adduct may be reacted with a slight stoichiometric excess, preferably about 1 mole of adduct per about 1.1 mole of amidosulfonic acid. By means of a salt exchange, compounds with other cations, such as sodium and potassium may be prepared in a known manner.
The dispersions which are useful in the present invention may be prepared according to the known inversion method. In such a process, for example, the rosin is first melted and a small quantity of dispersing agent is added thereto, so that a water-in-oil dispersion is formed. Additional hot water is then added (water of inversion) accompanied by vigorous stirring, until a rosin-in-water emulsion is formed. The rosin solidifies during cooling, resulting in an aqueous dispersion of very finely distributed rosin particles.
The dispersions of the present invention may also be prepared with the use of an organic auxiliary solvent, such as benzene. After homogenizing, the benzene may again be removed in a substantially quantitative manner.
It is especially surprising that the process of the present invention results in the formation of very stable, aqueous dispersions with a high content of free rosin, in which the rosin is present in a very fine distribution. It is also surprising that the rosin does not display any substantial sedimentation phenomena after lengthy periods of storage. During sizing, the dispersions may also be processed without difficulty. Furthermore, the dispersions are compatible with most additives customarily employed in the manufacture of paper.
The present invention will be further described in the following non-limiting examples.
EXAMPLE 1
(Preparation of a fortified rosin based material)
930 g of balsamic rosin are melted with 70 g of fumaric acid and subsequently heated for 4 hours at 200° C. Subsequently, the fumaric acid is taken up completely.
EXAMPLE 2
(Preparation of a rosin ethylene oxide adduct)
300 g of balsamic rosin, together with 0.3% aqueous potassium lye are placed in an autoclave, which is flushed with nitrogen and subsequently freed from water at 120° to 130° C. Then, 440 g of ethylene oxide are added in batches with stirring, at 160° C., during which the pressure should not rise above 5 bar. After the entire quantity of ethylene oxide has been added, the reaction mixture is heated for another hour at this temperature.
EXAMPLE 3
300 g of a fortified rosin based material prepared according to Example 1 are reacted with 529 g of ethylene oxide in the same manner as in Example 2.
EXAMPLE 4
400 g of a rosin-acid ethylene oxide adduct prepared according to Example 2 are heated to 120° C. and 96 g of amidosulfonic acid added thereto in batches, during which care is taken, that the temperature does not exceed 120° C. This process takes about 1.5 hours, after which the reaction is allowed to continue for another 1.5 hours at 120° C., followed by cooling to 70° to 80° C. and neutralizing with monoethanolamine, until the pH value of a 10% aqueous solution is between 7 and 8. The corresponding potassium salt is prepared by means of a salt exchange with KOH.
EXAMPLE 5
328 g of a fortified rosinic acid ethylene oxide adduct prepared according to Example 3 are heated to 120° C. and 96 g of amidosulfonic acid added thereto in batches, during which care is taken that the temperature will not exceed 120° C. Further processing proceeds analogous to Example 4. In this process not all reactive groups are converted to the sulfate.
EXAMPLE 6
(Preparation of a rosin emulsion free from casein)
800 g of a rosin fortified with fumaric acid (prepared according to Example 1) are melted and, at 120° C., 4% of a dispersing agent according to Example 4 added thereto. (The dispersing agent can also be first dissolved in water. In this case, metering-in has to be performed slowly, since otherwise the escaped steam will cause too much development of foam.) When the rosin/dispersing agent mixture has reached a temperature of about 100° C., water is slowly added with simultaneous, vigorous stirring. The temperature of the added water is about 80° to 90° C. After the addition of about 400 ml of water, a highly viscous water-in-oil emulsion has been formed which, after more water is added, will turn into an oil-in-water emulsion. Approximately another 800 ml of water are then added, as a result of which a 40% emulsion is formed. During cooling, the emulsion is converted into a dispersion, the particles of which have an average size of 0.2 to 0.5 micron. The dispersion can be stored for an extended period of time (at least 3 months), without the occurrence of a sediment.
EXAMPLE 7 TO 10
In the following examples, the sizing agents pursuant to the invention are used for the sizing of paper with 0.75% abs.-dry application of size in an acid and neutral pH range, and compared with resin emulsions prepared with the addition of casein. The results of the sizing agent pursuant to the invention results in better Cobb values and, so far as ink and reflectance are concerned, at least in equally good data as resin emulsions with casein.
In all examples, the composition of the pulp was 50% pine sulfate, 25% birch sulfate and 25% beech sulfate. The degree of beating was 24° SR.
In Examples 7 and 8 the pH was set at 4.5 with alum, in Examples 9 and 10 it was adjusted to 6.5 with Na aluminate, or alum, respectively. In Examples 9 and 10, 0.04% by weight of Etadurin N76 was used in addition (Etadurin is a polyamidoamino-epichlorohydrin resin, which is used as wet strength agent, or retention agent). The following measuring methods were used:
1. Degree of sizing vs. ink, with the Hercules Sizing Tester, in keeping with the operating instructions of the manufacturer, Hercules, Inc., Wilmington, Del. The time is measured in seconds which elapses until the reflectance value of the paper drops to 80% when the testing ink has been applied to the paper and penetrates it.
2. Cobb test (DIN standard 53/32-1 minute)
a. Absorptivity vs. water, expressed in grams of water uptake per m 2 after 1 minute of contact with water.
b. Absorptivity vs. a 10% Na 2 CC 3 solution, expressed in grams of uptake per m 2 after a contact of 1 minute, as under 2.a. Additional details regarding the measuring methods can be found in the above-mentioned book by Engelhardt and others (see page 12).
TABLE______________________________________ Dispersing Cobb Ink 80% reflectanceExample Agent O.S. S.S. O.S. S.S.______________________________________7 4 17 16 190 3208 5 18 19 180 290resin emulsion 19 21 150 220with casein9 4 16 16 620 82010 5 15 16 740 868______________________________________
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An improved inversion process for the preparation of a paper sizing agent which is an aqueous dispersion containing a high content of free rosin in the form of fortified rosin and/or non-fortified rosin, water, and an anionic dispersing agent is disclosed. The improvement comprises using as the dispersing agent a polyethoxylated, sulfated rosin or a derivative thereof. There is also disclosed an aqueous dispersion useful as a paper sizing agent comprising from about 10 to about 60% of fortified and/or non-fortified rosin, from about 1 to about 10% of a polyethoxylated, sulfated rosin or a derivative thereof, based on the total weight of all solids in the dispersion, and a sufficient amount of water to form a dispersion.
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TECHNICAL FIELD
[0001] The present invention relates to improved products and processes for fabric laundering.
BACKGROUND OF THE INVENTION
[0002] Most people are aware that washing and wearing clothes is not good for them. Clothes suffer damage due to abrasion in the wash, particularly around seams and hems. On dark cellulosics (such as black jeans, for example) this damage exposes fibrillated regions of the textile which scatter light differently than undamaged regions.
[0003] While the damaged regions may have lost relatively small quantities of dye, they are very easy to perceive and produce a strong visual impact. It has been suggested to reduce the incidence of such damage by using lubricating agents in wash liquors. However the skilled worker is faced with a problem when choosing the right lubricant. Prior proposals have included acrylic materials, dextrans, oily and waxy materials.
[0004] Hydroxy ethyl cellulose (HEC) is widely commercially available and is well known as a thickener in a range of surfactant-containing products as well as in paints and other coatings. It is generally produced by the treatment of cellulose with ethylene oxide to give materials with a specified degree of substitution. Related materials are known which comprise other short alkyl chain substituents (typically C2-4). Hydroxy-alkyl derivatives of other beta 1-4 linked poly-saccharrides are also known.
[0005] In order to bring about viscosity changes HEC is typically present at levels of 1-2% wt on liquor, depending on the molecular weight of the polymer. It is known that bulk viscosity increases in a wash liquor can have beneficial effects on fabrics being laundered, as the increase in viscosity reduces certain fabric-fabric interactions which can cause degradation of the fabrics through such mechanisms as abrasion etc. However, viscosity increases have negative consequences as well. In particular, they can significantly reduce cleaning.
[0006] WO 99/14295 discloses compositions and methods for fabric treatment to impart appearance and integrity benefits, which utilise cellulosic based polymers having ether substituents on the hydroxyl groups of the glucose rings. The substituents take the form —OR where R is one of:
a) —H and —C1-4 alkyl (i.e. an unmodified hydroxyl or an alkyl ether, b) —(CH2) y —CO—OZ (i.e. a carboxyl terminated alkyl ether which can be esterified with another group, or c) —[Et.R 2 0] n -R H . In these compositions n is 0-5 and R H comprises an alkyl chain, so this comprises either a poly-oxyethylene linker to the alkyl chain or simply the alkyl chain connected to the backbone via an ether linkage.
[0010] The benefits disclosed in WO 99/14295 are believed to be obtained by the active component, i.e. the ether, associating itself with the fibres of the fabric to reduce or minimise the tendency for the fabric to deteriorate. It is believed that in many cases the association with or ‘recognition’ of cellulose by another beta 1-4 chemical species involves an interaction between the backbones of the cellulose and the beta 1-4 polymer.
[0011] None of the formulations mentioned above with reference to WO 99/14295 comprise a simple hydroxy alkyl derivative of the saccharide backbone. It has been thought that these materials would not associate with cellulose because the hydroxy alkyl groups would interfere with the backbone-backbone interaction that is believed to be necessary for cellulose recognition.
[0012] Several other documents relate to the use of hydroxy-ethyl cellulose (HEC) in laundry detergent products and processes. While several of these mention that HEC can bring cleaning benefits none address the issue of lubrication benefits.
[0013] U.S. Pat. No. 2,602,781 discloses the use of hydroxy-ethyl cellulose to enhance soil removal by synergy with the surfactant. Levels of HEC taught are between 1 and 63%, (preferably between 5 and 57%) by weight of product and the stain used was a mixture of carbon black and mineral oil. Tests would probably have been performed on white cloth (standard ‘Indian Head’ muslin) as they concerned removal of soil.
[0014] EP 467,485 is concerned with the provision of softness and antistatic benefits. The formulations comprise alkyl cellulose ethers selected from methyl cellulose, hydroxypropyl methyl cellulose and derivatives of hydroxyethyl cellulose wherein the terminal hydrogen of the hydroxyethyl group is replaced with an alkyl chain having 10-24 carbon atoms.
[0015] GB 1,537,287 discloses compositions which comprise 0.1% to 3% of a component selected from alkyl cellulose ethers, hydroxy-alkyl cellulose ethers and hydroxy-alkyl alkyl cellulose ethers. Hydroxy ethyl cellulose DS hydroxy ethyl 1.2 is mentioned (see page 7 lines 4ff). Closely related case U.S. Pat. No. 4,174,305 discloses cellulose based soil release polymers and mentions hydroxy-ethyl cellulose (column 6, lines 24ff). Both patents illustrate soil removal with dirty motor oil. Again, this patent contains no examples of the treatment of coloured cloth with HEC.
[0016] EP 0 331 237 discloses the use of a hydrophobically modified nonionic cellulose ether in a fabric softening composition. Hydroxy-ethyl cellulose is mentioned in the body of the patent but it is present only as an example of the substrate that is then modified to form the hydrophobically modified cellulose derivative. Preferred are derivatives of methyl, hydroxyethyl or hydroxypropyl cellulose which have been modified with a C 10 to C 24 hydrocarbon.
[0017] U.S. Pat. No. 6,200,351 B1 discloses the use of a soil release polymer based on a copolyester of a dicarboxylic acid and a diol or polydiol in the surfactant-free, pre-treatment step of an institutional washing process. Hydroxy-ethyl cellulose derivatives are mentioned (see colum5 lines 55ff).
BRIEF DESCRIPTION OF THE INVENTION
[0018] We have now determined that relatively low levels of hydroxy alkyl polysaccharides, which are themselves insufficient to give a marked viscosity increase are however, capable of giving benefits in a wash liquor in terms of reduced fabric abrasion and reduced dye pick-up for coloured cloth.
[0019] Accordingly, the present invention provides a method of treating coloured fabrics with a luminance (L*) less than 50 which comprises contacting the fabrics with a wash liquor comprising:
a) 0.1-0.001 g/L of a hydroxy C2-C4 alkyl derivative of a beta 1-4 polysaccharide, and, b) surfactant.
[0022] The invention also subsists in the use of a hydroxy C2-C4 alkyl derivative of a beta 1-4 polysaccharide, at a concentration of 0.1-0.005 g/L, in a surfactant containing wash liquor to reduce fabric abrasion.
[0023] Luminance (also known as lightness) is the measure of the brightness of a surface on a black-white scale. It is one of the triplet of independent measurements, the other two being chroma (C*, which measures saturation) and hue (H*, which measures chromatic tone), which can be used to characterise any colour by locating it in a ‘colour space’. Changes in these three values can be combined to give the well known measure ‘delta E’ which is often used to determine the change in colour of an article when it is washed.
[0024] In this specification the colour space used as a referent is the CIELAB (International Lighting Commission) system, also known as the CIE 1976 colour space. This is an internationally recognized standard. When L* is 0 the surface being considered is black. When L* is 100, the surface is a white standard. Such a white standard is supplied for use with the Datacolor™ Spectraflash SF600+ reflectance spectrometer.
[0025] Colours with luminance (L*) less than 50 are also known herein as ‘Class 3’ colours. Class 3 colours can be further separated into three sub-classes
high chroma (C*), saturated colours such as bright purple, and intense blue, low chroma muted tones such as browns and olives, and, those with little or no chroma e.g. black/dark grey (i.e. no or little chroma).
[0029] Class 3 colours are very sensitive to fading. Uneven colour changes occur very readily on Class 3 colours because the lightness differences between areas are large and thus particularly amenable to human perception.
[0030] Preferably the method of the invention is applied to articles which have low chroma and are most preferably black.
[0031] In typical embodiments of the invention the hydroxy C2-C4 alkyl derivative of a beta 1-4 polysaccharide is a cellulose derivative. Cellulose derivatives are widely available. It is believed that among the beta 1-4 polysaccharides cellulose itself shows excellent cellulose self recognition.
[0032] Preferably the hydroxy C2-C4 alkyl derivative is a hydroxy ethyl derivative. This material is not only commonly available, but also shows excellent lubrication benefits.
[0033] Preferably the degree of substitution (DS) is 1-3, more preferably 1.5-2.25. Most preferably the DS falls in the range 1.5-2.0. Lower DS levels have poor water solubility, which appears to be important for the lubricating effect. Higher levels appear to lead to problems with particulate soil redeposition.
[0034] Preferably the molecular weight of the beta 1-4 polysaccharide is 100,000 to 500,000 Dalton, preferably less than 300,000 Dalton. The beta 1-4 polysaccharide is preferably such that viscosity of the material is 300-400 cps at 2% solution (measured on a Brookfield viscometer using ASTM D2364). The solution viscosity under standard conditions is related to the molecular weight of the beta 1-4 polysaccharide, and the preferred materials have nearly Newtonian viscosity profiles between 1 and 10 reciprocal seconds.
[0035] Suitable hydroxy C2 alkyl derivatives of cellulose are available in the marketplace from Dow under the trade name “Cellosize” and from Hercules under the trade name “Natrasol”.
[0036] Preferred dosage levels are such that the in wash concentration of the beta 1-4 polysaccharide is 0.06-0.01 g/L. In typical European was conditions the dosage of a laundry product is 7 g/L in about 8-15 litres of water depending on the-machine and load.
[0037] Preferably the level of beta 1-4 polysaccharide is 0.1-3% wt on fully formulated product, more preferably 0.2-0.8% wt. In this specification, all percentages are weight percentages unless otherwise stated. A typical product would contain 0.5% wt of the polysaccharide which would give an in use concentration of around 0.035 g/L.
DETAILED DESCRIPTION OF THE INVENTION
[0000] Carriers and Product Form:
[0038] The compositions of the invention will generally be used in conjunction with a textile compatible carrier.
[0039] In the context of the present invention the term “textile compatible carrier” includes a component which can assist in the interaction of the polymer with the textile.
[0040] The carrier can also provide benefits in addition to those provided by the first component e.g. softening, cleaning etc.
[0041] The carrier may be a detergent-active compound or a textile softener or conditioning compound or other suitable detergent or textile treatment agent. Many of these (for example cationic softeners and anionic and nonionic detergents) fall within the general definition ‘surfactant’ as used herein. The surfactant may comprise the entire carrier or other, non-surfactant carrier materials may be present.
[0042] In a washing process, as part of a conventional textile washing product, such as a detergent composition, the textile-compatible carrier will typically be a detergent-active compound. Whereas, if the textile treatment product is a rinse conditioner, the textile-compatible carrier will be a textile softening and/or conditioning compound. These are described in further detail below.
[0043] The polymer is preferably used to treat the textile in the wash cycle of a laundering process.
[0044] The composition of the invention may be in the form of a liquid, solid (e.g. powder or tablet), a gel or paste, spray, stick or a foam or mousse. Examples include a soaking product, a rinse treatment (e.g. conditioner or finisher) or a main-wash product.
[0045] Liquid compositions may also include an agent which produces a pearlescent appearance, e.g. an organic pearlising compound such as ethylene glycol distearate, or inorganic pearlising pigments such as microfine mica or titanium dioxide (TiO 2 ) coated mica. Liquid compositions may be in the form of emulsions or emulsion precursors thereof.
[0000] Detergent Active Compounds:
[0046] If the composition of the present invention is itself in the form of a detergent composition, the textile-compatible carrier may be chosen from soap and non-soap anionic, cationic, nonionic, amphoteric and zwitterionic detergent active compounds, and mixtures thereof.
[0047] Many suitable detergent active compounds are available and are fully described in the literature, for example, in “Surface-Active Agents and Detergents”, Volumes I and II, by Schwartz, Perry and Berch (Interscience Publishers, 1958), or in the ‘Surfactant Science’ series (Edward Arnold Publishers, 1967 onwards).
[0048] The preferred textile-compatible carriers that can be used are soaps and synthetic non-soap anionic and nonionic compounds.
[0049] Anionic surfactants are well-known to those skilled in the art. Examples include alkylbenzene sulphonates, particularly linear alkylbenzene sulphonates having an alkyl chain length of C 8 -C 15 ; primary and secondary alkylsulphates, particularly C 8 -C 15 primary alkyl sulphates; alkyl ether sulphates; olefin sulphonates; alkyl xylene sulphonates; dialkyl sulphosuccinates; and fatty acid ester sulphonates. Sodium salts are generally preferred.
[0050] Nonionic surfactants that may be used include the primary and secondary alcohol ethoxylates, especially the C 8 -C 20 aliphatic alcohols ethoxylated with an average of from 1 to 20 moles of ethylene oxide per mole of alcohol, and more especially the C 10 -C 15 primary and secondary aliphatic alcohols ethoxylated with an average of from 1 to 10 moles of ethylene oxide per mole of alcohol. Non-ethoxylated nonionic surfactants include alkylpolyglycosides, glycerol monoethers, and polyhydroxyamides (glucamide).
[0051] Cationic surfactants that may be used include quaternary ammonium salts of the general formula R 1 R 2 R 3 R 4 N + X − wherein the R groups are independently hydrocarbyl chains of C 1 -C 22 length, typically alkyl, hydroxyalkyl or ethoxylated alkyl groups, and X is a solubilising cation (for example, compounds in which R 1 is a C 8 -C 22 alkyl group, preferably a C 8 -C 10 or C 12 -C 14 alkyl group, R 2 is a methyl group, and R 3 and R 4 , which may be the same or different, are methyl or hydroxyethyl groups); and cationic esters (for example, choline esters) and pyridinium salts.
[0052] The total quantity of detergent surfactant in the composition is suitably from 0.1 to 60 wt % e.g. 0.5-55 wt %, such as 5-50 wt %.
[0053] Preferably, the quantity of anionic surfactant (when present) is in the range of from 1 to 50% by weight of the total composition. More preferably, the quantity of anionic surfactant is in the range of from 3 to 35% by weight, e.g. 5 to 30% by weight.
[0054] Preferably, the quantity of nonionic surfactant (when present) is in the range of from 2 to 25% by weight, more preferably from 5 to 20% by weight.
[0055] Amphoteric surfactants may also be used, for example amine oxides or betaines.
[0000] Builders:
[0056] The compositions may suitably contain from 10 to 70%, preferably from 15 to 70% by weight, of detergency builder. Preferably, the quantity of builder is in the range of from 15 to 50% by weight.
[0057] The detergent composition may contain as builder a crystalline aluminosilicate, preferably an alkali metal aluminosilicate, more preferably a sodium aluminosilicate.
[0058] The aluminosilicate may generally be incorporated in amounts of from 10 to 70% by weight (anhydrous basis), preferably from 25 to 50%. Aluminosilicates are materials having the general formula:
0.8-1.5 M 2 O.Al 2 O 3 .0.8-6 SiO 2
where M is a monovalent cation, preferably sodium. These materials contain some bound water and are required to have a calcium ion exchange capacity of at least 50 mg CaO/g. The preferred sodium aluminosilicates contain 1.5-3.5 SiO 2 units in the formula above. They can be prepared readily by reaction between sodium silicate and sodium aluminate, as amply described in the literature.
[0059] Alternatively, or additionally to the aluminosilicate builders, phosphate builders may be used.
[0000] Textile Softening and/or Conditioner Compounds:
[0060] If the composition of the present invention is in the form of a textile conditioner composition, the textile-compatible carrier will be a textile softening and/or conditioning compound (hereinafter referred to as “textile softening compound”), which may be a cationic or nonionic compound.
[0061] The softening and/or conditioning compounds may be water insoluble quaternary ammonium compounds. The compounds may be present in amounts of up to 8% by weight (based on the total amount of the composition) in which case the compositions are considered dilute, or at levels from 8% to about 50% by weight, in which case the compositions are considered concentrates.
[0062] Compositions suitable for delivery during the rinse cycle may also be delivered to the textile in the tumble dryer if used in a suitable form. Thus, another product form is a composition (for example, a paste) suitable for coating onto, and delivery from, a substrate e.g. a flexible sheet or sponge or a suitable dispenser during a tumble dryer cycle.
[0063] Suitable cationic textile softening compounds are substantially water-insoluble quaternary ammonium materials comprising a single alkyl or alkenyl long chain having an average chain length greater than or equal to C 20 . More preferably, softening compounds comprise a polar head group and two alkyl or alkenyl chains having an average chain length greater than or equal to C 14 . Preferably the textile softening compounds have two, long-chain, alkyl or alkenyl chains each having an average chain length greater than or equal to C 16 .
[0064] Most preferably at least 50% of the long chain alkyl or alkenyl groups have a chain length of C 18 or above. It is preferred if the long chain alkyl or alkenyl groups of the textile softening compound are predominantly linear.
[0065] Quaternary ammonium compounds having two long-chain aliphatic groups, for example, distearyldimethyl ammonium chloride and di(hardened tallow alkyl) dimethyl ammonium chloride, are widely used in commercially available rinse conditioner compositions. Other examples of these cationic compounds are described in the above referenced “Surface-Active Agents and Detergents” and “Surfactant Science” reference books. Any of the conventional types of such compounds may be used in the compositions of the present invention.
[0066] The textile softening compounds are preferably compounds that provide excellent softening, and are characterised by a chain melting Lβ to Lα transition temperature greater than 25° C., preferably greater than 35° C., most preferably greater than 45° C. This Lβ to Lα transition can be measured by DSC as defined in “Handbook of Lipid Bilayers”, D Marsh, CRC Press, Boca Raton, Fla., 1990 (pages 137 and 337).
[0067] Substantially water-insoluble textile softening compounds are defined as textile softening compounds having a solubility of less than 1×10 −3 wt % in demineralised water at 20° C. Preferably the textile softening compounds have a solubility of less than 1×10 −4 wt %, more preferably less than 1×10 −8 to 1×10 −6 wt %.
[0068] Especially preferred are cationic textile softening compounds that are water-insoluble quaternary ammonium materials having two C 12-22 alkyl or alkenyl groups connected to the molecule via at least one ester link, preferably two ester links. Di(tallowoxyloxyethyl) dimethyl ammonium chloride and/or its hardened tallow analogue are especially preferred of the compounds of this type. Other preferred materials include 1,2-bis(hardened tallowoyloxy)-3-trimethylammonium propane chloride. Their methods of preparation are, for example, described in U.S. Pat. No. 4,137,180 (Lever Brothers Co). Preferably these materials comprise small amounts of the corresponding monoester as described in U.S. Pat. No. 4,137,180, for example, 1-hardened tallowoyloxy-2-hydroxy-3-trimethylammonium propane chloride.
[0069] Other useful cationic softening agents are alkyl pyridinium salts and substituted imidazoline species. Also useful are primary, secondary and tertiary amines and the condensation products of fatty acids with alkylpolyamines.
[0070] The compositions may alternatively or additionally contain water-soluble cationic textile softeners, as described in GB 2 039 556B (Unilever).
[0071] The compositions may comprise a cationic textile softening compound and an oil, for example as disclosed in EP-A-0829531.
[0072] The compositions may alternatively or additionally contain nonionic textile softening agents such as lanolin and derivatives thereof.
[0073] Lecithins are also suitable softening compounds.
[0074] Nonionic softeners include Lβ phase forming sugar esters (as described in M Hato et al Langmuir 12, 1659, 1666, (1996)) and related materials such as glycerol monostearate or sorbitan esters. Often these materials are used in conjunction with cationic materials to assist deposition (see, for example, GB 2 202 244). Silicones are used in a similar way as a co-softener with a cationic softener in rinse treatments (see, for example, GB 1 549 180).
[0075] The compositions may also suitably contain a nonionic stabilising agent. Suitable nonionic stabilising agents are linear C 8 to C 22 alcohols alkoxylated with 10 to 20 moles of alkylene oxide, C 10 to C 20 alcohols, or mixtures thereof.
[0076] Advantageously the nonionic stabilising agent is a linear C 8 to C 22 alcohol alkoxylated with 10 to 20 moles of alkylene oxide. Preferably, the level of nonionic stabiliser is within the range from 0.1 to 10% by weight, more preferably from 0.5 to 5% by weight, most preferably from 1 to 4% by weight. The mole ratio of the quaternary ammonium compound and/or other cationic softening agent to the nonionic stabilising agent is suitably within the range from 40:1 to about 1:1, preferably within the range from 18:1 to about 3:1.
[0077] The composition can also contain fatty acids, for example C 8 to C 24 alkyl or alkenyl monocarboxylic acids or polymers thereof. Preferably saturated fatty acids are used, in particular, hardened tallow C 16 to C 18 fatty acids. Preferably the fatty acid is non-saponified, more preferably the fatty acid is free, for example oleic acid, lauric acid or tallow fatty acid. The level of fatty acid material is preferably more than 0.1% by weight, more preferably more than 0.2% by weight. Concentrated compositions may comprise from 0.5 to 20% by weight of fatty acid, more preferably 1% to 10% by weight. The weight ratio of quaternary ammonium material or other cationic softening agent to fatty acid material is preferably from 10:1 to 1:10.
[0000] Other Components
[0078] Compositions according to the invention may comprise soil release polymers such as block copolymers of polyethylene oxide and terephthalate.
[0079] Other optional ingredients include emulsifiers, electrolytes (for example, sodium chloride or calcium chloride) preferably in the range from 0.01 to 5% by weight, pH buffering agents, and perfumes (preferably from 0.1 to 5% by weight).
[0080] Further optional ingredients include non-aqueous solvents, perfume carriers, fluorescers, colourants, hydrotropes, antifoaming agents, enzymes, optical brightening agents, and opacifiers.
[0081] Suitable bleaches include peroxygen bleaches. Inorganic peroxygen bleaching agents, such as perborates and percarbonates are preferably combined with bleach activators. Where inorganic peroxygen bleaching agents are present the nonanoyloxybenzene sulphonate (NOBS) and tetra-acetyl ethylene diamine (TAED) activators are typical and preferred.
[0082] Suitable enzymes include proteases, amylases, lipases, cellulases, peroxidases and mixtures thereof.
[0083] In addition, compositions may comprise one or more of anti-shrinking agents, anti-wrinkle agents, anti-spotting agents, germicides, fungicides, anti-oxidants, UV absorbers (sunscreens), heavy metal sequestrants, chlorine scavengers, dye fixatives, anti-corrosion agents, drape imparting agents, antistatic agents and ironing aids. The lists of optional components are not intended to be exhaustive.
[0084] The preferred mode of delivery of the compositions of the invention is in the form of a fabric washing powder. These are typically dosed at around 7 g/litre, into 15-20 litres of wash water. Thus around 2.5 g/litre of the beta 1-4 polysaccharide will be present in the wash liquor.
[0085] In order that the invention may be further and better understood it will be described below with reference to the following non-limiting examples.
EXAMPLES
Example 1
[0086] This example shows protection of new coloured fabrics from fabric abrasion during washing in a Quickwash™ with hydroxy ethyl cellulose (HEC) in a detergent powder composition
[0087] White woven cotton sheeting printed with a red and black “Manchester United” design was obtained from Abakhan Fabrics, Coast Road, Mostyn, Flintshire, CH8 9DX, UK, and cut into pieces measuring 20×20 cm and each edge overlooked to prevent fraying. This material was chosen because it is particularly sensitive to colour damage when washed.
[0088] A Datacolor™ Spectraflash SF600+ reflectance spectrometer was calibrated using white tile and black trap standards prior to measurement of the reflectance over the wavelength range 400-720 nm at specific points on each fabric piece. This was used to measure delta L and delta E, in accordance with the CIELAB method.
[0089] The fabrics were then washed in a Quickwash™ apparatus using the following protocol.
Apparatus Raitech ™ Quickwash ™ Plus. Powder 97 parts by weight of Persilm Original Non-Bio (ex Lever Faberge) as sold in the UK during the summer of 2002 and 3 parts by weight hydroxy ethyl cellulose (for example Cellosize ™ QP100MH, m. wt. 1,400,000). 16 g of this powder were dosed into the water with 4 g of antifoam granules Fabrics One coloured fabric piece was place in each of the five compartments of the Quickwash ™. Wash The Quickwash programme was executed as Conditions follows: 1. 30 second drain 2. Fill with 3 litres of 15° FH water at 40° C. 3. Machine paused and powder added 4. Programme resumed 5. Agitated for 15 minutes at 40° C. 6. Drain for 30 seconds 7. Fill with 3 litres of 15° FH water at 40° C. 8. Agitate for 5 minutes (Rinse) 9. Drain for 30 seconds 10. Dry at 4.0 bar for 1 minute 11. Dry at 3.5 bar for 1 minute 12. Dry at 3.0 bar for 2 minutes 13. Cool-down
[0090] These steps were repeated five times with each of a range of hydroxy-ethyl cellulose (HEC) materials (all Cellosize™ ex DOW), and for a control sample of UK Persil™ Non-Bio (ex Lever-Faberge) that did not contain any hydroxy-ethyl cellulose.
[0091] After the completion of the five washing and drying cycles the reflectance of each fabric was recorded at the same points using a calibrated Hunterlab™ Reflectance spectrometer and the delta E (total colour change) and delta L (luminance) values recorded.
[0092] Table 1 below shows results for these Quickwash assays. It can be seen that in all cases the addition of HEC at relatively low levels reduced the level of-colour fading by reducing the value of delta L.
TABLE 1 ‘Cellosize’ Hydroxy Ethyl Example Cellulose Delta L Control None 10.09 1a EP09 8.78 1b QP40 8.81 1c QP300 8.02 1d QP4400H 8.53 1e QP10000H 9.04 1f QP15000H 9.58 1g QP30000H 8.23 1h QP52000H 7.94 1I QP100MH 8.08
Example 2
[0093] This example shows how the inclusion of HEC prevents dye transfer from coloured cloth to a white monitor.
[0094] Dye transfer experiments were performed using the 97/3 mix of example 1 in a Tergotometer at a product dosage of 5 g/L, a liquor cloth ratio of 40:1, a temperature of 40 C, using 20 min wash and 2×5 min rinse. 4 white monitors were used together with 4 dyed clothes (each 10 cm square). Three dyes were used: Direct Red 80, Direct Green 26 and Direct Black 22, all unfixed
[0095] ‘Cielab’™ Standard delta E measurements were obtained (as described in Example 1) and are given in table 2 below. It can be seen that lower levels of dye were picked-up in the washes in which HEC was present as compared with the control (Persil™).
[0096] White light reflectance difference measurements (delta E) at the specified wavelengths are given in table 3. These show that, in general, significantly less reduction in reflectance was obtained with the compositions of the invention, containing a low level of HEC, than with the control (Persil™).
TABLE 2 Dye Pickup Example Red Green Black 3a (Control) 34.5 25.7 33.8 3b (example) 33.5 18.0 28.1
[0097]
TABLE 3
Reflectance
Loss
Red
Green
Black
Example
(540 nm)
(620 nm)
(610 nm)
4a (Control)
50.67
53.12
62.16
4b (example)
51.49
40.16
55.14
Example 3
[0098] Samples of white woven cotton (10 cm square) were stained with Dolomite clay (a process carried out by the supplier, Equest). The stained fabric was then attached to a larger piece of woven cotton and placed in a front-loading washing machine (Miele Novotronic™ TN450) along with sufficient white woven cotton ballast to make a load weight of 2.5 kg. The load was then washed using 110 g of Persil™ (as described above) containing 3% of hydroxyethyl cellulose with a molecular weight of 200,000 Dalton through a standard 40° C. cotton cycle. The process was repeated twice using new loads but with a hydroxyethyl cellulose derivatives with molecular weights of 470,000 and 1,400,000. The degree of stain removal was judged by measuring the delta E of the stain before and after washing. A higher value indicates more stain has been removed.
TABLE 4 M. wt. M. wt. M. wt. No HEC 200,000 470,000 1,400,000 ΔΔE 16.92 9.32 6.38 5.58
[0099] These results show that HEC is not (in the case of this stain and under these conditions) effective at improving stain removal. Moreover, a higher molecular weight HEC is more prone to causing problems with particulate stains.
Example 4
[0100] Samples of white woven cotton sheeting (10×10 cm) were stained with Stanley clay (supplied by Equest). The stained fabric was then attached to a larger piece of woven cotton and placed in a front-loading washing machine (Miele Novotronic TN450™) along with sufficient white woven cotton ballast to make a load weight of 2.5 kg. The load was then washed using 110 g of Persil™ containing varying levels of hydroxyethyl cellulose of molecular weight 200,000 through a normal 40° C. cotton cycle. The degree of stain removal was judged by measuring the delta E of the stain before and after washing. A higher value indicates more stain has been removed.
[0101] The experiment was then repeated but prior to the stain being applied, the fabric was washed (machine and conditions as above) in Persil™ containing varying levels of hydroxyethyl cellulose of molecular weight 200,000 through a normal 40° C. cotton cycle using 110 g of Persil™ containing the same amount of HEC as the fabric was prewashed in. As before, the difference in delta E was used to evaluate the degree of stain removed.
TABLE 5 Pre- Persil Persil Persil Persil Persil treat only only only only only Wash Persil Persil + Persil + Persil + Persil + only 0.5% HEC 1.0% HEC 2.0% HEC 3.0% HEC ΔΔE 28.54 28.55 29.16 24.03 23.78 Pre- Persil Persil + Persil + Persil + Persil + treat only 0.5% HEC 1.0% HEC 2.0% HEC 3.0% HEC Wash Persil Persil + Persil + Persil + Persil + only 0.5% HEC 1.0% HEC 2.0% HEC 3.0% HEC ΔΔE 28.54 23.48 20.62 20.46 19.40
[0102] These results show that at inclusion levels of HEC above 0.5%, particulate stain removal becomes increasingly problematical.
Example 5
[0103] The anti-abrasion benefit was determined by washing consumer articles in both European front-loading and Brazilian top-loading washing machines using normal washing powder and powder containing hydroxyethyl cellulose. The procedure used was as follows:
[0000] Wash loads:
[0104] A selection of 100% cotton garments were purchased from Asda™ and Matalan™. To remove and variability in the production of the garment, each was cut in half—one half washed in standard powder and the other half in powder containing hydroxyethyl cellulose. Thus the two halves could be compared after the process was complete.
[0105] Garments used: black denim jeans, dark blue shorts, dark blue T-shirt, dark blue rugby shirt, red/blue printed child's pajama top, blue denim waistcoat, brown sleeveless ribbed top. All these garments fall into the definition of ‘class three’ colours given above.
[0106] Each load comprised two halves of each garment type, a total of 14 garment “parts”, weighing 2 kg. Three loads were prepared in this manner. Two pieces of printed knitted cotton with a known abrasion profile were also included in each load to act as markers.
[0000] ‘European’ Wash Conditions
[0107] The wash processes were carried out in CMS computer-controlled washing machines (Miele Novotronic W980). This ensured that each wash cycle was identical (most modern front-loading washing machines vary the quantity of water depending on the nature of the fabrics present in the wash load). To further ensure that no “machine-dependant” results were obtained, three machines were used and the loads cycled through each machine in turn. In this way, and peculiarities in the washing machines was removed. The wash cycle used was as follows:
Fill, 15 litres Wash, 40° C., 35 minutes Flood, 10 litres Drain Rinse, 21 litres, 2 minutes Empty Rinse, 21 litres, 2 minutes Empty Rinse, 21 litres, 2 minutes Empty 1 st spin, 60 seconds @ 90 rpm followed by 120 seconds @ 400 rpm Rinse, 21 litres, 2 minutes 2 nd spin, 60 seconds @ 90 rpm followed by 60 seconds @ 400 rpm 3 rd spin, 60 seconds @ 90 rpm followed by 60 seconds @ 400 rpm 4 th spin, 60 seconds @ 90 rpm followed by 60 seconds @ 400 rpm
followed by 300 seconds @ 1200 rpm
Distribute, 60 seconds @ 90 rpm
[0125] Three loads were washed ten times using 105 g of Persil Performance™ (a bleach-containing biological washing powder). The other three loads were washed in 104.48 g Persil Performances™ containing 0.52 g of Cellosize™ QP300 (hydroxyethyl cellulose, m. wt. 200,000 ex Dow Chemicals).
[0126] After ten washes, the garments were tumble-dried in a Whirlpool™ Super Capacity Dryer for 70 minutes. They were then allowed to acclimate to the laboratory environment for 48 hours before being paneled.
[0000] ‘Brazilian’ Wash Conditions
[0127] The wash loads were carried out in top-loading Brastemp™ machines. The wash cycle comprised:
Fill, 65 litres water, ambient temperature, 2 minutes Agitate for 4- 5 minutes Stationary soak—26.5 minutes Mainwash—11 minutes Drain—5 minutes Spin cycle—2.5 minutes Fill for rinse—65 litres, ambient temperature, 2 minutes Rinse, 6 minutes Drain, drum stationary, 5 minutes Spin, 7 minutes
[0138] The control loads were washed ten times using 117 g of Brilhante™ (ex Lever Brasil) washing powder. The test loads were washed ten times using 116.42 g Brilhante™ with 0.58 g Cellosize™ QP300 QP300 (hydroxyethyl cellulose, m. wt. 200,000 ex Dow Chemicals). The loads were then dried and conditioned as above.
[0139] After the garments had conditioned, they were assessed by a team of 12 panelists. Each panelist was given a random selection of 14 garments from each test condition and asked to indicate which garment appeared to have been washed the least number of times (i.e. the least worn appearance). The garments were labeled with random 3-digit numbers for identification.
TABLE 6 Panelist scores, European conditions Article Control HEC Black Jeans 0 4 0 4 2 2 1 3 1 3 0 4 Total 4 20 Child's Top 2 2 2 2 0 4 1 3 2 2 1 3 Total 8 16 Ruby Shirt 0 4 2 2 1 3 0 4 0 4 0 4 Total 3 21 Sleveless Top 1 3 2 2 1 3 1 3 1 3 2 2 Total 8 16 Waistcoat 2 2 2 2 0 4 1 3 2 2 2 3 Total 8 16 T-Shirt 0 4 2 2 2 2 0 4 1 3 1 3 Total 6 18 Shorts 0 4 3 1 1 3 3 1 1 3 4 0 Total 12 12
[0140]
TABLE 7
Panelist scores, Brazilian Conditions
Article
Control
HEC
Black Jeans
2
2
2
2
1
3
1
3
1
3
0
4
Total
7
17
Child's Top
2
2
1
3
2
2
1
3
1
3
2
2
Total
9
15
Rugby Shirt
2
2
2
2
1
3
1
3
1
3
0
4
Total
7
17
Sleveless Top
0
4
2
2
3
1
3
1
3
1
1
3
Total
12
12
Waistcoat
0
4
3
1
2
2
1
3
1
3
3
1
Total
10
14
T-Shirt
2
2
0
4
2
2
0
4
3
1
2
2
Total
9
15
Shorts
4
0
0
4
2
2
3
1
1
3
0
4
Total
10
14
[0141] In all cases bar one, the panelists ranked the garments washed in powder containing hydroxyethyl cellulose as appearing less worn that those washed in conventional washing powder. In the remaining case there was, overall, no difference between the two treatments.
[0142] Colour measurements (delta E) were taken from the printed cotton fabrics. Lower values indicate less abrasion has taken place and the colours appear closer to new. These are shown in Table 8 below.
TABLE 8 Example Cloth Type Control Treated 2a Low Binder, Woven, Black 4.79 2.37 2b Low Binder, Woven, Blue 3.68 1.62 2c Low Binder, Woven, Green 5.61 3.10 2d Low Binder, Woven, Red 8.25 4.46 2e Normal Binder, Woven, Black 2.13 1.14 2f Normal Binder, Woven, Blue 2.03 1.14 2g Normal Binder, Woven, Green 3.57 2.87 2h Normal Binder, Woven, Red 7.21 5.69 2I Low Binder, Knitted, Black 8.95 7.10 2j Low Binder, Knitted, Blue 8.53 6.74 2k Low Binder, Knitted, Green 9.79 8.39 2l Low Binder, Knitted, Red 13.19 11.38 2m Normal Binder, Knitted, Black 3.94 3.00 2n Normal Binder, Knitted, Blue 2.66 1.80 2o Normal Binder, Knitted, Green 3.69 2.92 2p Normal Binder, Knitted, Red 8.36 7.24 2q Red/Black Print (Black 11.64 10.12 stripe) 2r Red/Black Print (Red Stripe) 16.48 15.22
[0143] Taken together these results show that HEC is effective at reducing some negative visual effects of washing on coloured garments. These same visual effects do not occur on white garments.
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A method of treating coloured fabrics with a luminance (L*)Less than 50, preferably black garments, which comprises contacting the fabrics with a wash liquor comprising:a) 0.1-0.001 g/L of a hydroxy C2-C4 alkyl derivative of a beta 1-4 polysaccharide, which is preferably hydroxyethyl cellylose andb) surfactant.
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BACKGROUND OF THE INVENTION
a. Field of Invention
This invention pertains to an improved cover for a suction box used in papermaking machines, wherein water is removed from a moving fabric or web by suction.
b. Description of the Prior Art
Various types of paper may be made at high speed and economically on so-called papermaking machines. In a papermaking machine, a slurry of wood pulp or other materials is dispensed onto an endless forming fabric. The forming fabric with the slurry moves past several suction boxes used to remove water from the slurry to form a continuous paper sheet. Since this sheet still has a high water content, it is usually transferred to a press section where it is contacted with at least one continuous press fabric and fed through press nips for the further removal of water by mechanical compression. The press fabric is then passed over a suction box where water is removed from the fabric. Thus the press fabric may be used in a continuous process.
One common type of suction box is provided with a cover having a slot extending across the full width of the press fabric. The slot is generally in the range of 3/8 to 3 inches in machine direction width. (The suction box is described herein as part of the press section of the papermaking machine, however it should be understood that it may also be used in the paper forming section). This type of suction box has been found to be unsatisfactory for a number of reasons. For example, as the seam of a machine seamable press fabric as described in U.S. Pat. No. 4,601,785 passes over the slot, the fabric makes a loud, unpleasant popping sound which increases the overall noise level produced by the machine. Also, as the seam passes over the slot in the suction box, it rubs against the slot edges causing the seam flap, formed of batt material, to wear out before the rest of the fabric. Thus, the useful life of the press fabric is reduced drastically. The fabric may also fail due to the flexing of the fabric adjacent to the seam due to the movement of the seam caused by vacuuming down into the slot.
OBJECTIVES AND SUMMARY OF THE INVENTION
In view of the above-mentioned disadvantages of the existing suction box covers, it is an objective of the present invention to provide an improved suction box cover which has no pronounced slot edges presented to the press fabric, thereby extending the useful life of the press fabric.
A further objective is to provide an improved box cover in which the flexing of the fabric at the slot is eliminated.
Yet another objective is to provide an improved box cover which reduces or eliminates the sound produced by prior art box covers. Since overall wear can be reduced by preventing the flexing of the fabric down into a slot, the batt layer of both on machine seamed fabrics and regular, endless press fabrics will also be exposed to less mechanical wear from the slot edges.
Other advantages of the invention shall become apparent from the following description of the invention. Briefly, the suction box constructed in accordance with this invention comprises a main body connected to a vacuum source to provide suction. A cover is secured to the box and is constructed and arranged to support a fabric moving continuously across it. The box cover is provided with a slot extending substantially across the width of the fabric and in communication with the main body of the box to apply suction to the fabric, to remove water therefrom. Advantageously, a wire (which could be a perforated sheet of steel, plastic, etc.) mesh is imbedded in the top section of the slot, covering the entire slot opening. The mesh prevents the fabric and its seam from deflection into the slot.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows an isometric view of a suction box with an improved cover constructed in accordance with the invention;
FIG. 2 shows a plan view of the cover of FIG. 1; and
FIG. 3 shows a side sectional view of the cover of FIGS. 1 and 2.
DETAILED DESCRIPTION OF THE INVENTION
Referring now to the Figures, a suction box 10 constructed in accordance with this invention includes a main body 12 which is connected to a vacuum source (not shown) by a connecting pipe 14. The box is provided with a solid cover 16 which is secured to the main body in a known manner. For example in FIG. 1, the cover 16 is secured to the main body in a dovetail joint, however other types of connections are equally suitable.
The cover is provided with a continuous slot 18 having a substantially uniform cross-section extending substantially along its length as shown. On the flat top surface 20 of the cover, there is a recess 22 surrounding slot 18. This recess may be for example about 1/4 inch wide. Disposed in this recess is a wire mesh 24 preferably in a manner such that it is coplanar with the top surface 20. The mesh 24 may be secured to cover 16 by various means including mechanical means (i.e. screws, clips or other fasteners designed to retain the mesh in the recessed area on both sides of the slot); chemical means (i.e. by application of a silicone or other type of adhesive); by molding the mesh integrally with the cover (if both the mesh and cover are made of a plastic material); or by sliding the mesh into grooves (not shown) precut on two opposite longitudinal edges of the slot.
Depending on the length of slot 18, the wire mesh may be made from a single piece or from two pieces butted together as at 26. The mesh is selected so that it provides a support for the press fabric without letting it protrude into the slot 18. The mesh has a plurality of holes such as 28 which are large enough so that as water is extracted from the fabric, the holes are not plugged up by papermaking fillers.
The operation of the suction box with the improved cover shall now be described. The suction box is disposed in a paper machine, such as for example its press section, transverse to the continuous path of a press fabric. The press fabric 30 passes over the cover in a continuous movement indicated by the arrow 32. The vacuum in suction box 10 extracts water from the fabric through slot 18 and mesh 24. The mesh is constructed and arranged to fit in recess 22 to support the fabric. Therefore the mesh prevents any contact between the fabric and the side walls defining slot 18, thereby eliminating undesirable noise, and reducing the wear on the fabric and its seam (not shown). As previously mentioned, the suction box may also be disposed in the forming section for removing water directly from a paper web through a forming fabric.
Preferably, the cover is molded from a high impact plastic material with a low coefficient of friction such as polyethylene. The wire mesh is preferably made of stainless steel, but could also be made of synthetic polymer materials.
Obviously numerous modifications may be made to this invention without departing from its scope as defined in the appended claims.
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An improved suction box for paper making machine includes a cover for contacting a press fabric with an elongated slot. The slot is covered with a mesh to eliminate noise and reduce wear on the fabric.
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BACKGROUND OF THE INVENTION
In positive displacement compressors, discrete volumes of gas are trapped and compressed with the trapped, compressed volumes being discharged from the compressor. The trapping of the volumes at suction pressure and their discharge at discharge pressure each produce pressure pulsations and the related noise generation. While mufflers can be made to attenuate noise in a particular frequency range, or ranges, variable speed compressors may operate over ranges beyond the effective range(s) of conventional absorptive mufflers. This may be due to operating at rotational speeds outside the peak performance region of the absorptive device or at speeds where absorptive techniques are inadequate e.g. at frequencies well below the quarter wave thickness of the absorptive material. Accordingly, there would be no effective attenuation of a variable speed positive displacement compressors over some ranges of normal operation where conventional absorptive mufflers are employed.
The flow of gas through a muffler is along a flow path defined by the pressure differential across the muffler. The direction of noise generation is not dictated by the flow direction. Reflected sound energy is generated each time there is a change in the cross section of the flow path with some of the sound energy being reflected in the opposite direction to that of the gas flow. It is through this mechanism that “reactive” type mufflers are designed to attenuate specific frequencies. In an absorptive muffler a portion of the flow path is defined by an absorptive material overlain by perforate metal, or the like. There is a trade off between flow resistance and noise reduction, with respect to the length and cross section of the flow path, in designing the muffler. Typical performance is limited by the relationship of the flow passage length to its height/minimum spacing in an absorptive device with peak attenuation occurring at a frequency related to the depth and impedance characteristics of the liner material.
SUMMARY OF THE INVENTION
The present invention is directed to an absorptive/reactive muffler including a central cylindrical section having an opening, preferably, at the downstream end and containing a plurality of Helmholtz resonators, a mix of quarter and half wave resonators with each of the resonators being turned to a slightly different frequency to provide wider bandwidth attenuation characteristics or a combination of Helmholtz and quarter and/or half wave resonators. The central cylindrical section is serially overlain by an absorptive material and a first perforate material. The perforate material defines the inner surface of the flow path. A second perforate annular surface is underlain with an absorptive material and is spaced from the first perforate material and coacts therewith to define the fluid flow path. Noise traveling along the fluid flow path reflects between the two surfaces of absorptive material overlain by the perforate material and is attenuated by the absorptive material. Upon reaching the end of the annular flow path, the impedance discontinuity defined by the change in flow cross section directs some of the generated noise into the central cylindrical section containing the resonators. If necessary, or desired, the outer annular surface partially defining the annular flow path may be smooth rather than lined with absorptive material overlain by perforate material.
It is an object of this invention to provide performance enhancement over conventional absorptive mufflers.
It is a further object of this invention to provide a muffler having enhanced performance in a plurality of narrow frequency bands. These objects, and others as will become apparent hereinafter, are accomplished by the present invention.
Basically, the preferred muffler includes an annular flow path for the gas with the center of the annulus having a plurality of resonators which are in open communication with the downstream end of the annular flow path. The flow path is at least partially lined by an absorptive material overlain by a perforate material.
BRIEF DESCRIPTION OF THE DRAWINGS
For a fuller understanding of the present invention, reference should now be made to the following detailed description thereof taken in conjunction with the accompanying drawings wherein:
FIG. 1 is a sectional view of a PRIOR ART absorptive muffler;
FIG. 2 is a sectional view of an absorptive/reactive muffler made according to the teachings of the present invention; and
FIG. 3 is a sectional view of a modified absorptive/reactive muffler made according to the teachings of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In FIG. 1, the numeral 10 generally designates a PRIOR ART absorptive muffler. Muffler 10 includes an outer hollow cylindrical housing portion 12 and an inner portion 14 which is suitably supported in said housing portion 12 and radially spaced therefrom so as to provide an annular flow path 20 therebetween. Inner portion 14 includes an inner cylindrical portion 14 - 1 closed at the upstream end by disc 14 - 2 which extends radially outward of the inner cylindrical portion 14 - 1 . Annular disc portion 14 - 3 is located at the downstream end of cylindrical portion 14 - 1 and extends radially outward therefrom. Cylindrical portion 14 - 1 and disc 14 - 2 coact to define cylindrical chamber C which is open at its downstream end to the flow path 20 but does not form a part of the flow path. Acoustical lining 16 surrounds inner cylindrical portion 14 - 1 and is held in place axially by discs 14 - 2 and 14 - 3 . Acoustical lining 17 lines a portion of the inner surface 12 - 1 of housing portion 12 and is held in place axially by annular discs 12 - 2 and 12 - 3 . Acoustical linings 16 and 17 may be of any suitable material such as foam or fiberglass. Acoustical linings 16 and 17 are overlain by perforate members 18 and 19 , respectively, which may be any suitable material such as plastic or metal.
In operation of muffler 10 , gas flow and sound enter annular flow path 20 at the left side of FIG. 1 and exit at the right side of FIG. 1 . The primary mechanism for reducing sound is the absorptive elements 16 and 17 located beneath perforate annuli 18 and 19 , respectively, which form the outer surface of inner portion 14 and the inner surface of housing portion 12 . In going through muffler 10 the sound reflects between the surface defined by perforate member 18 and the surface defined by perforate member 19 with sound passing through the perforations 18 - 1 of perforate member 18 and the perforations of 19 - 1 of perforate member 19 thereby being attenuated by absorptive elements 16 and 17 , respectively. Chamber C, which is an empty volume, acts as a one quarter wave resonator which attenuates the sound in a narrow frequency range.
Muffler 100 differs from muffler 10 in replacing a single quarter wave resonator with a series of slightly mis-tuned Helmholtz resonators providing a wide band of sound reduction at problematic frequencies. Inner portion 14 ′ is suitably supported in housing portion 12 . Muffler 100 has all of the structure of muffler 10 except: (1) disc 14 - 2 ′ has a hemispherical or other type of flow loss reducing geometry; (2) annular disc 14 - 3 ′ has a smaller opening than annular disc 14 - 3 ; (3) acoustical lining 16 has been replaced by a plurality of segments 16 - 1 separated by discs 14 - 4 , 14 - 5 , 14 - 6 and 14 - 7 ; and (4) acoustical lining 17 has been replaced by a plurality of segments 17 - 1 separated by discs 12 - 4 , 12 - 5 , 12 - 6 and 12 - 7 . The subdividing of acoustical lining 16 into segments 16 - 1 by solid disc separators 14 - 4 , 14 - 5 , 14 - 6 and 14 - 7 along the complete length of inner portion 14 ′ is such that discs 14 - 4 , 14 - 5 , 14 - 6 and 14 - 7 prevent the acoustic wave from traveling the complete length of the material of all of segments 16 - 1 in the flow direction. Rather, acoustic waves are forced to penetrate the material of segments 16 - 1 in directions primarily normal to the flow direction only. This type of absorptive device is termed a “locally reacting” muffler rather than the bulk device of FIG. 1 . Additionally, structure is located in the space corresponding to chamber C of muffler 10 . Specifically, perforate cylindrical member 30 , having a plurality of perforations 30 - 1 which may vary in size, extends within inner cylindrical portion 14 - 1 from annular disc 14 - 3 ′ to a point short of the inner surface of end disc 14 - 2 ′. Perforate member 30 has a closed end 30 a and is supported by annular end disc 14 - 3 ′ and a plurality of inner annular discs with three discs, 14 - 8 , 14 - 9 and 14 - 10 , being illustrated. Inner cylindrical portion 14 - 1 , perforate member 30 and discs 14 - 3 ′, 14 - 8 , 14 - 9 and 14 - 10 coact to define chambers C- 1 , C- 2 , C- 3 and C- 4 which define slightly mis-tuned Helmholtz resonators. Mistuning of chambers C- 1 through C- 4 is accomplished by varying the chamber volumes and/or the porosity through the number and/or hole size of perforations 30 - 1 communicating with each of the chambers C- 1 through C- 4 .
In operation of muffler 100 , the sound passing through the annular path 20 defined by the inner surface of housing portion 12 or perforate member 19 and the underlying absorptive element 17 and the surface defined by perforate member 18 and the underlying absorptive elements 16 - 1 is the same as in the case of muffler 10 . The difference and improvement provided by muffler 100 over muffler 10 is that due to the replacement of the single quarter wave resonator defined by chamber C with the Helmholtz resonators defined by chambers C- 1 , C- 2 , C- 3 and C- 4 . The Helmholtz resonators are similar but not identical and so are able to attenuate a range of frequencies. The attenuated frequencies may be specific frequencies, a wider band of frequency by slight mistuning, or a combination of both.
Muffler 200 differs from muffler 10 in replacing a single quarter wave resonator with a plurality of quarter and/or half wave resonators. Inner portion 14 ′ is suitably supported in housing portion 12 . Muffler 200 differs from muffler 100 in having a plurality of quarter and/or half wave resonators rather than a plurality of Helmholtz resonators. Muffler 200 has all of the structure of muffler 10 except disc 14 - 2 ′ has a hemispherical or other type of flow loss reducing geometry and annular disc 14 - 3 ″ has a smaller opening than annular disc 14 - 3 and supports tube 40 . In addition to tube 40 , tube 41 supported by annular disc 14 - 11 and tube 42 supported by annular disc 14 - 12 are located in the space corresponding to chamber C of muffler 10 . Tubes 40 , 41 and 42 are axially spaced and of different lengths. Inner cylindrical portion 14 - 1 , tubes 40 , 41 and 42 and discs 14 - 3 ″, 14 - 11 and 14 - 12 coact to define chambers C- 1 ′, C- 2 ′ and C- 3 ′ and slightly mis-tuned quarter and half wave resonators. For example, half wave resonators are defined by tubes 40 , 41 and 42 terminating with open-open end boundary conditions while one quarter wave resonators are defined by open-closed end boundary conditions.
The operation of muffler 200 is the same as that of muffler 10 and 100 relative to the sound passing through the annular path 20 defined by the inner surface of outer housing portion 12 or perforate member 19 and the underlying absorptive elements 17 - 1 and the surface defined by perforate member 18 and the underlying absorptive element 16 . The difference and improvement provided by muffler 200 over muffler 10 is that due to the replacement of a single quarter wave resonator defined by chamber C with a plurality of quarter and/or half wave resonators which are similar but not identical. The resonators collectively are able to attenuate a range of frequencies which may, for example, be specific frequencies, a wider band of frequencies by slight mistuning of the length of tubes 40 , 41 and/or 42 , or by a combination of both.
Although preferred embodiments of the present invention have been illustrated and described, other changes will occur to those skilled in the art. For example, the number and combination of types of resonators and the degree of mistuning will depend upon the specific application of the teachings of the present invention. Also, while segments are preferred, absorptive elements 16 - 1 an 17 - 1 may be made as single elements. It is therefore intended that the scope of the present invention is to be limited only by the scope of the appended claims.
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An absorptive and reactive muffler includes an annular flow path for the gas with the center of the annulus having a plurality of resonators which are in open communication with the downstream end of the annular flow path and make up the reactive portion of the muffler. The flow path is at least partially lined by an absorptive material overlain by a perforate material and makes up the absorptive portion of the muffler.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent application clams priority to U.S. Provisional Patent Application No. 621009,794 entitled OPTICALLY CLEAR ADHESIVES AND METHODS OF PRODUCING THE SAME, filed on Jun. 9, 2014, which is incorporated herein by reference in its entirety.
TECHNICAL FIELD
[0002] Embodiments disclosed herein relate generally to optically clear adhesives and methods of their production and use. The disclosed adhesives may contain features of both optically clear adhesive films and optically clear adhesive liquids. Certain embodiments of the disclosed optically clear adhesives may be useful in the assembly processes for a variety of devices, including, without limitation, optical display elements.
DESCRIPTION
[0003] Optically clear adhesives are widely used in electronic devices including mobile phones, televisions, tablets, watches, and those in automobile interiors, where optical clarity in display panels may be important. Such adhesives may provide benefits such as shock resistance, enhanced contrast, and improved brightness reduction. For example, in various types of devices, such as mobile phones, tablets, or computer pads, an optically clear adhesive (OCA) may be used to bond the top cover glass or film to the touch panel sensor plate. An OCA may also be used to fill the gap between the touch panel sensor plate and an LCD module.
[0004] There are currently two types of OCA products commercially available in the market: pre-coated films and liquid pastes. Commercially available examples of film OCAs include CEF 0807, CEF 0707 and CEF 08A05 from 3M Company, headquartered in Minnesota, USA. Commercially available examples of liquid paste OCAs include Loctite 3192, 3191 and 5192 from Henkel, headquartered in Dusseldorf, Germany.
[0005] The flow properties of an OCA are relevant to electronic touch panel bonding applications. In certain applications, a flowable OCA may he desirable. An OCA film which is flowable may help it conform to an uneven or rough surface, such as a surface with printed patterns inside a touch panel module. These printed patterns may have ink steps, and in some cases large ink steps, including those which may project from about 40 to about 70 microns above the surface of the glass or film substrate. In general, a liquid OCA is more flowable than a film OCA. A liquid OCA is typically cured after it is applied to optical elements.
[0006] The ease of die-cutting an OCA film is another relevant property. If an adhesive film is too soft, it may create processing difficulties which can result in a low yield for a die-cutting process. This may be especially true for an OCA with a thickness larger than about 100 microns, which is a thickness often used in optical display applications.
[0007] Disclosed herein are multi-layer OCA films and methods of making the films using web coating technologies. Such OCA films typically include a center layer and at least one outer layer. In some embodiments, the OCA films are two-layer films having an outer layer and a center layer. In other embodiments, the OCA films are three-layer films having a center layer and two outer layers. In such OCA films, the outer layers may be identical, while in others, they may be independently selected.
[0008] A schematic illustration of such a three-layer film is shown below, and is intended for illustrative purposes only. Thus, the illustration is not intended to limit the film in any manner, such as, for example, regarding the thicknesses of each layer relative to any other layer or to the entire film.
[0000]
outer layer
center layer
outer layer
[0009] In some embodiments, the disclosed optically clear adhesives may combine features of both film and liquid optically clear adhesives. More specifically, certain embodiments of the disclosed optically clear adhesives may include some or all of the features discussed herein.
[0010] The OCA may have a UV-curable outer layer with a tan delta (tan δ) value larger than about 1.0, as measured by dynamic mechanical analysis (DMA). A tan delta value may be used to estimate the ease of flow of the adhesive and is often used in describing pressure sensitive adhesives. Higher tan delta values are characteristic of adhesives that have better adhesive flow (good ink-wetting) and better stress relaxation.
[0011] Generally, commercially available OCA films have a tan delta value of between about 0.4 and about 0.7, and typically under about 1.0. The outer layer or layers of the disclosed optically clear adhesives may have a tan delta value of between about 0.9 and about 3.0, but may typically be above about 1.0. The disclosed OCA films may thus have at least one outer layer with a tan delta value which is above what may be commonly available commercially.
[0012] The disclosed OCA films are typically three-layer structures with a total thickness which may be from about 100 to about 300 microns, and may be coated via a standard web coating process or a precision web coating process,
[0013] In some embodiments, the OCA films may contain a center layer which has a thickness of between about 60 and about 180 microns with a high flexural modulus. In certain embodiments, the OCA films may include two outer layers, each with a thickness of between about 20 and about 60 microns. Each layer may be sized dependently or independently of the other layers.
[0014] In some OCA films of this disclosure, outer layers may each be UV-curable and may be designed to be cured after the adhesive is applied to a substrate. In some embodiments, the tan delta values of each of the two outer layers is between about 0.9 and about 3.
[0015] In some OCA films of this disclosure, the center layer of the OCA may have a tensile modulus larger than 0.3 Mpa,
[0016] In some OCA films of this disclosure, the OCA is sandwiched between two release liners (not shown in the illustration above). In certain instances, the OCA may contain a center layer with only a single outer layer.
[0017] The OCA may be optically clear with an optical transmission greater than about 90 and a haze of less than about 5%.
[0018] In some instances, the OCAs of this disclosure may exhibit strong adhesion to glass or another substrate, with an adhesion of greater than about 4 pounds/inch based on the 180 degree peel test at a 12 in/min line speed on an Instron® machine.
[0019] In certain embodiments, an optically clear adhesive may exhibit all of the above-listed properties. Alternatively, an OCA may exhibit only one, or a subset of, the listed properties.
[0020] The center layer of the optically clear adhesive may be a cross-linked pressure sensitive adhesive. It may be cured by radiation, such as UV light or an electron beam (ES), or it may be thermally cured. Exemplary UV cured pressure sensitive adhesives include the UV curable acrylic pressure sensitive adhesives disclosed in U.S. Pat. No. 8,361,632 by Everaerts and Xia. Exemplary thermally cured pressure sensitive adhesives include commercially available pressure sensitive adhesives from Henkel and Ashland. The center layer may also contain one or more photoinitiators, cross linkers, and/or solvents.
[0021] The outer layer or layers of a multi-layer optically clear adhesive each may be a UV-curable acrylate, UV- and/or moisture-curable silicone, and may contain at least one photoinitiator. Other components of an outer layer may include peroxide, melamine, isocyanate, and/or aziridine as, for example, a cross linker(s). Still other components of an outer layer may include plasticizers, tackifiers, solvents, and/or other additives. Exemplary solvents include toluene, methyl ethyl ketone (MEK), and ethyl acetate. An exemplary cross linker is aluminum triacetate.
[0022] Examples of UV-curable acrylates suitable for use in the center layer and/or outer layer or layers are monomeric and oligomeric acrylates, including those comprising 2-ethylhexyl acrylate (EHA); an aliphatic urethane oligomer such as CN9018 from Sartomer Company in Pennsylvania, USA; an acrylic ester such as CN9021 from Sartomer; a urethane acrylate such as Genomer 4188 from RAHN USA Corp., Aurora, Ill.; and an aliphatic urethane acrylate such as Genomer 4269 from RAHN USA. Examples of photoinitiators include alpha-hydroxy ketones and phosphine oxides such as Genocure LTM and TPO from RAHN USA, and lrgacure 184 and 819 from BASF.
[0023] In certain embodiments, the optically clear adhesive may contain a layer comprising a polyester, such as a modified saturated polyester Genomer 6043/M22 from RAHN USA. In some embodiments, the optically clear adhesive may contain a layer comprising 2-(2-ethoxyethoxy)ethyl acrylate, such as SR-256 from Sartomer.
[0024] In some embodiments, the OCA or a layer of the OCA may be coated from a pre-cured premixture. This may aid in the coating of a substrate to generate a defect-free, or substantially defect-free coating.
[0025] In some embodiments, the mixture may have a viscosity of about 2000 cps, which may be useful for coating a substrate via a slot-die method. Other coating methods could also be used. Other similarly suitable components may be known to one of skill in the art.
[0026] Methods of using the OCA films are also disclosed herein. In particular, it is contemplated that any of the components, principles, and/or embodiments discussed above may be utilized in either an OCA film or a method of using the same. For example, in an embodiment, a method can include use of the OCA films in bonding two or more surfaces. In another embodiment, a method can include use of the OCA films in bonding a first surface such as a top cover glass or film to a second surface such as a touch panel sensor plate. Additional steps and/or methods can also be employed.
EXAMPLES
[0027] The specific examples included herein are for illustrative purposes only and are not to be considered as limiting to this disclosure. The components used in the following examples are either commercially available or can be prepared according to standard literature procedures by those skilled in the art. In light of this disclosure, those of skill in the art will recognize that variations of these examples and other examples of the disclosed methods would be possible without undue experimentation.
[0028] The following is a sample formulation for the center layer of an exemplary embodiment of an optically clear adhesive:
[0000]
percentage of the
specific example of a
component by weight of
component type
component
the layer
urethane acrylate/2-
Genomer 4188/EHA
from about 10% to about
ethylhexyl acrylate
20%
polyester resin
Genomer 6043/M22
from about 50% to about
60%
acrylate resin
SR-256
from about 20% to about
30%
photoinitiator
Genocure LTM
from about 2% to about
5%
[0029] The following is a sample formulation for the center layer of an additional exemplary embodiment of an optically clear adhesive:
[0000]
percentage of the
specific example of a
component by weight of
component type
component
the layer
pressure sensitive
Durotak 230A
from about 50% to about
adhesive
100%
cross linker
Al(Ac) 3
from about 0 to about 10%
solvent
Toluene
from about 0 to about 50%
solvent
Ethyl acetate
from about 0 to about 50%
[0030] The following is a sample formulation for an outer layer or layers of an exemplary embodiment of an optically clear adhesive:
[0000]
percentage of the
specific example of a
component by weight of
component type
component
the layer
urethane acrylate/2-
Genomer 4188/EHA
from about 50% to about
ethylhexyl acrylate
100%
solvent
MEK
from about 0 to about 50%
solvent
Toluene
from about 0 to about 50%
photoinitiator
Genomer TPO
from about 0 to about 10%
photoinitiator
Irgacure 184
from about 0 to about 10%
[0031] References cited throughout this disclosure, including patents, are herein incorporated by reference in theft entirety.
[0032] References to approximations are made throughout this specification, such as by use of the terms “about” or “approximately.” For each such reference, it is to be understood that, in some embodiments, the value, feature, or characteristic may be specified without approximation. For example, where qualifiers such as “about,” “substantially,” and “generally” are used, these terms include within their scope the qualified words in the absence of their qualifiers.
[0033] Reference throughout this specification to “an embodiment” or “the embodiment” means that a particular feature, structure or characteristic described in connection with that embodiment is included in at least one embodiment. Thus, the quoted phrases, or variations thereof, as recited throughout this specification are not necessarily all referring to the same embodiment.
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This disclosure relates generally to optically clear adhesives and methods of their production. The disclosed adhesives may contain features of both optically clear adhesive films and optically clear adhesive liquids. The disclosed optically clear adhesives may be useful in the assembly processes for a variety of applications, including in the assembly of optical display elements.
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RELATED APPLICATION
The present application is based on the Applicant's U.S. Provisional Patent Application Ser. No. 60/017,340, entitled "System For Measuring Acid Concentration In An Alkylation Process", filed on Apr. 26, 1996.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the field of alkylation processes used primarily in the petroleum refining industry. More specifically, the present invention discloses a system for rapidly and accurately measuring acid concentration to optimize control in an alkylation process.
2. Statement of the Problem
Alkylation processes have long been widely used in the chemical field. In the petroleum refining industry, alkylation is commonly used to convert paraffins and olefins (e.g., isobutane and butene) that are byproducts of other refinery processes into octane and related compounds that are high quality fuels for engines. Highly concentrated sulfuric acid (H 2 SO 4 ) or hydrofluoric acid (HF) is used as a catalyst. There are several methods for alkylation that are well known in the petroleum refining art. While only one of these alkylation method is discussed in detail below, the present invention can be used for the measurement of acid concentration in other types of alkylation processes.
As shown in FIG. 1, isobutane, butene, and the acid catalyst are combined in a first contactor vessel 10. Efficient mixing with fine subdivision must be-provided by agitating the mixture. The resulting products are then drawn into a settler 11 where the high octane products are separated and withdrawn from the process. The remaining material is largely acid, but also contains significant amounts of water, paraffins, olefins, sulfonated compounds, and other contaminants. For example, the acid entering the first contactor 10 typically has a concentration of approximately 98 percent, while the acid concentration in the settler 11 is about 96 percent.
In the second stage of the process, acid from the first settler 11 is fed into a second contactor 12, as shown in FIG. 1, and mixed with additional isobutane and butene. The resulting products are drawn into the second settler 13 where the octane is separated and withdrawn. The acid concentration in the second settler 13 is reduced again by about 2 percent to approximately 94 percent.
This sequence of steps is repeated in the third and fourth stages by processing the acid and additional amounts of isobutane and butene through a third contactor 14 and third settler 15, and then through a fourth contactor 16 and fourth settler 17. The acid concentration in the third settler 15 is reduced to approximately 92 percent and the acid concentration in the fourth settler 17 is reduced to approximately 90 percent. The acid leaving the fourth settler 17 is shipped back to the manufacturer for regeneration.
The processing equipment is quickly damaged and the efficiency of the chemical process plunges if the acid concentration drops too low. If it becomes necessary to shut down the alkylation process, isobutane and butene will continue to be produced as byproducts of other petroleum refinery processes. These compounds cannot be readily stored and must be disposed of by flaring. This represents an economic loss to the refiner and can raise environmental concerns. Therefore, the concentration of the acid must be carefully controlled at each stage in the alkylation process to prevent downtime.
It is also important to minimize acid consumption to minimize operating costs. In a conventional plant, the acid leaving the fourth settler 17 is sampled once or twice each day. These samples are sent to a laboratory for analysis, which requires several hours to obtain results. This situation induces an operator to run the plant in a very conservative manner to avoid any possibility that the acid concentration in the alkylation process might fall too low. The conventional approach is to set the feed rate of acid into the first contactor 10 so that acid leaving the fourth settler 17 has a concentration of at least 90 percent. Additional acid can be fed directly into the second, third, and fourth contactors to ensure an adequate acid concentration at each step in the process. This conservative manner of operation causes a substantial increase in operating costs due to the large quantities of acid used by a typical plant over time.
Several prior art patents have been issued in this general field, including the following:
______________________________________Inventor U.S. Pat. No. Issue Date______________________________________Brandel 3,513,220 May 19, 1970Brandel 3,653,835 April 4, 1972Mayer 4,018,846 April 19, 1977Mayer 4,073,822 Feb. 14, 1978______________________________________
The Brandel patents disclose a specific gravity analyzer for controlling an alkylation process. The Brandel system continuously measures the specific gravity of the acid catalyst. Volatile organic compounds (VOCs) are stripped by heating the sample stream and using a differential pumping system. The specific gravity is then measured by a strain gauge 58 that monitors the buoyant force on a "displacemeter" 56 (i.e., a weight) immersed in the sample (column 5, lines 46-55). The Brandel system is designed for continuous operation by maintaining a continuous sample stream through the cavity 52 containing the displacemeter 56. However, nothing in Brandel suggests taking a series of density measurements over time from the same sample as VOCs escape.
The Mayer patents disclose a method of continuously controlling the water content of sulfuric acid used as a catalyst in an alkylation process. The catalyst is contacted with fuming sulfuric acid of known concentration at a sufficient flow rate to maintain the mixture at the point of incipient fuming. A SO 3 detector monitors the presence of SO 3 and controls the rate of fresh acid makeup by comparing the flowrates of SO 3 and the sample acid. This system requires a costly source of SO 3 of known concentration and large quantities of sample acid.
3. Solution to the Problem
None of the prior art references uncovered in the search measure acid concentration in an alkylation process by taking a series of sound velocity measurements over time for a single sample as VOCs escape and the sample stratifies. In the preferred embodiment, the velocity of sound through the sample is measured and a partial vacuum is drawn to accelerate dissipation of light VOCs over time. The time series of readings is normalized for temperature. A predetermined function using coefficients determined by statistical regression is then applied to the time series of readings to compute acid concentration. This system allows the acid concentration to be quickly determined with a high degree of accuracy, regardless of sample's VOC contents. A number of these systems can be used to monitor the acid concentration for each stage of the alkylation process to closely regulate the acid feed Fate for optimum efficiency.
SUMMARY OF THE INVENTION
This invention provides a system for measuring acid concentration in an alkylation process by making repeated measurements of the sound velocity through a sample over time as volatile organic compounds (VOCs) are allowed to escape and the sample stratifies. A partial vacuum can be used to accelerate dissipation of VOCs from the sample. A computer or micro processor applies a predetermined function to a series of these sound velocity measurements to compute the acid concentration in the sample. The function can be determined by regression against sound velocity measurements taken from samples having known acid concentrations. The system can be used either to generate a read-out to facilitate manual control of the alkylation process, or to automatically regulate the acid feed rate to maintain a desired acid concentration.
A primary object of the present invention is to provide a system for quickly and accurately determining acid concentration in an alkylation process.
Another object of the present invention is to provide a system for accurately monitoring acid concentration to minimize use of acid in an alkylation process, and thereby reduce operating costs and environmental concerns.
Yet another object of the present invention is to provide a system for accurately controlling operation of an alkylation plant to minimize down time.
These and other advantages, features, and objects of the present invention will be more readily understood in view of the following detailed description and the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention can be more readily understood in conjunction with the accompanying drawings, in which:
FIG. 1 is a simplified block diagram of an alkylation plant using the present invention to regulate the feed rate of acid into each contactor.
FIG. 2 is a simplified cross-sectional view of the monitor cell 20 used to hold a sample 21 of the acid catalyst.
FIG. 3 is a graph showing the velocity of sound in clean sulfuric acid as a function of temperature and concentration.
FIG. 4 is a graph showing the velocity of sound in the acid catalyst as a function of concentration and time as VOCs escape from the acid catalyst.
DETAILED DESCRIPTION OF THE INVENTION
Turning to FIG. 1, a schematic diagram is provided showing a four-stage alkylation plant that has been retrofitted with acid concentration monitoring systems 31, 32, 33, and 34, each embodying the present invention. As previously discussed, isobutane butene, and the acid catalyst are combined in a first contactor 10 and the resulting products are then drawn into a settler 11 where the high octane products are separated and withdrawn from the process. The first monitor 31 measures the acid concentration in the first settler 11.
In the second stage of the process, acid from the first settler 11 is fed into a second contactor 12 and mixed with additional isobutane and butene. The resulting products are drawn into the second settler 13 where the octane is separated and withdrawn. The second monitor 32 measures the acid concentration in the second settler 13. This sequence is repeated in the third and fourth stages by processing the acid and additional amounts of isobutane and butene through a third contactor 14 and third settler 15, and then through a fourth contactor 16 and fourth settler 17. The acid concentration in the third settler 15 is measured by the third monitor 33, and the acid concentration in the fourth settler 17 is measured by the fourth monitor 34.
FIG. 2 illustrates the acid concentration monitor. A monitor cell 20 is used to hold a sample 21 drawn from the acid phase contained in the settler. The sample 21 flows into the cell 20 through an inlet port 22 and inlet valve 23. The maximum fluid level of the sample 21 in the cell 20 is fixed by an overflow port 24. After the cell has been filled, the inlet valve 23 and overflow valve 25 are both closed and a partial vacuum is drawn through the vacuum port 26 for a period of time to accelerate dissipation of the VOCs from the sample 21. After a period of time, the vacuum is removed by venting the cell through vacuum port 26.
Two sonic transducers 27 and 28 located on opposing sides of the lower portion of the cell 20 are used to transmit and receive sonic pulses through the sample. In the preferred embodiment, both are piezoelectric transducers that can be used interchangeably to transmit and receive. An input voltage causes the transmitting transducer to generate a pulse, which is received by the other transducer, which generates an output voltage pulse. The delay between the input voltage and the resulting output voltage pulse is timed to determine the velocity of sound through the sample 21.
A computer processor 29 controls the sonic transducers 27, 28. After the monitor cell 20 has been filled with a sample 21, the processor 29 uses the sonic transducers 27, 28 to repeatedly measure the velocity of sound through the sample 21. In the preferred embodiment, these sound velocity measurements begin shortly after the sample 21 is drawn into the cell 20, continue through the period while the vacuum is on, and then continue for a fixed time thereafter (e.g., 10 to 30 minutes). After the sound velocity measurements have been made, the processor 29 controls the inlet valve 23 and overflow valve 25 to open and thereby allow the sample 21 to drain from the cell 20 through the inlet port 22.
A temperature sensor 30 (e.g., an RTD) is inserted into the cell 20 to measure the temperature of the sample 21. FIG. 3 is a graph showing the typical velocity of sound in clean sulfuric acid as a function of acid concentration and temperature. Note that the extreme right-hand region of the curves is approximately linear for acid concentrations of 85% to 100%, which greatly simplifies temperature normalization within the range of acid concentrations of interest. The processor 29 is programmed to normalize the sound velocity measurements for variations in the temperature measured by the temperature sensor 30.
FIG. 4 is a graph showing typical normalized sound velocities over time as a function of acid concentration. The curves in FIG. 4 include a distinctive initial dip as vacuum is applied. The curves show that sound velocity gradually rises as time passes after the initial dip. Sound velocity is proportional to the square root of bulk modulus divided by density. Stratification gradually causes density and bulk modulus changes in the sample 21, specifically at the measured point between the sonic transducers 27 and 28, thereby changing the measured sound velocity. By locating the measurement point at the bottom of the cell 20 and using a measurement method that is essentially a point measurement with respect to vertical displacement in the cell 20, the resolution of the measurement is maximized. Placing the sonic transducers 27, 28 at a different vertical position on the cell 20 would result in a different curve shape. For example, placing the sonic transducers 27, 28 across the upper portion of the sample 21 would result in a decreasing sound velocity curve. Sound velocity measurements could also be made with the sonic transducers 27, 28 located across the lower portion of the cell 20 as the sample 21 drains from the cell 20. This would extend the curves shown in FIG. 4 further to the right. These curves should gradually decrease as the upper portions of the sample 21 pass between the sonic transducers 27, 28 as the cell 20 drains.
The processor 29 is also programmed to apply a predetermined function to a series of the normalized sound velocity measurements to calculate the acid concentration in the sample 21. In the preferred embodiment, this function has the following form:
Concentration=C.sub.0 +C.sub.1 V.sub.Final +C.sub.2 V.sub.Initial +C.sub.3 V.sub.Min
with the coefficients (C 0 through C 3 ) being determined by linear regression against the initial sound velocity (V Initial ), minimum sound velocity (V Min ), and final sound velocity (V Final ) using the normalized sound velocity curves illustrated in FIG. 4. For example, linear regression using the data shown in FIG. 4 results in the following coefficients:
C.sub.0 =1657.083
C.sub.1 ==2.25644
C.sub.2 =0.017772
C.sub.3 =0.000799
In the preferred embodiment, the processor 29 uses the sonic transducers 27, 28 to measure the initial sound velocity (V Initial ) shortly after the sample 21 is drawn into the cell 20. The processor 29 repeatedly measures the sound velocity during the period while the vacuum is on, and calculates the minimum sound velocity (V Min ) encountered during this period. A fixed time (e.g., 10 to 30 minutes) is allowed to elapse after the vacuum is turned off before the processor 29 measures the final sound velocity (V Final ). These sound velocities are normalized by the processor 29 to compensate for temperature variations and are used as input variables in the function discussed above.
It should be expressly understood that other equivalent statistical methodologies could be used in place of linear correlation. For example, coefficients can be determined by non-linear regression. The initial, final, and minimum sound velocities are used as the input variables in the preferred embodiment because empirical studies indicate that this is sufficient for highly accurate measurements of acid concentration. However, other alternatives exist to using these three sound velocity measurements. A regression could be performed using an extended time series of measurements, logarithmic fits, or a series of measurements could be integrated over time to provide an alternative input variable.
Other types of instruments can be employed to produce related measurements, particularly since sound velocity and density are related as previously mentioned. For example, a densitometer can be used to directly measure changes in the density of the sample over time. A viscometer would also provide an indirect measurement of density.
Returning to FIG. 1, it should be noted that the acid concentration monitors 31-34 can be used to adjust control valves 41, 42, 43, and 44 regulating the feed rate of acid into each of the contactors 10, 12, 14, and 16. The embodiment shown allows direct control of all four stages of the alkylation plant. Each monitor cell 31-34 adjusts its control valve to maintain a desired acid concentration set point for its stage of the alkylation plant. It should be understood that this configuration could be simplified by using a single acid concentration monitor cell to control only the last stage of the alkylation plant, or two monitors could be used to control the first and last stages, respectively. The acid concentration monitors 31-34 can also provide a visual display to allow a human operator to manually control the acid feed rate.
The above disclosure sets forth a number of embodiments of the present invention. Other arrangements or embodiments, not precisely set forth, could be practiced under the teachings of the present invention and as set forth in the following claims.
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A system for measuring acid concentration in an alkylation process by repeatedly measuring the density, viscosity or velocity of sound through a sample over time as volatile organic compounds (VOCs) are allowed to escape and the sample stratifies. A partial vacuum can be used to accelerate dissipation of light VOCs from the sample. A processor applies a predetermined function to a series of these sound velocity measurements to compute the acid concentration in the sample. The function can be determined by statistical regression against sound velocity measurements taken from samples having known acid concentrations. The system can be used either to generate a read-out to facilitate manual control of the alkylation process, or to automatically regulate the acid feed rate to maintain a desired acid concentration.
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FIELD OF THE INVENTION
This invention relates generally to electronic engine control systems. More particularly the invention relates to an electronic engine control system that develops and utilizes a data signal representative of net output torque being produced by a running engine. The invention is especially useful in the operation of internal combustion engines, such as diesel engines, that power vehicles, such medium and heavy trucks.
BACKGROUND AND SUMMARY OF THE INVENTION
The ability of an internal combustion engine to perform in a desired manner may at times depend on its ability to meet certain torque demands. It is known that the torque output of a representative internal combustion engine is speed-dependent over the range of speeds that the engine can develop. A general way to characterize performance of a particular engine model is by graph plots of torque vs. speed and horsepower vs. speed.
While a particular engine model may be representatively described by representative graph plots like those just mentioned, the mass-production usage of such an engine model will yield a universe of actual engines for any one of which actual graph plots like those just mentioned may depart from the representative ones. It is believed that engine and vehicle performance can be improved by utilizing data signals from the actual engine and vehicle to develop an engine net output torque data signal representing the input torque to the vehicle's drivetrain for propelling the vehicle.
The invention endows an electronic engine control system with an ability to develop a data signal that accurately represents engine net output torque produced by a running engine. It is believed that such a signal can be used to improve engine and vehicle performance. For example, an engine net output torque data signal may be used to provide better definition for transmission shift points, particularly automatic transmission shift points. Such a signal may also be a useful input to a vehicle traction control system. It may also serve as a useful diagnostic or maintenance tool.
The present invention relates to an electronic control system for an engine in which the electronic system develops an accurate engine net output torque data signal, based on the actual engine itself, recognizing, and taking into account, a number of various factors that may be different from engine to engine in mass-produced engines. It is believed that at least some of these factors may heretofore not have been perceived as significant in enabling engine and vehicle improvements to be attained.
One general aspect of the invention relates to an electronic control for a combustion engine that forms a portion of an automotive vehicle powertrain and has an output shaft for powering a drivetrain portion of the powertrain to propel the vehicle, the control comprising: at least one ambient parameter variable input source representing a respective ambient parameter useful in deriving gross torque output of the combustion engine; at least one operating variable input source representing a respective operating parameter useful in deriving a reduction in gross torque output of the combustion engine due to operation of the combustion engine; and a processor for processing a respective signal correlated to the at least one ambient parameter variable input source and for processing a respective signal correlated to the at least one operating parameter variable input source to derive torque at the output shaft of the engine for powering the drivetrain to propel the vehicle.
Another general aspect relates to an automotive vehicle comprising: a powertrain that includes a combustion engine having an output shaft powering a drivetrain to propel the vehicle; at least one ambient parameter variable input source representing a respective ambient parameter useful in deriving gross torque output of the combustion engine; at least one operating variable input source representing a respective operating parameter useful in deriving a reduction in gross torque output of the combustion engine due to operation of the combustion engine; a processor for processing a respective signal correlated to the at least one ambient parameter variable input source and for processing a respective signal correlated to the at least one operating parameter variable input source to derive torque at the output shaft of the engine for powering the drivetrain to propel the vehicle; and a utilization device in the drivetrain whose operation is controlled at least at times by the derived torque.
Still another general aspect relates to a method in a control for a combustion engine that forms a portion of an automotive vehicle powertrain and has an output shaft for powering a drivetrain portion of the powertrain to propel the vehicle, the method comprising: measuring at least one ambient parameter variable input representing a respective ambient parameter useful in deriving gross torque output of the combustion engine; measuring at least one operating variable input source representing a respective operating parameter useful in deriving a reduction in gross torque output of the combustion engine due to operation of the combustion engine; and deriving torque at the output shaft of the engine for powering the drivetrain to propel the vehicle by processing a respective signal correlated to the at least one ambient parameter variable input source and processing a respective signal correlated to the at least one operating parameter variable input source.
The foregoing, along with further aspects, features, and advantages of the invention, will be seen in this disclosure of a presently preferred embodiment of the invention depicting the best mode contemplated at this time for carrying out the invention. This specification includes drawings, now briefly described, followed by detailed description that will make reference to these drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevation view of an engine-powered vehicle having an electronic engine control system embodying principles of the present invention.
FIG. 2 is a general schematic hardware diagram of the electronic engine control system, including further detail related to the present invention.
FIGS. 3A and 3B is a general schematic software diagram embodying principles of the present invention implementing engine net output torque calculation in the electronic engine control system.
DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 illustrates an automotive vehicle 10, a medium or heavy truck for example, having a chassis containing a powertrain that includes an internal combustion engine 12, herein described as a diesel engine. Engine 12 has a crankshaft including a flywheel at which the engine develops engine net output torque for a drivetrain through which engine 12 propels the vehicle. The engine flywheel is operatively coupled to a multi-gear transmission 16, either through a clutch 14 in the case of a manually shifted transmission or through a torque converted in the case of an automatic transmission. The transmission is coupled by a driveshaft 17 to driven wheels of a rear axle assembly 19. The engine net output torque for propelling truck 10 is applied from the engine flywheel as an input to the clutch in the case of a manual transmission, and to the torque converter in the case of an automatic.
Engine 12 is a fuel-injected diesel engine having individual fuel injectors that inject diesel fuel into the engine cylinders in properly timed relation to engine operation. An electronic engine control 18 that includes a microprocessor 20 is associated with engine 12 and schematically shown in FIG. 2. Control 18 utilizes various input data signal sources. Microprocessor 20 processes certain data signals in accordance with programmed algorithms to develop certain signals used in the performance of various functions associated with operation of engine 12 and truck 10. The signals processed by microprocessor 20 may be ones that originate at external sources (input variables) and/or signals that are generated internally by microprocessor 20 (local variables). Although microprocessor 20 is a hardware item, the reader should recognize that FIG. 2 is not intended to depict particular internal hardware architecture; hence the Figure shows several instances of signal processing ahead of processing that is designated as a torque calculator.
One of the many functions performed by engine control 18 is to control the timing of the fuel injections by issuing injection control signals that control the opening and closing of the fuel injectors. Control 18 develops these control signals by monitoring various input data signals and processing them in accordance with algorithms programmed in microprocessor 20.
One or more accessory devices may be powered by engine 12. FIG. 1 shows an engine fan 22 mounted at the front of engine 12 for drawing air through a radiator 24 of a cooling system for the engine. Engine 12 may have a pulley at the front of its crankshaft that is operatively coupled with fan 22 through a selectively engageable and disengageable fan drive 26. Fan drive 26 may comprises a solenoid-operated clutch that is under the control of engine control 18. When the clutch solenoid is energized, the clutch is engaged to place the fan in driven relationship to the engine crankshaft; when the clutch is not energized, the clutch is disengaged, placing the fan in non-driven relationship to the crankshaft. The engine control monitors various data signals to determine when fan drive 26 should be engaged and disengaged.
FIG. 1 shows a second accessory 28, namely an air-conditioning compressor, mounted near the front of engine 12 for cooling the interior of a driver's cab 30 of truck 10. The engine crankshaft is operatively coupled with compressor 28 through a selectively engageable and disengageable compressor clutch 32. Clutch 32 is solenoid-operated. When its solenoid is energized, clutch 32 is engaged to place compressor 28 in driven relationship to the engine crankshaft; when the solenoid is not energized, clutch 32 is disengaged, placing the compressor in non-driven relationship to the crankshaft. Clutch 32 is under the control of an air conditioning system for cab 30.
FIG. 2 shows a number of data signal inputs (representing input variables) to control 18. An EOT source provides a data signal that represents engine oil temperature; such a source may be a remote temperature sensor and some signal processing may occur before the torque calculator acts on the engine oil temperature. The engine oil temperature is used as an indication of engine operating temperature. A BAP source provides a data signal that represents barometric absolute pressure; such a source may be a remote barometric pressure sensor and some signal processing may occur before the torque calculator acts on barometric absolute pressure. An AIT source provides a data signal that represents air inlet temperature, which may be substantially ambient air temperature; such a source may be a remote temperature sensor and some signal processing may occur before the torque calculator acts on the air inlet temperature. An MGP source provides a data signal that represents engine boost pressure; such a source may be a remote manifold absolute pressure (MAP) sensor sensing intake manifold absolute pressure and some signal processing may occur before the torque calculator acts on the engine boost pressure.
The torque calculator also utilizes engine speed (rpm) as an input, represented by a signal N, which may be developed through processing crank angle signals from a corresponding sensor. An EFC signal is a binary logic signal indicating whether fan 22 is engaged with, or disengaged from, the engine crankshaft. An ACD signal is a binary logic signal indicating whether compressor 28 is engaged with, or disengaged from, the crankshaft. An MFDES signal represents fuel mass being injected into engine 12. Although the pulse widths of fuel injection command signals for pulsing the engine fuel injectors to cause fuel injections are representative of injected fuel masses, each pulse width by itself is a volume measurement and must be compensated for temperature before it can provide a true mass measurement of injected fuel. As will be more fully explained later, a DIT -- CRPWR signal and a DIT -- TCT -- COMP signal are derived from the occurrence of certain vehicle operating conditions that are attended by certain changes, actual or incipient, in engine speed; they utilize crankshaft position-based timing as a source. An ENG -- LD -- PCT signal represents actual engine load as a percentage of maximum engine load.
Microprocessor 20 processes these signals in accordance with FIGS. 3A and 3B to develop the signals ATA -- AE -- TRQ and CAN -- AE -- TRQ, which represent the value of present net engine output torque, and are broadcast over both an ATA data link and a CAN data link. In order to adapt microprocessor 20 for the particular engine model, data related to the engine model is programmed into the microprocessor through a CAN parameter messages port. The signal CAN -- REFENG -- TRQ represents a reference torque that is particular to that engine. The programming of engine model data for the particular engine may serve to program one or more of various function generators and/or look-up tables.
In order for the signals EOT, BAP, AIT, and MGP to be considered valid for processing by microprocessor 20, the value of each must lie within a respective predetermined range. Whenever anyone of these four signals falls outside the respective range, a respective fault flag is set and a respective default value is substituted and processed by microprocessor 20 instead of the actual value from the respective source. In FIG. 3A, the respective reference numerals 100, 102, 104, 106 indicate this screening of each of these four source signals. An actual EOT, BAP, AIT, or MGP signal is deemed valid, and therefore utilized in the engine net output torque calculation, only if it falls with a valid range for the respective signal. A respective "out of range high" signal, such as EOT -- F -- ORH in the case of signal EOT, and a respective "out of range low" signal, such as EOT -- F -- ORL, define the limits of each valid range. If a source, such as the EOT source, has a value outside its valid range, it is deemed invalid, in which case a default value signal, such as EOT -- TQ -- DEF in the case of signal EOT, is utilized for the engine net output torque calculation.
After screening, and any consequent substitution of a default value, each of the four signals forms an input for a respective function generator, or look-up table, FN020, FN021, FN022, and FN2003(PWR). As shown in FIGS. 3A, the first three of these utilize only a single input while the fourth FN2003(PWR) utilizes the signal N as a second input. Depending on the respective input values, the function generators, or look-up tables, supply respective output signals whose values are functionally related to the input values in accordance with the function generator or look-up table as the case may be.
The input variable signals ENG -- LD -- PCT and N are inputs to a further look-up table, FN2000(PWR), which produces a local variable output signal TQ -- WARM whose value is functionally related to the two input values by the look-up table. The signal TQ -- WARM represents the nominal torque that would be produced by a typical engine of the particular engine model when operating at a nominal temperature that is considered fully warmed up and at nominal values of barometric absolute pressure and air inlet temperature. Look-up table FN2000(PWR) therefore corresponds to a map containing a table of such torque values for corresponding engine speeds over the operating speed range of the engine.
Each of the respective function generators, FN020, FN021, and FN022 compensates the respective source for changes from its nominal value that have an influence on the torque produced by the engine. These compensated signals are TQ -- BAP -- MULT, TQ -- AIT -- MULT, and TQ -- EOT -- MULT.
The reference numerals 110, 112, and 114 designate successive multiplications of signal TQ -- WARM by the respective local variable signals TQ -- AIT -- MULT, TQ -- EOT -- MULT, and TQ -- BAP -- MULT. These local variable signals are therefore in the nature of factors that are applied to nominal torque values generated by look-up table FN2000 at various engine speeds. In this way the torque calculation is compensated by departures of engine temperature, air temperature, and barometric pressure from nominal. The resulting product forms an input to an adder represented by the summing junction symbol 116.
The other signal input to summing junction 116 is the local variable signal TQ -- MGP from look-up table FN2003(PWR). That look-up table relates engine torque to engine boost at each of a number of different speeds spanning the range of engine speeds. The sum of the values of the two local signal inputs to summing junction 116 is designated TQ -- GROSS, and it represents the gross output torque of engine 12.
In order to calculate the engine net output torque, further processing of engine gross output torque is required. Such processing includes the subtraction of accessory torque due to any operation of accessories, such as fan 22 and compressor 32, by engine 12. The respective reference numerals 118, 120 represent processing of data, including accessory operating parameters EFC and ACD, concerning these two accessories.
A respective function generator FN023, FN024 is associated with a respective accessory 22, 32 to correlate the accessory torque to engine speed over a range of engine speeds. If a respective accessory is engaged in driven relationship with the engine crankshaft, the output signal from the respective function generator FN023, FN024 is passed to a summing junction 122. The sum forms a local variable signal TQ -- ACC which is subtracted from the signal TQ -- GROSS at a subtraction junction 124 to yield a signal TQ -- BASE which represents engine base torque. If an accessory is not engaged in driven relationship with engine 12, it does not result in a subtraction from the gross engine torque.
As shown in FIG. 3B, a further correction of the TQ -- BASE signal is performed by an operating condition torque adjustment. This correction is performed using two look-up tables, FN2001(PWR) and FN2002(PWR). The values of two data signals DIT -- CRPWR and DIT -- TCT -- COMP are added together at a summing junction 126, and the result is an input DIT -- ADJ to look-up table FN2001(PWR). Because of the nature of each signal, to be explained below, it is typical that at any given time, at most only one of them is of any consequence insofar as having an effect on the torque calculator.
The other input to look-up table FN2001(PWR) is signal MFDES. The output of look-up table FN2001(PWR) is a signal TQ -- DIT -- ADJ input to look-up table FN2002(PWR). The other input to look-up table FN2002(PWR) is the engine speed signal N. The output of look-up table FN2002(PWR) is a signal TQ -- ADJ -- MULT.
Operating condition torque adjustment takes into account fuel injection timing offsets due to changes occurring as a result of particular operating modes. The signal DIT -- CRPWR represents the effect of the vehicle being operated in cruise control mode where injector timing offsets may occur in order to maintain a set vehicle speed. The signal DIT -- TCT -- COMP represents the effect of transients such as may occur when the vehicle is being throttled down or up in a manner necessitating injector timing offsets. Multiplication of the two signals TQ -- ADJ -- MULT and TQ -- BASE ,as indicated by the reference numeral 128, yields the signal TQ -- NET, which is thereafter properly dimensioned for broadcast on the respective data links ATA and CAN. Dimensioning can provide actual torque in desired units of measurement and/or percentage of reference torque. Microprocessor 20 may operate to perform the torque calculation routine at a rate of 20 hz.
While a presently preferred embodiment of the invention has been illustrated and described, it should be appreciated that principles of the invention are applicable to all embodiments and uses that fall within the scope of the following claims.
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An electronic control (18) for a combustion engine that forms a portion of an automotive vehicle powertrain and has an output shaft for powering a drivetrain portion (14, 16, 17, 19) of the powertrain to propel the vehicle. The control has at least one ambient parameter variable input source representing a respective ambient parameter (EOT, BAP, AIT, and MAP) useful in deriving gross torque output of the combustion engine. The control also has at least one operating variable input source (EFC, ACD, DIT -- ADJ) representing a respective operating parameter useful in deriving a reduction in gross torque output of the combustion engine due to operation of the combustion engine, and a processor for processing a respective signal correlated to the at least one ambient parameter variable input source and for processing a respective signal correlated to the at least one operating parameter variable input source to derive torque at the output shaft of the engine for powering the drivetrain to propel the vehicle.
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FIELD OF THE INVENTION
This invention belongs to the mechanical engineering field, more specifically of the electromechanical devices, commonly known as home appliances, especially applied to washing machines and the like, exactly a washing method and recirculation control associated to a washing machine provided with washing water recirculation with controlled flow.
BACKGROUND OF THE INVENTION
The washing machine is a very popular home appliance used to automatically clean clothes. It uses water as its main element. It basically consists of a reservoir which is filled with water, on which the mechanical system shakes the pieces of clothing to be washed. The contemporary machines are manufactured as two basic models, front loading or top loading. The top loading machines receive the clothes in a vertically mounted cylinder, with a central agitator and a top cover. The front loading machines have a horizontally mounted cylinder, with no central agitators, but with a watertight door and with a sight glass.
Both models have the capacity to automatically wash, propelled by an electric motor, conducting washing, rinsing and centrifugation runs. Currently, the use of electronic components replaces complex mechanical systems previously used to control the washing. They control, for example, the water level, one of the main functionalities of washing machines in the current art.
The control by means of electromechanical pressostates, which are devices used to perceive pressures or pressure differences and which, in the case of washing machines, can be translated by differences in the liquids level, is conducted by reading the level indicated by the pressure generated by a water column, which forces a diaphragm, thus activating an electric contact in a single determined point, with the disadvantage of not being able to identify the manometric height and present a continuous reading.
In its turn, the electronic pressostate forwards point-to-point information on the water column height by means of a transducer which varies the output voltage or current according to the pressure applied in the input, allowing a more precise control, admitting, in the most modern machines, the water input control.
The water level control in washing machines is also widely diffused, defining the water volume to be used in washing, upon the user's choice or a previously defined configuration for the equipment, based on a sensor, which is commonly the pressostate, which receives the pressure exerted by the water volume.
Another important event, besides the level control, among the other functionalities introduced in washing machines is recirculation.
Water recirculation is a common feature in washing machines, which is generally intended to homogenize cleaning agents and water, besides increasing the washing efficiency and collecting lints which are released from the clothes and which may affect the equipment performance. In addition, it can minimize the amount of water used for washing through water circulation optimization inside the equipment in certain steps of the washing run.
In order to improve water recirculation during the washing process, perforated baskets were developed, for which the number and size of the holes are dimensioned in order to decrease the total drainage area, thus decreasing the liquid flow from the basket to the tub, causing a delay in the process of balancing the manometric heights upon water recirculation, allowing the accumulation of a decreased amount of liquid in the tub, enabling a lower total water volume to be used in the washing process.
Despite of the recirculation advent, problems related to this functionality can be found as, for example, the excess of foam and high noise level. These problems are generated by air-water mixture, caused by the lack of water input flow control in the basket compared with the output flow from the basket to the tub, in addition to causing a non-uniform flow of the input of liquids into the basket. Without control, water drainage is not uniform when air and water are mixed in the bottom of the tank. This flow range can be significantly decrease when a controllable pump is used.
Currently, due to the mixture of air and water which occurs when the washing machine tub is empty, the use of common detergent generates a lot of foam, thus preventing a complete washing with this type of product from occurring.
Canadian Patent 1112889, according to FIG. 10, describes a washing machine which recirculates water or rinsing water. Its recirculation water input is intended to fully empty the tub, thus generating foam and noise during its operation. The remaining liquid is located in a recess of the tub, forming a pool, in order to prevent the pressostate from indicating that the tub is empty.
Document WO053042, according to FIG. 8, shows a washing machine provided with water recirculation, with the objective to empty the tub during recirculation, however, due to the lack of pump control, it does not maintain a minimum liquid level, producing foam and noise.
Document EP1783264, according to FIG. 9, reports a washing machine equipped with recirculation and a variable speed pump, however, the water level between the tub and the basket remains the same and does not save water
Invention ES8604326 in the public domain, describes the recirculation process, very common in a washing machine, with recirculation controlled by two pressostates and level control elements calibrated for higher and lower level.
Document EP0278461 in public domain, describes the discharge and recirculation flow control process of washing machines based on two pressure sensors adapted to determine the minimum and maximum liquid levels present in the referred machine.
SUMMARY DESCRIPTION
This disclosure describes a washing machine provided with recirculation with controlled flow. It further presents a washing liquid level control method, associated with the referred machine, providing economy of resources such as water and cleaning products, guaranteeing an effective washing of clothing and similar articles, associated with lower foam formation and generation of noise during the washing process, thus improving the operation of the equipment, besides having the other recirculation and level control functionalities comprised in the current state of the art. Thus, it is evident that all these characteristics make the product free from the inconveniences found in the current state of the art, as previously mentioned.
It has a pool, consisting an a small internal reservoir formed by a recess in the tub, which guarantees the maintenance of a minimum liquid level by a recirculation pump flow control, thus avoiding the formation of foam by the air-water mixture in the mentioned pump, and as a result, reducing the level of noise during the operation.
The present disclosure provides an objective to present a method and a washing machine with the function of recirculating liquids from the bottom of the tub to the upper part of the basket which contains the clothes to be washed, in order to use a lower amount of water and increase the efficiency of the washing process, associated with an innovative method to adjust the washing and rinsing liquid level in the washing tub during the washing of clothing and similar articles, also allowing to minimize the noise and generation of foam.
The controlled recirculation described herein is an evolution of the existing techniques. In this concept, instead of using a two-state pump (turned-off or nominal speed), the disclosure proposes a pump working method intended to vary its speed and, consequently, its flow.
An aspect of the disclosure is to present a control intended to improve the recirculation concept, besides magnifying its application.
The use of a controllable pump and of a level reader allows the development of a method which is able to close a control loop on which it is possible to adjust a flow so that the system contains a small amount of water in the bottom of the machine; however, an amount which is large enough to prevent the mixture of air with water from occurring in the pump. This decreases the amount of generated foam, allowing the user to use common detergent.
In addition, considering that the traditional drainage pumps produce a lot of noise being at nominal speed and with little water in the bottom of the tank, the use of the machine and the proposed method allows decreased noise through minimizing the water-air mixture.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1 to 6 describe, schematically, sequentially, a washing process considering the proposed recirculation system.
FIG. 1 reveals a schematic view of the tub filling step with the washing liquid, where it can be noted the position of the washing basket ( 3 ) in relation to the washing tub ( 2 ), as well as the recirculation ( 9 ) and drainage ( 8 ) hoses, the pool ( 6 ) and the pump ( 7 ).
FIG. 2 shows a schematic view of the beginning of the washing liquid recirculation process step, where it can be noted, then, the difference of water level between the basket ( 3 ) and the tub ( 2 ) caused by the difference of input and output flow of water of the basket ( 3 ), being the washing water collected in the pool ( 6 ) and impelled by the pump ( 7 ) through the recirculation hose ( 9 ).
FIG. 3 depicts a schematic view of the washing step, consisting in the agitation of the clothes in a wash environment, i.e., the basket ( 3 ) completed with water in recirculation regimen from the pumping of the liquid collected in the pool ( 6 ) through the recirculation hose ( 9 ) using the pump ( 7 ).
FIG. 4 shows a schematic view of the washing water drainage step, where the liquid contained in the basket ( 3 ) is drained, flowing through the tub ( 2 ), being collected in the pool ( 6 ) and pumped by the pump ( 7 ) through the drainage hose ( 8 ).
FIG. 5 shows a schematic view of the centrifugation step, where the washing liquid contained in the basket ( 3 ) is drained, flowing through the tub ( 2 ), being collected in the pool ( 6 ) and pumped by the pump ( 7 ) through the drainage hose ( 8 ).
FIG. 6 reveals a schematic view of the complete washing process termination step with the basket ( 3 ) and the tub ( 2 ) being emptied, with a small amount of water remaining in the pool ( 6 ).
FIG. 7A shows an upper schematic view of the tub ( 2 ) highlighting the position of the pool ( 6 ) in relation to the referred tub ( 2 ).
FIG. 7 shows a sectional view of the disposition of the proposed recirculation system, evidencing the level sensor ( 5 ) in the pool ( 6 ) and the basket ( 3 ) with a reduced number of holes ( 4 ) inserted in the tub ( 2 ), being the liquid recirculated from the pool ( 6 ) upon the impulse generated by the pump ( 7 ) through the recirculation hose ( 9 ).
FIG. 8 shows a sectional view of another recirculation system described in the art, where it is noted the liquid being recirculated ( 8 ) directly from the tub ( 2 ) to the basket ( 3 ), further having a level sensor ( 5 a ), a pump ( 7 ) for recirculation and a reservoir ( 6 a ).
FIG. 9 reveals a sectional view of traditional recirculation systems described in the art, on which the basket ( 3 ) perforated throughout it side surface and the pressostate ( 5 ) present in the tub ( 2 ), with the pump ( 7 ) collecting the liquid in a reservoir ( 6 a ).
FIG. 10 depicts a sectional view of an alternative recirculation system described in the art, where it is noted the liquid being recirculated from the tub ( 2 ) to the basket ( 3 ) by means of a pump ( 7 ) through a duct ( 1 ) without maintaining a minimum level.
FIG. 11 shows a block diagram of the washing water level control logic.
FIG. 12 shows a side perspective view of a basket ( 3 ) perforated throughout its entire side surface, commonly used in the current art.
FIG. 13 reveals a side perspective view of the perforated basket ( 3 ) of the proposed solution, evidencing the decrease in number and size of the holes ( 4 ).
DETAILED DESCRIPTION
This invention comprises a washing machine having a recirculation and a washing liquid level control method.
The referred machine, according to FIG. 7 , basically comprises a washing tub ( 2 ) equipped with a pool ( 6 ), perforated basket ( 3 ), two-way pump ( 7 ), level sensor ( 5 ), recirculation hose ( 9 ), drainage hose ( 8 ) and control circuit (not shown).
For the operation of the washing machine, the level sensor ( 5 ) reads the water column height in the tub ( 2 ), sends this information to the control circuit which processes the information and sends a signal to the two-way pump motor ( 7 ) so that it operates in the recirculation direction and ranges its speed, thus changing the water flow in order to maintain a minimum liquid level in the tub's ( 2 ) pool ( 6 ) in order to avoid cavitations in the pump ( 7 ) thus making the process less noisy and with decreased foam formation.
To better understand the invention shown here, the analysis of the attached figures is required. FIG. 1 shows the initial process specifically proposed in the water filling step of the machine. After filling, according to a pre-programming of the control panel, it is noted that the manometric heights in the tub ( 2 ) and in the basket ( 3 ) are equal.
FIG. 2 shows the beginning of the washing and recirculation process, without the mechanical action of the agitator, in a preferred configuration. In this step, the manometric heights between the basket ( 3 ) and the tub ( 2 ) are different and the process consists in emptying the tub ( 2 ) and filling the basket ( 3 ) up to a programmed level (according to the program parameters), through the pump ( 7 ) in its water recirculation function. In this phase, the pump flow ( 7 ) is higher than the water flowing from the basket ( 3 ) to the tub ( 2 ).
During the entire process, the water level is monitored by the electronic circuit by means of signals originated by the level sensor ( 5 ).
Once the programmed washing level is reached, the washing operation is started with the mechanical movement of the agitation elements (agitator, propeller or basket ( 3 )). In this step, the objective is to maintain the highest liquid level inside the perforated basket ( 3 ) and the lowest level inside the tub ( 2 ), without allowing the pool ( 6 ) from being empty, as it can be noted in FIG. 3 . It is noted that there is a liquid flow from the basket ( 3 ) to the tub ( 2 ) via lower holes located in the basket ( 3 ). By this time, the basket ( 3 ) flow is equal to the recirculation flow. Thus, the accumulation of a lower amount of liquid is allowed in the tub ( 2 ), enabling the washing machine to operate with a lower total volume of water for the washing process.
Following the washing step, the drainage step is started according to FIG. 4 ; in this phase the pump ( 7 ) changes the direction of rotation so as to pump water to the drainage hose ( 8 ) for discard. In an alternative mode, this process can be performed by a second pump, while a main pump is only used for recirculation. Another possibility is the use of a directing valve selectively fluidly coupling the single pump with the one input and two outputs.
Following the drainage step (which does not necessarily imply the basket being completely empty), centrifugation is started, as shown in FIG. 5 . In this step, it is noted the total emptying of the basket ( 3 ) by the action of the centrifugal force caused by the high speed rotation of the basket ( 3 ), being complemented by the pump ( 7 ) action to discard the excess of liquid. FIG. 6 shows the machine condition when the cycle is terminated.
FIG. 7 schematically illustrates a preferred mode of the washing machine provided with recirculation with controlled flow. It is noted in the lower portion of the tub ( 2 ) a pool ( 6 ) which is responsible for guaranteeing a minimum liquid level for the correct operation of the proposed method. The pool ( 6 ) (i.e., a sub-reservoir) is formed by a recess in a small bottom portion of the tub ( 2 ), and is better viewed in detail in FIG. 7A . The machine further has a level sensor ( 5 ) which reads the water level contained in the pool ( 6 ) and sends the information to the electronic circuit (not shown) which commands the machine functions. The solution further includes a pump ( 7 ) with an input and two outputs, responsible for draining and recirculating the washing liquid. The proposed machine still includes a basket ( 3 ), a recirculation hose ( 9 ) and a drainage hose ( 8 ). The basket ( 3 ), shown in FIG. 13 , contains a smaller amount of holes ( 4 ) in order to present a lower flow compared with a traditional basket, as shown in FIG. 12 .
The proposed method uses a closed loop system as described in FIG. 11 , which continuously monitors of the liquid level in the tub ( 2 ). The control system acts on the pump ( 7 ) according to the liquid level reading in the tub ( 2 ). The action is performed as the pump ( 7 ) rotor speed changes.
Despite of the internal oscillations occurring during washing (agitation, for example), the method is sufficiently precise to work in order to absorb such variations.
The present invention further minimizes the water flow variations from the recirculation hose ( 9 ) to the basket ( 3 ) input due to the slight attenuation of the control method, once it allows a more uniform flow of liquid.
This invention is not limited to the representations commented or illustrated here, and should be understood in its wide scope. A number of changes and other representations of the invention will come to mind of those skilled in the art, with the benefit of the teaching presented in the previous descriptions and attached drawings. In addition, it should be understood that the invention is not limited to the specific disclosed form, and that change and other forms are understood as included within the scope of the attached claims. Although specific terms are used herein, they are used only as a generic and descriptive form and should not be construed as limiting.
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A washing machine provided with recirculation with controlled flow. It further presents a method to control the level of the washing liquid, associated to the said machine, providing economy of resources such as water and cleaning products, guaranteeing an effective washing of clothes and similar articles, still associated with a decreases foam formation and lower nose emissions during the process, thus improving the operation of the equipment. The washing machine is provided with a washing tub ( 2 ), a basket ( 3 ), a two-way pump ( 7 ), level sensor ( 5 ), pool ( 6 ), recirculation hose ( 9 ), drainage hose ( 8 ) and control circuit.
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BACKGROUND OF THE INVENTION
The present invention relates to bar code readers and more specifically to a bar code scanner with laser beam oscillator.
Bar code readers are well known for their usefulness in retail checkout and inventory control. They are typically connected to a point-of-sale (POS) terminal, along with other peripherals.
Typical bar code scanners generally have very good throughput on easy to read bar code labels. What separates the exceptional scanners is the ability to read difficult bar code labels such as small, poorly printed, low contrast, wrinkled, Reduced Space Symbology (RSS), and two-dimensional (2D) bar code labels. Because most scanners have a distinct, stationary scan pattern with a finite number of scan lines, the probability of the lines locating and reading these difficult bar code labels may be quite low. Furthermore, a raster scan pattern is required to be able to read the new 2D bar code labels.
Therefore, it would be desirable to provide a bar code scanner that is capable of reading a wide variety of bar code labels.
SUMMARY OF THE INVENTION
In accordance with the teachings of the present invention, a bar code scanner with laser beam oscillator is provided.
The bar code scanner includes a laser for producing a laser beam, a mirrored spinner, and a laser beam oscillator optically located between the laser and the mirrored spinner for continuously deflecting the laser beam about an undeflected path of the laser beam.
It is accordingly an object of the present invention to provide a bar code scanner with laser beam oscillator.
It is another object of the present invention to provide a bar code scanner capable of reading a wide variety of bar code labels, including small, poorly printed, low contrast, wrinkled, Reduced Space Symbology (RSS), and two-dimensional (2D) barcode bar code labels.
BRIEF DESCRIPTION OF THE DRAWINGS
Additional benefits and advantages of the present invention will become apparent to those skilled in the art to which this invention relates from the subsequent description of the preferred embodiments and the appended claims, taken in conjunction with the accompanying drawings, in which:
FIG. 1 is a block diagram of a bar code scanner;
FIG. 2 is a block diagram of a laser beam oscillator;
FIG. 3 is a diagrammatic view of the bar code scanner illustrating operation of the laser beam oscillator;
FIG. 4 is a diagrammatic view of an alternative oscillator for the laser beam oscillator;
FIGS. 5A–5D are diagrammatic views illustrating operation of various types of laser beam oscillating elements; and
FIGS. 6A and 6B illustrate the difference between a stationary scan pattern and a scan pattern having a laser beam oscillator.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to FIG. 1 , bar code reader 10 includes laser 12 , laser beam oscillator 14 , spinner 16 , pattern mirrors 18 , collector 20 , and detector 22 .
Laser 12 produces a laser beam. Laser 12 preferably includes a laser diode, and may additionally include a focusing lens or lenses, and a collimating aperture for directing the laser beam along a path from laser 12 .
Laser beam oscillator 14 deflects the laser beam from its undeflected path. Laser beam oscillator 14 continuously varies the angle of the laser beam to generate groups of raster scan patterns containing an infinite number of scan lines about original stationary scan lines. This raster effect causes the scan lines to fill much more of the exit window, making detection and reading of bar code labels easier. This raster effect also allows scanner 10 to read two-dimensional bar code labels. The substantial increase in pattern density allows scanner 10 to read truncated bar code labels and Reduced Space Symbology (RSS) bar code labels.
Advantageously, deflection of the laser beam prior to spinner 16 , as opposed to after spinner 16 , requires much less power, space, and cost, and is more reliable.
Spinner 16 directs the oscillating laser beam to pattern mirrors 18 . Spinner 16 preferably includes planoreflective mirrored surfaces oriented at different angles to produce a plurality of different oscillating scanning beams from the oscillating laser beam. Spinner 16 additionally directs light reflected from item 30 to collector 20 . Spinner 16 is rotated by motor 34 .
Pattern mirrors 18 direct oscillating scanning beams from spinner 16 to create oscillating scan lines for scanning item 30 . Pattern mirrors 18 also direct the light reflected from item 30 to spinner 16 .
Pattern mirrors 18 preferably include a plurality of flat mirrors arranged in different positions and different orientations so as to create a plurality of different oscillating scan lines that scan item 30 from a plurality of different directions.
Collector 20 collects the light reflected from item 30 and directs it to detector 22 . Collector 20 may include a focusing mirror or lens.
Detector 22 converts the light reflected from item 30 into electrical signals.
Processing and decoding circuitry 24 processes the electrical signals, converts the electrical signals to digital signals, and decodes the digital signals to produce bar code information associated with bar code 32 .
Turning now to FIG. 2 , laser beam oscillator 14 includes oscillating element 36 .
Oscillating element 36 rotates, translates, tilts, or otherwise deflects laser beam 60 from laser 12 about an undeflected path 66 to produce a variable scan pattern. Oscillating element 36 may include a window flat, wedge, prism, mirror, piezoelectric device, acousto-optical beam deflector, diffractive beam deflector, or any other optical element that would produce a rotation or linear translation of laser beam 60 about its undeflected path 66 .
Oscillator 38 causes oscillating element 36 to rotate, translate, or tilt. Oscillator 38 may include a motor or propeller driven by windage from spinner 16 . Oscillator 38 may also include a piezoelectric device, a galvanometer, an acousto-optical device, or a voice coil.
With reference to FIG. 3 , an example embodiment of bar code reader 10 is illustrated in more detail.
Oscillating element 36 includes a flat mirror and oscillator 38 includes a motor.
Oscillating element 36 oscillates and reflects laser beam 60 towards spinner 16 . Oscillating element 36 is mounted within aperture 52 of collector 20 .
Pattern mirrors 44 and 48 direct oscillating laser beam 62 along a ray path from spinner 16 through window 50 .
With reference to FIG. 4 , oscillator 38 may include a propeller to eliminate the cost, power consumption, and reliability issues of a second motor. The propeller is driven by windage 74 from spinner 16 . Wall 72 creates a channel which directs windage 74 to airflow tube 70 . Airflow tube 70 directs windage 74 to the propeller. Oscillating element 36 is mounted to the hub of the propeller.
Turning now to FIGS. 5A–5D , operations of various optical elements used as oscillating element 36 are illustrated.
FIG. 5A illustrates a flat refractive window element. This type of optical element produces translation of laser beam 60 through tilting of the refractive window element, and rotation of laser beam 60 through tilting and rotation of the refractive window element.
FIG. 5B illustrates a refractive wedge window element. This type of optical element produces a tilt and rotation of laser beam 60 about the unoscillated beam path 66 through rotation of the refractive wedge window element.
FIG. 5C illustrates a prism element. This type of optical element produces a rotation of laser beam 60 about the unoscillated beam path 66 through rotation of the prism element.
FIG. 5D illustrates a flat mirror element. This type of optical element reflects laser beam 60 to produce a tilt and rotation of laser beam 60 about the unoscillated beam path 66 through rotation of the mirror element.
Turning now to FIGS. 6A and 6B , the difference in area coverage of exit window 50 is illustrated. Area coverage is related to pattern density and ease of detecting and decoding bar code label 32 .
With reference to FIG. 6A , five groups of scan lines 82 – 88 in an example scan pattern each contain four scan lines. The four scan lines are produced by a mirrored spinner 16 having four planoreflective surfaces oriented at different angles.
With reference to FIG. 6B , the scan lines in the same five groups of scan lines 82 – 88 are made to oscillate by laser beam oscillator 14 . Oscillation provides greater scan line coverage. A large enough amplitude can cause oscillating scan lines to overlap, resulting in a dramatic increase in scan line coverage of window 50 . In more complex scan patterns containing many more groups of scan lines, a higher percentage of window 50 may be covered.
Although the invention has been described with particular reference to certain preferred embodiments thereof, variations and modifications of the present invention can be effected within the spirit and scope of the following claims.
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A bar code scanner with laser beam oscillator which rasters a laser beam to produce more scan line coverage. The bar code scanner includes a laser for producing a laser beam, a mirrored spinner, and a laser beam oscillator optically located between the laser and the mirrored spinner for continuously deflecting the laser beam about an undeflected path of the laser beam.
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This application is a US National Stage of International Application No. PCT/CN2012/070176, filed 10 Jan. 2012, designating the United States, and claiming priority to Chinese Patent Application No. 201110003807.7, filed with the State Intellectual Property Office of China on Jan. 10, 2011 and entitled “access control method and device”, which is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
The present invention relates to the field of communications and particularly to an access control method and device.
BACKGROUND OF THE INVENTION
M2M, the abbreviation of Machine to Machine, refers to a type of service for communication between one machine and another. The Internet of Things (IOT) refers to an application of M2M to a wide area network, particularly a mobile operator network, where a radio network of a mobile network operator acts as a platform to offer machine to machine radio data transmission services of industry users through specialized industry User Equipments (UEs) in numerous transmission schemes (Code Division Multiple Access (CDMA)/Global System for Mobile communication (GSM)/Short Message Service (SMS), etc.)
M2M/IOT services with a potential market are widely geographically distributed, and can be deployed at any network reachable location for real unattended watching instead of costly attended watching, which may be of both great significance and a great potential market value to information acquisition of electric power, water conservancy, oil exploitation, ore exploitation, environment conservancy, weather, tobacco, finance and other industries.
The use of a radio network for communication is one of preferred solutions for widely distributed M2M UEs, and data information acquired by sensors is typically transmitted over a General Packet Radio Service (GPRS) network for some existing industry applications, e.g., remote metering, water level monitoring, etc. There is a pressing demand for a radio network along with the development of M2M applications.
When a large number of M2M UEs access a network densely, there will be a considerable load on both a radio network and a core network, and consequently there will be inevitable congestion and an increase in failure ratio of inter-human communication. However, only one wait time is carried in a Radio Resource Control (RRC) Connection Rejection message in the prior art without distinguishing between a Core Network (CN) overload and a Radio Access Network (RAN) overload. On one hand, the wait time is so short, for example, 16 seconds in a Long Term Evolution (LTE) system, that the UEs will access the network too frequently, which may discourage network congestion from being alleviated; and on the other hand, CN congestion and RAN congestion can not be treated differently, thus resulting in a too rough granularity of access control.
SUMMARY OF THE INVENTION
Embodiments of the invention provide an access control method and device so as to perform better access control.
An access control method applicable to the RAN side includes:
determining, by a Radio Access Network (RAN) whether a UE is allowed for an access to the RAN and a CN according to current load conditions of the RAN and the CN and device or service information reported by the UE in an random access procedure; and
when an access to at least one of the RAN and the CN is rejected, sending, by the RAN, to the UE an indication message carrying a wait time corresponding to the access rejecting network.
A method for processing a message in an access procedure applicable to the UE side includes:
receiving, by a UE, an indication message carrying a wait time corresponding to an access rejecting network after sending an access request;
parsing, by the UE, the indication message for the wait time corresponding to the access rejecting network; and
rejecting, by the UE, a further access to the access rejecting network according to the wait time corresponding to the access rejecting network.
A device of radio access network includes:
a control module configured to determine whether a UE is allowed for an access to the RAN and a CN according to current load conditions of the RAN and the CN and device or service information reported by the UE in an random access procedure; and
an interface module, when an access to at least one of the RAN and the CN is rejected, configured to send to the UE an indication message carrying a wait time corresponding to the access rejecting network.
A user equipment includes:
an interface module configured to receive an indication message carrying a wait time corresponding to an access rejecting network after sending an access request;
a parsing module configured to parse the indication message for the wait time corresponding to the access rejecting network; and
a control module configured to reject a further access to the access rejecting network according to the wait time corresponding to the access rejecting network.
A core network device includes:
a control module configured to determine whether the device is overloaded, and if so, to determine a wait time for an overload; and
an interface module configured to send to an RAN an overload control message carrying the wait time for an overload.
In the embodiments of the invention, a Radio Access Network (RAN) determines access control for the RAN and a Core Network (CN) in an access procedure, and if there is an access rejecting network, that is the network is overloaded, the RAN carries in an indication message to a UE a wait time corresponding to the access rejecting network. In other words, the RAN can set targeted wait times respectively for overload conditions of the RAN and the CN to perform better access control and thus avoid as much as possible network congestion and a considerable delay in access of the UE.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a general flow chart of an access control method at the network side according to an embodiment of the invention;
FIG. 2 is a general flow chart of an access control method at the UE side according to an embodiment of the invention;
FIG. 3 is a flow chart of an access control method at both the RAN side and the UE side according to an embodiment of the invention;
FIG. 4 is a flow chart of an access control method without distinguishing a single-CN node overload but only with a wait time according to an embodiment of the invention;
FIG. 5 is a flow chart of an access control method without distinguishing a single-CN node overload but with a wait time and an RAN overload indicator according to an embodiment of the invention;
FIG. 6 is a flow chart of an access control method by distinguishing a single-CN node overload and reporting an S-TMSI according to an embodiment of the invention;
FIG. 7 is a flow chart of an access control method by distinguishing a single-CN node overload and reporting a GUMMEI according to an embodiment of the invention;
FIG. 8 is a structural diagram of a device of radio access network according to an embodiment of the invention;
FIG. 9 is a general structural diagram of a UE according to an embodiment of the invention;
FIG. 10 is a detailed structural diagram of a UE according to an embodiment of the invention; and
FIG. 11 is a structural diagram of a core network device according to an embodiment of the invention.
DETAILED DESCRIPTION OF THE EMBODIMENTS
In embodiments of the invention, a Radio Access Network (RAN) determines access control for the RAN and a Core Network (CN) in an access procedure, and if there is an access rejecting network, that is, the network is overloaded, the RAN carries in an indication message to a UE a wait time corresponding to the access rejecting network. In other words, the RAN can set targeted wait times respectively for overload conditions of the RAN and the UN to perform better access control and thus avoid as much as possible network congestion and a considerable delay in access of the UE.
For a wait time in an RRC Connection Rejection message in the prior art, a wait time for a CN overload is not distinguished from a wait time for an RAN overload. In the embodiment, a wait time in an RRC Connection Rejection message in the prior art is taken as a wait time for an RAN overload, and a wait time for a CN overload is represented by adding a new Information Element (IE). Thus access control is performed respectively on the different networks to thereby offer a finer granularity of access control. Also in order to extend a range of the wait time, the wait time can be a value different from a wait time indicated in the message, for example, can be the power of the wait time indicated in the message with 2 being a base, etc.
Referring to FIG. 1 , a general flow of an access control method at the network side in the embodiment is as follows.
Step 101 : A Radio Access Network (RAN) determines whether an access to the RAN and a CN is allowed according to current load conditions of the RAN and the CN and device or service information reported by a UE in a random access procedure. This determination process may take place after an RRC Connection Request message is received or may take place after an RRC Connection Setup Complete message is received. The UE may report the device or service information in the RRC Connection Request message or may report the device or service information in the RRC Connection Setup Complete message.
Step 102 : When an access to at least one of the RAN and the CN is rejected, the RAN sends to the UE an indication message carrying a wait time corresponding to the access rejecting network. If the CN is overloaded, that is, an access to the CN is rejected, the carried wait time includes a wait time for a CN overload; if the RAN is overloaded, that is, an access to the RAN is rejected, the carried wait time includes a wait time for an RAN overload; or if both the RAN and the CN are overloaded, the carried wait times include the wait time for a CN overload and the wait time for an RAN overload. If access control is determined for the access request and neither the RAN nor the CN is overloaded (that is, both the RAN and the CN allow an access thereto), the RAN sends an RRC Connection Setup message to the UE; or if access control is determined after an RRC connection setup is completed and neither the RAN nor the CN is overloaded, the RAN operates at it is without sending a RRC Connection Release message to the UE.
As opposed to the network side, an implementation method at the UE side in an access procedure will be introduced.
Referring to FIG. 2 , a general flow of an access control method at the UE side in the embodiment is as follows.
Step 201 : A UE receives an indication message carrying a wait time corresponding to an access rejecting network after sending an access request. The wait time includes a wait time for an RAN overload, or a wait time for a CN overload, or both the wait time for an RAN overload and the wait time for a CN overload.
Step 202 : The UE parses the indication message for the wait time corresponding to the access rejecting network.
Step 203 : The UE accesses the access rejecting network according to the wait time corresponding to the network. The UE performs access control according to the wait time for an RAN overload upon discovering the presence of the wait time for an RAN overload in the indication message. The UE performs access control according to the wait time for a CN overload upon discovering the presence of the wait time for a CN overload in the indication message. The UE performs access control according to the wait times for RAN and CN overloads upon discovering the presence of the wait times for RAN and CN overloads in the indication message.
An access procedure involves interaction between an RAN and a UE, and an implementation process of an access control will be introduced below in connection to both the RAN and UE sides.
Referring to FIG. 3 , a flow of an access control method at both the RAN side and the UE side in the embodiment is as follows.
Step 301 : A UE sends to an RAN an RRC Connection Request message which may carry device or service information and a setup reason of the UE. The device or service information includes one of the following information: an indicator of whether it is a low-priority access UE or service; an indicator of whether it is a roaming UE as well as specific roaming sub-class information; an indicator of whether it is a time-tolerable UE or service; an indicator of whether it is a time-controllable UE or service; and an indicator of whether it is a small-data-amount UE or service. The device or service information may further include other device or service-related information which will not be enumerated here. The setup reason includes one of the following reasons: an emergency call initiated by the UE, an access of the called UE (mt-Access), a high-priority access, signalling initiated by the UE (mo-Signalling), data transmission (mo-Data) and a low-priority access, where different setup reasons can correspond to different access priorities.
Step 302 : The RAN determines whether the UE is allowed for an access to the RAN and a CN according to the device or service information and the setup reason of the UE and obtained current load information of the networks and proceeds to the step 303 when the UE is rejected for an access to at least one of the RAN and the CN; otherwise, the RAN proceeds to the step 304 . The current load information of the networks obtained in the RAN includes load information of the RAN and load information of the CN, that is, load conditions of the RAN and the CN. The load information of the CN may be sent to the RAN from a Mobility Management Entity (MME) in an Overload Start message or configured to the RAN by an Operation, Administration and Maintenance (OAM) entity. The load information of the CN includes, for example, all of low-priority access UEs or services being rejected for a non-emergent call; all of caller data service and low-priority access UEs or services being rejected; all of caller signalling services and low-priority access UEs or services being rejected for a non-emergent call; and only an emergency service and a callee access being allowed. In the embodiment, the load information of the CN may further include a wait time for a CN overload, and the wait time may correspond to a rejecting reason.
Step 303 : The RAN sends to the UE an RRC Connection Reject message carrying a wait time corresponding to the access rejecting network and proceeds to the step 305 .
Before the step 303 , the RAN may determine a wait time corresponding to the access rejecting network upon determining that there is an overloaded network. The MME sends a reference value of the wait time to the RAN in the Overload Start message, or the OAM entity configures a reference value of the wait time to the RAN. The RAN determines a final wait time from the reference value. Here there are numerous implementations, for example, the RAN takes the reference value directly as the wait time; or the RAN generates a random number and takes the power of the random number with the reference value being a base as the wait time; or the reference value is a range, e.g., 1-3600, and the RAN generates a random number in the reference range and takes the random number as the wait time; or the RAN generates a random number no less than the reference value and takes the random number as the wait time. There are other possible wait time determinations applicable to the embodiment as long as a load stress on the network side can be alleviated. Wait times for both RAN and CN overloads can be determined as above. Preferably, the wait time in the embodiment is in seconds.
Step 304 : The RAN sends an RRC Connection Setup message to the UE and proceeds to the step 306 .
Step 305 : The UE performs network access control according to the wait time corresponding to the access rejecting network, for example, will reject a further access to the network.
Step 306 : The UE sends an RRC Connection Setup Complete message to the RAN.
In the step 305 , if the UE receives the RRC Connection Reject message carrying a valid wait time of the CN, the UE may transfer the wait time for a CN overload to all internal Non-Access Stratum (NAS) for processing. If the UE receives the RRC Connection Reject message carrying a wait time for an RAN overload, the UE may start and set a T302 timer according to the wait time for an RAN overload. The UE controls the access to be halted through the NAS and the T302 timer. The T302 timer is a timer specified in the standard, and in the existing standard, there is only one wait time in the Connection Reject message, and the UE has to start the T302 timer according to the wait time upon reception of the RRC Connection Reject message and can not reinitiate an access attempt until expiration. In the invention, a wait time is newly added in this message. The original wait time still corresponds to the T302 timer.
There is another implementation of the embodiment in which the RAN determines access control for the RAN according to the device or service information and the setup reason of the UE and the obtained current load information of the network, and if an access is rejected, the RAN sends to the UE an RRC Connection Reject message carrying a wait time for an RAN overload, and then the UE performs a wait process; or if an access is allowed, the RAN sends an RRC Connection Setup message to the UE and sets up an RRC connection with the UE, and after the setup is completed, the RAN determines access control for the CN, and if an access to the CN is rejected, the RAN sends an RRC Connection Release message to the UE and disconnects the RRC connection with the UE; otherwise, the RAN performs a registration process with the CN.
Since the RAN can determine access control in different phases, there are numerous indicators of whether to allow an access to the RAN and the CN, and access control can be determined by distinguishing a single-CN node overload or without distinguishing a single-CN node overload, there are numerous implementations of the entire access process, which will be detailed below in connection with several embodiments. Particularly, “without distinguishing a single-CN node overload” refers to that a CN overload with all of MMEs in the entire MME pool being overloaded is not distinguished from a CN overload with only a part of MMEs being overloaded, that is, the RAN determines the entire CN to be overloaded upon reception of load information of n MMEs, where the preconfigured parameter n represents a lower number than the total number of MMEs in the MME pool connected with the RAN. “Distinguishing a single-CN node overload” refers to that the RAN determines an MME to be overloaded upon reception of load information of that MME and determines the other MMEs in the MME pool not to be overloaded upon reception of no load information of the other MMEs.
Referring to FIG. 4 , a flow of an access control method without distinguishing a single-CN node overload but only with a wait time in this embodiment is as follows.
Step 401 : A UE sends to an RAN an RRC Connection Request message which may carry device or service information and a setup reason of the UE.
Step 402 : The RAN determines whether an access to the RAN and a CN is allowed according to the device or service information and the setup reason of the UE and obtained current load information of the networks and proceeds to the step 403 when an access to at least one of the RAN and the CN is rejected; otherwise, the RAN proceeds to the step 404 . Particularly, the entire CN is determined to be overloaded as long as the current load information of the networks obtained in the RAN includes overload control information of any MME, and if the setup reason of the UE satisfies an access reason to reject the access in the overload control information of the MME, the access request of the UE is rejected. In this embodiment, load information of an MME includes overload control information of the MME.
Step 403 : The RAN sends to the UE an RRC Connection Reject message carrying a wait time for an RAN overload or carrying wait times respectively for an RAN overload and for a CN overload and proceeds to the step 405 .
Step 404 : The RAN sends an RRC Connection Setup message to the UE and proceeds to the step 406 .
Step 405 : The UE parses the RRC Connection Reject message and rejects a further access to the networks according to the wait times for an RAN overload and for a CN overload.
Step 406 : The UE sends an RRC Connection Setup Complete message to the RAN.
In the step 403 , if the CN is not overloaded (that is, an access to the CN is allowed) and the RAN is overloaded (that is, an access to the RAN is rejected), the RRC Connection Reject message does not carry the wait time for a CN overload but only carries the wait time for an RAN overload. Then in the step 405 , the UE determines that the CN is not overloaded and the RAN is overloaded upon discovering the presence of only the wait time for an RAN overload and simply performs a process according to the wait time for an RAN overload, e.g., starts and sets a T302 timer, etc.
If the CN is overloaded, the RRC Connection Reject message carries the wait time for a CN overload. In the step 405 , the UE transfers the wait time for a CN overload to an internal NAS for processing upon discovering the presence of the wait time for a CN overload.
In the case that both the CN and the RAN are not overloaded, the wait time for an RAN overload can be set to a specified value, and the UE ignores the wait time for an RAN overload or waits according to the wait time for an RAN overload upon discovering the wait time for an RAN overload to be a specified value which can be set to least wait time value specified by a system, and different least wait time values may be specified by different systems.
In the case that the CN is overloaded, if the RAN is also overloaded, the wait time for an RAN overload is not a specified value, and the UE performs a process according to the wait time for an RAN overload. When both the CN and the RAN are overloaded, the UE obtains the wait times for RAN and CN overloads and has an RRC layer in the UE maintain a T302 timer and an NAS therein maintain a timer corresponding to the wait time for a CN overload. The RRC layer notifies the NAS that the T302 timer is started or expires. When the T302 timer is validated, the NAS prohibits all of access requests to be initiated. When the T302 timer is invalidated (is not started or expires), the NAS decides whether to prohibit an access from being initiated according to the timer corresponding to the wait time for a CN overload and the setup reason. Specifically, the UE is allowed for an access at the NAS, and whether the UE ultimately can be allowed for an access will be further decided under a rule of the Access Stratum (AS) layer.
In order to alleviate an access load at the network side, whether the access is allowed to be initiated can alternatively be determined at the UE side. For example, the UE records a setup reason corresponding to an RRC connection corresponding to the indication message upon receiving the indication message and knowing from the indication message that the CN is overloaded. When there is another access to be performed in the range of the wait time, if a setup reason for the current access request has an access priority no higher than that of the recorded setup reason, the access is prohibited, or if the setup reason for the current access request has a higher access priority than that of the recorded setup reason, the timer corresponding to the wait time is invalidated, and an access request is sent.
Referring to FIG. 5 , a flow of an access control method without distinguishing a single-CN node overload but with a wait time and an RAN overload indicator in this embodiment is as follows.
Step 501 : A UE sends to an RAN an RRC Connection Request message which may carry device or service information and a setup reason of the UE.
Step 502 : The RAN determines whether an access to the RAN and a CN is allowed according to the device or service information and the setup reason of the UE and obtained current load information of the networks and proceeds to the step 503 when an access to at least one of the RAN and the CN is rejected; otherwise, the RAN proceeds to the step 504 . Particularly, the entire CN is determined to be overloaded as long as the current load information of the networks obtained in the RAN includes overload control information of any MME, and if the setup reason of the UE satisfies an access reason to reject the access in the overload control information of the MME, the access request of the UE is rejected.
Step 503 : The RAN sends to the UE an RRC Connection Reject message carrying a wait time for an RAN overload and an RAN overload indicator as well as a wait time for a CN overload when the CN is overloaded and proceeds to the step 505 . Particularly, the RAN overload indicator may indicate whether the RAN is overloaded and may further indicate whether the wait time for an RAN overload is valid, and when the RAN overload indicator is an RAN overload indicator indicating the RAN to be overloaded, it also indicate the carried wait time for an RAN overload to be valid; or when the RAN overload indicator is an RAN overload indicator indicating the RAN not to be overloaded, it also indicates the carried wait time for an RAN overload to be invalid.
Step 504 : The RAN sends an RRC Connection Setup message to the UE and proceeds to the step 506 .
Step 505 : The UE parses the RRC Connection Reject message and rejects a further access to the networks according to the RAN overload indicator and the wait times for an RAN overload and for a CN overload.
Step 506 : The UE sends an RRC Connection Setup Complete message to the RAN.
In the step 503 , when the CN is overloaded and the RAN is not overloaded, the carried wait time includes the wait time for a CN overload, and the RAN overload indicator is an RAN overload indicator indicating the RAN not to be overloaded. In this case, the RRC Connection Reject message may also carry the wait time for an RAN overload although the wait time for an RAN overload is invalid. Then in the step 505 , the UE transfers the wait time for a CN overload to an internal NAS for processing upon discovering the presence of the wait time for a CN overload and ignores the wait time for an RAN overload upon discovering the RAN overload indicator to be an RAN overload indicator indicating the RAN not to be overloaded. When the RAN is overloaded and the CN is not overloaded, the wait time includes the wait time for an RAN overload, and the RAN overload indicator is an RAN overload indicator indicating the RAN to be overloaded. In this case, the RRC Connection Reject message does not carry the wait time for a CN overload. Then in the step 505 , the UE performs a process according to the wait time for an RAN overload upon discovering the RAN overload indicator to be an RAN overload indicator indicating the RAN to be overloaded and will not perform a process with respect to the wait time for a CN overload upon discovering the absence of the wait time for a CN overload.
When both the RAN and the CN are overloaded, the carried wait times include the wait times for an RAN overload and for a CN overload, and the RAN overload indicator is an RAN overload indicator indicating the RAN to be overloaded. Then in the step 505 , the UE performs a process according to the wait time for an RAN overload upon discovering the RAN overload indicator to be an RAN overload indicator indicating the RAN to be overloaded and transfers the wait time for a CN overload to the internal NAS for processing upon discovering the presence of the wait time for a CN overload. In this case, the UE obtains the wait times for an RAN overload and for a CN overload and has an RRC layer in the UE maintain a T302 timer corresponding to the wait time for an RAN overload and the NAS therein maintain a timer corresponding to the wait time for a CN overload. The RRC layer notifies the NAS that the T302 timer is started or expires. When the T302 timer is validated, the NAS prohibits all of access requests to be initiated. When the T302 timer is invalidated (is not started or expires), the NAS decides whether to prohibit an access from being initiated according to the timer corresponding to the wait time for a CN overload and the setup reason.
With a single-CN node overload being distinguished, the RAN may determine whether an MME corresponding to the UE is overloaded and thus performs a slightly different access control process. Moreover, the RAN may determine the corresponding MME from a System Architecture Evolution (SAE)-Temporary Mobile Subscriber Identity (S-TMSI) in the RRC Connection Request message or determine the corresponding MME from a Globally Unique MME Identifier (GUMMEI) in the RRC Connection Setup Complete message.
Referring to FIG. 6 , a flow of an access control method by distinguishing a single-CN node overload and reporting an S-TMSI in this embodiment is as follows.
Step 601 : A UE sends to an RAN an RRC Connection Request message which may carry an S-TMSI and device or service information and a setup reason of the UE.
Step 602 : The RAN determines an access control for the RAN according to the device or service information and the setup reason of the UE and obtained current load information of the networks (including the RAN and a CN) and deter nines access control for an MME indicated by the S-TMSI, and if the MME is overloaded and prohibits an access for the RRC setup reason of the UE, the RAN determines the CN to be overloaded; otherwise, the RAN determines the CN not to be overloaded, and the RAN proceeds to the step 603 when an access to at least one of the RAN and the CN is rejected; otherwise, the RAN proceeds to the step 604 .
Step 603 : The RAN sends to the UE an RRC Connection Reject message carrying a wait time corresponding to the access rejecting network and proceeds to the step 605 . Particularly, for contents of and a process to parse the RRC Connection Reject message, reference may be made to the embodiment illustrated in FIG. 5 .
Step 604 : The RAN sends an RRC Connection Setup message to the UE and proceeds to the step 606 .
Step 605 : The UE parses the RRC Connection Reject message and rejects a further access to the access rejecting network according to the wait time corresponding to the network.
Step 606 : The UE sends an RRC Connection Setup Complete message to the RAN.
Referring to FIG. 7 , a flow of an access control method by distinguishing a single-CN node overload and reporting a GUMMEI in this embodiment is as follows.
Step 701 : A UE sends to an RAN an RRC Connection Request message which may carry device or service information and a setup reason of the UE.
Step 702 : The RAN determines an access control for the RAN according to the device or service information and the setup reason of the UE and obtained load information of the RAN and proceeds to the step 703 when the RAN is overloaded; otherwise, the RAN proceeds to the step 705 .
Step 703 : The RAN sends to the UE an RRC Connection Reject message carrying a wait time for an RAN overload.
Step 704 : The UE parses the RRC Connection Reject message and rejects a further access to the network according to the wait time for an RAN overload.
Step 705 : The RAN sends an RRC Connection Setup message to the UE.
Step 706 : The UE sends an RRC Connection Setup Complete message carrying a GUMMEI to the RAN.
Step 707 : The RAN determines an access control for a CN according to the device or service information and the setup reason of the UE and obtained load information of the CN and proceeds to the step 708 when the CN is overloaded; otherwise, the RAN proceeds to the step 709 .
Step 708 : The RAN sends to the UE an RRC Connection Release message carrying a wait time for a CN overload and proceeds to the step 710 .
Step 709 : The RAN registers with the CN.
In the step 707 , the RAN determines whether there is an S 1 interface between an MME corresponding to the GUMMEI and the RAN and whether the MME allows the UE for an access.
The RAN firstly determines whether there is an S1 interface between the MME corresponding to the GUMMEI and the RAN, and if there is an S1 interface, the RAN further determines whether there is overload control information of the MME, and if there is overload control information, the RAN further determines whether the setup reason requested by the UE belongs to setup reasons to reject an access in the overload control information, and if so, the RAN proceeds to the step 708 . If there is an S1 interface and there is no overload control information, that is, the MME is not overloaded, the RAN proceeds to the step 709 for the MME. If there is no S1 interface, the RAN searches a MME pool for a non-overloaded MME and proceeds to the step 709 or finds out an MME which is overloaded but does not reject the setup reason of the UE, and if all of MMEs in the MME pool are overloaded and reject the setup reason of the UE, the RAN proceeds to the step 708 .
Step 710 : The UE parses the RRC Connection Release message and rejects a further access to the network according to the wait time for a CN overload.
An implementation process of access control has been known from the foregoing description, and this process is generally performed by the RAN and the UE, so internal structures and functions of the RAN and the UE will be introduced below.
Referring to FIG. 8 , a device of radio access network in this embodiment includes a control module 801 and an interface module 802 . The device of radio access network may be a NodeB (e.g., an evolved NodeB (eNB)) or a Radio Network Controller (RNC) or other access devices.
The control module 801 is configured to generate various messages and to determine whether an access to the RAN and a CN is allowed according to current load conditions of the RAN and the CN and device or service information reported by a UE in a random access procedure. The control module 801 is further configured to determine a wait time for a CN overload by determining by itself for the UE the wait time for a CN overload according to the current load condition of the network and the information reported by the UE or by determining for the UE the wait time for a CN overload from a wait time, indicated by an MME or an OAM entity, which is further randomized, and to determine the wait time for an RAN overload by determining by itself for the UE the wait time for an RAN overload. Specifically, an access request carries the device or service information and a setup reason of the UE. The control module 801 determines whether the RAN is overloaded, and if so, it determines the RAN to be overloaded; otherwise, it determines the RAN not to be overloaded; and it determines whether the UE is allowed for an access to the CN according to the device or service information and the setup reason of the UE and an overload indicator for the CN, and if so, it determines the CN not to be overloaded; otherwise, it determines the CN to be overloaded.
The device or service information includes one of the following information: an indicator of whether it is a low-priority access UE or service; an indicator of whether it is a roaming UE as well as specific roaming sub-class information; an indicator of whether it is a time-tolerable UE or service; an indicator of whether it is a time-controllable UE or service; and an indicator of whether it is a small-data-amount UE or service. The device or service information may further include other device or service-related information.
When an access to at least one of the RAN and the CN is rejected, the interface module 802 connected with the UE and the CN is configured to send to the UE an indication message carrying a wait time corresponding to the access rejecting network.
Without distinguishing a single-CN node overload, the RAN sends the indication message carrying the wait time corresponding to the access rejecting network in an RRC Connection Reject message. With a single-CN node overload being distinguished, if the access request does not carry a UE identifier corresponding to an MME with which the UE registers, the following steps are further included: an RRC Connection Setup Complete message sent from the UE is received; and if the RRC Connection Setup Complete message carries the UE identifier corresponding to the MME with which the UE registers and the MME corresponding to the UE identifier is overloaded and has an S1 interface with the RAN, or all of MMEs in a MME pool are overloaded, then the RAN sends the indication message carrying the wait time corresponding to the access rejecting network in an RRC Connection Release message; or if the access request carries the UE identifier corresponding to the MME with which the UE registers, the RAN sends the indication message carrying the wait time corresponding to the access rejecting network in an RRC Connection Reject message.
There are numerous forms of the indication message, and which network is overloaded and a corresponding wait time may be indicated to the UE in different information Elements (IEs). For example, the RRC Connection Rejection message further includes an RAN overload indicator indicating whether the RAN is overloaded; when the CN is overloaded and the RAN is not overloaded, the wait time corresponding to the access rejecting network includes a wait time for a CN overload, and the RAN overload indicator is an RAN overload indicator indicating the RAN not to be overloaded; when the RAN is overloaded and the CN is not overloaded, the wait time includes the wait time for an RAN overload, and the RAN overload indicator is an RAN overload indicator indicating the RAN to be overloaded; and when both the RAN and the CN are overloaded, the wait times include the wait times for RAN and CN overloads, and the RAN overload indicator is an RAN overload indicator indicating the RAN to be overloaded.
Alternatively, the RRC Connection Rejection message further includes the wait time for an RAN overload, which is a specified value, when the RAN is not overloaded. In other words, if the CN is not overloaded (that is, an access to the CN is allowed) and the RAN is overloaded (that is, an access to the RAN is rejected), then the RRC Connection Rejection message does not carry the wait time for a CN overload but only the wait time for an RAN overload. If the CN is overloaded and the RAN is not overloaded, the RRC Connection Rejection message carries the wait time for a CN overload and the wait time for an RAN overload, but the wait time for an RAN overload is a specified value. If both the CN and the RAN are overloaded, the RRC Connection Rejection message carries the wait time for a CN overload and the wait time for an RAN overload, and the wait time for an RAN overload is not a specified value.
Referring to FIG. 9 , a user equipment in this embodiment includes an interface module 901 , a parse module 902 and a control module 903 .
The interface module 901 is configured to receive an indication message carrying a wait time corresponding to an access rejecting network after sending an access request. The wait time corresponding to the access rejecting network includes a wait time for an RAN overload or a wait time for a CN overload or both the wait time for an RAN overload and the wait time for a CN overload. The interface module 901 receives the indication message carrying the wait time corresponding to the access rejecting network in an RRC Connection Reject message; and the interface module 901 is further configured to send an RRC Connection Setup Complete message. The RRC Connection Setup Complete message may carry a UE identifier corresponding to an MME with which the UE registers, and then the interface module 901 may receive the indication message carrying the wait time corresponding to the access rejecting network in an RRC Connection Release message; and if the access request carries the UE identifier corresponding to the MME with which the UE registers, the interface module 901 receives the indication message carrying the wait time corresponding to the access rejecting network in an RRC Connection Reject message.
The parse module 902 is configured to parse the indication message for the wait time corresponding to the access rejecting network.
The control module 903 is configured to reject a further access to the access rejecting network according to the wait time corresponding to the network. Specifically, the control module 903 may start and set a T302 timer according to the wait time for an RAN overload, and an NAS part in the control module 903 may perform a wait process according to the wait time for a CN overload.
Particularly, the control module 903 is configured to determine the CN not to be overloaded and the RAN to be overloaded upon discovering the presence of only the wait time for an RAN overload in the RRC Connection Reject message and to simply perform a process according to the wait time for an RAN overload, for example, start and set the T302 timer, etc., and to reject a network access attempt of the UE when the T302 timer is started.
The control module 903 transfers the wait time for a CN overload to the internal NAS for processing upon discovering the wait time for a CN overload to be carried in the RRC Connection Reject message and to reject a network access attempt of the UE when a timer corresponding to the wait time for a CN overload is started.
The control module 903 ignores the wait time for an RAN overload or performs a process with respect to the wait time for an RAN overload upon discovering the wait time for an RAN overload to be carried in the RRC Connection Reject message and to be a specified value.
When the control module 903 discovers the wait time for a CN overload and the wait time for an RAN overload to be carried in the RRC Connection Reject message and the wait time for an RAN overload not to be a specified value, an RRC layer in the control module 903 maintains the T302 timer, and the NAS maintains the timer corresponding to the wait time for a CN overload. The RRC layer notifies the NAS that the T302 timer is started or expires. When the T302 timer is validated, the NAS prohibits all of access requests to be initiated. When the T302 timer is invalidated (is not started or expires), the NAS decides whether to prohibit an access from being initiated according to the timer corresponding to the wait time for a CN overload and a setup reason.
The interface module 901 may receive the indication message carrying the wait time for a CN overload in an RRC Connection Release message. The control module 903 transfers the wait time for a CN overload to the internal NAS for processing upon discovering the wait time for a CN overload to be carried in the RRC Connection Release message and to reject a network access attempt of the UE when the timer corresponding to the wait time for a CN overload is started.
The RRC Connection Reject message further includes an RAN overload indicator indicating whether the RAN is overloaded. The control module 903 transfers the wait time for a CN overload to the internal NAS for processing upon discovering the presence of the wait time for a CN overload and ignores the wait time for an RAN overload upon discovering the RAN overload indicator to be an RAN overload indicator indicating the RAN not to be overloaded.
The control module 903 performs a process according to the wait time for an RAN overload upon discovering the RAN overload indicator to be an RAN overload indicator indicating the RAN to be overloaded and will not perform a process with respect to the wait time for a CN overload upon discovering the absence of the wait time for a CN overload.
The control module 903 performs a process according to the wait time for an RAN overload upon discovering the RAN overload indicator to be an RAN overload indicator indicating the RAN to be overloaded and rejects a network access attempt of the UE when the T320 timer is started, and transfers the wait time for a CN overload to the internal NAS for processing upon discovering the presence of the wait time for a CN overload. In this case, the control module 903 obtains the wait times for an RAN overload and for a CN overload, the RRC layer in the control module 903 maintains the T302 timer, and the NAS maintains the timer corresponding to the wait time for a CN overload. The RRC layer notifies the NAS that the T302 timer is started or expires. When the T302 timer is validated, the NAS prohibits all of access requests to be initiated. When the T302 timer is invalidated (is not started or expires), the NAS decides whether to prohibit an access from being initiated according to the timer corresponding to the wait time for a CN overload and the setup reason.
Preferably, when the CN is overloaded, the user equipment further includes a record module 904 with reference to FIG. 10 . The record module 904 is configured to record a setup reason corresponding to an RRC connection corresponding to the indication message upon discovering the indication message to carry the wait time for a CN overload. When there is another access to be performed when the timer corresponding to the wait time for a CN overload is started, if a setup reason for the current access request has an access priority no higher than that of the recorded setup reason, the control module 903 prohibits the access, or if the setup reason for the current access request has a higher access priority than that of the recorded setup reason, the control module 903 invalidates the timer corresponding to the wait time for a CN overload and allows the access request to be sent.
Referring to FIG. 11 , a core network device in this embodiment includes a control module 1101 and an interface module 1102 . The core network device may be an MME or an OAM entity.
The control module 1101 is configured to determine whether the core network device is overloaded, and if so, to determine a wait time for an overload. The control module 1101 may reject an access of some setup reasons according to an overload condition of the core network device and determine an appropriate wait time for these rejected setup reasons.
The interface module 1102 is configured to send to an RAN an overload control message carrying the wait time for an overload.
An MME may determine the wait time according to its own overload condition and overload conditions of other core network nodes and send the wait time to the RAN. An OAM entity may obtain load conditions of respective MMEs and determine hereby the wait time for an overload and then send the wait time to the RAN. The RAN may obtain a plurality of wait times for an overload with respect to a plurality of MMEs. Without distinguishing a single-CN node overload, the RAN may determine a wait time for a CN collectively from the obtained plurality of wait times for an overload, for example, select the maximum one of them, the average value thereof, etc. With a single-CN node overload to be distinguished, the RAN determines the wait time for a CN from a wait time for an overload of an MME with which a UE registers.
In the embodiments of the invention, a Radio Access Network (RAN) determines access control for the RAN and a Core Network (CN) an access procedure, and if there is an access rejecting network, that is, the network is overloaded, the RAN carries in an indication message to a UE a wait time corresponding to the access rejecting network. In other words, the RAN may set targeted wait times respectively for overload conditions of the RAN and the CN to perform better access control and thus avoid as much as possible network congestion and a considerable delay in access of the UE. The embodiments of the invention provide numerous structures of the indication message and may notify the UE of which network is overloaded and the corresponding wait time in these numerous structures to thereby facilitate flexible configuration. Moreover, corresponding implementation solutions are provided for numerous determinations of access control to thereby accommodate a variety of network demands.
Those skilled in the art shall appreciate that the embodiments of the invention can be embodied as a method, a system or a computer program product. Therefore the invention can be embodied in the form of an all-hardware embodiment, an all-software embodiment or an embodiment of software and hardware in combination. Furthermore the invention can be embodied in the form of a computer program product embodied in one or more computer useable storage mediums (including but not limited to a disk memory, an optical memory, etc.) in which computer useable program codes are contained.
The invention has been described in a flow chart and/or a block diagram of the method, the device (system) and the computer program product according to the embodiments of the invention. It shall be appreciated that respective flows and/or blocks in the flow chart and/or the block diagram and combinations of the flows and/or the blocks in the flow chart and/or the block diagram can be embodied in computer program indications. These computer program indications can be loaded onto a general-purpose computer, a specific-purpose computer, an embedded processor or a processor of another programmable data processing device to produce a machine so that the indications executed on the computer or the processor of the other programmable data processing device create means for performing the functions specified in the flow(s) of the flow chart and/or the block(s) of the block diagram.
These computer program indications can also be stored into a computer readable memory capable of directing the computer or the other programmable data processing device to operate in a specific manner so that the indications stored in the computer readable memory create an article of manufacture including indication means which perform the functions specified in the flow(s) of the flow chart and/or the block(s) of the block diagram.
These computer program indications can also be loaded onto the computer or the other programmable data processing device so that a series of operational steps are performed on the computer or the other programmable data processing device to create a computer implemented process so that the indications executed on the computer or the other programmable data processing device provide steps for performing the functions specified in the flow(s) of the flow chart and/or the block(s) of the block diagram.
Evidently those skilled in the art can make various modifications and variations to the invention without departing from the scope of the invention. Thus the invention is also intended to encompass these modifications and variations thereto so long as the modifications and variations come into the scope of the claims appended to the invention and their equivalents.
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Disclosed is an access control method, for use in implementing improved access control. The method comprises: during a random access process, on the basis of a current load of a random access network (RAN) and a core network (CN) and of terminal or service information reported by a user equipment (UE), the RAN judging whether or not access to the RAN and to the CN is allowed; when access is denied by at least one network between the RAN and the CN, the RAN transmitting to the UE an instruction message having attached therein a backoff time corresponding to the access denying network. Also disclosed is a device for implementing the method.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority benefit of U.S. Provisional Patent Application No. 60/392,171, filed Jun. 26, 2002. The content of that application is hereby incorporated by reference herein in its entirety.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not applicable.
REFERENCE TO AN APPENDIX
[0003] Not applicable.
TECHNICAL FIELD
[0004] This invention relates to porphyrin-polyamine conjugate compounds used for treatment of cancer and other diseases.
BACKGROUND OF THE INVENTION
[0005] Cancer is the third most common cause of death in the world according to the World Health Organization, after heart disease and infectious disease. Cancer is the second most common cause of death (after heart disease) in the developed world. Accordingly, discovery of new and effective treatments for cancer is a high priority for health care researchers.
[0006] Cancer is often treated by using chemotherapy to selectively kill or hinder the growth of cancer cells, while having a less deleterious effect on normal cells. Chemotherapeutic agents often kill rapidly dividing cells, such as cancer cells; non-malignant cells which are dividing less rapidly are affected to a lesser degree. Other agents, such as antibodies attached to toxic agents, have been evaluated for use against cancers. These agents target the cancer cells by making use of a characteristic specific to the cancer, for example, higher-than-normal rates of cell division, or unique antigens expressed on the cancer cell surface.
[0007] As toxic agents specifically targeted against cancer cells can enhance therapeutic efficacy, reduce undesirable side effects, or both, many efforts have been made to achieve selective localization of well-defined chemical materials in malignant tumors. A significant advance in the field occurred with the introduction of tetraphenylporphine sulfonates (TPPS), which are non-naturally occurring porphyrins (Winkelman J. (1962) Cancer Res. 22:589). A hematoporphyrin derivative (HPD) was also found to localize in tumors (Lipson R L, Baldes, E J, & Gray M S (1967) Cancer 20: 2255). HPD is a complex mixture of porphyrins currently used as a sensitizer derivative that concentrates in tumor cells and destroys them after the tumor is irradiated with light or a laser beam (Dougherty T J, (1987) Photochem. Photobiol. 45:879). A wide variety of porphyrins and porphyrin analogues have been found to be selectively taken up by tumors, such as the naturally occurring porphyrins; for example, the octacarboxylic uroporphyrins, the tetracarboxylic coproporphyrins, and the dicarboxylic protoporphyrin. Synthetic porphyrins are also selectively taken up by tumors; among them are the meso-tetraphenyl porphyrins and the different porphyrin sulfonates TPPS 4 , TPPS 3 , TPPS 2 a and TPPS 1 , which are listed in order of decreasing number of sulfonic acid substituents and decreasing hydrophilicity. Many factors determine the uptake and concentration of porphyrins in the tumors; one important factor is the structure (hydrophobicity, size, polarity) of the drug; another important factor is the formulation in which it is delivered (Sternberg E and Dolphin D (1996) Current Med Chemistry 3, 239). The mechanism(s) of porphyrin localization in tumors is still not entirely clear; the more hydrophobic porphyrins are preferentially incorporated in the lipid core of lipoproteins. Tightly aggregated porphyrins circulate as unbound pseudomicellar structures which can be entrapped in the interstitial regions of the tumor, can be localized in macrophages, or can enter neoplastic cells via pinocytotic processes. Low density lipoproteins (LDL), which are endocytosed by neoplastic cells through a specific receptor-mediated pathway, display the most selective release of porphyrins into the tumors (Jori G (1989) Photosensitizing Compounds, Ciba Foundation Symp 146, pp 78-94).
[0008] The present invention describes the synthesis and cytotoxic actions of porphyrin-polyamine conjugates. They are taken up by the tumor cells due to their porphyrin moiety, while the polyamine moiety provides the cytotoxic effects (see International Patent Application Nos. WO 00/66587 and WO 02/10142, and U.S. Pat. Nos. 6,392,098, 5,889,061, and 5,677,350).
SUMMARY OF THE INVENTION
[0009] The invention provides porphyrin-polyamine conjugate compounds and compositions comprising such compounds.
[0010] In one embodiment, the invention embraces a composition comprising a compound according to the formula
[0011] wherein at least one of J 1 , J 2 , J 3 , J 4 , J 5 , J 6 , J 7 and J 8 is independently M, where M is selected from the group consisting of
—(B-A-B) x -G-(B-A-B) m —(N(P)—B-A-B) n —K
[0012] wherein each A is independently selected from the group consisting of: a nonentity, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 8 cycloaryl, C 3 -C 12 cycloalkenyl, C 3 -C 12 cycloalkynyl, C 1 -C 12 alkanol, C 3 -C 12 cycloalkanol, and C 3 -C 8 hydroxyaryl;
[0013] each B is independently selected from the group consisting of: a nonentity, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 8 cycloaryl, C 3 -C 12 cycloalkenyl, C 3 -C 12 cycloalkynyl, C 1 -C 12 alkanol, C 3 -C 12 cycloalkanol, and C 3 -C 8 hydroxyaryl;
[0014] and with the proviso that each —B-A-B— unit contain at least one carbon atom;
[0015] wherein G is independently selected from the group consisting of —N(P)—, —(C═O)—N(P)—, —N(P)—(C═O)—, and a nonentity;
[0016] x is independently 0 or 1;
[0017] m is independently 0 or 1;
[0018] n is independently an integer from 0 to 20;
[0019] each P is independently selected from the group consisting of H and C 1 -C 12 alkyl;
[0020] K is independently selected from the group consisting of H, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 3 -C 8 cycloaryl, C 3 -C 12 cycloalkenyl, C 3 -C 12 cycloalkynyl, C 1 -C 12 alkanol, C 3 -C 12 cycloalkanol, and C 3 -C 8 hydroxyaryl, and Q;
[0021] where each Q is independently selected from the group consisting of
where each P is independently selected from the group consisting of H and C 1 -C 12 alkyl, each D is selected from the group consisting of H and C 1 -C 32 alkyl, y is an integer from 1 to 8, and z is an integer from 0 to 5, and where the Q moiety is attached to the remainder of the molecule at any C or N atom in the Q moiety (including C atoms in the D or P moieties) by removing a hydrogen atom, a P substituent, or a D substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule;
[0022] and where the remaining members or member of J 1 , J 2 , J 3 , J 4 , J 5 , J 6 , J 7 and J 8 are each independently selected from the group consisting of H, —B-A-B, —COOH, —SO 3 H, —B-A-B—COOH, or —B-A-B—SO 3 H, where each A and each B are independently selected as defined above and with the proviso that each —B-A-B— unit has at least one carbon atom.
[0023] In another embodiment, M excludes moieties of the form
—K 1 -G 5 -L 5 -(N(P 5 )-A 5 ) n -K 2
where K 1 is independently selected from the group consisting of C 1 -C 8 alkyl and where the valence to the left of K, attaches to the porphyrin ring;
G 5 is —O—, —(C═O)—, —C(═O)—O—, —O—(C═O)—, —O—(C═O)—O—, —O—(C═O)—N—, —N—(C═O)—O—, or a nonentity;
L 5 is C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloaryl, C 1 -C 8 alkoxy, C 1 -C 8 alkyl-C 3 -C 8 cycloalkyl, C 1 -C 8 alkyl-C 3 -C 8 cycloaryl, C 1 -C 8 alkoxy-C 3 -C 8 cycloaryl, C 3 -C 8 cycloalkyl-C 3 -C 8 cycloaryl, C 3 -C 8 cycloalkyl-C 1 -C 8 alkyl, C 3 -C 8 cycloaryl-C 1 -C 8 alkyl, C 3 -C 8 cycloaryl-C 1 -C 8 alkoxy, C 3 -C 8 cycloaryl-C 3 -C 8 cycloalkyl, or a nonentity;
each A 5 is independently selected from the group consisting of C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloaryl, C 3 -C 8 cycloalkenyl, and C 3 -C 8 cycloalkynyl;
P 5 is selected from the group consisting of H and C 1 -C 8 alkyl;
n is an integer from 2 to 8;
and K 2 is independently selected from the group consisting of H, C 8 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloaryl, C 3 -C 8 cycloalkenyl, C 3 -C 8 cycloalkynyl, C 1 -C 8 alkanol, C 3 -C 8 cycloalkanol, and C 3 -C 8 hydroxyaryl.
[0024] In another embodiment, G is independently selected from —(C═O)—N(P)— and —N(P)—(C═O)—. In another embodiment, the Q moiety is attached to the remainder of the molecule at any N atom in the Q moiety by removing a P substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule. In another embodiment, each A and B substituent, if present, is selected from C 1 -C 12 alkyl. In another embodiment, at least one A substituent comprises a cyclopropane group.
[0025] In another embodiment, the invention embraces a composition comprising a compound according to the formula
where J 1 and J 2 are independently —(B-A-B) x -G-(B-A-B) m —(N(P)—B-A-B) n —K;
J 3 , J 4 , J 6 and J 8 are independently selected from methyl and ethyl; and
J 5 and J 7 are independently selected from methyl, ethyl, and —SO 3 H. In another embodiment, J 1 and J 2 are independently —(B-A-B)-G-(B-A-B)—(N(P)—B-A-B) n —K. In another embodiment, at least one B-A-B unit comprises a cycloalkyl moiety, such as a cyclopropyl moiety. In another embodiment, J 1 and J 2 are independently —C 1 -C 12 alkyl-G-C 1 -C 12 alkyl-(N(P)—B-A-B) n —K. In another embodiment, J 1 and J 2 are independently —C 1 -C 12 alkyl-(C═O)—N(P)—C 1 -C 12 alkyl-(N(P)—B-A-B) n —K. In another embodiment, J 1 and J 2 are independently —(CH 2 ) 2 C(═O)N(P 2 )—C 1 -C 4 alkyl-[NH(CH 2 CH 2 CH 2 CH 2 )] f C 1 -C 12 alkyl, where P 2 is H, methyl, or ethyl, and f is an integer from 1 to 10.
[0026] In still further embodiments, J 1 and J 2 are identical.
[0027] In still further embodiments, whenever any embodiment comprises a Q moiety (that is, whenever any K is Q), only one D moiety is selected from the group consisting of C 1 -C 32 alkyl and all remaining D moieties are H; three P groups are selected from the group consisting of —H and —CH 3 and the fourth P group is absent and the Q moiety is attached to the remainder of the molecule at that valence; and y is 2, 3, or 4 and z is 0, 1, or 2.
[0028] In further embodiments, whenever any embodiment comprises a Q moiety, Q can be
BRIEF DESCRIPTION OF THE DRAWING(S)
[0029] FIG. 1 . is a graph depicting the in vitro effects of increasing concentrations of SL-11209 on the growth of cultured human prostate cancer cells DUPRO.
[0030] FIG. 2 . is a graph depicting the in vitro effects of increasing concentrations of SL-11211 on the growth of cultured human prostate cancer cells DUPRO.
[0031] FIG. 3 . is a graph depicting the in vitro effects of increasing concentrations of SL-11209 on the survival of cultured human prostate cancer cells DUPRO after 5 days of treatment.
[0032] FIG. 4 . is a graph depicting the in vitro effects of increasing concentrations of SL-11211 on the survival of cultured human prostate cancer cells DUPRO after 3 days of treatment.
[0033] FIG. 5 . is a graph depicting the in vitro effects of increasing concentrations of SL-11211 on the survival of cultured human prostate cancer cells DUPRO after 5 days of treatment.
[0034] FIG. 6 . is a graph depicting the in vitro effects of increasing concentrations of SL-11217 on the survival of cultured human prostate cancer cells DUPRO after 3 and 5 days of treatment.
[0035] FIG. 7 . is a graph depicting the in vitro effects of increasing concentrations of SL-11211 on the survival of cultured human prostate cancer cells PC3 after 5 days of treatment.
[0036] FIG. 8 . is a graph depicting the in vitro effects of increasing concentrations of SL-11217 on the survival of cultured human prostate cancer cells PC3 after 5 days of treatment.
[0037] FIG. 9 . is a graph depicting the in vitro effects of increasing concentrations of SL-11237 on the survival of cultured human prostate cancer cells PC3 after 5 days of treatment.
[0038] FIG. 10 . is a graph depicting the in vitro effects of 10 μM SL-11217 and SL-11237 on the growth of cultured human pancreatic cancer cells BxPC3.
[0039] FIG. 11 . is a graph depicting the in vitro effects of 10 μM SL-11217 and SL-11237 on the growth of cultured human pancreatic cancer cells Panc1.
[0040] FIG. 12 . is a graph depicting the in vitro effects of increasing concentrations of SL-11217 on the survival of cultured human brain tumor cells U251MG NCI after 3 days of treatment.
[0041] FIG. 13 . is a graph depicting the in vitro effects of increasing concentrations of SL-11237 on the survival of cultured human brain tumor cells U251MG NCI after 3 days of treatment.
[0042] FIG. 14 depicts the effects of SL-11237 via oral administration. Male athymic nude mice were given subcutaneous injections of 0.75×10 6 DU145 cells on Day 0. Beginning on Day 10, mice were treated once weekly for 3 weeks with acidified water, 100 mg/kg, or 500 mg/kg of SL-11237 via oral gavage at 10 ml/kg dosing volume (the third treatment was actually 400 mg/kg in the high dose group). The top panel depicts average tumor volume in the mice. The bottom panel depicts average body weight of the mice.
DETAILED DESCRIPTION OF THE INVENTION
[0043] The invention is directed to various novel porphyrin-polyamine conjugate compounds and compositions containing them as described herein. The invention includes all salts of the compounds described herein. Particularly preferred are pharmaceutically acceptable salts. Pharmaceutically acceptable salts are those salts which retain the biological activity of the free bases and which are not biologically or otherwise undesirable. The desired salt may be prepared by methods known to those of skill in the art by treating the compound with an acid. Examples of inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids include, but are not limited to, formic acid, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, sulfonic acids, and salicylic acid. Salts of the compounds with amino acids, such as aspartate salts and glutamate salts, can also be prepared.
[0044] The invention also includes all stereoisomers of the compounds, including diastereomers and enantiomers, as well as mixtures of stereoisomers, including, but not limited to, racemic mixtures. Unless stereochemistry is explicitly indicated in a structure, the structure is intended to embrace all possible stereoisomers of the compound depicted.
[0045] The term “alkyl” refers to saturated aliphatic groups including straight-chain, branched-chain, cyclic groups, and combinations thereof, having the number of carbon atoms specified, or if no number is specified, having up to 12 carbon atoms. “Straight-chain alkyl” or “linear alkyl” groups refers to alkyl groups that are neither cyclic nor branched, commonly designated as “n-alkyl” groups. Examples of alkyl groups include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, butyl, n-butyl, isobutyl, sec-butyl, t-butyl, pentyl, n-pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, neopentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and adamantyl. Cyclic groups can consist of one ring, including, but not limited to, groups such as cycloheptyl, or multiple fused rings, including, but not limited to, groups such as adamantyl or norbornyl. Preferred subsets of alkyl groups include C 1 -C 12 , C 1 -C 10 , C 1 -C 8 , C 1 -C 6 , C 1 -C 4 , C 1 -C 2 , C 3 -C 4 , C 3 , and C 4 alkyl groups.
[0046] “Substituted alkyl” refers to alkyl groups substituted with one or more substituents including, but not limited to, groups such as halogen (fluoro, chloro, bromo, and iodo), alkoxy, acyloxy, amino, hydroxyl, mercapto, carboxy, benzyloxy, phenyl, benzyl, cyano, nitro, thioalkoxy, carboxaldehyde, carboalkoxy and carboxamide, or a functionality that can be suitably blocked, if necessary for purposes of the invention, with a protecting group. Examples of substituted alkyl groups include, but are not limited to, —CF 3 , —CF 2 —CF 3 , and other perfluoro and perhalo groups.
[0047] “Hydroxyalkyl” specifically refers to alkyl groups having the number of carbon atoms specified substituted with one —OH group. Thus, “C 3 linear hydroxyalkyl” refers to —CH 2 CH 2 CHOH—, —CH 2 CHOHCH 2 —, and —CHOHCH 2 CH 2 —.
[0048] The term “alkenyl” refers to unsaturated aliphatic groups including straight-chain (linear), branched-chain, cyclic groups, and combinations thereof, having the number of carbon atoms specified, or if no number is specified, having up to 12 carbon atoms, which contain at least one double bond (—C═C—). Examples of alkenyl groups include, but are not limited to, —CH 2 —CH═CH—CH 3 ; and —CH 2 —CH 2 -cyclohexenyl, where the ethyl group can be attached to the cyclohexenyl moiety at any available carbon valence. The term “alkynyl” refers to unsaturated aliphatic groups including straight-chain (linear), branched-chain, cyclic groups, and combinations thereof, having the number of carbon atoms specified, or if no number is specified, having up to 12 carbon atoms, which contain at least one triple bond (—C≡C—). “Hydrocarbon chain” or “hydrocarbyl” refers to any combination of straight-chain, branched-chain, or cyclic alkyl, alkenyl, or alkynyl groups, and any combination thereof. “Substituted alkenyl,” “substituted alkynyl,” and “substituted hydrocarbon chain” or “substituted hydrocarbyl” refer to the respective group substituted with one or more substituents, including, but not limited to, groups such as halogen, alkoxy, acyloxy, amino, hydroxyl, mercapto, carboxy, benzyloxy, phenyl, benzyl, cyano, nitro, thioalkoxy, carboxaldehyde, carboalkoxy and carboxamide, or a functionality that can be suitably blocked, if necessary for purposes of the invention, with a protecting group.
[0049] For all of the foregoing definitions, preferred subsets of the groups include C 1 -C 12 , C 1 -C 10 , C 1 -C 8 , C 1 -C 6 , C 1 -C 4 , C 1 -C 2 (when chemically possible), C 3 -C 4 , C 3 , and C 4 groups.
[0050] “Aryl” or “Ar” refers to an aromatic carbocyclic group having a single ring (including, but not limited to, groups such as phenyl) or multiple condensed rings (including, but not limited to, groups such as naphthyl or anthryl), and includes both unsubstituted and substituted aryl groups. “Substituted aryls” refers to aryls substituted with one or more substituents, including, but not limited to, groups such as alkyl, alkenyl, alkynyl, hydrocarbon chains, halogen, alkoxy, acyloxy, amino, hydroxyl, mercapto, carboxy, benzyloxy, phenyl, benzyl, cyano, nitro, thioalkoxy, carboxaldehyde, carboalkoxy and carboxamide, or a functionality that can be suitably blocked, if necessary for purposes of the invention, with a protecting group.
[0051] “Heteroalkyl,” “heteroalkenyl,” and “heteroalkynyl” refer to alkyl, alkenyl, and alkynyl groups, respectively, that contain the number of carbon atoms specified (or if no number is specified, having up to 12 carbon atoms) which contain one or more heteroatoms as part of the main, branched, or cyclic chains in the group. Heteroatoms include, but are not limited to, N, S, O, and P; N and O are preferred. Heteroalkyl, heteroalkenyl, and heteroalkynyl groups may be attached to the remainder of the molecule either at a heteroatom (if a valence is available) or at a carbon atom. Examples of heteroalkyl groups include, but are not limited to, groups such as —O—CH 3 , —CH 2 —O—CH 3 , —CH 2 —CH 2 —O—CH 3 , —S—CH 2 —CH 2 —CH 3 , —CH 2 —CH(CH 3 )—S—CH 3 , —CH 2 —CH 2 —NH—CH 2 —CH 2 —, 1-ethyl-6-propylpiperidino, 2-ethylthiophenyl, and morpholino. Examples of heteroalkenyl groups include, but are not limited to, groups such as —CH═CH—NH—CH(CH 3 )—CH 2 —. “Heteroaryl” or “HetAr” refers to an aromatic carbocyclic group having a single ring (including, but not limited to, examples such as pyridyl, thiophene, or furyl) or multiple condensed rings (including, but not limited to, examples such as imidazolyl, indolizinyl or benzothienyl) and having at least one hetero atom, including, but not limited to, heteroatoms such as N, O, P, or S, within the ring. Unless otherwise specified, heteroalkyl, heteroalkenyl, heteroalkynyl, and heteroaryl groups have between one and five heteroatoms and between one and twelve carbon atoms. “Substituted heteroalkyl,” “substituted heteroalkenyl,” “substituted heteroalkynyl,” and “substituted heteroaryl” groups refer to heteroalkyl, heteroalkenyl, heteroalkynyl, and heteroaryl groups substituted with one or more substituents, including, but not limited to, groups such as alkyl, alkenyl, alkynyl, benzyl, hydrocarbon chains, halogen, alkoxy, acyloxy, amino, hydroxyl, mercapto, carboxy, benzyloxy, phenyl, benzyl, cyano, nitro, thioalkoxy, carboxaldehyde, carboalkoxy and carboxamide, or a functionality that can be suitably blocked, if necessary for purposes of the invention, with a protecting group. Examples of such substituted heteroalkyl groups include, but are not limited to, piperazine, substituted at a nitrogen or carbon by a phenyl or benzyl group, and attached to the remainder of the molecule by any available valence on a carbon or nitrogen, —NH—SO 2 -phenyl, —NH—(C═O)O-alkyl, —NH—(C═O)O-alkyl-aryl, and —NH—(C═O)-alkyl. If chemically possible, the heteroatom(s) as well as the carbon atoms of the group can be substituted. The heteroatom(s) can also be in oxidized form, if chemically possible.
[0052] The term “alkylaryl” refers to an alkyl group having the number of carbon atoms designated, appended to one, two, or three aryl groups.
[0053] The term “alkoxy” as used herein refers to an alkyl, alkenyl, alkynyl, or hydrocarbon chain linked to an oxygen atom and having the number of carbon atoms specified, or if no number is specified, having up to 12 carbon atoms. Examples of alkoxy groups include, but are not limited to, groups such as methoxy, ethoxy, and t-butoxy.
[0054] The term “alkanoate” as used herein refers to an ionized carboxylic acid group, such as acetate (CH 3 C(═O)—O (−1) ), propionate (CH 3 CH 2 C(═O)—O (−1) ), and the like. “Alkyl alkanoate” refers to a carboxylic acid esterified with an alkoxy group, such as ethyl acetate (CH 3 C(═O)—O—CH 2 CH 3 ). “(O-haloalkyl alkanoate” refers to an alkyl alkanoate bearing a halogen atom on the alkanoate carbon atom furthest from the carboxyl group; thus, ethyl ω-bromo propionate refers to ethyl 3-bromopropionate, methyl ω-chloro n-butanoate refers to methyl 4-chloro n-butanoate, etc.
[0055] The terms “halo” and “halogen” as used herein refer to Cl, Br, F or I substituents.
[0056] “Protecting group” refers to a chemical group that exhibits the following characteristics: 1) reacts selectively with the desired functionality in good yield to give a protected substrate that is stable to the projected reactions for which protection is desired; 2) is selectively removable from the protected substrate to yield the desired functionality; and 3) is removable in good yield by reagents compatible with the other functional group(s) present or generated in such projected reactions. Examples of suitable protecting groups can be found in Greene et al. (1991) Protective Groups in Organic Synthesis, 2nd Ed. (John Wiley & Sons, Inc., New York). Amino protecting groups include, but are not limited to, mesitylenesulfonyl (Mes), benzyloxycarbonyl (CBz or Z), t-butyloxycarbonyl (Boc), t-butyldimethylsilyl (TBDIMS or TBDMS), 9-fluorenylmethyloxycarbonyl (Fmoc), tosyl, benzenesulfonyl, 2-pyridyl sulfonyl, or suitable photolabile protecting groups such as 6-nitroveratryloxy carbonyl (Nvoc), nitropiperonyl, pyrenylmethoxycarbonyl, nitrobenzyl, dimethyl dimethoxybenzil, 5-bromo-7-nitroindolinyl, and the like. Hydroxylprotecting groups include, but are not limited to, Fmoc, TBDIMS, photolabile protecting groups (such as nitroveratryl oxymethyl ether (Nvom)), Mom (methoxy methyl ether), and Mem (methoxy ethoxy methyl ether), NPEOC (4-nitrophenethyloxycarbonyl) and NPEOM (4-nitrophenethyloxymethyloxycarbonyl).
[0057] Synthesis of Porphyrin-Polyamine Conjugates: Overview
[0058] Syntheses are described with reference to the schemes below. The synthesis of SL-11211 (Scheme 1) started with acetal 1 that was protected by mesitylene sulfonation to give 2. Alkylation of the known triamide 3 with 4-bromobutyronitrile following the procedure described previously (see Examples), reduction of the resulting nitrile and mesitylene sulfonation of the free amine gave octaamide 4. Treatment of 4 with 1,4-dibromobutane gave 5, that was then condensed with 2 to afford 6. Cleavage of the acetal residue of 6 resulted in the aldehyde 7, that was subjected to reductive amination with ethylamine to give 8. The amine was then condensed with mesoporhyrin dihdrochloride to the porphyrin diamide 9; deprotection of the amino residues of 9 gave SL-11211.
[0059] The synthesis of SL-11233 (Scheme 2) started with the known triamide 10 that was alkylated with 1,4-dibromobutane to give 11. The latter is condensed with 2 to give 12, the acetal cleaved to aldehyde 13, and the latter reductively aminated to 14. Condensation of 14 with deuteroporphyrin IX 2,4-disulfonic acid gave 15. Cleavage of the protecting groups in 15 allowed the synthesis of SL-11233.
[0060] The synthesis of SL-11235 started with the condensation of 8 and deuteroporphyrin IX-2,4-disulfonate to give 16 (Scheme 3). Deprotection of the amino residues gave SL-11235 eicosahydrobromide.
[0061] The synthesis of SL-11236 started with the condensation of 8 and N-methylmesoporphyrin IX to give 17, that was then deprotected to give SL-11236 eicosahydrobromide (Scheme 3).
[0062] The synthesis of SL-11237 started with the previously described cyclic amine 18 (patent cyclic polyamines) that was condensed with mesoporphyrin IX. dihydrochloride to give SL-11237 (Scheme 3).
[0063] The synthesis of SL-11217 (Scheme 4) started with the known cyclopropyl derivative 19, that was hydrolyzed to the acid and the latter transformed into its chloride 20. Condensation of 20 with a protected N-ethyl 1,4-diaminobutane gave 21, that was reduced with diborane and then acylated with mesitylenesulfonyl chloride to give 22. Alkylation of 22 with dibromobutane in the presence of sodium iodide gave 23, that was condensed with ethylamine to give 24.
[0064] Condensation of 24 with mesoporphyrin IX dihydrochloride gave 25, deprotection of the amino residues gave SL-11217 hydrobromide.
[0065] The synthesis of SL-11209 started with the known amine 26 that was alkylated with the benzyl ether of 4-bromobutanol to give 27 (Scheme 5). Hydrolysis of the benzyl ether gave the alcohol 28, the alcohol was protected by reaction with t-butyloxycarbonyl anhydride to give 29, and the latter oxidized to the aldehyde 30. Reductive amination of 30 gave 31. In tandem, reduction of the diester of mesoporphyrin gave the dialdehyde 32. Condensation of 32 with 31, followed by acid deprotection of the amino residues gave SL-11209.
[0066] The synthesis of SL-11210 started with the known nitrile 33 that was reduced to the amine and the latter condensed with 32 following a reductive amination procedure (Scheme 6). Deprotection of the amino residues gave SL-11210.
[0067] Reductive amination procedures allowed the condensation of 18 and aldehyde 32 that gave SL-11257 (Scheme 7)
[0068] Therapeutic Use of Porphyrin-Polyamine Conjugate Compounds
[0069] Porphyrin-polyamine conjugate compounds of the present invention are useful for treatment of a variety of diseases caused by uncontrolled proliferation of cells, including cancer, particularly prostate cancer. The compounds are used to treat mammals, preferably humans. “Treating” a disease using a porphyrin-polyamine conjugate compound of the invention is defined as administering one or more porphyrin-polyamine conjugate compounds of the invention, with or without additional therapeutic agents, in order to prevent, reduce, or eliminate either the disease or the symptoms of the disease, or to retard the progression of the disease or of symptoms of the disease. “Therapeutic use” of the porphyrin-polyamine conjugate compounds of the invention is defined as using one or more porphyrin-polyamine conjugate compounds of the invention to treat a disease, as defined above.
[0070] In order to evaluate the efficacy of a particular porphyrin-polyamine conjugate compound for a particular medicinal application, the compounds can be first tested against appropriately chosen test cells in vitro. In a non-limiting example, porphyrin-polyamine conjugate compounds can be tested against tumor cells, for example, prostate tumor cells. Exemplary experiments can utilize cell lines capable of growing in culture as well as in vivo in athymic nude mice, such as LNCaP. Horoszewicz et al. (1983) Cancer Res. 43:1809-1818. Culturing and treatment of carcinoma cell lines, cell cycle and cell death determinations based on flow cytometry; enzyme assays including ODC, SAMDC and SSAT activities; and high pressure liquid chromatography detection and quantitation of natural polyamines and polyamine analogs are described in the art, for example, Mi et al. (1998) Prostate 34:51-60; Kramer et al. (1997) Cancer Res. 57:5521-27; and Kramer et al. (1995) J. Biol. Chem. 270:2124-2132. Evaluations can also be made of the effects of the porphyrin-polyamine conjugate compound on cell growth and metabolism.
[0071] Analysis begins with IC 50 determinations based on dose-response curves ranging from 0.1 to 1000 μM performed at 72 hr. From these studies, conditions can be defined which produce about 50% growth inhibition and used to: (a) follow time-dependence of growth inhibition for up to 6 days, with particular attention to decreases in cell number, which may indicate drug-induced cell death; (b) characterize porphyrin-polyamine conjugate compound effects on cell cycle progression and cell death using flow cytometry (analysis to be performed on attached and detached cells); (c) examine porphyrin-polyamine conjugate compound effects on cellular metabolic parameters. Porphyrin-polyamine conjugate compound effects can be normalized to intracellular concentrations (by HPLC analysis), which also provide an indication of their relative ability to penetrate cells. Marked differences in porphyrin-polyamine conjugate compound uptake can be further characterized by studying the compound's ability to utilize and regulate the polyamine transporter, as assessed by competition studies using radiolabeled spermidine, as previously described in Mi et al. (1998). Porphyrin-polyamine conjugate compounds could also enter the cells by a diffusion mechanism.
[0072] In Vivo Testing of Porphyrin-Polyamine Conjugate Compounds
[0073] Porphyrin-polyamine conjugate compounds found to have potent anti-proliferative activity in vitro towards cultured carcinoma cells can be evaluated in in vivo model systems. The first goal is to determine the relative toxicity of the compounds in non-tumor-bearing animals, such as DBA/2 mice. Groups of three animals each can be injected intraperitoneally with increasing concentrations of a porphyrin-polyamine conjugate compound, beginning at, for example, 10 mg/kg. Toxicity as indicated by morbidity is closely monitored over the first 24 hr. A well-characterized polyamine analog compound, such as BE-333, can be used as an internal standard in these studies, since a data base has already been established regarding acute toxicity via a single dose treatment relative to chronic toxicity via a daily×5 d schedule. Thus, in the case of porphyrin-polyamine conjugate compounds, single dose toxicity relative to BE-333 is used to project the range of doses to be used on a daily×5 d schedule. The toxicity of the porphyrin-polyamine conjugate compound can also be tested versus the free polyamine compound, that is, versus the same polyamine which is present in the porphyrin-polyamine conjugate compound but without a conjugated porphyrin.
[0074] After the highest tolerated dosage on a daily×5 d schedule is deduced, antitumor activity is determined. Typically, tumors can be subcutaneously implanted into nude athymic mice by trocar and allowed to reach 100-200 mm 3 before initiating treatment by intraperitoneal injection daily×5 d. Most porphyrin-polyamine conjugate compounds can be given in a range between 10 and 200 mg/kg. Porphyrin-polyamine conjugate compounds can be evaluated at three treatment dosages with 10-15 animals per group (a minimum of three from each can be used for pharmacodynamic studies, described below). Mice can be monitored and weighed twice weekly to determine tumor size and toxicity. Tumor size is determined by multi-directional measurement from which volume in mm 3 is calculated. Tumors can be followed until median tumor volume of each group reaches 1500 mm 3 (i.e., 20% of body weight), at which time the animals can be sacrificed. Although the initial anti-tumor studies focuses on a daily×5 d schedule, constant infusion can be performed via Alzet pump delivery for 5 days since this schedule dramatically improves the anti-tumor activity of BE-333 against A549 human large cell hung carcinoma. Sharma et al. (1997) Clin. Cancer Res. 3:1239-1244. In addition to assessing anti-tumor activity, free porphyrin-polyamine conjugate compound levels and free polyamine levels in tumor and normal tissues can be determined in test animals.
[0075] Methods of Administration of Porphyrin-Polyamine Conjugate Compounds
[0076] The porphyrin-polyamine conjugate compounds of the present invention can be administered to a mammalian, preferably human, subject via any route known in the art, including, but not limited to, those disclosed herein. Methods of administration include but are not limited to, oral, intravenous, intraarterial, intratumoral, intramuscular, topical, inhalation, subcutaneous, intraperitoneal, gastrointestinal, and directly to a specific or affected organ. The porphyrin-polyamine conjugate compounds described herein are administratable in the form of tablets, pills, powder mixtures, capsules, granules, injectables, creams, solutions, suppositories, emulsions, dispersions, food premixes, and in other suitable forms. The compounds can also be administered in liposome formulations. The compounds can also be administered as prodrugs, where the prodrug undergoes transformation in the treated subject to a form which is therapeutically effective. Additional methods of administration are known in the art.
[0077] The pharmaceutical dosage form which contains the compounds described herein is conveniently admixed with a non-toxic pharmaceutical organic carrier or a non-toxic pharmaceutical inorganic carrier. Typical pharmaceutically-acceptable carriers include, for example, mannitol, urea, dextrans, lactose, potato and maize starches, magnesium stearate, talc, vegetable oils, polyalkylene glycols, ethyl cellulose, poly(vinylpyrrolidone), calcium carbonate, ethyl oleate, isopropyl myristate, benzyl benzoate, sodium carbonate, gelatin, potassium carbonate, silicic acid, and other conventionally employed acceptable carriers. The pharmaceutical dosage form can also contain non-toxic auxiliary substances such as emulsifying, preserving, or wetting agents, and the like. A suitable carrier is one which does not cause an intolerable side effect, but which allows the novel porphyrin-polyamine conjugate compound(s) to retain its pharmacological activity in the body. Formulations for parenteral and nonparenteral drug delivery are known in the art and are set forth in Remington's Pharmaceutical Sciences, 18th Edition, Mack Publishing (1990). Solid forms, such as tablets, capsules and powders, can be fabricated using conventional tableting and capsule-filling machinery, which is well known in the art. Solid dosage forms, including tablets and capsules for oral administration in unit dose presentation form, can contain any number of additional non-active ingredients known to the art, including such conventional additives as excipients; desiccants; colorants; binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrollidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; tableting lubricants, for example magnesium stearate, talc, polyethylene glycol or silica; disintegrants, for example potato starch; or acceptable wetting agents such as sodium lauryl sulfate. The tablets can be coated according to methods well known in standard pharmaceutical practice. Liquid forms for ingestion can be formulated using known liquid carriers, including aqueous and non-aqueous carriers, suspensions, oil-in-water and/or water-in-oil emulsions, and the like. Liquid formulations can also contain any number of additional non-active ingredients, including colorants, fragrance, flavorings, viscosity modifiers, preservatives, stabilizers, and the like. For parenteral administration, porphyrin-polyamine conjugate compounds can be administered as injectable dosages of a solution or suspension of the compound in a physiologically acceptable diluent or sterile liquid carrier such as water or oil, with or without additional surfactants or adjuvants. An illustrative list of carrier oils would include animal and vegetable oils (e.g., peanut oil, soy bean oil), petroleum-derived oils (e.g., mineral oil), and synthetic oils. In general, for injectable unit doses, water, saline, aqueous dextrose and related sugar solutions, and ethanol and glycol solutions such as propylene glycol or polyethylene glycol are preferred liquid carriers. The pharmaceutical unit dosage chosen is preferably fabricated and administered to provide a final concentration of drug at the point of contact with the cancer cell of from 1 μM to 10 mM. More preferred is a concentration of from 1 to 100 μM. The optimal effective concentration of porphyrin-polyamine conjugate compounds can be determined empirically and will depend on the type and severity of the disease, route of administration, disease progression and health and mass or body area of the patient. Such determinations are within the skill of one in the art. Porphyrin-polyamine conjugate compounds can be administered as the sole active ingredient, or can be administered in combination with another active ingredient, including, but not limited to, cytotoxic agents, antibiotics, antimetabolites, nitrosourea, vinca alkaloids, polypeptides, antibodies, cytokines, etc.
EXAMPLES
[0078] The following examples are provided to illustrate the invention, and are not intended to limit the invention in any manner.
Synthesis of SL11211
Example 1
N— Mesitylenesulfonyl 4-aminobutyraldehyde diethyl acetal 2
[0079] Amine 1 (Aldrich) (3.5 g, 21.7 mol) was dissolved in a mixture of chloroform (30 ml) and 1N sodium hydroxide (24 ml) and 15 ml of mesitylenesulfonyl chloride dissolved in 15 ml of chloroform were added at 5° C. The mixture was stirred for 2 h, the reaction mixture was then diluted with chloroform (50 ml), the organic layer was separated, washed with a saturated solution of ammonium chloride, dried (Na 2 SO 4 ), and evaporated to dryness. The residual oil crystallized after drying and was used in the next step without further purification; 7.0 g (95%) of 2 were obtained; 1 HNMR (CDCl 3 ): ppm 1.15(t,6H), 1.55 (m,4H), 2.30 (s, 3H), 2.65 (s, 6H), 2.95 (q, 2H), 3.40-3.55 (m, 4H), 4.40 (t, 1H), 4.90 (t, 1H), 6.95 (s, 2H); 13 CNMR (CDCl 3 ): ppm 15.19, 20.80, 22.85, 24.55, 30.83, 42.39, 61.40, 102.41, 131.84, 133.82, 138.99, 141.92.
Example 2
[0080] 1 N, 6 N, 11 N, 16 N, 21 N, 26 N, 31 N, 36 N-Octakis(mesitylensulfonyl)-1,6,11,16,21,26,31,36-octaazaoctatriacontane 4 was obtained starting with compound 3 (U.S. PAT APPL. 60/329,982) following the homologation procedure described in WO 00/66587; namely, alkylation with 4-bromobutyronitrile, followed by reduction of the nitrile and protection of the free amino residue with mesitylenesulfonyl chloride. Starting with 7 g of 3, 5.6 g (70%) of 4 were obtained over the aforementioned three synthetic steps; 1 HNMR (CDCl 3 ): 0.95 (t,3H), 1.30 (m, 28H), 2.30 (s, 24H), 2.55 (m, 48H), 2.75 (t, 1H), 3.0 (m, 30H), 6.95 (, 16H); 13 CNMR (CDCl 3 ): 12.71, 20.93, 22.78, 24.49, 24.79, 25.68, 40.07, 41.91, 44.59, 44.95, 131.98, 133.39, 138.94, 139.96, 142.06.
Example 3
3 N, 8 N, 13 N, 18 N, 23 N, 28 N, 33 N, 38 N-Octakis(mesitylenesulfonyl)-3,8,13,18,23,28,33,38-octaaza-42-bromo-dotetracontane 5
[0081] To a solution of amide 4 (5.6 g, 2.8 mmol) and 1,4-dibromobutane (3.6 g, 16.8 mmol) in 45 ml of DMF kept at 5° C. was added 135 mg (3.36 mmol) of NaH (60% dispersion in mineral oil) with constant stirring. The mixture was kept at 22° C. for 18 h; the solvent was then evaporated to dryness, the residue dissolved in chloroform, washed twice with a saturated solution of ammonium chloride, the organic layer separated, dried (Na 2 SO 4 ) and evaporated to dryness. The residue was crystallized from ethyl acetate-hexane; 5.3 g (88%) of 5 were obtained; mp 109° C.; 1 HNMR (CDCl 3 ): 0.95 (t, 3H), 1.40 (m, 32H), 2.30 (s, 24H), 2.50 (m, 48H), 3.00 (m,32H), 3.25 (t, 2H), 6.95 (s, 16H); 13 CNMR (CDCl 3 ): 12.68, 20.89, 22.68, 24.42, 25.78, 29.61, 32.77, 40.03, 44.51, 44.89, 45.04, 131.95, 133.46, 139.91, 142.28.
Example 4
3 N, 8 N, 13 N, 18 N, 23 N, 28 N, 33 N, 38 N, 43 N-Nonakis(mesitylenesulfonyl)-3,8,13,18,23,28,33,38,43-nonaaza-heptatetracontylaldehyde diethyl acetal 6
[0082] To a solution of amide 5 (5.19 g, 2.43 mmol) and acetal 2 (0.915 g, 2.67 mmol) in 50 ml of DMF kept at 5° C. was added 128 mg (3.20 mmol) of NaH (60% dispersion in mineral oil) with constant stirring. The mixture was kept at 22° C. for 18 h and the work up followed the procedure reported for 5; 5.0 g (86%) of 6 were obtained; mp 102.4° C.; 1 HNMR (CDCl 3 ): 0.95 (t, 3H), 1.15 (t, 6H), 1.30 (m, 36H), 2.30 (s, 27H), 2.50 (s, 54H), 3.05 (m,36H), 3.45 (m,m, 4H), 6.95 (s,18H); 13 CNMR (CDCl 3 ): 12.68, 15.26, 20.89, 22.67, 24.57, 30.81, 40.04, 4456, 44.88, 45.23, 102.31, 131.88, 133.39, 139.91, 142.19.
Example 5
3 N, 8 N, 13 N, 18 N, 23 N, 28 N, 33 N, 38 N, 43 N-Nonakis(mesitylenesulfonyl)-3,8,13,18,28,33,38,43-nonaaza-heptatetracontylaldehyde 7
[0083] Acetal 6 (5.0 g) was dissolved in acetone (140 ml) and water (1.5 ml), Amberlyst-15 resin (600 mg) was added and the reaction mixture was stirred for 1 h; the resin was filtered, the solvent evaporated to dryness in vacuo, and the oily residue was used in the next step without further purification; 1 HNMR (CDCl 3 ): 0.95 (t,3H), 1.30(m,36H), 1.72 (m,2H), 2.30 (s,27H), 2.52(s,s, 54H), 3.05 (m,36H), 6.95(s,18H), 9.60 (s, 1H); 13 CNMR (CDCl 3 ): 12.85, 19.89, 21.07, 22.92, 24.60, 24.92, 40.21, 40.79, 44.73, 45.06, 132.13, 133.54, 140.10, 142.47, 200.94; MS (MALDI): 2345.2 (M+Na + ), 2361.2 (M+K + ).
Example 6
3 N, 8 N, 13 N, 18 N, 23 N, 28 N, 33 N, 38 N, 42 N-Nonakis(mesitylenesulfonyl)-3,8,13,18,23,28,33,38,42,47-decaaza-nonatetracontane 8
[0084] To a solution of 4.2 g (1.7 mmol) of aldehyde 7 in 120 ml of DCE, were added 7 ml (8 eq) of a 2M solution of ethylamine in THF. The mixture was kept at 22° C. for 18 h with constant stirring, after which sodium triacetoxyborohydride (720 mg, 3.4 mol) was added. After 2 h at 22° C., the mixture was washed (2×20 ml) with a saturated solution of sodium bicarbonate, dried, and evaporated to dryness. The residue was purified by flash chromathography using Cl 3 CH/MeOH (5% to 10%) as eluant; 2.8 g (68%) of 8 were recovered; 1 HNMR (Cl 3 CD): 0.95 (t,3H), 1.10 (t,3H), 1.30(m, 36H), 2.25 (s, 27H), 2.50(m, 58H), 3.05 (m, 36H), 2.25 (s, 27H), 2.50 (m, 58H), 3.05 (m, 36H), 6.95 (s, 18H); 13 CNMR (CDCl 3 ): 12.66, 14.53, 20.89, 22.74, 24.70, 39.99, 43.73, 44.50, 44.84, 45.17, 48.57, 131.93, 133.31, 139.90, 142.28; MS (MALDI): 2351.92 (M+H + ), 2373.10 (M+Na + ), 2389.97 (M+K + ).
Example 7
Mesoporphyrin IX-bis[ 3 N, 8 N, 13 N 18 N, 23 N, 28 N, 33 N, 38 N, 42 N-nonakis(mesitylenesulfonyl)-3,8,13,18,23,28,33,38,42,47-decaazanonatetracontyl amide]9
[0085] A mixture of amine 8 (750 mg, 0.3 mmol), mesoporphyrin IX (102 mg, 1.4 mmol), and diisopropylethylamine (0.25 ml, 1.4 mmol) in 30 ml of DMF were cooled to 5° C. and kept under a nitrogen atmosphere while 204 mg (0.54 mmol) of HBTU were added. The reaction mixture was stirred for 2 h, the solvent evaporated to dryness, the residue dissolved in chloroform, washed twice with a saturated bicarbonate solution, the organic layer dried (Na 2 SO 4 ) and evaporated to dryness. The residue was purified by chromathography on silica gel using ethyl acetate:hexane (9:1) as eluant; 630 mg (75%) of 9 were recovered; MS (ESI): 5239.3 (M+H + ); 5261.3 (M+Na + ).
Example 8
Porphyrin conjugate SL11211 eicosahydrobromide
[0086] Porphyrin amide 9 (630 mg) was dissolved in a mixture of methylene chloride (12 ml). 30% hydrogen bromide in glacial acetic acid (12 ml), and phenol (900 mg). The reaction mixture was kept at 22° C. for 18 h with stirring, the reaction product was then extracted into water (35 ml), the aqueous layer washed with methylene chloride (3×12 ml), the aqueous solution evaporated to dryness, and the residue crystallized from water/ethanol; 300 mg of SL-11211 hydrobromide (86%) were obtained; mp. 250° C. (dec); MS (ESI): 1958.4 (M+H + , free base), 1980 (M+Na + ).
Example 9
3 N, 8 N, 13 N-Tri(mesitylenesulfonyl)-3,8,13-triaza-17-bromoheptadecane 11
[0087] Intermediate 11 was prepared starting with 10 (ref) and following the procedure described for 5. Starting with 3.6 g of 10 were obtained 2.77 g (65%) of 11; 1 HNMR (CDCl 3 ): 0.98 (t,3H), 1.40 (m, 8H), 1.65 (m,4H), 2.30 (s, 9H), 2.60 (s,18H), 3.10 (m,12H), 3.30 (t, 2H), 6.95 (s,6H); 13 CNMR (CDCl 3 ): 12.75, 20.91, 22.72, 24.58, 25.85, 29.66, 32.79, 40.07, 44.59, 45.10, 131.90, 133.23, 140.03, 142.32.
Example 10
3 N, 8 N, 13 N, 18 N-Tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraaza-doeicosanylaldehyde diethyl acetal 12
[0088] Prepared from 11 following the procedure described for 6. Starting with 2.8 g of 11 were obtained 3.5 g (97%) of acetal 12; 1 HNMR (CDCl 3 ): 1.00 (t, 3H), 1.15 (t, 6H), 1.35 (m, 16H), 2.35 (s, 12H), 2.55(s, 24H), 2.10(m,16H), 3.50 (m, 4H), 4.35 (t,1H), 6.95(s, 8H); 13 CNMR (CDCl 3 ): 12.70, 15.26, 20.87, 22.44, 24.52, 30.81, 40.04, 44.55, 45.00, 45.23, 61.18, 102.31, 131.87, 133.35, 139.97, 142.18.
Example 111
3 N, 8 N, 13 N, 18 N-Tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraaza-doeicosanylaldehyde 13
[0089] The aldehyde was obtained from 12 following the procedure described for 7. From 3.5 g of acetal 12, were obtained 2.9 g (90%) of aldehyde 13; 1 HNMR (CDCl 3 ): 0.95 (t, 3H), 1.35(m, 12H), 1.75 (m,2H), 2.30(m, 14H), 2.45(s, 24H), 3.05 (m, 2H), 2.30 (m, 14H), 2.45 (s, 24H), 3.05 (m, 16H), 6.95 (s, 8H), 9.60 (s, 1H); 13 CNMR (CDCl 3 ): 12.63, 19.68, 20.80, 22.67, 24.68, 26.32, 39.98, 40.54, 43.70, 44.50, 45.06, 131.88, 133.04, 140.32, 142.22, 200.71.
Example 12
3 N, 8 N, 13 N, 18 N-Tetrakis(mesitylenesulfonyl)-3,8,13,18,23-pentaazapentacosane 14
[0090] Amine 14 was prepared from 13 following the procedure described for 8. Starting with 4.7 g of 13 were obtained 3.5 g (72%) of amine 14; 1 HNMR (CDCl 3 ): 1.00 (t, 3H), 1.15(t, 3H), 1.40 (m, 16H), 2.30(s, 12H), 2.60 (m, 28H), 3.10(m, 16H), 6.95(s, 8H); 13 CNMR(CDCl 3 ): 11.70, 12.65, 20.83, 22.69, 23.46, 24.67, 39.96, 42.59, 44.47, 45.07, 46.60, 131.81, 133.26, 139.82, 142.36.
Example 13
2,4-Disulfonyl-Deuteroporphyrin IX-bis[ 3 N, 8 N, 13 N, 18 N-tetrakis(mesitylenesulfonyl)-3,8,13,18,23-pentaazapentacosyl amide] 15
[0091] Porphyrin conjugate 15 was prepared by condensation of 14 with deuteroporphyrin IX disulfonate following the procedure described for 9. From 200 mg of 14 and 70 mg of the porphyrin, 144 mg (55%) of 15 were obtained; MS(MALDI): 2808.79 (M+H + ), 2830.55 (M+Na + ), 2853 (M+2Na + ), 2875.52 (M+ 3 Na + ).
Example 14
Porphyrin conjugate SL11233 decahydrobromide
[0092] Conjugate SL-11233 was obtained from 15 following the procedure described for SL-11211. From 144 mg of 15 were obtained 60 mg (55%) of SL-11233 decahydrobromide; MS (ESI): 1350 (M+H + , M=free base).
Example 15
2,4-Disulfonyl-Deuteroporphyrin IX-bis [ 3 N, 8 N, 13 N, 18 N, 23 N, 28 N, 33 N, 38 N, 42 N-nonakis(mesitylenesulfonyl)-3,8,13,18,23,28,33,38,42,47-decaaza-nonatetracontyl amide] 16
[0093] Porphyrin conjugate 16 was prepared by condensation of amine 8 (216 mg) and deuteroporphyrin IX disulfonate (34 mg) following the procedure described for 9; 140 mg (57%) of 16 were obtained; MS(MALDI): 5342 (M+H + ), 5363 (M+Na + ).
Example 16
Porphyrin conjugate SL-11235 eicosahydrobromide
[0094] Conjugate SL-11235 was obtained from 140 mg of 16 following the procedure described for the synthesis of SL-11211; 70 mg (72%) of SL-11235 eicosahydrobromide were obtained; MS (MALDI): 2062.0(M+H + , M=free base), 1031 (M*/2), 688.0 (M*/3).
Example 17
N-Methyl mesoporphyrin IX-bis[ 3 N, 8 N, 13 N, 18 N, 23 N, 28 N, 33 N, 38 N, 42 N nonakis(mesitylenesulfonyl)-3,8,13,18,23,28,33,38,42,47-decaaza-nonatetracontyl amide] 17
[0095] Amide 17 was prepared by condensation of amine 8 (404 mg) with N-methyl mesoporphyrin IX (50 mg) following the procedure described for 9; 226 mg (50%) of 17 were obtained; MS (MALDI): 5253 (M+H + ).
Example 18
Porphyrin conjugate SL-11236 eicosahydrobromide
[0096] SL-11236 was prepared from 215 mg of 17 following the procedure described for the synthesis of SL-11211; 75 mg (52%) of SL-11236 eicosahydrobromide were obtained; MS(MALDI): 1972.0 (M+H + , M=free base), 1989.0 (M+NH 4 + ), 986.6 (M + /2).
Example 19
Porphyrin conjugate S111237 decahydrochloride
[0097] SL-11237 was prepared by condensation of 424 mg (0.6 mmol) of amine 18 and 191 mg (0.3 mmol) of mesoporphyrin IX following the procedure described for 9. SL-11237 was purified by chromathography on silica gel using chloroform/methanol/ammonium hydroxide: 8/2/0.1 as eluant; the eluted residue was further crystallized from methanol/hydrogen chloride/ethyl acetate; 430 mg (73%) of SL-11237 decahydrochloride were obtained; MS(ESI): 1579.6 (M+H + , M=free base), 1725.6 (M+4HCl), 1871.8 (M+8HCl), 790.23 (M + /2), 527.21 (M + /3), 790.23(M + /2).
Synthesis of SL-11217
Example 20
trans-2-Cyanocyclopropanecarbonyl chloride 20
[0098] 1N Sodium hydroxide (71.9 ml, 71.9 mmol) was added to a solution of nitrile 19 (Payne G B, JOC (1967) 32, 3351) (10.0 g, 71.9 mmol) in 40 ml of methanol. The mixture was stirred during 1 h, the methanol was evaporated, conc.HCl was added to pH 2, the solution extracted with ethyl ether (3×30 ml), the pooled organic layers were dried (Na 2 SO 4 ) and evaporated to dryness. The residual solid (7.4 g, 93%) was used in the next step without further purification. It was dissolved in thionyl chloride (13 ml), the mixture was heated to 65° C./4 h, the thionyl chloride was then distilled off and 20 was purified by distillation at 50° C./0.5 mm; 4.3 g (54% over two steps) were obtained; 1 HNMR (Cl 3 CD): 1.80 (m, 2H), 2.25 (m, 1H), 2.80 (m, 1H); 13 CNMR (Cl 3 CD); 8.62, 1701, 30.20, 117.46, 171.34.
Example 21
trans 2-Nitrile-1-(N-ethyl-N-mesitylenesulfonyl-aminobutyl) cyclopropanecarboxamide 21
[0099] A solution of acyl chloride 20 (4.36 g, 33.7 mmol) in THF (43 ml) was added dropwise to a solution of N-ethyl-N(mesitylenesulfonyl)-1,4-diamine (10.0 g, 33.7 mmol) (ref) and triethylamine (2.9 ml) in 100 ml of THF while the mixture was kept at 5° C. under nitrogen. Triethylammonium chloride precipitated; the mixture is further kept at 22° C. during 18 h, then extracted with ethyl acetate (80 ml), the organic layer washed with 2N HCl (10 ml), then with a saturated ammonium chloride solution (10 ml), dried (Na 2 SO 4 ), and evaporated to dryness. The residue was purified by flash chromathography on silica gel using hexane/ethyl acetate: 6/4 as eluant; 10.3 g (78%) of 21 were obtained; 1 HNMR (CDCl 3 ): 10.2 (t, 3H), 1.35(m,1H), 1.55 (m, 5H), 1.90 (m, 1H), 2.05 (m, 1H), 2.35 (s, 3H), 2.60 (s, 6H), 3.25 (m, 6H), 6.35 (t, 1H), 6.95 (s, 2H); 13 CNMR (Cl 3 CD): 4.44, 12.59, 20.87, 22.62, 22.69, 25.00, 26.37, 39.42, 40.04, 44.63, 120.14, 131.91, 133.23, 140.00, 142.37, 168.17.
Example 22
trans 1N-(Mesitylenesulfonyl)-2N(mesitylenesulfonyl)-2N(1′-N,N-(mesitylenesulfonyl)ethylaminobutyl)1,2-diaminomethylcyclopropane 22
[0100] Amide 21 (8.5 g, 21.7 mmol) was dissolved in 40 ml of THF, 156 ml of THF.1M BH3 were added and the solution was heated at 70° C. during 2 h. The solution was cooled to 5° C., 30 ml of 6N HCl was slowly added while stirring, and the mixture was kept at 5° C. during 18 h. The pH of the mixture was then adjusted to pH 10 with 50% potassium hydroxide, the oil that separated was extracted into chloroform (3×50 ml), the organic extracts were dried (Na 2 SO 4 ), and evaporated to dryness. The residue was dissolved in 100 ml of chloroform, 50 ml of 2N sodium hydroxide were added, the mixture cooled to 5° C., and mesitylenesulfonyl chloride (8.2 g, 386 mmol) dissolved in 10 ml of chloroform were added with efficient stirring. After 2 h, the organic layer was separated, dried (Na 2 SO 4 ), and evaporated to dryness. The residue was purified by flash chromathography on silica gel using hexane/ethyl acetate: 7/3 as eluant; 11.33 g (69% over two steps) of 22 were obtained; 1 HNMR (Cl 3 CD): 0.40 (t, 2H), 0.95 (m, 5H), 1.25 (m, 4H), 2.25 (s, 9H), 2.35-2.65 (m, s, s, 20H), 2.85-3.30 (m, 8H), 5.50 (t, 1H), 6.95 (s, 6H); 13 CNMR (CDCl 3 ) 10.02, 12.63, 16.15, 17.57, 20.87, 22.63, 22.69, 22.89, 24.01, 24.61, 39.97, 44.49, 44.89, 46.52, 48.28, 131.85, 132.34, 133.39, 133.97, 139.01, 139.97, 140.30, 141.73, 142.22, 142.60; MS (TOF): 768.2 (M+Na + ), 784.2 (M+K + ).
Example 23
3 N, 8 N, 13 N-Tris(mesitylenesulfonyl)-17-iodo-((E)-10,11-cyclopropane)-3,8,13-triaza-heptadecane 23
[0101] Triamide 22 (10.3 g, 13.8 mmol) was dissolved in 100 ml of DMF, cooled to 5° C., and sodium hydride (662 mg, 16.5 mmol) was added. The reaction mixture reached 22° C. when 1,4-dibromobutane (29.8 g, 138 mmol) and sodium iodide (20.7 g, 138 mmol) were added, and the mixture was heated at 75° C. for 90 min. The solution was evaporated to dryness, the residue dissolved in chloroform, the solution was washed with sodium thiosulfate, dried (Na 2 SO 4 ), and evaporated to dryness. The residue was purified on a silica gel column using hexane/ethyl acetate; from 8/2 to 7/3 as eluant; 10.8 g (84%) of 23 were obtained; 1 HNMR (Cl 3 CD): 0.40 (m, 2H), 0.80 (m, 2H), 1.02 (t, 3H), 1.40(m, 4H), 1.60 (m, 4H), 2.30 (s, 9H), 2.60 (s, 18H), 2.80-3.30 (m, 14H), 6.95 (s, 6H); 13 CNMR (Cl 3 CD): 5.73, 11.01, 12.73, 16.07, 20.93, 22.74, 24.41, 25.65, 27.96, 29.62, 30.35, 32.92, 40.03, 44.40, 44.58, 45.24, 131.93, 140.09, 142.34, 142.48.
Example 24
3 N, 8 N, 13 N, 18 N-Tris(mesitylenesulfonyl)-((E)-10,11-cyclopropane) 3,8,13,18-tetraazaeicosane 24
[0102] Triamide 23 (10.8 g, 11.6 mmol) was dissolved in 25 ml of THF and a 2M ethylamine solution in methanol was added (150 ml). The solution was heated at 65° C. during 16 h, then evaporated to dryness, the residue dissolved in chloroform, the chloroform washed with a concentrated solution of ammonium chloride, dried (Na 2 SO 4 ), evaporated to dryness, and the residue purified by column chromathography on silica gel using from 5% to 10% methanol in chloroform as an eluant; 9.3 g (94%) of 24 were obtained; 1 HNMR (Cl 3 CD): 0.40 (t, 2H), 0.80 (m, 3H), 1.03 (t, 3H), 1.20 (t, 3H), 1.35 (m, 4H), 1.55 (m,4H), 2.25 (s, 9H), 2.40-3.35 (s, m, 34H), 6.95 (s, 6H); 13 CNMR (Cl 3 CD): 11.02, 12.70, 13.70, 16.04, 20.90, 22.71, 24.37, 24.76, 25.57, 40.02, 43.43, 44.57, 45.18, 45.33, 48.02, 48.83, 131.91, 133.13, 140.04, 142.34; MS (ESI): 846 (M+H + ).
Example 25
Mesoporphyrin IX-bis [ 3 N, 8 N, 13 N, 18 N-tris(mesitylenesulfonyl)-((E)-10,11-cyclopropane)-3,8,13,18-tetrazaeicosanylamide] 25
[0103] Porphyrin diamide 25 was prepared by the condensation of 8.9 g (10.5 mmol) of 24 and mesoporphyrin IX (3.2 g, 5 mmol) following the procedure described for 9; 9.24 g (83%) of 25 were obtained; MS (MALDI): 2241 (M+Na + ).
Example 26
SL-11217 octahydrobromide
[0104] SL-11217 was prepared by cleavage of the protecting groups of 4.6 g of 25 following the procedure described for the synthesis of SL-11211; 3.4 g (96%) of SL-11217 octahydrobromide were obtained; mp>250° C. (dec), crystallized from methanol/ethyl acetate; MS (ESI): 1128.2 (M+H + ), 1150 (M+Na + ), 1167 (M+K + ), 564.6 (M+/2).
Synthesis of SL-11209 dodecahydrochloride
Example 27
Benzyl 3 N, 8 N, 13 N, 18 N-Tetrakis(mesitylenesulfonyl)-3,8,13,18-tetraazauneicosanyl alcohol 27
[0105] A suspension of NaH (60% in mineral oil, 440 mg, 14 mmol) in DMF (50 ml) was slowly added to a stirred solution of benzyl-4-bromobutyl ether (3.33 g, 13.7 mmol) and amide 26 (5.41 g, 5.48 mmol) (WO 00/66587) in DMF (100 ml) kept at 5° C. The reaction mixture was stirred for 10 h at 50° C., quenched with 5 ml of H 2 O at 0° C., and evaporated to dryness in vacuo. The residue was taken up in ethyl acetate, washed with H 2 O, and purified on a silica gel column using ethyl acetate/hexane: 3/7 as eluant; 5.1 g, (81%) of 27 were obatained; 1 H-NMR (CDCl 3 ): 0.97 (t, J=7.1 Hz, 3H), 1.2-1.5 (m, 16H), 2.27 (s, 3H), 2.29 (s, 9H), 2.55 (s, 24H), 2.9-3.2 (m, 16H), 3.31 (t, J=6.0 Hz), 4.41 (s, 2H), 6.9-7.0 (m, 8H), 7.2-7.4 (m, 5H).
Example 28
3,8,13,18-Tetrazauneicosanyl alcohol 28
[0106] A solution of 30% HBr in glacial acetic acid (90 ml) was added to a stirred solution of 27 (4.50 g) and phenol (12.65 g) in methylene chloride (45 ml) at 0° C. The cooling bath was removed and the reaction mixture was stirred for 24 h at 20° C. The reaction mixture was quenched with H 2 O (90 ml), washed with methylene chloride, and concentrated to dryness in vacuo. The residue was cooled to 0° C., basified with 2N sodium hydroxide (9 ml), followed by 50% potassium hydroxide (9 ml). The product was extracted with chloroform (7×10 ml); 1.07 g (81%) of 28 were obtained; 1 H-NMR (CDCl 3 ): 1.10 (t, J=7 Hz, 3H), 1.40-1.75 (m, 16H), 2.55-2.75 (m, 16H), 3.57 (t, J=5.0 Hz); 13 C-NMR (CDCl 3 ): 15.23, 27.55, 27.92, 28.58, 32.35, 44.02, 49.35, 49.66, 49.80, 62.32.
Example 29
3 N, 8 N, 13 N, 18 N— Tetrakis(butyloxycarbonyl)-3,8,13,18-tetrazauneicosanyl alcohol 29
[0107] A solution of 10% sodium carbonate (26 ml) was added to a solution of tetramine 28 (634 mg, 1.92 mmol) in dioxane (16 ml). Di-tert-butyl dicarbonate (2.5 g, 11.5 mmol) in dioxane (16 ml) was added into the reaction mixture at 0° and stirred for 10 h at 20° C. The reaction mixture was diluted with chloroform (200 ml), washed with water, then with brine, dried (Na 2 SO 4 ), evaporated to dryness, and purified by chromathography on a silica gel column using ethyl acetate/hexane:4/6 as eluant; 1.34 g, (96%) of 29 were obtained; 1 H-NMR (CDCl 3 ): 1.09 (t, J=7.1 Hz, 3H), 1.4-1.7 (m, 52H), 3.05-3.3 (m, 16H,), 3.67 (t, J=5.8 Hz, 2H).
Example 30
3 N, 8 N, 13 N, 18 N-Tetrakis(butyloxycarbonyl)-3,813,18-tetrazauneicosanyl aldehyde 30
[0108] Oxalyl chloride (2N solution in methylene chloride, 0.821 μl, 1.64 mmol) was diluted with anhydrous methylene chloride (6 ml) at −60° C. DMSO (223 μl, 2.59 mmol) in methylene chloride (3 ml) was added to the mixture, the latter stirred for 5 min at −60° C., and 29 (1.12 g, 1.53 mmol) dissolved in methylene chloride (9 ml) was added to the reaction mixture. After 30 min of stirring at −60° C., triethylamine (1.06 ml, 14.46 mmol) was added to the reaction mixture and the temperature was allowed to rise to 20° C. (ca. 1.5 h). The reaction mixture was diluted with methylene chloride, washed with H 2 O, saturated sodium bicarbonate, and brine. The organic layer was concentrated to dryness in vacuo and purified by column chromatography on silica gel using ethyl/acetate/hexane:3/7 as eluant; 989 mg (89%) of 30 were obtained; 1 H-NMR (CDCl 3 ): 1.09 (t, J=7.0 Hz, 3H), 1.4-1.6 (m, 48H), 1.84 (m, 2H), 2.45 (t, J=6.8, 2H), 3.05-3.3 (m, 16H), 9.78 (s, 1H).
Example 31
3 N, 8 N, 13 N, 18 N, 23 N-Tetrakis(butyloxyarbonyl)-3,8,13,18,23-pentaza-pentaeicosane 31
[0109] Platinum oxide (100 mg) was reduced in methanol (30 ml) with hydrogen at 30 psi. for 15 min. Aldehyde 30 (989 mg, 1.36 mmol) dissolved in a 2M solution of ethylamine in ethanol (7 ml) was added to the hydrogenation flask, and the mixture hydrogenated for 10 h at 50 psi. The catalyst was removed by filtration through celite and the filtrate was concentrated to dryness in vacuo; 1.0 g (99%) of 31 were obtained; 1 H-NMR (CDCl 3 ): 1.09 (t, J=7.6 Hz, 3H), 1.12 (t, J=7.2 Hz, 3H), 1.3-1.65 (m, 50H, CH 2 ), 1.66 (m, 2H), 2.71 (m, 2H), 3.1-3.3 (m, 18H). MS-MALDI (m/z):758.8 (M + , 100%), 744 (30%).
Example 32
1,3,5,8-Tetramethyl-Z 4-diethyl-6,7-di(propionaldehyde)porphyrin 32
[0110] Diisobutylaluminum hydride (1.16 ml of 1.5 M solution in toluene, 1.74 mmol) was added to a solution of mesoporphyrin IX dimethyl ester (500 mg, 0.84 mmol) in CH 2 Cl 2 (10 ml) at −78° C., the mixture was stirred at this temperature for 1 h, then quenched with a saturated solution of NH 4 Cl (1 ml), followed by a 3.7% solution of HCl (2 ml). The temperature of the reaction mixture was allowed to rise to 20° C., the product was extracted with CH 2 Cl 2 , dried (Na 2 SO 4 ), and purified on a column of silica gel using ethyl acetatelhexane:3/7 as eluant, 330 mg (73%) of 32 were obtained; 1 HNMR (CDCl 3 ): 1.86 (t, J=7.6 Hz, 6H), 3.39 (t, J=7.4 Hz, 6H), 3.60 (s, 6H), 3.62 (s, 6H), 4.04.2 (m, 4H), 4.5-4.45 (m, 4H), 9.97 (s, 1H), 10.04 (s, 1H), 10.05 (s, 1H), 10.06 (s, 1H), 10.065 (s, 1H), 10.07 (s, 1H).
Example 33
SL-11209 dodecahydrochloride
[0111] Amine 31 (182 mg, 0.24 mmol) and dialdehyde 32 (58 mg, 0.11 mmol) were mixed in 1,2-dichloroetane (3 mL) and sodium triacetylborohydride (60 mg, 0.28 mmol) was added at 22° C., the mixture was stirred for 3.5 h and then quenched with a solution of sodium bicarbonate. The reaction mixture was diluted 3 times with chloroform, washed with H 2 O, dried (Na 2 SO 4 ) and concentrated to dryness in vacuo. The residue was dissolved in methylene chloride, cooled to 0° C. and trifluoroacetic acid added. After stirring for 1.5 h, the cooling bath was removed, the mixture was evaporated to dryness.
[0112] The residue was dissolved in 10% HCl, the aqueous layer washed with chloroform, and the water removed in vacuo; 134 mg (74%) of crude SL-11209 were obtained. The product was purified by HPLC (Column: 21.5 mm×250 mm, C 18 Dynamax, eluent A=0.1% TFA, eluent B=0.088% TFA in 90% acetonitrile). The pure product was dissolved in 10% HCl (5 mL), and evaporated to dryness in vacuo. 1 H NMR (D20): 1.16 (t, J=7.0 Hz, 6H), 1.34 (t, J=7.3 Hz, 6H), 1.60-2.00 (m, 38H), 2.50-2.70 (m, 4H), 2.90-3.30 (m, 40H) 3.50-3.65 (m, 4H), 3.75 (s, 6H), 3.82 (s, 6H), 4.20-4.35 (m, 4H), 4.45-4.60 (m, 4H), 10.5 (bs, 4H). MS (MALDI), 1240.6 [M+Na] + , 1218.4, [M+1] + .
SLIL-11210 dodecahydrochloride
Example 34
1,3,5,8-Tetramethyl-Z 7-diethyl-6,7-bis[ 3′ N, 8′ N, 13′ N, 18′ N-tetrakis (mesitylenesulfonyl)-3′,8′,13′,18′,23′-pentaazaheptaeicosane]porphyrin 34
[0113] A solution of nitrile 33 (1.6 g, 1.5 mmol) (U.S. PAT APPL. 60/329,982) in ethanol (90 ml) and chloroform (1.6 ml) was hydrogenated in the presence of PtO 2 (160 mg) under 50 psi for 10 h, the suspension filtered through a celite cake, evaporated to dryness and dried in vacuo. The product was dissolved in 1,2-dichloroetane (10 mL), dialdehyde 32 (370 mg, 0.69 mmol) was added followed by triethylamine (0.23 ml, 1.67 mmol). The reaction was stirred for 20 h, after which sodium triacetylborohydride (352 mg, 1.66 mmol) was added and the mixture further stirred for 3.5 h. The reaction mixture was quenched with a solution of sodium bicarbonate, thrice its volume of chloroform was added; the organic layer was washed with H 2 O, dried, and evaporated to dryness in vacuo. The residue was dissolved in methylene chloride (20 mL), cooled to 0° C., made basic with 2N sodium hydroxide (5 mL) and mesitylsulfonyl chloride (333 mg, 1.5 mmol) was added. After 10 h of stirring at 22° C. and following the usual workup the reaction product was purified by column chromatography on silica gel using chloroform/ethyl acetate; 9/1 as eluant; 729 mg (35%) of 34 were obtained; 1 H NMR (CDCl 3 ): 0.93 (t, J=7.14 Hz), 1.05-1.50 (m,) 1.50-1.70 (m), 1.90 (t, J=7.14 Hz), 2.05 (s), 2.07 (s), 2.08 (s), 2.13 (s), 2.16 (s), 2.21 (s), 2.24 (s), 2.29 (s), 2.41 (s), 2.45 (s), 2.49 (s), 2.52 (s), 2.70-3.10 (m), 3.10-3.25 (m), 3.40-3.52 (m), 3.53 (s), 3.54 (s), 3.66 (s), 3.85-4.00 (m), 4.0-4.2 (m), 5.97 (s), 6.02 (s), 6.75 (s), 6.79 (s), 6.84 (s), 6.87 (s), 6.92 (s), 9.69 (s), 10.08 (s), 10.14 (s); MS (MALDI), 3007.02 [M+Na] + , 2985.05 [M+1] + , 2983.95 [M] + , 1493.58 [M] 2+.
Example 35
SL-11210 dodecahydrochloride
[0114] SL-11210 was prepared from 34 following the procedure described for the synthesis of SL-11211. From 730 mg of 34 were obtained 360 mg (69%) of the dodecahydrobromide; 1 HNMR (D20): δ 1.34 (t, J=7;3 Hz, 6H), 1.70-2.00 (m, 38H), 2.50-2.70 (m, 4H), 3.05-3.35 (m, 36H), 3.40-3.55 (m, 4H), 3.78 (2s, 6H), 3.82 (2s, 6H), 4.20-4.40 (m, 4H), 4.40-4.60 (m, 4H), 10.40 (bs, 4H). MS (free base, MALDI), 1161.95 [M] + . The dodecahydrobromide was converted into dodecahydrochloride after HPLC purification and treatment of the eluate with 20% HCl. MS (free base, MALDI), 1162.02 [M] + , 581.82 [M] 2+ .
Example 36
SL-11257 dodecahydrochloride
[0115] Amine 18 (310 mg, 0.44 mmol), dialdehyde 32(118 mg, 0.22 mmol), and triethylamine (0.16 ml) were dissolved in 27 ml of dichloroethane. The reaction was kept at 22° C. during 18 h, sodium triacetoxyborohydride (186 mg, 10.9 mmol) was then added, the reaction mixture was kept for further 2 h, it was then diluted with chloroform, the solution washed with saturated sodium bicarbonate, dried (Na 2 SO 4 ), and evaporated to dryness. The residue was purified by column chromathography on silica gel using chloroform/methanol/ammonium hydroxide; 8/2/0.3 as eluant; 190 mg of SL-11257 were obtained. After purification by HPLC, 90 mg (20%) of pure material were obtained; MS (MALDI): 1551.8 (M+H + , M=free base), 311.18 (M + /2), 388.79(M + /4), 517.8 (M + /3), 776.03 (M + /2).
Example 37
MTT Assay
[0116] A conventional MTT assay was used to evaluate percent cell survival. Exponentially growing monolayer cells were plated in 96-well plates at a density of 500 cells per well and allowed to grow for 24 hours. Serial dilutions of the drugs were added to the wells. Six days after drug treatment, 25 μl of MTT solution (5 mg/ml) was added to each well and incubated for 4 hours at 37° C. Then 100 μl of lysis buffer (20% sodium dodecyl sulfate, 50% DMF, and 0.8% acetic acid, pH 4.7) was added to each well and incubated for an additional 22 hours. A microplate reader (“EMAX”-brand, Molecular Devices, Sunnyvale, Calif.) set at 570 nm was used to determine the optical density of the cultures. Results are expressed as a ratio of the optical density in drug-treated wells to the optical density in wells treated with vehicle only. Tables 1, 2, and 3 below describe the results of the assays on various cell lines. FIGS. 1-13 also indicate the effects of the compounds on various cell lines.
[0117] Other suitable assays for testing the compounds of the invention are described in International Patent Application Nos. WO 00/66587 and WO 02/10142, and U.S. Pat. Nos. 6,392,098, 5,889,061, and 5,677,350
TABLE 1 Effect of Porphyrin Polyamine Analogues on Human Prostate Tumor Cell Growth by the MTT assay ID 50 (μM) values for Human prostate tumor Cell Lines Tsu-pr1- Compounds DuPro PC-3 DU145 LnCap Tsu-pr1 ADR SL-11209 1.4 1.7 — — — SL-11211 0.46 1.7 — — 0.35 0.66 SL-11217 3.6 2.8 — — — — SL-11233 1.4 3.9 >31.25 >31.25 — — SL-11235 0.12 0.45 0.17 0.2 — — SL-11236 0.08 0.49 0.14 0.2 — — SL-11237 1.9 1.7 — — 1.87 12.62 — Not done
[0118]
TABLE 2
Effect of Porphyrin Polyamine Analogs on Human
Pancreatic Cancer Cell Growth by MTT Assay.
ID 50 (μM) values for Human
Pancreatic Cancer Cell Lines
Compounds
BxPC-3
Panc-1
SL-11217
6.87
6.38
SL-11237
5.92
12.45
[0119]
TABLE 3
Effect of Porphyrin Polyamine Analogs on Human
Brain Tumor Cell Growth by MTT Assay.
ID 50 (μM) values for Human
Brain Tumor Cells U251MG
Compounds
NCI
SL-11217
5.65
SL-11237
2.30
Example 38
Oral Administration of SL-11237
[0120] Male athymic nude mice were given subcutaneous injections of 0.75×10 6 DU145 cells on Day 0. Beginning on Day 10, mice were treated once weekly for 3 weeks with acidified water, 100 mg/kg, or 500 mg/kg of SL-11237 via oral gavage at 10 ml/kg dosing volume (the third treatment was actually 400 mg/kg in the high dose group). The results are depicted in FIG. 14 , where the top panel depicts average tumor volume in the mice. The bottom panel of FIG. 14 depicts average body weight of the mice. Oral administration thus provides an effective and convenient means of administering the compounds of the invention.
[0121] All references, publications, patents and patent applications mentioned herein are hereby incorporated by reference herein in their entirety.
[0122] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be apparent to those skilled in the art that certain changes and modifications may be practical. Therefore, the description and examples should not be construed as limiting the scope of the invention, which is delineated by the appended claims.
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Porphyrin-polyamine conjugate compounds are disclosed which have anticancer and antitumor effects. The porphyrin moiety selectively localizes in tumors, while the polyamine moiety serves as a cytotoxic agent. Methods of making and using the porphyrin-polyamine conjugate compounds are also disclosed.
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BACKGROUND OF THE INVENTION
1. Field Of The Invention:
The present invention relates to a bar-type constructional element of high flexural strength containing at least one component for absorbing forces or bending moments.
2. Description of The Prior Art:
In the construction of mechanical designs, particularly in the fields of mechanical engineering and toolmaking, it is often necessary to use constructional elements of high flexural strength, i.e. riqid elements, which exhibit minimum flexure even when long horizontal extensions and, in particular, long, free, unsupported lengths are involved. Pipes, struts and trelliswork are generally regarded as rigid constructional elements. Such conventional rigid constructional elements are, however, unsuitable for many applications since they are too heavy or are too expensive to manufacture. Glassor carbon-fibre-reinforced plastics are used in the manufacture of light, rigid constructional elements although the former also do not produce satisfactory results in every case because of their occasionally disadvantageous temperature coefficients and their residual flexibility which is an inherent material property. On the other hand, such fibre-reinforced plastics are used precisely in the manufacture of components in which flexibility is desired, e.g. skis and glider wings. Other rigid constructional elements are prestressed components which are generally in the form of solid structures, for example made of concrete, which are prestressed by means of steel cables or rods. They are not generally suitable for mechanical engineering and toolmaking and are principally used in building and bridge construction. Ceramics are intrinsically suitable for light, rigid components of great strength, although ceramic components have the disadvantage that they fracture relatively easily with excessive loading and are also susceptible to impact loads. They therefore have only limited applicability in mechanical engineering and toolmaking.
SUMMARY OF THE INVENTION
It is an object of the present invention to create a bar-type constructional element of high flexural strength which avoids the disadvantages of the constructional elements of this type known in the art and which, taking due account of the forces acting on it, has an optimum cross-sectional profile with minimum weight and mass without being at risk of fracturing if subjected to excessive loading or impact loads, and which further can be mass-produced economically and avoids the disadvantages of the elements of this type known in the art.
In accordance with the invention there is provided a bar-type constructional element of high flexural strength, containing at least one component for absorbing forces or bending moments, wherein the component has at least a core of ceramics or ceramic-like material.
In view of the fact that the second moment of inertia of a rectangular cross-section increases with the cube of its height it can be advantageous to select as a constructional element in accordance with the invention an element of great height and small width. The flexure of such an element when subjected to a force is inversely proportional to its modulus of elasticity. It is therefore advisable to select a material with a high modulus of elasticity and a low density. On the basis of these criteria ceramics or ceramic-like materials appear suitable. The generic term ceramics covers a variety of materials with different properties adapted to the particular application, which properties range from being an almost perfect insulator to a superconductor. Most applications exploit their high temperature resistance, the good wear properties or the high electrical resistance. For the application proposed below the high flexural strength, high modulus of elasticity, high compression strength, linear thermal expansion coefficient and low density are principally of interest. However, the disadvantages of these materials, mainly connected with their tendency to fracture when subjected to excessive loads, must be compensated for by suitable design features of the invention.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
Advantageous embodiments of the invention will be described below with reference to the drawing, in which:
FIG. 1 is a longitudinal cross-section through a bar-type constructional element in accordance with the invention in the form of a rail for length-measuring instruments;
FIG. 2 is a cross-section through the bar-type constructional element of FIG. 1;
FIGS. 3a-3h show further advantageous cross-sections for bar-type constructional elements in accordance with the invention;
FIG. 4 is a variation of a constructional element in accordance with the invention.
DETAILED DESCRIPTION OF THE INVENTION
The rail 1 shown in FIG. 1 consists of a plurality of bodies 2 of rectangular cross-section made of ceramics or ceramic-like material which are arranged in a line and, in the preferred embodiment, hollow. The row of bodies made of individual ceramic parts with their face ends advantageously ground flat forms a constructional component of high compression strength and low density which is held together by prestressing devices of high tensile strength to form a rigid body. To this end, in the embodiment of a bar-type constructional element shown, a first end plate 6 is directly connected to the last body 2 at one end of the row of bodies, at the left-hand end in the drawing. Prestressing steel rods 3 are anchored in the end plate 6 such that the end plate 6 serves a force transmission element which transfers the compression forces DK generated by the prestressing of the prestressing steel rods 3 to the bodies 2. At the other end of the row of bodies a second end plate 7 is either directly connected to the last body 2 or, as shown in the drawing, via an adjustment device, for example in the form of a screw 5, which presses against a cover plate 8 located flush against the last body 2. Like the first end plate 6, the second end plate 7 serves as an anchorage for the prestressing steel rods 3. The compression forces DK occurring between the end plates 6 and 7 which are generated by the prestressing of the prestressing steel rods 3 are transmitted on this side of the line of bodies via a screw 5 located in a thread in the second end plate 7 to the cover plate 8 such that the individual bodies 2 are clamped between the end plate 6 and the cover plate 8, forming a solid, rigid constructional component.
The prestressing devices, in this case in the form of prestressing steel rods 3, must not necessarily act via adjustment devices, in this case in the form of the screw 5 and the cover plate 8, on the bodies 2 since the second end plate 7 can be located directly on the last body 2 a with the first end plate 6. The advantage of using adjustment devices, however, is that possible uneven tensions in the prestressing devices, in this case the two prestressing steel bars 3, can be equalised. In addition, they permit precise adjustment of the compression forces DK acting on the bodies 2. It is self-evident that the prestressing devices used to produce the tensions required to form the rigid constructional component from the adjacent bodies can differ from those described above. Depending on the type and application of the constructional element, mechanical, hydraulic, thermal or other suitable prestressing means can be used which transfer their tensile forces ZK to the row of bodies as compression forces DK in a wide variety of ways.
As mentioned above, the bodies consist of ceramics or ceramic-like material since, while having a low relative density, ceramic bodies have very great strength, especially compression strength, and great resistance to flexing stresses, especially rigidity and torsion resistance. In addition, the temperature coefficient of ceramics can be set such that it matches that of the material used for the prestressing devices, especially prestressing steel rods, with the result that the initial tension of the row of bodies remains constant over the whole relevant temperature range or that the finished constructional element has the desired temperature coefficient. Further advantages of ceramic bodies are that they can be mass produced economically and they require no mechanical treatment longitudinally. Only their face ends require treatment to ensure plane-parallel finishes. However, since ceramics are brittle, with the result that there is the danger of fracture even with minor deformations and light impact forces, it is recommended that a plurality of short bodies 2 be placed in a row in order to achieve the required length of rail 1. Since short ceramic bodies are simpler and cheaper than long ones this offers additional economic advantages. The action of unpredicted lateral forces, exceeding the flexural strength of the constructional element with its segment-like structure and resulting in a bending moment and thus a deformation of the rail 1 in one plane, i.e. in warping of the rail 1, cannot fracture the bodies 2 made of ceramics or ceramic-like material since they can tilt themselves relative to each other against the prestressing forces, i.e. the tensile forces ZK or compression forces DK acting on them longitudinally. The bar-type constructional element of the invention is thus, on the one hand, extremely rigid and torsion-resistant because of the prestressing and the materials used, while remaining light in weight, but can also, on the other hand, absorb excessive deformation forces in the form of transverse forces acting laterally on it an suffer no damage.
It can be seen from FIG. 2 that, if necessary, the constructional element of the invention, here the rail 1, can be formed into a block 9, in a preferred embodiment using a filler made of, for example, plastics material, especially if the element is a visible part in a machine or took, for example a rail for length-measuring instruments. In order to protect the plastic block 9, in which the bodies 2, the prestressing steel rods 3 and, if applicable, the adjustment devices 5 and 8 are embedded, against damage and, if required, to provide supplementary mechanical rigidity for the bar-type constructional element, the block 9 can be enclosed with a cladding which can be in the form of an one-piece metallic profile section or, as shown in the drawing, in the form of, for example, two metallic angle plates 4.
In the embodiment of a constructional element in accordance with the invention as described above, in this case a rail 1 for measurement instruments, the element involved is a prestressed element which essentially consists of a plurality of linearly configured bodies 2 made of ceramics or a ceramic-like material of high compression strength and low relative density with prestressing devices of high tensile strength, in this case in the form of prestressing steel rods 3. This combination in the invention of ceramic bodies with prestressing devices and, possibly, a mechanically solid cover enables the shape of the ceramic and constructional element profile to be optimised, taking due account of the forces acting on it and the total weight or mass of the constructional element, and possibly the feasibility of industrial-scale production. The adjustment devices for setting the initial stress, in this case in the form of the screw 5 and the cover plate 8, enable an optimum coordination of the initial stress of the row of bodies and the anticipated forces to be achieved. The embedding of the row of bodies and the prestressing devices in a block, for example of plastic, enables the essential components to be protected against external influences and the constructional element to be coordinated cosmetically with its intended application. Depending on the application area, the constructional element of the invention can be further provided with a single- or multi-part cover which can perform both mechanical and cosmetic functions.
Depending on the type of use for the constructional element of the invention and/or a function of the forces anticipated to be acting upon it, a different cross-section from the rectangular cross-section of the bodies 2 described above can be advantageous. It may be appropriate to use more or less than two prestressing steel rods 3 or similar prestressing devices. In FIGS. 3a-3h some advantageous cross-sections are illustrated; those in the upper row are mainly suitable for absorbing transverse forces acting in one plane only, whereas those cross-sections depicted in the lower row can absorb transverse forces acting in various directions.
The main feature of the constructional element in accordance with the invention is that it possesses optimum flexural strength with minimum weight and, thanks to its segment-like prestressed structure, does not fracture even when subjected to excessive deformation forces. It is obvious that constructional elements in accordance with the invention are suitable not only as rails for measurement instruments for large lengths, as described above, but also particularly for sliding callipers. Moreover, they can be usefully employed, with particular reference to mechanical engineering and toolmaking, wherever rigid, lightweight, linear constructional components are required. The bodies and thus the bar-type constructional elements in accordance with the invention as described above with the aid of FIGS. 3a-3h can, of course, have a different cross-section from the rectangular cross-section illustrated, depending on the transverse and deformation forces which must be anticipated. The prestressing devices can also be routed through hollow spaces in the bodies. More or less than two prestressing steel rods or similar prestressing devices can be used. The initial tension and the length of the individual bodies can be selected individually as a function of the deformation and flexing forces which are anticipated or must be withstood without damage by the constructional element. The material, ideally plastics material, used for filling or lining the constructional element of the invention, can also be selected as a function of the intended application. This also applies to the cladding which may be necessary.
FIG. 4 shows another embodiment of a constructional element in accordance with the invention. This is constructed as a composite element in which thin but tall sheet-type bodies 2' are positioned ion their sides adjacent to each other and held together by adhesive or another filler material. Since in many applications a high flexural strength has only to act in one axis, in FIG. 4 the z--z axis, it is appropriate to design the constructional element such that it can flex moderately in its y--y axis without damage, i.e. without any permanent deformation or fracture. To this end, the y--y dimension of bodies 2' is set such that they have the necessary flexibility in the y--y axis. By use of an adhesive or filler material with a certain elasticity the bodies 2' can slide over each other in their longitudinal plane x--x when a bending moment acts in the y--y axis. The consequence of these provisions is that this embodiment of the constructional element can absorb large forces Fz in its z--z axis without flexing and other forces Fy in its y--y axis without fracturing. With this embodiment of the constructional element too it is appropriated to provide a, for example, metallic cladding, possibly consisting of two or more angle plates, the latter intended to protect the corners and/or to effect precise mechanical guidance in the x--x longitudinal plane while also increasing the rigidity of the constructional element.
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In the fields of mechanical engineering and toolmaking there is a frequent requirement for light but very strong constructional elements of high flexural strength, particularly as constructional components with minimum flexure despite unsupported free lengths. In the case of measurement instruments, for example, there is the problem that the rail (1) must, if possible, suffer no flexure even if used completely unsupported and with external forces acting upon it, if the reading is not to be incorrect. To this end, a constructional element in accordance with the invention with a plurality of bodies (2) made of, for example, ceramics which are connected using prestressing devices (3) or adhesives to form a rigid constructional component is presented. This structure prevents the ceramic elements from fracturing as a result of excessive bending moments since they can tilt or slide relative to each other. The bodies (2) and prestressing devices (3) can be placed in a block which may be provided with external cladding, whether partial or whole.
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FIELD OF THE INVENTION
[0001] The invention relates to a gastric bands, methods of implanting gastric bands, including the use of robotic assisted surgery, and related accessories.
BACKGROUND OF THE INVENTION
[0002] Morbid obesity is a serious medical condition. In fact, morbid obesity has become highly pervasive in the United States, as well as other countries, and the trend appears to be heading in a negative direction. Complications associated with morbid obesity include hypertension, diabetes, coronary artery disease, stroke, congestive heart failure, multiple orthopedic problems and pulmonary insufficiency with markedly decreased life expectancy. With this in mind, and as those skilled in the art will certainly appreciate, the monetary and physical costs associated with morbid obesity are substantial. In fact, it is estimated the costs relating to obesity are in excess of one hundred billion dollars in the United States alone.
[0003] A variety of surgical procedures have been developed to treat obesity. The most common currently performed procedure is Roux-en-Y gastric bypass (RYGB). This procedure is highly complex and is commonly utilized to treat people exhibiting morbid obesity. Other forms of bariatric surgery include Fobi pouch, bilio-pancreatic diversion, and gastroplastic or “stomach stapling”. In addition, implantable devices are known which limit the passage of food through the stomach and affect satiety.
[0004] In view of the highly invasive nature of many of these procedures, efforts have been made to develop less traumatic and less invasive procedures. Gastric-banding is one of these methods. Gastric-banding is a type of gastric reduction surgery attempting to limit food intake by reducing the size of the stomach. In contrast to RYGB and other stomach reduction procedures, gastric-banding does not require the alteration of the anatomy of the digestive tract in the duodenum or jejunum.
[0005] Since the early 1980's, gastric bands have provided an effective alternative to gastric bypass and other irreversible surgical weight loss treatments for the morbidly obese. Several alternate procedures are performed under the heading of gastric-banding. Some banding techniques employ a gastric ring, others use a band, some use stomach staples and still other procedures use a combination of rings, bands and staples. Among the procedures most commonly performed are vertical banded gastroplasty (VBG), silastic ring gastroplasty (SRG) and adjustable silastic gastric banding (AGB).
[0006] In general, the gastric band is wrapped around an upper portion of the patient's stomach, forming a stoma that is less than the normal interior diameter of the stomach. This restricts food passing from an upper portion to a lower digestive portion of the stomach. When the stoma is of an appropriate size, food held in the upper portion of the stomach provides a feeling of fullness that discourages over eating.
[0007] However, when items such as adjustable gastric bands and their inflation ports are implanted into the body cavity, the incision point becomes a possible avenue for micro-organisms such as bacteria and virus to enter the body thereby resulting in infection. If the sterility of the materials being implanted is compromised, bacteria may also colonize the implanted device and cause infection.
SUMMARY OF THE INVENTION
[0008] An implantable surgical device including an elongated flexible inflatable portion, an elongated flexible and substantially inextensible band portion. The band portion has a distal end, a proximal end and a longitudinal axis therebetween. The band portion is attached to the inflatable portion along an inner face thereof. The band portion and/or the inflatable portion is at least partially coated with an anti-microbial coating.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 is a perspective view of the suture tab extender secured to a gastric band.
[0010] FIG. 2 is a perspective view of the removable suture tab extender.
[0011] FIG. 3 is a perspective view of the gastric band secured about the stomach.
[0012] FIGS. 4 , 5 and 5 a are various perspective views of a gastric band in accordance with the present invention.
[0013] FIGS. 6 , 7 and 8 show the various steps in the attachment of the gastric band using the present suture tab extender.
[0014] FIG. 9 is a perspective view of a suture tab extender in accordance with a further embodiment.
[0015] FIG. 10 is a perspective view of a suture tab extender in accordance with an alternate embodiment.
[0016] FIGS. 11 , 12 , 13 and 14 respectively show a perspective view of a balloon, a perspective view of a belt, a cross sectional view of a gastric band and a perspective view of the gastric band in accordance with another embodiment of the present invention.
[0017] FIGS. 15 and 16 respectively show a perspective view of a gastric band and a cross sectional view of the gastric band in accordance with an alternate embodiment of the present invention.
[0018] FIG. 17 is a cross sectional view of a gastric band in accordance with another embodiment of the present invention.
[0019] FIGS. 18 , 19 , 20 and 21 respectively show a perspective view of a belt, a perspective view of a balloon, a cross sectional view of a gastric band and a perspective view of the gastric band in accordance with yet another embodiment of the present invention.
[0020] FIGS. 22 to 31 show various embodiments of a balloon type gastric band with differing supply tube locations.
[0021] FIGS. 32 to 43 show various embodiments of suture tab extenders with differing attachment structures.
DETAILED DESCRIPTION
[0022] The detailed embodiments of the present invention are disclosed herein. It should be understood, however, that the disclosed embodiments are merely exemplary of the invention, which may be embodied in various forms. Therefore, the details disclosed herein are not to be interpreted as limiting, but merely as the basis for the claims and for teaching one skilled in the art how to make and/or use the invention.
[0023] With reference to FIGS. 1 and 2 , a removable suture tab extender 100 for use in conjunction with a gastric band 10 is disclosed. The extender 100 is designed to enhance usage of gastric bands 10 and aid with the use of the gastric band latching mechanism 20 . In particular, the extender 100 provides a mechanism for assisting in the passage of the first latching member 22 of the latching mechanism 20 through the second latching member 26 of the latching mechanism 20 by either threading or pushing the first latching member 22 through the second latching member 26 or by inserting a grasper through the second latching member 26 , grasping the tip of the extender 112 , and pulling it back through the second latching member 26 to lock.
[0024] To attach the extender 100 to the gastric band 10 , the tether strap 108 of the extender 100 is threaded through an aperture 38 in the tip of the latching mechanism 20 . This tether strap 108 is then glued to the rest of the extender 100 inside a coupling indent 110 . In accordance with an alternate embodiment, and with reference to FIG. 10 , the extender 300 may be provided with a pocket 311 positioned at the end of the coupling indent 310 in which the tether strap 308 may be glued.
[0025] The extender 100 is easily removed or cut apart from the gastric band 10 once the gastric band 10 is properly positioned and secured about the stomach, thereby minimizing the risk of “sharp” band edges if the band itself was cut. To remove the extender 100 , the tether strap 108 is cut between the aperture 38 in the tip 36 of the gastric band 20 and the coupling indent 110 containing the glued tether strap 108 . This allows the extender 100 to be removed in one piece, leaving the gastric band 100 completely intact without any “sharp” band edges.
[0026] The extender 100 may further be provided with a recess 109 (see FIG. 2 ) on the extender 100 for inserting scissors between the tip 36 of the gastric band 20 and the tether strap 108 to better facilitate cutting off the extender 100 . The extender 100 is completely removed from the body after it has been cut off of the gastric band 10 . The extender 100 also allows for the creation of an interim lock permitting adjustment around the stomach before final locking of the latching mechanism 20 . Although a preferred embodiment has the extender cut off for one piece removal from the gastric band body, an alternate embodiment would entail leaving the extender in place on the gastric band and utilizing the interim lock (that is, the retention member 114 , 214 that is described below in greater detail) as an additional permanent locking position for use with varying stomach sizes.
[0027] In practice, and with reference to FIG. 3 , the present suture tab extender 100 is secured to the first end 14 of the gastric band 10 adjacent the first latching member 22 to form a single band/extender functional unit. Thereafter, the gastric band 10 , with the extender 100 secured thereto, is inserted behind the stomach. The first latching member 22 of the latching mechanism 20 , as well as the extender 100 , are then pushed or pulled through the second latching member 26 of the latching mechanism 20 . The addition of the present suture tab extender 100 provides a longer region for grasping and manipulation of the first latching member 22 as it is passed about the stomach and through the second latching member 26 .
[0028] In accordance with a preferred embodiment, and as will be discussed below in greater detail, the suture tab extender 100 is an elongated, elastomeric component that attaches to the first end 14 of the gastric band 10 to assist in mating and locking the first latching member 22 with the second latching member 26 . The extender 100 is preferably attached to a tab 24 at the first end 14 of the gastric band 10 to hold the extender 100 in place. The extender 100 is removable with one cut through the tether strap 108 on the extender 100 and incorporates a recess or an open recess, for example, a cuplike feature, 106 for coupling the first end 14 of gastric band 10 and extender 100 close together so as to move as an integral unit.
[0029] More specifically, and as will be greater appreciated based upon the following disclosure, the tab 24 of the gastric band 10 is positioned within the recess 106 of the extender 100 and is safely and securely coupled thereto using a tether strap 108 . In addition, and in accordance with the preferred embodiment, the second end of the extender may include a suture loop 105 for compatibility with a Goldfinger-like device 150 . As those skilled in the art will certainly appreciate, the Goldfinger-like device 150 assists in passing the gastric band 20 through the retro-gastric tunnel. Alternately, for surgeons who use other devices for passing the gastric band 20 through the retro-gastric tunnel, the gripping section, or flat tip, 112 of the extender 100 is compatible with these band-passing devices as well. In general a Goldfinger instrument is an articulating band passing device used to perform blunt dissection behind the stomach before passing the gastric band. It is articulated and fed behind the stomach. In the tip of the Goldfinger instrument there is a notch that a suture loop can catch on. Once the suture is caught, the Goldfinger instrument is pulled out of the retro-gastric tunnel and the suture loop pulls the band with it. Alternately, to facilitate use with these other band passing-devices, a length of the extender may be round (like tubing) behind the flat tip so that the extender is easier to orient.
[0030] The removable extender 100 is designed for use with a variety of gastric bands. By way of example, the extender is designed for use with gastric bands as disclosed in commonly owned U.S. patent application Ser. No. 11/182,072, filed Jul. 15, 2005, entitled “LATCHING DEVICE FOR GASTRIC BAND”, which is incorporated herein by reference.
[0031] In general, and with reference to FIGS. 4 , 5 and 5 a, the gastric band 10 includes a band body 12 having a first end 14 and a second opposite end 16 . The band body 12 and latching mechanism 20 are preferably manufactured from silicone. Although, and as will be discussed below in greater detail, the gastric band is a balloon type gastric band, the present latching mechanism may be used in conjunction with a variety of band structures without departing from the spirit of the present invention.
[0032] As briefly mentioned above, the gastric band 10 is shaped and dimensioned to circumscribe the stomach at a predetermined location reducing the size of the stomach. The gastric band 10 employs a flexible latching mechanism 20 capable of locking and unlocking without destruction of the latching mechanism 20 or significant reduction in retention capabilities after re-locking. The first and second ends 14 , 16 respectively act as both male and female members depending on the direction of motion and intent to lock or unlock the latching mechanism 20 of the present gastric band 10 .
[0033] The first end 14 includes a shell member, or first latching member, 22 generally composed of a hollow, half-moon shaped shell with a tab 24 for gripping and pulling through a collar member, or second latching member, 26 composed of a semi-circular shaped aperture 30 on the second end 16 . The half-moon shell of the first latching member 22 collapses as it is pulled or pushed through the collar member 26 by a grasper. The collar member 26 includes a tongue 28 such that the shell member 22 slides through the semi-circular shaped aperture 30 and under the tongue 28 during latching. Once the shell member 22 passes the tongue 28 , the roles change. The first end 14 functions as a female component when the shell member 22 resiliently returns to its original shape and is allowed to slide back onto the second end 16 (now a male component) and over the tongue 28 . As such, the shell member 22 functions as both a male component and female component during operation of the latching mechanism 20 and the collar member 26 functions as both a male component and female component during operation of the latching mechanism 20 ; that is, the shell member 22 functions as a male component during insertion through the collar member 26 and a female component thereafter when the tongue 28 is seated therein. Unlocking is achieved by employing graspers to pull the first end 14 forward away from the second end 16 removing the tongue from the shell member 22 . The M-shape of the shell member 22 permits it to collapse and move under the tongue 28 and through the collar member 26 .
[0034] More particularly, the shell member 22 at the first end 14 of the gastric band 10 is generally a half-moon shaped shell with an open, wide end 32 tapering toward a narrow end 34 adjacent the tip 36 of the first end 14 . The shell member 22 is substantially hollow and is formed from a material, for example, silicone, which permits compression and expansion thereof.
[0035] Referring to FIG. 5 a, the shell member 22 is formed with a substantially M-shaped outer surface 23 a when viewed from the wide end 32 thereof. That is, the outer surface of the shell member 22 has a substantially M-shaped profile, while the inner surface 23 b of the shell member 22 adjacent the wide end 32 has a substantially smooth semi-circular profile. The single M-shaped profile has been found to improve flexibility and control as the shell member 22 is passed through the collar member 26 . In addition, the inclusion of the M-shape in the wide end 32 of the shell member 22 permits ease of unlocking as it will be easier and more controllable for one to compress the shell member 22 .
[0036] The shell member 22 is slid through the collar member 26 as discussed above. Thereafter, the center 54 of the M-shaped wide end 32 returns to its original shape and fits over the tongue 28 . When the gastric band 10 is unlatched, the shell member 22 is pulled forward away from the collar member 26 and the M-shaped shell member 22 permits it to move under the tongue 28 and through the collar member 26 . The preformed shape of the shell member 22 not only acts as a guiding feature for the tongue 28 to slide over the shell member 22 during unlocking, but will also allow the shell member 22 to more easily slide back through the aperture 30 of the collar member 26 .
[0037] An aperture 38 is formed within the tab 24 adjacent the tip 36 of the first end 14 and the narrow end 34 of the shell member 22 . The aperture 38 is shaped and dimensioned for receipt of a suture or grasper commonly used in the installation of gastric bands. In addition, the tab 24 is formed with protrusions 39 assisting in grabbing the tab 24 during locking and unlocking.
[0038] Also at the first end 14 , but on the opposite side of the shell member 22 from the aperture 38 and adjacent the wide end 32 of the shell member 22 is a rearwardly extending gripping member 51 . The gripping member 51 is shaped and dimensioned to permit dual directional access for locking and unlocking of the latching mechanism 20 . More particularly, the gripping member 51 includes protrusions 56 along the top and bottom surfaces 53 , 55 thereof. These protrusions facilitate gripping thereof along a first directional orientation. The gripping member 51 is further formed with an “hour glass” shape having a reinforced central section 57 . The reinforced central section 57 allows for gripping in a second directional orientation.
[0039] Secure fastening of the shell member 22 with the collar member 26 is achieved by ensuring that after the shell member 22 compresses while passing through the collar member 26 , the shell member 22 returns to its original shape and the wide end 32 of the shell member 22 abuts with the first edge 46 of the collar member 26 .
[0040] Latching is further enhanced by providing the collar member 26 with a tongue 28 extending from the collar member 26 away from the tip 50 of the second end 16 . The tongue 28 is shaped and dimensioned to seat within the wide end 32 of the shell member 22 after the shell member 22 has passed through the collar member 26 and the gastric band 10 is tensioned as the first and second ends 14 , 16 are drawn toward each other with the shell member 22 straining to move back through the collar member 26 toward an unlatched positioned. With this in mind, the tongue 28 may be downwardly oriented such that it slides with the shell member 22 in a convenient and reliable manner. The tongue 28 may be distinctly colored to provided an indication as to whether the latching mechanism 20 is properly locked.
[0041] Gripping of the second end 16 is further enhanced through the provision of a forward facing gripping member 58 , that is, a gripping member facing the tip 50 of the second end 16 . The forward facing gripping member 58 is shaped and dimensioned to permit dual directional access for locking and unlocking of the latching mechanism 20 . More particularly, the gripping member 58 includes protrusions 59 along the top and bottom surfaces 62 , 64 thereof. These protrusions 59 facilitate gripping thereof along a first directional orientation. The gripping member 58 is further formed with an “hour glass” shape having a reinforced central section 60 . The reinforced central section 60 allows for gripping in a second directional orientation.
[0042] The gripping member 58 is shaped and dimensioned to receive and center the shell member 22 as it passes through the collar member 26 . The gripping member 58 also assists in compressing the shell member 22 as it passes through the collar member 26 .
[0043] In accordance with a preferred embodiment of the present invention, the gastric band is a balloon-type gastric band as shown in FIGS. 11 to 16 . With this in mind, the gastric band 410 is generally composed of a substantially inextensible band portion or reinforcing belt 412 to which an elongated inflatable portion or balloon 414 is secured. The belt 412 includes a first end 416 and a second end 418 to which the first and second latching members 422 , 426 are respectively secured. The belt 412 further includes an inner surface 428 and an outer surface 430 . The outer surface 430 is substantially smooth and forms a substantial portion of the outer surface 431 of the gastric band 410 when it is secured about a patient's stomach. The inner surface 428 of the belt 412 is shaped and dimensioned for attachment to the outer surface 438 of the balloon 414 .
[0044] With regard to the balloon 414 , it also includes a first end 432 , a second end 434 , an inner surface 436 and an outer surface 438 . The inner surface 436 is substantially smooth and is shaped and dimensioned for engaging the patient's stomach when the gastric band 410 is secured thereto. The outer surface 438 of the balloon 414 is shaped and dimensioned for coupling with the inner surface 428 of the belt 412 .
[0045] Referring to FIGS. 11 to 16 , the belt 412 and balloon 414 may be respectively coupled by either overmolding or separate molding with subsequent adhesive bonding (similar numerals are used for the different embodiments). Regardless of the manufacturing technique, the outer surface 438 of the balloon 414 is formed with a groove 439 shaped and dimensioned for receiving the belt 412 . Referring to FIGS. 15 and 16 , wherein the belt 412 is adhesively bound to the balloon 414 , the groove 439 is formed with a glue gap 439 a shaped and dimensioned for receipt of a small amount of adhesive without adversely affecting the position of the belt 412 within the groove 439 .
[0046] In accordance with an alternate embodiment, and with reference to FIG. 17 , it is contemplated the balloon 414 ′ and the belt 412 ′ may be coupled by adding a layer of uncured material 413 ′ (similar in composition to components) between the balloon 414 ′ and belt 412 ′, and curing them together. In addition, a layer of reinforcing structure 415 ′ (mesh, dissimilar material, or higher durometer silicone material) is contained within the layer of uncured material 413 ′. This reinforcing structure 415 ′ is encapsulated within the device upon assembly and curing, and provide additional structure or different mechanical properties to the product.
[0047] In addition, and with reference to FIGS. 18 to 21 , yet a further gastric band 410 ″ construction is contemplated in accordance with the present invention. In accordance with this embodiment, the belt 412 ″ is secured along an internal surface 417 ″ of the balloon 414 ″, with the outer surface 428 ″ of the balloon 414 ″ forming the exposed outer surface 430 ″ of the gastric band 410 ″. As with the embodiments disclosed above, the internal surface 417 ″ is formed with a groove 439 ″ shaped and dimensioned for receiving the belt 412 ″. Secure positioning of the belt 412 ″ within the groove 439 ″ is achieved through provision of a glue gap 439 a ″ along the groove 439 ″ and a retaining snap 439 b ″ along the length of the groove 439 ″. The glue gap 439 a ″ is substantially similar to that employed in accordance with the embodiment disclosed with reference to FIGS. 16 and 17 .
[0048] As to the retaining snap 439 b ″, the groove 439 ″ is constructed with opposed, inwardly directed protrusions 439 c ″ shaped and dimensioned to engage the belt 412 ″, and temporarily retain the belt 412 ″ within the groove 439 ″, while the glue used to couple the belt 412 ″ and balloon 414 ″ cures during the gluing operation. More particularly, the inwardly directed protrusions 439 c ″ are shaped and dimensioned to wrap about the belt 412 ″ in a manner holding it within the groove 439 c″.
[0049] In accordance with a preferred embodiment, the belt 412 ″ is positioned within the balloon 414 ″ in the following manner. The belt 412 ″ is threaded through one of the balloon openings 433 ″, 435 ″ on either end 432 ″, 434 ″ of the balloon 414 ″. The retaining snap 439 b, specifically protrusions 439 c ″, on the groove 439 of the balloon 414 ″ temporarily hold the components together while they are being glued via a long needle inserted between the balloon 414 ″ and the belt 412 ″. Alternately, it is contemplated the balloon can be overmolded onto the belt.
[0050] In accordance with preferred embodiments, and as briefly discussed above, the balloon and belt may be secured together by either adhesive bonding, comolding, overmolding or mechanical connection (for example, coupling sleeves), which secures the balloon and belt in a manner resulting in the coupling of these distinct gastric band components. Where the belt and balloon are overmolded, a plug 415 would be used to close the core outlet in the balloon for the overmold and the plug 415 would be integral to the gastric band structure (see FIGS. 14 & 15 ). As those skilled in the art will certainly appreciate, co-molding is essentially the same procedure as overmolding, but materials of different properties are shot in the mold at the same time. As with overmolding, comolding requires a plug to close the core outlet in the balloon.
[0051] Regardless of how the product is molded or assembled together, the belt and balloon components may consist of the same materials or different materials (material durometer, fillers such as BaSO 4 , TiO 2 , colorants, etc.). In addition, features within the same component (i.e. the locking features or end caps) may vary in composition. These features may be adhered to the rest of the product with adhesive, mechanical fastening (i.e., snap fits), welding, co-molding, or overmolding. Although the belt is disclosed as being secured to an outer surface of the balloon, it is contemplated the belt may be internal or external to the balloon surface or integrated into the balloon, without departing from the spirit of the present invention.
[0052] For assembly methods allowing the adherence of different components (that is, adhesive bonding, mechanical connection, overmolding), unique belt and balloon components may be combined to provide variable configurations. For example, belts with different locking mechanisms may be interchanged with balloons of different lengths to provide the possibility of multiple combinations of products.
[0053] The balloon 414 is constructed to enhance contact with the stomach wall when applied thereto. With this in mind, and as will be discussed below in greater detail, the balloon 414 is constructed as a precurved, low pressure, high volume balloon. The balloon 414 is constructed to maintain a soft and flexible surface (low pressure) when applied to the stomach tissue. The balloon 414 is also constructed to provide 360 degree coverage to prevent tissue pinching or discontinuities in stomach shape, and, as such, may employ the balloon construction disclosed in commonly owned U.S. patent application Ser. No. 11/182,070, entitled “GASTRIC BAND WITH MATING END PROFILES”, filed Jul. 15, 2005, which is incorporated herein by reference. The balloon 414 is further constructed such that it reaches it fully inflated and encircling configuration with minimal “folds”. In addition, the balloon 414 is constructed to exhibit no folds or creases (single axis, not dual axis) when all fluid is evacuated therefrom.
[0054] With the foregoing in mind, the balloon 414 employed in accordance with a preferred embodiment of the present application is constructed of an elastomeric material. Due to the design of this balloon, it does not inflate or expand in a manner causing high strain in balloon when filled during gastric band adjustment. Rather, the balloon 414 is adapted to receive a large volume of fluid under a relatively low pressure. In this way, the balloon 414 receives fluid during application, but does not inflate or expand in a traditional manner creating strain along the walls of the balloon 414 . In other words, when the balloon 414 is filled up to the volume recommended to achieve maximum stomach restriction, there is no expansion of the balloon material. Instead, the balloon 414 fills to some percentage of its total theoretical volume (that is, maximum fill volume). Since the balloon 414 is not filled even close to its maximum fill volume, it remains low pressure, allowing the balloon 414 to conform to the stomach rather than the stomach to a rigid balloon.
[0055] In accordance with a preferred embodiment of the present invention, the balloon 414 is designed with a maximum capacity of between approximately 10 cc and approximately 18 cc, and preferably 18 cc, although it will be fully filled for functioning in accordance with the present invention to achieve the smallest stoma size with approximately 9 cc to approximately 12 cc, and preferably 9 cc. By providing a balloon 414 , which is not at its capacity when properly filled for functioning, the softness and conformance of the balloon is improved. While specific volumes are disclosed in accordance with a preferred embodiment of the present invention, those skilled in the art will appreciate the filling volumes may be varied without departing from the spirit of the present invention.
[0056] In addition, the balloon 414 is fabricated such that it exhibits a curved configuration when unstressed. Although a variety of curvatures are possible within the spirit of the present invention, the curved configuration is designed to offer a radius of curvature of approximately 0.5 inches to approximately 1.5 inches. In addition, it is contemplated the balloon may have a varying radius as it extends about its length. In general, the balloon curvature is designed to approximate the curvature required to bring the first and second latching members 422 , 426 into approximation or contact when the balloon 414 is unbiased and left to assume a relaxed configuration. By fabricating the balloon 414 with an inherent curvature, folds created upon the application of fluid are substantially decreased. With this in mind, the belt is similarly pre-curved to reduce folds and approximate the first and second latching members 422 , 426 .
[0057] As those skilled in the art will certainly appreciate, the belt 412 is constructed to have a curvature approximately the same that of the balloon 414 such that undesirable tension between the belt 412 and balloon 414 is reduced. In addition, and in consideration of the precurved nature of the belt 412 , the belt 412 readily conforms to the outer surface of the stomach and the belt 412 .
[0058] Contact with the stomach tissue is further enhanced by providing the balloon 414 with a concave cross-section along the balloons inner surface 436 . This cross sectional configuration helps to facilitate evacuation and straightening thereof.
[0059] By implementing the structural criteria outlined above, the balloon 414 deflates with no creases or bulges forming on the inner surface 436 of the balloon 414 , a low pressure and pre-curved balloon 414 is achieved and the balloon 414 changes shape when it is filling (zip-lock bag filling up). As to the change in shape, the balloon 414 is constructed such that it has a relatively wider and flatter cross section prior to filling along a cross section transverse to the longitudinal axis of the balloon 414 . When the balloon 414 is subsequently filled during application to the stomach of a patient, the transverse cross sectional shape of the balloon 414 changes to that of a rounder balloon exhibiting a narrower cross section with a greater distance between the inner and outer surfaces 436 , 430 thereof. With this in mind, it is further contemplated that the balloon cross section may be molded in a rounded rectangular shape, wherein the “corners” provide support, distribute the change in shape and reduce folds. By providing a balloon which is wide and flat prior to filling, the distance between the inner surface of the balloon and the belt is reduced. This reduces the ultimate profile of the gastric band and improves the ability of the gastric band to be readily delivered for deployment.
[0060] As those skilled in the art will certainly appreciate, a supply tube is used to connect the internal cavity of the balloon of the gastric band with a pressurized fluid source. The utilization of the tube with a remote fluid source allows for controlled inflation and deflation of the balloon in a predetermined manner. The exact position of the tube is important in that the surgeon does not want tubing to be a visual obstruction during locking and/or other manipulation of the gastric band. In addition, once placement of the gastric band is complete, the tube should not cause irritation to surrounding tissue (for example, sticking directly into the liver or spleen). Surgeons also do not want to pull the tube through a retro-gastric tunnel, since they cannot easily see if the tissue is being damaged. The tube should also be able to act as a safe grasping location for manipulation of the gastric band, the tube must not kink at the junction to the gastric band and prevent fluid flow, and the tube location should facilitate passage of the band through a small trocar.
[0061] With this in mind, and in accordance with various preferred embodiments of the present invention, different tube placements are shown with reference to FIGS. 22 to 31 . As each these various embodiments show, the tube is positioned at an end of the gastric band. By positioning the tube at an end of the gastric band it has been found that forces upon the tube, gastric band, and, ultimately the stomach, are reduced. This positioning also enhances the ability of the tube and gastric band to flex for insertion and expand to its original shape upon deployment.
[0062] Referring to FIG. 22 , the tube 540 is oriented to exit the gastric band 510 from the outer surface thereof. In accordance with a preferred embodiment of this design, the tube 540 is positioned such that is comes out the outer surface 531 of the gastric band 510 just below a longitudinally extending midline 542 of the gastric band 510 . The tube 540 is positioned so that is placed clear of the latching mechanism 520 and obliquely angled relative to the longitudinal axis (in accordance with a preferred embodiment at an angle of approximately 34°) of the gastric band 510 to allow easy insertion through a trocar.
[0063] Referring to FIG. 23 , the tube 640 is molded on the second end 634 of the balloon 614 . In particular, the tube 640 is molded at the very end of the balloon 614 , and is integrated into the balloon shape. As with the prior embodiment, the tube 640 is obliquely oriented relative to the longitudinally axis of the gastric band 610 and is similarly positioned below a longitudinally extending midline of the gastric band 610 . The offset allows for the balloon ends 632 , 634 to meet without interference from the tube 640 .
[0064] A further embodiment is shown with reference to FIG. 24 , wherein the tube 740 exits the balloon 714 off a lateral side 744 , that is, a very bottom surface, of the balloon 714 as it is positioned within the patient. The tube 740 entry point is substantially aligned with the second latching member 726 relative to the longitudinal axis of the gastric band 710 . As with the prior embodiments, the tube 740 is obliquely oriented relative to the longitudinally axis of the gastric band 710 .
[0065] As shown in FIGS. 25 and 26 , the tube 840 connection is integrated into one of the sides of the latching members. In accordance with the disclosed embodiment, it is integrated into the second latching member 826 , although it is contemplated it could be integrated with the first latching member 822 without departing from the spirit of the present invention. The tube 840 enters the second latching member 826 and extends therethrough into the body of the balloon 814 . Once the tube 840 is inside the body of the balloon 814 , it angles to the centerline (or midline 842 ) of the balloon 814 for even filling of saline. The tube 840 is also obliquely oriented relative to the longitudinally axis of the gastric band 810 and is similarly positioned below a longitudinally extending midline 842 of the gastric band 810 . The offset allows for the balloon ends 832 , 834 to meet without interference from the tube 840 .
[0066] Yet other embodiments are shown respectively with reference to FIGS. 27 and 28 . In accordance with one embodiment as shown in FIG. 27 , the tube 940 is molded into the plug 946 used to cap the core portion of the balloon 914 . In accordance with the other embodiment as shown in FIG. 28 , the tube 1040 is molded as an integral portion of the second latching member 1026 . The fluid passageway, therefore, extends through the tube 1040 , into passageways 1048 formed in the second latching member 1026 and ultimately into the balloon 1014 . More particularly, once the tube 1040 enters into a bridge of the second latching member 1026 (that is, where the second latching member 1026 defines the aperture), it splits into a bifurcated tube 1052 that goes into the balloon 1014 via both walls 1054 of the aperture 1030 of the second latching member 1026 .
[0067] Still another embodiment is shown in FIGS. 29 and 30 , wherein the tube 1140 is integrated into one of the sides of the latching mechanism 1120 , preferably, the second latching member 1126 . The tube 1140 then runs through a gusset 1156 from the back of the second latching member 1126 to allow for a low entry angle into the balloon 1114 .
[0068] Referring to FIG. 31 , the tube 1240 entry is integrated into the belt 1212 (and more particularly, the second latching member 1226 ) to allow for separate molding of the belt 1212 and balloon 1214 . By being attached to the second latching member 1226 , the tube 1240 could be used to find the location of the latching mechanism 1220 once the implant has been encapsulated into the fibrous tissue. As with the prior embodiments, the tube 1240 is obliquely oriented relative to the longitudinally axis of the gastric band 1210 and is similarly positioned below a longitudinally extending midline 1242 of the gastric band 1210 . The offset allows for the balloon ends 1234 to meet without interference from the tube 1240 .
[0069] In addition, any of the tubing configurations disclosed with reference to FIGS. 22 through 31 could incorporate some type of strain relief member to reduce fatigue as the tubing flexes back and forth in the body. Such strain relief would be achieved by positioning a length of thicker material at the tubing entry point into the balloon (see for example 1156 on FIG. 29 , similarly shown but not called out in FIG. 31 ). The length of thicker material allows the tubing to take a larger curve as it is bent away from the joint between the tube and the balloon. In other words, this length of material that has been thickened increases the stiffness of the tubing in this region to allow the tubing to flex without kinking and moves the point of flexing further away from the vulnerable joint between the band, balloon, and tubing. The strain relief member would be made preferably of silicone, but other materials (plastics, metals, etc.) could also be used. Also, in all of these embodiments, the tubing to could be connected to either the belt or the balloon by any one of multiple manufacturing methods, such as overmolding or assembling and gluing.
[0070] Although the present invention is described for use in conjunction with gastric bands, those skilled in the art will appreciate the above invention has equally applicability to other types of implantable bands. For example, bands are used for the treatment of fecal incontinence. One such band is described in U.S. Pat. No. 6,461,292. Bands can also be used to treat urinary incontinence. One such band is described in U.S. Patent Application Publication No. 2003/0105385. Bands can also be used to treat heartburn and/or acid reflux. One such band is described in U.S. Pat. No. 6,470,892. Bands can also be used to treat impotence. One such band is described in U.S. Patent Application Publication No. 2003/0114729.
[0071] Referring to FIGS. 1 and 2 , the extender 100 includes an elongated body member having a first end 102 and second end 104 . The first end 102 includes an open recess 106 shaped and dimensioned to receive the tab 24 of the first latching member 22 at the first end 14 of the gastric band 10 . The first end 102 of the extender 100 is further provided with a tether strap 108 . The tether strap 108 is shaped and dimensioned for passage through the aperture 38 formed in the tab 24 and ultimate attachment within a coupling indent 110 formed in the outer surface of the first end 102 of the extender 100 . In this way, the tether strap 108 extending from the extender 100 loops through the tab 24 readily coupling the first end 102 of the extender 100 the first latching member 22 for selective attachment and detachment.
[0072] The second end 104 of the extender 100 includes a gripping section 112 shaped and dimensioned to facilitate gripping thereof as the extender 100 is passed through the collar member 26 and the gastric band 10 is applied around a patient's stomach. In addition, there is a suture loop 105 for compatibility with Goldfinger instruments 150 as discussed above and the gripping section, or flat end, 112 of the extender 100 is compatible with other band passing devices. Between the first end 102 and the second end 104 of the extender 100 is formed a laterally extending retention member 114 . The retention member 114 is semi-circular when viewed along a planar, transverse cross section. The retention member 114 tapers to widen as it extends toward the first end 102 of the extender 100 in a manner creating a surface over which the collar member 26 may slide during latching for interim attachment of the extender 100 to the collar member 26 . The taper creates an engagement surface 118 which holds the collar member 26 between the enlarged first end 102 of the extender 100 and the retention member 114 when the first end 102 of the extender 100 is temporarily latched to the collar member 26 .
[0073] Although an extender with a recess and retention member in accordance with a preferred embodiment is disclosed above, the extender may take other forms without departing from the spirit of the present invention. For example, and in accordance with another preferred embodiment shown with reference to FIG. 9 , the extension member 200 includes an elongated body member having a first end 202 and second end 204 . The first end 202 includes an enclosed, pocket recess, more particularly a pocket, 206 shaped and dimensioned to fully receive the tab 24 of the first latching member 22 at the first end 14 of the gastric band 10 . The first end 202 of the extension member 200 is further provided with a tether strap 208 . The tether strap 208 is shaped and dimensioned for passage through the aperture 38 formed in the tab 24 and ultimate attachment within a coupling indent 210 formed in the outer surface of the first end 202 of the extension member 200 . In this way, the first end 202 of the extension member 200 may be readily and selectively secured and detached from the first latching member 22 .
[0074] The second end 204 of the extension member 200 includes a series of protrusions 212 shaped and dimensioned to facilitate gripping thereof as the extension member 200 is passed through the collar member 26 and the gastric band 10 is applied around a patient's stomach. The second end 204 also includes a suture loop 205 extending therefrom. Between the first end 202 and the second end 204 of the extension member 200 is formed a laterally extending retention member 214 . The retention member 214 includes first and second engagement members 216 , 218 . The engagement members 216 , 218 are tapered to widen as they extend toward the first end 202 of the extension member 200 in a manner creating a surface over which the collar member 26 may slide during latching for interim attachment of the extension member 200 to the collar member 26 prior to complete latching of the gastric band 10 latching mechanism 20 (after which the extension member 200 is detached from the gastric band 10 ). The taper creates opposed engagement surfaces 220 , 222 which hold the collar member 26 between the enlarged first end 202 of the extension member 200 and the engagement members 216 , 218 when the first end 202 of the extension member 200 is temporarily latched to the collar member 26 .
[0075] Regardless of the extender construction utilized in accordance with a gastric band, it is important the extender be readily accessed for removal with little possibility for error. The two key issues in removal of an extender revolve around a surgeon's ability to identify the extender, in particular, that part of the extender requiring manipulation for removal thereof, and proceed to remove the extending in accordance with the removal mechanism employed. With this in mind, various embodiments for ensuring clear visualization and convenient cutting have been developed. Any of the embodiments described below can incorporate a visual indicator such as color (on either the entire extender, the tether strap, or the only the region to be cut) or a visible suture to indicate to the surgeons that this is a separate component from the gastric band that should be removed. In addition, these embodiments also provide various means in which the extender may be attached to the gastric band (tether strap, suture, etc.).
[0076] More particularly, and with reference to FIGS. 32 , 33 35 and 36 , the extender 1300 adjacent the first end 1302 thereof or the tether strap 1508 , 1608 of the extender 1500 , 1600 is provided with one or more bumps or ramps 1330 , 1530 , 1630 at a location adjacent the open coupling indent, or pocket, 1310 into which the tether strap 1308 , 1508 , 1608 of the extender 1300 , 1500 , 1600 is to be positioned. By providing a bump or ramp 1330 , 1530 , 1630 at this position (on either the first end of the extender or on the tether strap), the tether strap 1308 , 1508 , 1608 is held above the first end 1302 and the surgeon is able to readily visualize the location of the tether strap 1308 , 1508 , 1608 . The bump or ramp 1330 , 1530 , 1630 location is at a position adjacent the point at which the tether strap 1308 , 1508 , 1608 is to be cut for removal of the extender 1300 , 1500 , 1600 and, therefore, provides the surgeon a visual indicator as to the cut location. In accordance the embodiment shown with reference to FIG. 35 , two bumps 1530 a, 1530 b wrap completely around the tether strap 1508 and define an area at which a surgeon should cut the tether strap 1508 .
[0077] In addition to improving visualization of the tether strap, in each embodiment the bumps or ramp raise the tether slightly above the gastric band, increasing the space between the tether and the gastric band to provide an improved passageway for position scissors therein for cutting of the tether and ultimate removal of the extender. Visualization of the cutting location in accordance with this embodiment is enhanced by providing a gap or a notch 1332 , 1432 , 1532 along the tether strap 1308 , 1408 , 1508 (see FIGS. 32 , 33 , 34 and 35 ). In particular and with reference to FIGS. 32 , 33 and 43 , the suture loop at the second end of the extender 1300 , 2200 is continued throughout the body of the extender 1300 , 2200 with the suture 1334 , 2234 extending through the tether strap 1308 , 2208 and functioning as a reinforcing member. However, a portion of the suture 1334 , 2234 is exposed along the tether strap 1308 , 2208 at a predetermined location such that when the tether strap 1308 , 2208 is passed through aperture 38 of the gastric band tab 24 and wrapped about the gastric band 10 to secure the two components together, the gap 1332 , 2232 is positioned at the desired location for cutting.
[0078] Similarly, and as is seen if FIGS. 34 and 35 , the tether strap 1408 , 1508 may have a localized region that is smaller than the remainder of the tether strap 1408 , 1508 allowing for cutting in a single step. More particularly, the localized region is preferably a notch 1432 , 1532 formed along the tether strap 1408 , 1508 . In addition, because the gap or notch 1432 , 1532 is readily differentiated based upon its physical appearance from the remainder of the tether 1408 , 1508 , a surgeon may easily identify the location requiring cutting. It is contemplated either the notch or gap design could be used in conjunction with the bump described above with reference to FIGS. 32 , 33 , 36 , 42 and 43 , although these designs could certainly be employed without the bump where certain design considerations dictate.
[0079] Other embodiments are disclosed with reference to FIGS. 37 , 39 and 40 . These embodiments employ a reinforcing member, for example, a suture 1734 , 1934 to aid in the connection of the extender 1700 , 1900 to the tip of the gastric band. In one application (see FIG. 37 ), the suture 1734 holds the tether strap 1708 down upon the body thereof. As such, and rather than cutting the tether strap 1708 itself as disclosed above with reference to the various embodiments, the securing suture 1734 is cut to thereby release the tether strap 1708 for removal of the extender 1700 . Alternately, the suture may be used to tie down the strap and as such, secure the tether to the extender without the assistance of adhesive. Although a suture is disclosed as a reinforcing member in accordance with a preferred embodiment, other reinforcing structures, for example, mesh, may be used within the spirit of the present invention.
[0080] In another related embodiment shown in FIGS. 39 and 40 , the suture material of the suture loop 1905 is extended to run the length of the extender 1900 such that the suture material 1934 , extends from the first end 1902 of the extender 1900 (substantially replacing the tether of the prior embodiments). This allows the extender 1900 to wrap a suture 1934 through an aperture 38 in the tip of the gastric band 10 and engage a projection 1936 extending from the first end 1902 of the extender 1900 . In addition to securing the gastric band in a reliable and convenient manner, this embodiment provides additional benefits in that the suture 1934 now has a loop at the first end 1902 and the second end 1904 of the extender 1900 . This increases the strength of the extender 1900 because the suture cannot pull out of the extender independent of extender material failure.
[0081] Referring to FIG. 38 , another embodiment is disclosed. In accordance with this embodiment, the tip 1812 of the gastric band 1810 is seated within the recess 1806 formed in the extender 1800 . However, the recess 1806 and the tip 1812 of the gastric band 1810 include a snap feature providing a semi-mechanical locking mechanism between the gastric band 1810 and the extender 1800 . Such an embodiment would improve the ability of the extender 1800 to lead and guide the tip 1812 of the gastric band 1810 in concert without twisting or flipping. Such a semi-mechanical locking mechanism could be utilized in conjunction with the other tether securing arrangements as a means for providing redundant securing of the extender to the gastric band. It is further contemplated this embodiment may have suture 1811 around the tip 1812 of the gastric band 1810 and the recess 1806 of the extender 1800 (like FIG. 37 ) to compress the region where the snap fitting tip 1812 fits within the recess 1806 of the extender 1800 . When the surgeon cuts and removes the surrounding suture 1811 , they can then expand the flexible silicone extender 1800 over the snap fitting tip 1812 on the front of the tab to separate the extender 1800 from the gastric band 1810 in one piece.
[0082] Further and with reference to FIG. 41 , a suture 2034 is similarly utilized in securing the extender 2000 to the gastric band. However, the projection 2036 to which the extender 2000 is secured is designed such that it may be peeled away. As such, when it is desired to remove the extender 2000 , one need only peel away the projection 2036 to release the extender 2000 and thereby no cutting is required.
[0083] Referring to FIG. 42 , another embodiment is disclosed. In accordance with this embodiment, the tether 2108 of the extender 2100 is lengthened to allow the glue position 2138 to be moved a forward position on the open recess 2106 extender 2100 . This allows the tether 2108 of the extender 2100 to be cut at line 2140 to remove the extender 2100 . More particularly, the open recess 2106 includes a forward and 2106 a positioned toward the middle of the extender 2100 and a rearward position 2106 b positioned near the first end 2102 of the extender 2100 . The glue position 2138 is at the forward end 2106 a. This is still a one-piece removal, only the length of the location for cutting has changed. This embodiment allows the tether 2108 to bow for improved access with scissors or other tools when the front of the extender is flexed upwardly since the tether is only glued at one end 2106 a.
[0084] In accordance with yet another embodiment, and with reference to FIG. 43 , a flange or stopper 2242 is positioned at a preset point along the length of the tether 2208 . This enables positioning of the gap 2232 in the tether 2208 relative to the position of the extender 2200 where the suture 2234 needs to be cut and to avoid having suturing contact with the gastric band hole during band pulling. The stopper 2242 is positioned to engage the tab surrounding the aperture so as to limit the extent to which the tether 2208 may pass therethrough. The portion of the tether 2208 adjacent the stopper 2242 may be tapered and the section that is positioned inside the aperture of the gastric band can be larger in cross section to provide a snug fit with the hole of the gastric band. As with prior embodiments the tether will includes a gap or notched section for identification and cutting thereof. In addition, the suture loop runs fully through the extender and may be utilized by tying it into a knot that is molded within the enlarged section of the stopper so as to improve the strength of the extender tether.
[0085] When devices such as adjustable gastric bands are implanted into the body cavity, the incision point becomes a possible avenue for micro-organisms such as bacteria and virus to enter the body thereby resulting in infection. If the sterility of the materials being implanted is compromised, bacteria may also colonize the implanted device and cause infection. This can be overcome by coating them with antimicrobial agent. The above described gastric band can be coated with anti-microbials such as silver sulfadiazine and pipericillin. This will drastically reduce the infection rate and the mortality associated with it. The coating is not visible to the naked eye and is therefore not shown explicity in the figures. However, it is contemplated that the outersurfaces of the inextensible band portion or reinforcing belt 412 and the elongated inflatable portion or balloon 414 could be coated as well as the latching members 422 , 426 . In addition, the supply tube used to connect the internal cavity of the balloon of the gastric band with a pressurized fluid source could be coated as well.
[0086] The standard method of application of these antibiotics is by dipping the device into a solution of antimicrobial agent and allowing it to cover the surface. Other methods are to dissolve the agent into a permeable polymer barrier and dipping the device into the solution.
[0087] Another common antimicrobial agent used for this type of application is chlorhexidine acetate or gluconate. In its basic state, this anti-microbial agent has low solubility in water. When reacted with a weak acid, the salt form is readily soluble in water. Chlorhexidine is applied onto the implantable medical device and then converted into its free-base form so that its release is slow but steady. Implantable bariatric devices such as ports, bands, inflatable balloons, staples and clips that stay in the body for a long time could be coated with anti-microbial agents to reduce bacteria colonization.
[0088] It will become readily apparent to those skilled in the art that the above invention has equally applicability to other types of implantable bands. For example, bands are used for the treatment of fecal incontinence. One such band is described in U.S. Pat. No. 6,461,292 which is hereby incorporated herein by reference. Bands can also be used to treat urinary incontinence. One such band is described in U.S. Patent Application 2003/0105385 which is hereby incorporated herein by reference. Bands can also be used to treat heartburn and/or acid reflux. One such band is described in U.S. Pat. No. 6,470,892 which is hereby incorporated herein by reference. Bands can also be used to treat impotence. One such band is described in U.S. Patent Application 2003/0114729 which is hereby incorporated herein by reference.
[0089] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. For example, as would be apparent to those skilled in the art, the disclosures herein have equal application in robotic-assisted surgery. In addition, it should be understood that every structure described above has a function and such structure can be referred to as a means for performing that function. Accordingly, it is intended that the invention be limited only by the spirit and scope of the appended claims.
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An implantable surgical device including an elongated flexible inflatable portion, an elongated flexible and substantially inextensible band portion. The band portion has a distal end, a proximal end and a longitudinal axis therebetween. The band portion is attached to the inflatable portion along an inner face thereof. The band portion and/or the inflatable portion is at least partially coated with an anti-microbial coating.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 10/316,876, filed Dec. 12, 2002, which is hereby incorporated herein in its entirety by reference.
BACKGROUND OF THE INVENTION
[0002] The invention relates to mobile location devices, which make advantageous use of wireless transmission methods to provide device location information. Such location information may be the current geographical location of the device, and/or location dependent information. The mobile location devices may be dedicated location devices, but may alternatively provide other functionality, such as the ability to make telephone calls or provide user diary services, for example, as that provided by a Personal Digital Assistant (PDA).
[0003] The term mobile is used in the sense that it describes a device, which is not fixed in any one geographical location but moves location over time. Such devices may be portable and/or may be temporarily or permanently attached to any moveable object, such as a vehicle, person or animal. With such devices being moveable, and thus not always located near an external power supply, these devices often incorporate a built-in power supply, which would require periodic recharging and/or replacement. Nevertheless, in certain cases, a mobile location device may be temporarily or permanently driven by an external power supply, such as mains power or a vehicle battery in the case of a mobile location device permanently fixed to a vehicle and arranged to obtain power from the vehicle battery. All such forms of devices are within the scope of the present invention.
SUMMARY OF THE INVENTION
[0004] In a first aspect, the present invention provides a mobile location device comprising geographical location means to provide device geographical location information and motion detection means to detect motion of the device, wherein the geographical location means is arranged to provide device geographical location information according to whether motion of the mobile location device is detected by the motion detecting means. As the provision of geographical location information consumes power, associating the provision of location information according to whether motion of the device is detected reduces power consumption. The invention advantageously updates location information based on movement, when changes in location are likely to be the greatest, and when the device is likely to be in use. Thus, the present invention avoids location information updates when there is little or no movement i.e. location information updates are rationed.
[0005] The motion detection means may comprise one or more motion sensors configured to detect changes in tilt/yaw/horizontal/vertical/rotational position individually, in multiples or in combination.
[0006] The motion detection means may comprise means to detect changes in device geographical location. This may be by having comparison means to compare a previous geographical location with the current geographical location to determine whether changes in geographical location have occurred. Changes of geographical location may be horizontal, vertical or a combination thereof.
[0007] The motion detection means may be configured to detect any changes in motion, or may be configured to detect changes in motion above a threshold level. Embodiments detecting threshold level of changes will further reduce power consumption by associating the provision of geographical location information, and thus power consumption, with major, and not minor, changes.
[0008] The device may be configured to provide device geographical location information immediately upon the detection of device motion.
[0009] Preferably, the device comprises control means arranged to monitor device motion detected by the motion detection means over successive time periods and control the operation of the geographical location means in response to whether device motion has been detected over one, or a combination of more than one, successive time period. The same, or different, time period(s) may be used.
[0010] Preferably, the control means is configured to control the operation of the geographical location means to provide device geographical location information at the end of one or more of the time periods. Thus, rather than provide location information immediately on the detection of motion, this embodiment of the present invention monitors motion over a period of time, and at the end of the time period provides geographical location information. Accordingly, the provision of geographical location information is delayed to the end of the time period, resulting in fewer times when location information is provided, and thus an overall reduction in power consumption.
[0011] The control means may be configured to use a first time period when device motion has been detected and a second time period when device motion is not detected. Thus, it would be possible to, for example, provide device geographical location information at 15-minute intervals whenever the device is in motion, and at 1-week intervals when the device is not moving. Such an embodiment may be modified to provide device location information immediately upon detection of device motion and then again at one regular time interval during the detection of continued motion, and at a reduced time interval upon subsequent detection of no motion.
[0012] In a preferred embodiment, the control means may be configured to operate the geographical location means at regular intervals regardless of whether device motion has been detected. Preferably, the control means is configured to operate the geographical location means at regular intervals upon detection of no motion by the motion detection means over a particular time period.
[0013] Thus, geographical location information is provided even if the device has been motionless for a period of, for example, 1-week. In such a case, the control means may be further configured to provide information on the operative state of the device e.g. whether it is still working or device battery life status. This operative state information may be sent in the form of a Short Message Service (SMS) message, which may be sent back to the device to notify the user or to a third party terminal. The mobile location device may be configured to provide operative state information at regular intervals, regardless of whether device motion has been detected.
[0014] Preferably, the mobile location device comprises programming means to allow the control means time periods to be set, for example, by a user of the device. The programming means may be a keypad on the device. However, the programming may be done via an external accessory such as a keyboard, or via any other terminal equipment that can access the device. Such terminals can be, for example, mobile phones or PCs. The device may be configured such that programming commands may be given by using software that is specific to the operating system of the device, or by using SMS messages.
[0015] The mobile location device may be arranged such that the association between the means to provide device geographical location information and the motion detection means can be activated and/or deactivated. Thus, it will be possible to switch on/off the link between the provision of location information and motion. This may be by operation of actuation means, preferably located on the mobile location device. In a preferred embodiment, the control means is arranged to activate/deactivate the geographical location means according to whether motion of the device has been detected. This would, of course, be activation of the means to provide device geographical location information upon detection of motion, and deactivation upon detection of no motion, or motion below a particular threshold level.
[0016] In a preferred embodiment, the control means is arranged to control the operation of the geographical location means to obtain current device geographical information upon detection of device motion by the motion detecting means. Thus, up-to-date location information will be provided when the device is in motion. Preferably, the control means is configured to control the operation of the geographical location means to obtain current geographical location information at a reduced frequency when device motion is not detected by the motion detecting means.
[0017] Mobile location devices may comprise wireless transmission means to obtain the current geographical location information of the device. In one embodiment, the geographical location means comprises wireless transmission means and wherein the device is arranged such that the operation of the wireless transmission means to obtain the current geographical location information is based on detection of motion by the motion detection means. Obtaining the current geographical location of the device consumes power, and by further associating the obtaining of the current geographical location information with motion of the device, this embodiment of the present invention reduces power consumption. Furthermore, this association of the operation of the wireless transmission means would free up valuable bandwidth with wireless transmissions being rationed. Again, any motion, or motion above a threshold level, may be used to trigger the operation of the wireless transmission means to obtain the geographical location information.
[0018] The provision of geographical location information may be to a user of the device. In such a case, the geographical location means may comprise user display means to display geographical location information to a user of the device. The geographical location means may comprise sound means to provide geographical location information to a user of the device. The geographical location means may comprise both user display and sound means.
[0019] The provision of device geographical location information may be to a third party. In such a case, the geographical location means would be arranged to provide the geographical location information to a third party terminal. This would preferably be done by wireless transmission means incorporated into the mobile location device. Advantageously, this embodiment would free up bandwidth by having wireless third party transmissions between the mobile location device and the third party terminal associated with motion of the mobile location device. This embodiment would also reduce overall power consumption, not only of the mobile location device but also of the third party terminal. The mobile location device may be arranged such that the same wireless transmission means obtains the current geographical location information and provides the current geographical location information to a third party terminal, or at least that both the wireless transmission means share some common components.
[0020] The geographical location means may be arranged to provide geographical location information to a third party terminal by transmissions directly between a third party terminal and the mobile location device, or indirectly via a communications network. The third party terminal may be another mobile location device or may be an access point device of a wireless local area network (WLAN), a cellular basestation, or other network device.
[0021] The geographical location means may be arranged to provide device geographical location information to a third party terminal and/or to the user of the mobile location device. Alternatively, the geographical location means may be arranged to solely provide geographical location information to a third party terminal/device. So, for example, in the case of the provision of information solely to a third party terminal, the mobile location device would not necessarily require a user display means. Such a device would have particular security applications in, for example, tracking the movement of ex-convicts on parole. Furthermore, if such a mobile location device was attached to a precious article, the geographical location of the device, and thus the precious article, could be monitored from a remote terminal, preferably a mobile terminal such as a cellular telephone. This may be conveniently done using Internet transmission paths.
[0022] In a further embodiment, the device may be configured to receive location dependent information content from a third party terminal to which device geographical location information has been provided by the geographical location means. Such a mobile location device would preferably comprise wireless transmission means arranged to receive the location dependent information and sound and/or display means to provide this location dependent information to the user. Examples of such location dependent information may be directions/distance to a particular place from the present location, and/or retail offers from retail outlets in the vicinity of the present location i.e. so called “value added services”.
[0023] Satellite (e.g. Global Position System (GPS), Assisted Global Positioning System (A-GPS)) or cellular based (e.g. Cell-ID, Enhanced Observed Time Difference (E-OTD), RTT/IP-DL) location technologies can be the means to provide device geographical location information, and in appropriate embodiment, location dependent information content. Bluetooth™ technology may also be used to provide such information. The mobile location devices according to the present invention may use any of these technologies singly or in combination, and any future developments in location technology. However, cellular and Bluetooth™ based technologies have the distinct advantage over GPS technology in that they also provide an uplink channel which can be used to send the device geographical location information to other remote terminals/sources.
[0024] Preferred embodiments of the present invention will use technology which provides one or more uplink transmission channels. In a preferred embodiment, the mobile location device is a cellular device, and the geographical location means provides device geographical information by connecting to cellular network device.
[0025] The mobile location device may be configured to itself comprise the location technology. However, the device may be configured to obtain geographical location information by accessing location technology incorporated in a neighbouring terminal or device. For example, as well as location determination from pre-programmed beacons or access point devices, a mobile location device according to the present invention, such as a PDA, could access the GPS technology in a neighbouring phone or vehicle to obtain the approximate geographical location information of the device. Thus, the mobile location devices of the present invention have at least the ability to obtain device geographical location information, if not from specific location technology incorporated within the device then by using location technology located in neighbouring terminals or devices.
[0026] In the particular case of mobile location devices with a portable in-built power supply, such as a battery, the reduced power consumption increases battery life and accordingly increases device-operating life. The reduced power consumption also reduces the requirement to recharge or replace the battery, and thus the frequency of battery rechargements/replacements is reduced.
[0027] In certain cases, the mobile location device may comprise a rechargeable power supply. Such power supplies are known to only be rechargeable a finite number of times before they become ineffective. Accordingly, by reducing the recharging frequency, the present invention increases the overall operating life of such rechargeable power supplies.
[0028] In a second aspect, the present invention provides a method of operating a mobile location device comprising detecting device motion by using device motion detection means, and using device geographical location means to provide device geographical location information in response to detection of motion of the mobile location device by the motion detecting means.
[0029] Methods of operating a mobile location device having one or more, or combinations thereof, of the preferred features according to the first aspect of the invention, mutatis mutandis, can equally be applied to the second aspect of the invention and are also within the scope of the present invention.
[0030] In a third aspect, the present invention provides a method of operating a mobile location device comprising obtaining, using device wireless transmission means, device geographical location information according to detection of device motion.
[0031] Methods of operating a mobile location device having one or more, or combinations thereof, of the preferred features according to the first aspect of the invention, mutatis mutandis, can be equally applied to the third aspect of the invention and are also within the scope of the present invention.
[0032] In a fourth aspect, the present invention provides a method of providing location-based information content to a mobile location device by providing device geographical location information according to detection of motion of the device.
[0033] Methods of providing location based information content to a mobile location device having one or more, or combinations thereof, of the preferred features according to the first aspect of the invention, mutatis mutandis, can be equally applied to the fourth aspect of the invention and are also within the scope of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] Specific embodiments of the invention will now be described with reference to the following Figures in which:
[0035] FIG. 1 is a schematic illustration of one embodiment of a mobile location device according to the present invention.
DETAILED DESCRIPTION OF INVENTION
[0036] Take the specific case of a mobile location device in the form of a location tag 10 . The tag 10 is a device meant to be attached to any movable object and to give information of its geographical location. The location tag 10 is a cellular device, whose purpose is to be located through an applicable cellular location based technology. This location tag 10 is meant to be used e.g. for vehicles, boats, pets, or even large, movable belongings where the location tag 10 can preferably be hidden. In one preferred embodiment, the owner of a vehicle, for example, can oversee the whereabouts of his/her vehicle using a mobile communications device, such as a cellular telephone. The location can be conveniently tracked by viewing a geographical map displayed on, for example a Nokia Communicator™ or a Personal Computer, upon which is displayed the current location of the tag 10 .
[0037] The location tag 10 is shown schematically in FIG. 1 . It comprises control circuitry 20 arranged to receive tag motion information detected by the motion sensor 30 . The control circuitry 20 is also arranged to control the operation of the geographical location circuitry 40 , this circuitry providing the geographical location of the tag 10 . Conveniently, the geographical location circuitry 40 may be part of the cellular circuitry 50 , via which transmission between the tag 10 and the cellular network takes place.
[0038] The control circuitry 20 is configured to monitor the tag motion information provided by the motion sensor 30 . Upon detection of tag motion, the control circuitry 20 is configured to activate the geographical location circuitry 40 . The control circuitry 20 is arranged to keep the geographical location circuitry 40 activated during continued motion and deactivated during periods of rest. Furthermore, regardless of the tag motion information provided by the motion sensor 30 , the control circuitry 20 is arranged to activate the geographical location circuitry 40 at defined intervals. The control circuitry 20 is also programmable so that the periods of activation of the geographical location circuitry 40 can be changed. So, for example, rather than activating the geographical location circuitry 40 continuously during tag motion, the control circuitry 20 can be programmed to activate the geographical location circuitry 40 at 15-minute intervals.
[0039] When using GPS technology, the geographical location circuitry 40 obtains the particular location information of the tag 10 from a satellite, and uses the cellular circuitry to send this information to a cellular network device, via an uplink transmission channel. The cellular network device then accesses geographical location based information content associated with the particular location of the tag 10 . This information is stored in a network database. The associated geographical location based information content is then transmitted to the location tag 10 . Advantageously, the network device may check user preferences stored on the network device to aid in the selection of user relevant location based information content, prior to this information being sent to the location tag 10 .
[0040] However, in the case of the tag 10 only using cellular technology, activation of the geographical location circuitry 40 would enable it to communicate with the cellular network devices and allow the network to identify the location of the tag 10 using triangulation of the tag 10 via network basestations. Location based information content may be provided as before. The geographical location circuitry 40 may also, or separate to processing carried out by the network to determine geographical location of the tag 10 , process data provided via the network to determine the geographical location of the tag 10 .
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A mobile location device comprising geographical location means to provide device geographical location information and motion detection means to detect motion of the device, wherein the geographical location means is arranged to provide device geographical location information according to whether motion of the mobile location device is detected by the motion detecting means.
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FIELD OF INVENTION
[0001] The present invention concerns methods of fabricating integrated circuits, particularly methods of forming interconnects from copper and other metals.
BACKGROUND OF THE INVENTION
[0002] Integrated circuits, the key components in thousands of electronic and computer products, are interconnected networks of electrical components fabricated on a common foundation, or substrate. Fabricators typically use various techniques, such as layering, doping, masking, and etching, to build thousands and even millions of microscopic resistors, transistors, and other electrical components on a silicon substrate, known as a wafer. The components are then wired, or interconnected, together to define a specific electric circuit, such as a computer memory.
[0003] Interconnecting millions of microscopic components typically entails covering the components with an insulative layer of silicon dioxide, etching small holes in the insulative layer to expose portions of the components underneath, and digging trenches in the layer to define a wiring pattern. Then, through metallization, the holes and trenches are filled typically with aluminum, to form line-like aluminum wires between the components. The aluminum wires are typically about one micron thick, or about 100 times thinner than a human hair.
[0004] Silicon dioxide and aluminum are the most common insulative and conductive materials used to form interconnections today. However, at sub-micron dimensions, that is, dimensions appreciable less than one micron, aluminum and silicon-dioxide interconnection systems present higher electrical resistances and capacitances which waste power and slow down integrated circuits. Moreover, at these smaller dimensions, aluminum exhibits poor electromigration resistance, a phenomenon which promotes disintegration of the aluminum wires at certain current levels. This ultimately undermines reliability, not only because disintegrating wires eventually break electrical connections but also because aluminum diffuses through surrounding silcon-dioxide insulation to form short circuits with neighboring wires. Thus, at submicon dimensions, aluminum and silicon-dioxide interconnection systems waste power, slow down integrated circuits, and compromise reliability.
[0005] Copper appears, because of its lower electrical resistivity and higher electromigration resistance to be a promising substitute for aluminum. And, many polymers, for example, fluorinated polyimides, because of their lower dielectric constants, appear to be promising substitutes for silicon dioxide. Thus, a marriage of copper with these polymers promises to yield low-resistance, low-capacitance interconnective structures that will improve the efficiency and speed of integrated circuits.
[0006] Unfortunately, copper reacts with these polymers to form conductive copper dioxide within these polymers, reducing their effectiveness as low-capacitance insulators and ultimately leaving the copper-polymer promise of superior efficiency and speed unfulfilled.
SUMMARY OF THE INVENTION
[0007] To address these and other needs, the inventor has developed methods of making copper-polymer interconnection systems with reduced copper oxide. Specifically, one method uses a non-acid-based polymeric precursor, such as ester, instead of the typical acid precursor, to form a polymeric layer, and then cures the layer in a reducing or non-oxidizing atmosphere, thereby making the layer resistant to oxidation. Afterward, a zirconium, hafnium, or titanium layer is formed on the polymeric layer to promote adhesion with a subsequent copper layer. With the reduced formation of copper oxide, the method yields faster and more efficient copper-polymer interconnects.
[0008] Moreover, reducing copper-dioxidation facilitates micron and sub-micron spacing of polymer-insulated copper conductors, which would otherwise require spacings of 10 or more microns. Accordingly, another aspect of the invention is an integrated circuit including at least two conductors which are separated by no more than about one micron of a polymeric insulator. Thus, the inventor provides a method that not only yields copper-polymer interconnects of superior speed and efficiency, but also yields integrated circuits with unprecedented spacing of copper-polymer interconnects.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The invention is described with reference to the following figures, wherein like numerals refer to like features:
[0010] [0010]FIG. 1 is a cross-sectional view of an integrated-circuit assembly at an early fabrication stage, including transistors 14 a and 14 b , an insulative layer 16 , contacts 16 a and 16 b , and a silicon nitride layer 17 ;
[0011] [0011]FIG. 2 is a cross-sectional view of the FIG. 1 integrated-circuit assembly after formation of a polymeric layer 18 over contacts 16 a and 16 b and layer 17 and after formation of a trench 20 ;
[0012] [0012]FIG. 3 is a top view of the FIG. 2 integrated-circuit assembly, showing position of the trench relative contacts 16 a and 16 b;
[0013] [0013]FIG. 4 is another cross-sectional view of the FIG. 3 integrated-circuit assembly, taken along line 4 - 4 to show depth and width of the trench;
[0014] [0014]FIG. 5 is a cross-sectional view of the FIG. 4 assembly after formation of a copper-adhesion layer 22 and a copper layer 24 ;
[0015] [0015]FIG. 6 is a cross-sectional view of the FIG. 5 assembly after removal of excess portions of layers 22 and 24 leaves copper conductor 24 ′;
[0016] [0016]FIG. 7 is a cross-sectional view of the FIG. 6 assembly taken along line 7 - 7 after formation of another polymeric layer 26 having a via hole 28 ;
[0017] [0017]FIG. 8 is a top view of the FIG. 7 assembly, showing position of the via hole relative conductor 24 ′;
[0018] [0018]FIG. 9 is a cross-sectional view of the FIG. 8 assembly after formation of a copper-adhesion layer 30 and copper contact 32 ;
[0019] [0019]FIG. 10 is a cross-sectional view of an integrated-circuit assembly having two copper conductors 24 a ′ and 24 b ′ in a polymeric insulator 18 , with the conductors separated by no more than about one micron; and
[0020] [0020]FIG. 11 is a block diagram of an integrated memory circuit which incorporates the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0021] The following detailed description, which references and incorporates FIGS. 1 - 11 , describes and illustrates one or more specific embodiments of the invention. These embodiments, offered not to limit but only to exemplify and teach the invention, are shown and described in sufficient detail to enable those skilled in the art to practice the invention. Thus, where appropriate to avoid obscuring the invention, the description may omit certain information known to those of skill in the art.
[0022] FIGS. 1 - 9 show a number of exemplary integrated-circuit assemblies, which taken collectively and sequentially, illustrate an exemplary method of the present invention. The method, as shown in FIG. 1, a cross-sectional view, begins with a known integrated-circuit assembly or structure 11 , which can be within any integrated circuit, an integrated memory circuit, for example. Assembly 11 includes a substrate 12 . The term “substrate,” as used herein, encompasses a semiconductor wafer as well as structures having one or more insulative, semi-insulative, conductive, or semiconductive layers and materials. Thus, for example, the term embraces silicon-on-insulator, silicon-on-sapphire, and other advanced structures.
[0023] Substrate 12 supports a number of integrated elements 14 , such as transistors 14 a and 14 b . Transistors 14 a and 14 b are covered by a 100-nanometer-thick, insulative layer 16 , which, for example, comprises a silicon oxide. A silicon-nitride layer 17 , also 100-nanometers thick, covers layer 16 . Extending through layers 16 and 17 are two tungsten vias (or contact plugs) 16 a and 16 b electrically connected to respective transistors 14 a and 14 b . Although omitted from FIGS. 1 - 9 for clarity, assembly 11 preferably includes a titanium-nitride (TiN) diffusion barrier between vias 16 a and 16 b and transistors 14 a and 14 b.
[0024] [0024]FIG. 2 shows that the first step of the exemplary method entails forming a polymeric layer 18 atop layer 17 . As used herein, the term “polymeric” encompasses organic polymers, organic oligomers, and organic monomers. Collectively, these may be described as materials containing one or more mer units having a carbon-chain backbone. In addition, “polymeric” encompasses materials having properties similar to those of organic polymers. For instance, organic polymers characteristically have high ductility, low elastic modulus, low compressive-yield strength, and/or low thermal-expansion coefficients. Moreover, as used herein, polymeric encompasses polymer precursors, or bases.
[0025] In the exemplary embodiment, polymeric layer 18 begins as a non-acid polymeric precursor, that is, a precursor with a pH greater than about 6. Examples of polymeric precursors include a polyimide ester, such as the type sold by E.I. du Pont de Nemours under the tradename PI-2801, or a polymeric-precursor derivative based on fluorine, bromine, or other elements from the fluorine periodic group. Other embodiments form polymeric layer 18 as a foamed polymer, which will generally have a lower dielectric constant than most non-foamed polymers and thus provides further capacitance reductions. An example of a foamed polymer is taught in co-pending and co-assigned patent application Ser. No. 08/892,114 filed Jul. 14, 1997. This application, entitled Method of Forming Insulating Material for an Integrated Circuit and Integrated Circuits Resulting from Same, is incorporated herein by reference.
[0026] Subsequent to its formation from a non-acid precursor, polymeric layer 18 is cured, with the resultant layer having a thickness of about 500 nanometers. In the exemplary embodiment, the curing procedure has three phases: the first at 125° C. for 15 minutes, the second at 250° C. for 30 minutes, and the third at 375° C. for 30 minutes, with the second and third phases occurring in a non-oxidizing, or reducing, atmosphere to inhibit oxidation. Some exemplary atmospheres are pure hydrogen or mixtures of about 3-to-10% hydrogen with nitrogen, argon, or helium. Starting with the non-acid precursor and curing according to this procedure ultimately reduces the amount of oxidization that occurs in subsequent processing by about four fold. Therefore, unlike conventional polymeric processing, this procedure prevents or reduces increases in the dielectric constant of polymeric layer 18 .
[0027] The next step, best illustrated in FIG. 3, a top view of the FIG. 2 assembly, is to define the stud and wiring patterns on layer 18 , using for example suitable masking and etching techniques. In the exemplary embodiment, this entails using reactive-ion etching or any selective-material-removal technique to form a trench 20 , which will ultimately define a conductor for connecting vias 16 a and 16 b . FIG. 3 shows that trench 20 has ends 20 a and 20 b which correspond with respective vias 16 a and 16 b . FIG. 4, a cross-section of assembly 11 taken along line 4 - 4 in FIG. 3, shows that trench 20 has a depth 20 d of about 500 nanometers to expose vias 16 a and 16 b , and a width 20 w of about 250 nanometers. Thus, in this exemplary embodiment, trench 20 has an approximate aspect ratio of 2-to-1.
[0028] The next step, shown in FIG. 5, entails applying a 10-nanometer-thick adhesion layer 22 on layer 18 , inside and outside trench 20 . The principle purpose of the adhesion layer, which may also be called a seed, contact, or cladding layer, is to promote adherence of a copper layer formed in the next step. Examples of suitable adhesion-layer materials include zirconium, hafnium, titanium. Zirconium, however, is preferable to titanium since it has at least a ten-fold lower solubility in copper.
[0029] Next, to form a copper conductor, the method fills trench 20 , as FIG. 5 shows, by depositing a 975-nanometer-thick copper layer 24 on layer 22 and inside trench 20 . In some embodiments another 10-nanometer-thick adhesion layer is formed atop copper layer 24 to inhibit copper oxidation during later processing, particularly during curing of subsequent polymeric layers. To reduce copper oxidation, one embodiment performs the adhesion-material and the copper deposition at temperatures less than 450° C., another embodiment at temperatures between about 250 and 350° C., and another at around 300° C.
[0030] In the 250-350° C. range, a thin layer of Cu 5 Zr (or Beta), tends to initially form at the interface of the copper and zirconium layers, inhibiting diffusion of zirconium into the copper and preventing it from significantly increasing resistance of the copper. A similar effect may be achieved by electroplating the copper and heat-treating the zirconium and copper layers at 250-350° C. for one to two hours, before curing the polymer. Inhibiting the diffusion of zirconium into the copper ultimately yields a copper conductor with a conductivity greater than 95 percent of IACS, or International Annealed Copper Standard. The International Annealed Copper Standard (IACS) is 1.7241 microhm-centimeters at 20 C, or 17.241 nanaohm-meters. Thus, the exemplary copper conductor has a conductivity greater than about 16.4 nanaohm-meters. However, in other embodiments the conductor is in the range of 14 nanohm-meters or greater.
[0031] Afterwards, excess copper and zirconium on the surface are then removed using a chemical-mechanical polishing technique. FIG. 6 shows the resulting metal conductor 24 ′, which electrically connects vias 16 a and 16 b and therefore connects transistors 14 a and 14 b . Formation of conductor 24 ′ completes the first level of metallization.
[0032] [0032]FIG. 7 shows that the second level metallization starts with formation and curing of a second polymeric layer 28 on layer 22 . In some embodiments, layer 28 has a composition similar to polymeric layer 18 . Subsequently, the method cures layer 28 , again following a three-phase curing procedure with temperatures similar to those used for layer 18 . The first phase preferably occurs in hydrogen, high-purity forming gas, or a non-oxidizing high-purity argon, and the second and third phases preferably occur in a non-oxidizing atmosphere of high-purity argon. In contrast to conventional curing procedures, this curing procedure, devised primarily for second and subsequent polymeric layers, takes particular care to avoid inciting reactions with and between existing polymeric and copper structures, for example, layer 18 and conductor 24 ′. Therefore, this procedure safeguards the dielectric strength of polymeric layer 18 .
[0033] After curing polymeric layer 28 , the method defines a stud and/or wiring pattern using any suitable technique. The exemplary embodiment defines a vertical stud, or via, hole 28 a in layer 28 , using masking and etching techniques. (Hole 28 a may also be viewed as the cross-section of a trench, defining a wire that intersects, or contacts, copper conductor 24 ′ which lies below.) Other embodiments form hole 28 a along with other wiring trenches similar to trench 20 , according to conventional dual-damascene techniques, which fill via holes and trenches in one metallization. FIG. 8 shows the position of hole 28 a relative transistors 14 a and 14 b , vias 16 a and 16 b , and conductor 24 ′ from the first metallization level.
[0034] The next steps form a 10-nanometer-thick adhesion layer 30 , similar to adhesion layer 22 , on polymeric layer 28 , as well as a copper layer 32 on layer 28 . (Other embodiments form an additional adhesion layer on copper layer 32 .) Layers 30 and 32 , in the exemplary embodiment, are deposited at approximately 300° C. As already noted, depositing zirconium and copper at this temperature tends to form a thin interfacial layer of Cu 5 Zr (not shown) between layers 30 and 32 , which ultimately enhances conductivity of the resulting conductor. Subsequent annealing also promotes formation of this interfacial layer.
[0035] After completion of layer 32 , excess copper and adhesion-layer material are removed, for example, by chemical-mechanical polishing. FIG. 9 shows that the resulting integrated-circuit assembly includes a copper via 34 ′ electrically connected to underlying conductor 24 ′ and thus also connected to transistors 14 a and 14 b . Subsequent metallizations would follow similarly.
[0036] In addition to preservation of the dielectric constant of the polymeric layers, the oxidation reductions stemming from the present invention also allow closer spacing of copper conductors in polymeric insulators, particularly micron and sub-micron spacing. FIG. 10, a juxtaposition of two of the assemblies shown in FIG. 6, shows two side-by-side copper structures (for example contact plugs or wires) 24 a ′ and 24 b ′ separated by a distance 25 which is less than about one micron in one embodiment. In various embodiments, distance 25 is less than about 0.75 microns, less than about 0.5 microns, or less than about 0.25 microns. In contrast, conventional techniques for forming copper-polymer interconnections require intra-polymer conductor spacings of 20 or more microns to maintain isolation of the conductors after uninhibited formation of conductive copper dioxide in the polymer between conductors. Thus, the micron and submicron spacings of the present invention provide a dramatic improvement.
Exemplary Embodiment of an Integrated Memory Circuit Incorporating the Copper-Polymer Interconnection System
[0037] [0037]FIG. 11 shows one example of the unlimited number of applications for the copper-polymer interconnections of the present invention: a generic integrated memory circuit 40 . Circuit 40 , which operates according to well-known and understood principles, is generally coupled to a processor (not shown) to form a computer system. More precisely, circuit 40 includes a memory array 42 which comprises a number of memory cells 43 , a column address decoder 44 , and a row address decoder 45 , bit lines 46 , word lines 47 , and voltage-sense-amplifier circuit 48 coupled to bit lines 46 .
[0038] In the exemplary embodiment, each of the memory cells, the address decoders, and the amplifier circuit includes two or more zirconium-clad copper conductors embedded in polymeric insulation according to the present invention. In addition, connections between the address decoders, the memory array, the amplifier circuit are implemented using similar copper-polymer interconnects. The spacings of these conductors, in some embodiments, follow the micron and submicron spacings noted for FIG. 10.
Conclusion
[0039] The present invention provides a method of forming copper-polymer interconnections systems, which reduces the tendency of polymers to react with copper and form undesirable copper oxides. Formation of these copper oxides would otherwise reduce the effectiveness of the polymers as low-capacitance insulators and thus offset their ability to improve speed and efficiency of integrated circuits. Thus, the present invention ultimately facilitates the fabrication of integrated circuits having superior speed and efficiency. Moreover, because the reduction in oxidation allows closer placement of polymer-insulated copper wires, the invention also facilitates denser integrated circuits, that is, circuits with greater numbers of components in the same space.
[0040] The embodiments described above are intended only to illustrate and teach one or more ways of practicing or implementing the present invention, not to restrict its breadth or scope. The actual scope of the invention, which encompasses all ways of practicing or implementing the invention, is defined only by the following claims and their equivalents.
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A typical integrated circuit interconnects millions of microscopic transistors and resistors with aluminum wires buried in silicon-dioxide insulation. Yet, aluminum wires and silicon-dioxide insulation are less attractive than copper wires and polymer-based insulation, which promise both lower electrical resistance and capacitance and thus faster, more efficient circuits. Unfortunately, current techniques cannot realize the promise because copper reacts with the polymer-based insulation to form copper dioxide within the polymer, reducing effectiveness of the copper-polymer combination. Accordingly, the inventor devised a method which uses a non-acid-precursor to form a polymeric layer and then cures, or bakes, it in a non-oxidizing atmosphere, thereby making the layer resistant to copper-dioxidizing reactions. Afterward, the method applies a copper-adhesion material, such as zirconium, to the layer to promote adhesion with a subsequent copper layer. With reduced copper-dioxide, the resulting interconnective structure facilitates integrated circuits with better speed and efficiency.
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REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of application Ser. No. 09/596,516 filed Jun. 19, 2000 now U.S. Pat. No. 6,463,090 and entitled: Communication In High Rise Buildings.
BACKGROUND OF THE INVENTION
This invention relates to a communication system within a building and more particularly to communication along convoluted and non-linear paths in a building.
A typical situation to which this invention is addressed is one where a number of people who occupy space in a large building operate computers and have a requirement to interact with each other and have access to each others' files and an Internet service provider on a real time basis. In order to satisfy this requirement, these computers must be interconnected in some manner and also connected with an Internet service provider. To accomplish this, a network is created which interconnects the computers through a central unit called a server, which acts as a library for files as well as a traffic controller. The computers and server are connected to each other by means of a series of copper wire or fiberoptic cables. As a result, all equipment is fixed in position, not able to be moved and encumbered by masses of cables which may require the construction of special raceways beneath raised floors. These installations are costly, time consuming to install, and difficult to modify. If computers must be moved to new locations in the building, the installation network of cables, raised floors and any other special construction must be abandoned and a new installation created.
In addition, for any of the computers which are part of the network to be connected to an Internet service provider, a router must be connected to the server and this router must also be connected to a special copper wire or fiberoptic telephone company cable. This equipment and cabling is also fixed in position and would be abandoned if the system location were to be changed. In addition, substantial fees must be paid on an ongoing basis to a telephone company in order to connect the computers through the server to an Internet service provider which are exclusive of any fees paid to the Internet service provider for their service.
An alternate to the creation of cabling networks is wireless communication. However, to date this technique has yielded limited results in that effective communication can only be accomplished for short distances and is subject to interference from spurious signals (noise), loss of transmitted signal strength (attenuation), and areas where no signal can be received (null points). Null points result from reflected signals canceling primary signals under certain conditions. All of these types of interference are present in severe form in large buildings as a result of phenomena unique to this environment.
Also, in order to create a wireless link to an Internet service provider, a cable must be installed the entire length of the building which leads to an antenna located on the roof of the building. Each computer or server must then be cable connected to this riser cable in order to communicate outside the building with the wireless Internet service provider.
A major purpose of this invention is to provide an inexpensive and reliable communication link between any number of computers located within a large building in a fashion that provides an ability to readily relocate, modify and reconfigure the network within the building.
A further purpose of this invention is to provide inexpensive and reliable communication between any number of electronic stations within a large building.
It is a further purpose of this invention to provide the above objects in a system that would also optionally permit a reliable and simplified access to an Internet service provider.
BRIEF DESCRIPTION
In brief, this invention enables effective communication between stations in large buildings having non-linear and convoluted transmission paths. The objectives recited above are met by use of two-way wireless spread spectrum transmission and reception involving directional polarized antennas coupled to specific transmission paths. Those paths may be (a) the stairwell shafts of the building, or (b) a zone outside of the building adjacent to the skin of the building which is accessed through the windows of the building or (c) paths through corridors along a floor of a large building, or any combination of these paths.
The construction of large buildings makes wireless communication within the buildings unreliable because electromagnetic energy is absorbed and reflected in unpredictable and uncontrollable ways.
It has been found that electromagnetic energy will migrate through a building effectively if it can be coupled to paths which are available in most buildings. One of these paths is the stairwells and corridors. Another path is a zone adjacent to the skin of the building which is accessed through windows. Sending signals through these paths provides markedly better results than does other methods.
To couple energy to these paths, two types of directional antennas are employed. Both types of antennas are patch type having an included angle of less than 60°. These antennas are deployed to generate a radiation pattern which aims them at the locations where access can be had to the corridors, stairwells and/or windows.
A first patch type antenna is linear polarized with a horizontal electrical field. This provides enhanced signal strength over substantial distances in part as a result of ground reflections.
A second patch type antenna employs circular polarization. The circular polarization enables the receiver to ignore reflected signals and receive only the primary signal. The circular polarization minimizes the existence of null points.
Both types of antennas direct the electromagnetic energy across a floor to access and transmit through corridors, stairwells and out of windows along a vertical zone adjacent to the skin of the building and back in other windows. Reception using similar antenna arrangements receive these signals.
The transmission and reception employs a transceiver using a spread spectrum technique that involves a hybrid frequency hopped/direct sequence modulated signal of a known type such as is disclosed in the text “Spread Spectrum Systems With Commercial Applications”, Robert C. Dixon, 3 rd edition, copyright in 1994 by John Wiley & Sons, Inc. publisher at 605 3 rd Avenue, New York, N.Y. 10158
The linear polarized antenna and the circular polarized antenna are connected to a switching circuit at the transmitter and the receiver so that the signals generated are transmitted and received as packets of data alternating between the two antennas. The switch is at a predetermined rate that is greater than the hopping rate of the spread spectrum signal.
There are three major types of situations in which this invention will be usefully employed.
An example of the first type of situation is where a plurality of computers at different places within the building are linked together through the transmission provided by the system. In this kind of situation, computers are not necessarily in fixed locations; although there are cases where fixed locations are either required or preferred.
A second type of situation is one where by reasons of fire code and/or building construction, the stations of communication used in the system are in fixed locations, some of which may be in a nook or cranny creating a dead spot where the usual type of communication would not work.
One fire safety situation is where a door may have to become locked or unlocked in response to a particular signal. The location of that door is normally predetermined and the system is well adapted to be able to communicate with the control mechanism for the door regardless of its location.
A third situation is a mobile situation. For example, there may be communication between fire fighters or rescue workers in a building where a fire causes damage to the communication links.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 schematically illustrates a large multi-story building showing the coupling of a signal from a station through a stairwell and along the zone adjacent to the outside skin of the building.
FIG. 2 is a highly schematic illustration of transmission paths on particular floors of the FIG. 1 building.
FIG. 3 schematically illustrates a large convoluted floor space in a building showing the coupling of a signal from a station through the passageways in the floor space.
FIG. 4 is a highly schematic illustration of transmission paths on the FIG. 3 floor including transmission along the outside wall of the building.
FIG. 5 is a high level block diagram of a multi-station system embodiment of the invention.
FIG. 6 is a block diagram illustrating one computer system, one server and a PBX component of the FIG. 5 system showing the antenna arrangement.
FIG. 7 is a block diagram showing the transceiver and switching equipment used at a given station to permit alternate transmission of circular polarized packets and linear polarized packets when in the transmitting mode and alternate reception of circular polarized packets and linear polarized packets when in the receiving mode.
FIG. 8 is a block diagram showing equipment associated with a server.
FIG. 9 is a block diagram showing equipment associated with the PBX.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIGS. 1 and 2 illustrate an embodiment of this invention applied to a large multi-story building. FIGS. 3 and 4 illustrate an embodiment of this invention applied to a single large floor of a building with convoluted passageways within that floor.
FIGS. 5 through 9 illustrate, in essentially block form, the equipment relationships involved in implementing the systems illustrated in FIGS. 1 through 4 .
FIGS. 1 and 2 and 5 through 9 are the same as FIGS. 1 and 2 and 3 through 7 of the referenced patent application Ser. No. 09/596,516.
The FIG. 1 system is an arrangement in a large multi-story building 12 to provide signal transmission along selected paths. Specifically, stairwell shafts 14 and zones 16 located outside the building adjacent to the skin of the building are employed as transmission paths. These paths have been found to enable successful communication between virtually any two locations within the building.
As shown in FIG. 2 , each floor 24 in a multi-story large building 12 has access ways to stairwells 14 and windows 28 thereby enabling the coupling of electromagnetic energy (signals) to the stairwell shafts and to the area outside the building that is adjacent to the skin of the building. These stairwells and window access ways also enable electromagnetic energy signals to enter any floor after having been transmitted through the stairwell shafts 14 and the zones 16 outside the building adjacent to the skin of the building.
The FIG. 3 and FIG. 4 embodiment illustrates the embodiment of the invention in which application is made to a large complicated floor space in a building in which various walls and barriers 100 effectively block the transmission of relatively low level electromagnetic energy and make possible, or at least impractical, point-to-point communication between many points in the floor involved.
FIG. 3 is a highly schematic illustration in which the walls 100 of the floor are shown as if they were transparent so that paths 106 through which energy passes will be more readily visualized.
FIG. 4 is a plan schematic that illustrates these paths 106 a bit more clearly.
More specifically, the FIGS. 3 and 4 embodiment might be used with a fire alarm system in which communications are needed between the fire command station 110 , a smoke detector 112 , a public address and fire alarm speaker 114 and various fire alarm manual pull stations 116 . Each of the stations 112 , 114 , 116 requires a transceiver in order to provide appropriate communication between the station and the fire command station 110 . There might be certain individual stations which are passive in that they receive a command from the center station 110 and respond thereto without requiring transmission back. Such stations would not require a transceiver. However, many such stations do and will require a transceiver.
By virtue of this invention, effective communication using spread spectrum technology on directional antennas is made along at least the paths 106 indicated by arrows.
To the extent there are windows 108 on the floor involved, there will be a certain amount of transmission out a window along the exterior skin of the building and into another window. Such transmission will also be employed to facilitate this communication.
As shown in FIG. 5 , a multiple number of stations having computers 32 (or other active electronic signaling devices) located anywhere in a large multi-story building or on a large floor having multiple transmission barriers are each coupled to an associated spread spectrum transceiver 34 . These spread spectrum transceivers employ two-way wireless electromagnetic communication over paths that include corridors, stairwells 14 and through windows and zones 16 adjacent to the outer skin of the building to and from a spread spectrum transceiver 36 which is associated with a server 38 . The computers 32 that are in communication with one another through the server 38 can be located virtually any place in the building because of their access to stairwells and windows that provide sufficient channels for the spread spectrum electromagnetic radiation.
FIG. 5 shows further communication that can be had through a second spread spectrum transceiver 37 associated with the server 38 to wireless PBX equipment 42 and a spread spectrum transceiver 40 coupled to the wireless PBX 42 . The PBX 42 can be used to provide transmission over a standard land line PBX 41 or through a wireless spread spectrum transceiver 44 .
FIG. 6 shows certain additional details of the FIG. 5 system. Each station transceiver 34 associated with a computer 32 provides transmission to and from the computer 32 throughout two antennas. One of the antennas 46 is a circular polarized directional antenna. The other antenna 48 is a horizontal linear polarized directional antenna.
These antennas 46 and 48 are patch type antennas having an included angle of less than 60°. This antenna design provides enhanced concentration of radiated power along the transmission paths.
The circular polarization of the antennas 46 has been found to minimize the existence of null points. The antennas 48 are linear polarized with a horizontal electric field. The horizontal electric field enhances reflection from the floors of the building along which the electromagnetic energy is directed thereby minimizing energy loss. The signals from both type of antennas 46 , 48 are coupled through the corridors, stairwells and windows and thus along the zones adjacent to the outside of the building so that communication can be had through the server 38 between computer stations almost anywhere in the building.
The spread spectrum transceiver 36 associated with the server 38 is appropriately synchronized to the spread spectrum transceivers 34 by known techniques.
In analogous fashion, communication between the server 38 and a wireless PBX 42 is through synchronized spread spectrum transceivers 37 and 40 respectively employing respective circular polarized directional antenna 54 and horizontal linear polarized directional antenna 56 for the transceiver 37 and circular polarized directional antenna 58 and horizontal linear polarized antenna 60 for the transceiver 40 . Also wireless communication with the worldwide Internet is accomplished using transceiver 44 employing antennas 81 and 82 .
FIG. 7 illustrates a computer network adapter used with each computer station 32 . The antennas 46 , 48 provide both transmission of broadcast information from the computer network adapter as well as receipt of broadcast information to the computer network adapter. The reception component of the adapter includes a low noise amplifier 54 , a receiver 55 and a data input module 56 which transfers the demodulated signal to the baseband processor 57 . The transmission component of the adapter includes a data output module 58 which transfers the data to be transmitted from the baseband processor 57 , a transmitter 59 and a higher power output amplifier 60 .
The baseband processor and controller 57 receives information from and transfers information to the computer 32 through an input/output module 62 . The baseband processor and controller 57 gives instructions to the antenna select controller 63 which then switches the two directional polarized antennas 46 , 48 to particular configurations in accordance with these instructions during transmission and reception. The received signal strength indicator 64 measures the relative signal strengths of the signals received by the two directional polarized antennas 46 , 48 and enables only the largest signal to be processed. A diplexer 65 protects the receiving segment of the adapter from signals generated by the transmitting segment. An antenna switching clock 71 , which is a component of the baseband processor and controller, determines when the appropriate timing sequence has been arrived at to enable reception or transmission. It also signals the antenna select control 63 to switch between antennas at each transmitted or received frequency before moving to the next transmitted or received frequency.
FIG. 8 illustrates the network adapter employed with the server 38 in somewhat greater detail. The reception, transmission and processing of information is accomplished in a manner similar to that employed by the computer adapter including the directional polarized set of antennas 50 , 52 , a transceiver 36 including a baseband processor and controller and an input/output module 73 . However, this unit also includes a message memory section 74 which stores requests while earlier requests are being processed. A second set of directional polarized antennas 54 and 56 , transceiver 37 , and message memory section 75 are used to communicate with the wireless PBX 42 . They operate at different frequencies and with different modulation sequences. Therefore, the transceivers 36 and 37 can operate independent of each other.
The channel controller 78 determines which section will receive information from and transfer information to the server through the server network adapter input/output module 73 and thereby regulates the traffic within the server network adapter.
FIG. 9 illustrates the wireless PBX 42 in somewhat greater detail. The antenna and transceiver configurations and method of transferring information to and from the bus 87 are similar to those employed by the computer network adapter ( FIG. 5 ) and the server network adapter ( FIG. 6 ). A bus controller 89 determines which transceiver points will be enabled and effects this through the wireless network server assign enable module 88 . This module enables only the transceiver so designated to communicate with the bus 87 . The bus controller 89 also determines which land line PBX 41 or section thereof will be connected to the wireless PBX 42 for transfer of information to and from server network adapters ( FIG. 8 ). Coordination of server transceiver ports and land line PBX units is accomplished by the bus controller 89 when assigning the appropriate transceiver port enable 86 and PBX assign enable 90 simultaneously.
A separate transceiver 96 and antennas 81 and 82 tuned to the frequency employed by an Internet service provider is used to communicate with a wireless Internet service provider. An assign enable input 98 will be activated when this feature is employed.
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A system for communicating between stations which are at a number of different locations in a large building in which radio transmission is achieved through corridors or stairwell shafts or through windows along a zone outside of the building or any combination thereof. This system employs communication through spread spectrum transceivers and a set of directional antennas. At each station, one of the antennas is circular polarized and the other is linear polarized with a horizontal electrical component to facilitate reflection off the floors of the building. The spread spectrum is a hybrid frequency hopped and direct sequence modulated signal.
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CROSS-REFERENCE
[0001] This patent claims priority from U.S. provisional application No. 60/264,010 filed Jan. 25, 2001, entitled Modular Kiosk.
FIELD OF THE INVENTION
[0002] The present invention relates to the field of automated kiosks.
BACKGROUND OF THE INVENTION
[0003] Electronic kiosks are devices which consist of two groups of parts, namely (1) electronic hardware components and (2) a housing for the components.
[0004] With respect to the hardware, the programmability of digital computers means that a system consisting of a monitor, with a pointing device such as a touchscreen or a touch pad and/or keyboard, and a computer (CPU), can perform a variety of functions. If the basic system is expanded by adding a printer, camera, speakers, a microphone, card readers, or other peripherals, and is connected to remote information sources by wire or wireless means, it can perform a wider variety of tasks, including e-mail, videoconferencing and database access.
[0005] The purpose of the kiosk housing is to prevent access or damage to fragile components, to draw attention the device, and to protect sensitive components from environmental elements, thereby making it feasible to provide the equipment contained therein to the public for their use in an unsupervised setting. Access to the internal components of the housing is necessary to provide maintenance and to replenish consumable supplies, such as paper. Thus, protection of the hardware components must be ensured, while allowing access to the housing for servicing.
[0006] Kiosks are designed for specific uses. The housing is provided with mountings for the required internal components, fascia for the projection of devices such as monitors, and apertures for the introduction and removal of credit cards or the issue of printed material or cash.
[0007] Some kiosks currently available and others as described in patents may have certain modular aspects. U.S. Pat. No. 5,702,166 to Lee describes a collection of kiosks for multiple users, each kiosk designed so that they may be connected to other kiosks in an octagon-like structure. U.S. Pat. No. 5,761,071 to Bernstein et al. depicts a kiosk containing a computer arrangement, with the video display, CPU, keyboard and mouse connected by wiring.
[0008] A limitation of the prior art kiosks is that the selection of components utilized within the kiosk must be defined prior to design and fabrication of the kiosk housing. Furthermore, once the kiosk housing has been fabricated, it is not possible to change the selection of components or the relative size and shape of components without rebuilding or significantly altering the housing by cutting, grinding or re-machining. It is expensive and time consuming to design and build kiosks due to the need to create a new design for the kiosk housing each time a new set of hardware components or functions are required.
[0009] Another limitation of kiosks of the prior art is the inaccessibility of the internal hardware components for servicing. It is desirable that kiosks, which are normally located in busy areas, are as compact as possible. However, positioning a number of hardware components in a compact enclosure creates problems for servicing. U.S. Pat. No. 6,010,065 to Ramachandran et al. teaches one means to address this problem, using a service door on the kiosk and a rollout tray containing some of the serviceable components.
SUMMARY OF THE INVENTION
[0010] A kiosk housing has been invented which allows one to utilize a wide selection of different hardware components within one kiosk housing. This design allows the kiosk designer to select the desired components closer to the time that the kiosk is assembled. This new kiosk also allows one to readily change hardware components after the kiosk is in the field, without the need for cutting, grinding or re-machining.
[0011] The present invention also provides modular components supported on a service door, such that, upon opening the service door, the components are readily accessible for servicing (i.e. are no longer contained within the body of the kiosk, but are projecting from the inner face of the service door and thus are more readily accessible for servicing). The kiosk thus allows for unprecedented clear access the internal hardware components for servicing.
[0012] The present invention teaches an automated kiosk comprising (a) a cabinet; (b) a face frame releasably securable to the cabinet; (c) a plurality of cross members secured to the face frame; and (d) a plurality of hardware components releasably secured to the cross members. The hardware components may be sized and configured such that they project substantially directly inward into the cabinet when the face frame is secured to the cabinet.
[0013] In an embodiment, the edge of the face frame may be hinged to a corresponding edge of the cabinet. The cross members may be releasably secured to the face frame. At least one of the cross members may be releasably securable in a plurality of configurations in relation to the face frame. At least one of the plurality of cross members may be secured to at least one of the plurality of hardware components indirectly, such that at least one of the plurality of cross members is secured to a faceplate and the faceplate is secured to at least one of the plurality of hardware components.
[0014] One of the plurality of hardware components may be a keyboard, and the keyboard may be secured to the face frame indirectly by a keyboard housing, and the keyboard housing is secured to the face frame. The plurality of cross members may be secured to the face frame indirectly, such that the plurality of cross members is secured to a housing and the housing is secured to the face frame. There may be a plurality of housings secured to the face frame. The kiosk may have a faceplate on an upper portion of the face frame, the faceplate configured such that a top of the faceplate projects farther out from the face frame than a bottom of the faceplate.
[0015] The invention also teaches an automated kiosk comprising a cabinet, a front face frame, and a plurality of hardware components secured to the face frame. The kiosk may have a door in the kiosk, the door configured to allow access to the hardware components. The face frame may be the door.
[0016] In another embodiment, the hardware components may be secured to the face indirectly, such that the hardware components are secured to a plurality of cross members and the plurality of cross members is secured to the face frame. The hardware components may be sized and configured such that they project substantially directly inward into the cabinet when the face frame is secured to the cabinet. At least one of the cross members may be releasably securable in a plurality of configurations in relation to the face frame. In another embodiment, at least one of the plurality of cross members may be secured to at least one of the plurality of hardware components indirectly, such that at least one of the plurality of cross members is secured to a faceplate and the faceplate is secured to at least one of the plurality of hardware components. The plurality of cross members may be secured to the face frame indirectly, wherein the plurality of cross members is secured to a housing and the housing is secured to the face frame.
[0017] The invention also teaches a method of modifying a kiosk of the invention, comprising the steps of (a) removing a hardware component or a faceplate from the kiosk; (b) repositioning a cross member on the kiosk; and (c) installing a new hardware component on the kiosk.
[0018] The invention further teaches a method of constructing a kiosk of the invention comprising the steps of: (a) assembling a cabinet to a face frame; (b) receiving an order which designates the hardware components required for the kiosk; (c) securing a plurality of cross members to the face frame in a configuration suitable for receiving the designated hardware components; and (d) securing the designated hardware components to the cross members.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] A better understanding of the invention will be had by now referring to the accompanying drawings in which:
[0020] [0020]FIG. 1 is a front perspective view illustrating a kiosk of the present invention with the front door open.
[0021] [0021]FIG. 2 is a front perspective view showing the internal configuration of a kiosk of FIG. 1 with the front door closed.
[0022] [0022]FIG. 3 is a front perspective view of a kiosk of the present invention.
[0023] [0023]FIG. 4 is a front perspective view of an alternative embodiment of a kiosk of the present invention.
[0024] [0024]FIG. 5 is a front perspective view of a further alternative embodiment of a kiosk of the present invention.
[0025] [0025]FIG. 6 is a front perspective view of a further alternative embodiment of a kiosk of the present invention.
[0026] [0026]FIG. 7 is a front view of a front face frame of a kiosk of the present invention.
[0027] [0027]FIG. 8 is a side view of a kiosk of the present invention.
[0028] [0028]FIG. 8A is a detail view of FIG. 8 at A.
[0029] [0029]FIG. 8B is a vertical sectional detail view of FIG. 8 at B or C.
[0030] [0030]FIG. 8C is a vertical sectional detail view of an alternate embodiment of FIG. 8 at B or C.
[0031] [0031]FIG. 8D is a vertical sectional detail view of FIG. 8 at D.
[0032] [0032]FIG. 8E is a vertical sectional detail view of FIG. 8 at E.
[0033] [0033]FIG. 8F is a vertical sectional detail view of FIG. 8 at 8 F.
[0034] [0034]FIG. 8G is a horizontal sectional detail view of both left and right side of FIG. 8 at G.
[0035] [0035]FIG. 8H is a horizontal sectional detail view of an alternate embodiment of FIG. 8 at G.
DETAILED DESCRIPTION OF EMBODIMENTS
[0036] As used herein, “kiosk housing” refers to housing which allows user access to user interface portions of hardware components while preventing public access to fragile or removable portions of the components, thereby making it possible to provide the user interface equipment to the public for their use in an unsupervised or semi-supervised setting. Service access to the internal components of the housing is necessary to provide maintenance and to replenish consumable supplies, such as paper.
[0037] As seen in FIG. 1, the kiosk housing 10 has a base cabinet 12 . Fastened to cabinet 12 by a hinge 16 at one vertical edge, and fasteners 18 opposite, is face frame 14 . Face frame 14 is, in turn, fastened to and supporting upper frame 86 and main frame 88 . In an alternative embodiment, as shown in FIG. 8H, the face frame may be integral to main frame 88 .
[0038] As seen in FIG. 7, an arrangement of cross members 20 are fastened to main frame 88 and to other cross members 20 by fasteners 18 . Cross members 20 and main frame 88 thus form a grid of fastening surfaces, with openings between of a variety of dimensions, to provide for the mounting of faceplate elements. Cross members 20 are formed with a series of holes 17 running lengthwise along the cross members. Holes 17 are suitable for receiving fasteners 18 . Providing the series of holes 17 facilitates reconfiguration of the cross members, allowing one to reconfigure the kiosk housing to receive different components using only simple hand tools. Faceplates 22 are fastened to cross members 20 (as seen in FIG. 8F), or main frame 88 (as seen in FIG. 8C). As seen in FIG. 8F, faceplates 22 in turn support hardware components 24 , configured for access by a user to user access portions of components 24 through the faceplate 22 .
[0039] Projecting inward from door 28 on a substantially horizontal plane are the bodies (i.e. non-user access portions) of various hardware components which have portions that require access for the user. Shown in FIG. 1 are the housings for the portions of speakers 48 , camera 46 , paper roll and printer 58 , video display screen 54 , data ports 56 , and card reader 52 . Components which do not require direct user interface, such as computer unit 34 , fire suppression system 42 , power supply 62 , and UPS system 38 are secured within cabinet 12 . The components are interconnected by wiring (not shown), and are secured to the door 28 , as described above. Thus, the hardware components are independent components suitable for easy removal and replacement with like or different components, as desired.
[0040] With the cabinet 12 and face frame 14 hinged at one edge, the cabinet may be opened for servicing or the replacement of consumable materials, without requiring the disconnection of any of the components, by passing their respective conductors between the two halves of the cabinet in the vicinity of the hinge. The lock or fasteners are arranged to also provide compression of a seal which may be interposed between the edges of the rear and front cabinets, in cases where a high degree of contaminant exclusion is required.
[0041] In the illustrated case in FIG. 1, face frame 14 is fastened to and supports upper frame 86 . Upper frame 86 , in turn, is fastened to and supports lighting 44 (seen in FIG. 1), and graphic panel 64 via cross member 20 and faceplate 22 forming a clamp for graphic panel 64 (best seen in FIG. 8D). As an alternate method of fixing graphic panel 64 , it may be fastened directly to upper frame 86 , as shown in FIG. 8C. Graphic panel 64 is constructed of a semi-transparent material or the like, such as polycarbonate glazing, to allow light from lighting 44 to shine through, forming an upper backlit transparency housing.
[0042] As best seen in FIG. 8, upper frame 86 is configured to allow graphic panel 64 to tilt downwards. This angle of presentation of the top (advertising) fascia allows a user to view the advertising while standing at the machine. Also seen in FIG. 8, the keyboard housing 72 is angled to project outwards to provide a more ergonomically useful keyboard surface.
[0043] Face frame 14 is also fastened to and supports main frame 88 . Main frame 88 , in turn, is fastened to and supports cross member 20 . Cross members 20 and main frame 88 , in turn, support faceplates 22 (best seen in FIG. 8F). Faceplates 22 , in turn, support hardware components 24 (best seen in FIG. 8E). Main frame 88 is also fastened to and supports keyboard housing 72 . Keyboard housing 72 , in turn, contains keyboard 50 , secured via a faceplate system such as that shown in FIG. 8.
[0044] The assembly allows for the easy addition or removal of any face frame support element and their respective faceplates. In other embodiments the face frame 14 can be further subdivided according to the present method or any similar method which suits a similar set of housing components.
[0045] As shown in FIG. 8F, cross members 20 may be flanged rigid bars forming a grid of fastening surfaces. In other embodiments, cross members 20 may be channels or tubes.
[0046] At the junction of upper frame 86 and main frame 88 , these two frames are secured with fastener 18 , with a gasket 29 located between the frames.
[0047] The assembly of face frame 14 , main frame 88 , upper frame 86 , cross members 20 , faceplates 22 , and hardware components 24 constitute a modular door 28 .
[0048] As seen in FIG. 2, the kiosk and its components are sized and configured such that, there is no interference between the front, user access door components, and the rear, cabinet installed, non-access components, nor is there interference between the walls 36 of cabinet 12 and the components secured to door 28 , when the door 28 is closed.
[0049] In the embodiment shown in FIG. 1 and FIG. 8G, modular door 28 is fastened to cabinet 12 with a hinge 16 at one edge, and fasteners 18 opposite. In other embodiments, door 28 may be secured to the cabinet by fasteners at all the edges. In other embodiments, hinge 16 may be located at a different edge, such as the top or bottom edge of the cabinet.
[0050] Faceplates 22 are generally flat and provide for the installation of components as described elsewhere. Such flat parts are easily fabricated by a variety of methods from any suitable sufficiently ridged material, without the need for tooling, or with simple tooling or with programmable machines.
[0051] Faceplates 22 are fastened by fasteners 18 , such as studs, hooks, threaded bosses or some other arrangement on the rear surface of the faceplate 22 . The securing and releasing portions (such as bolts 19 ) for fasteners 18 are only accessible at the rear surface of the face frame 14 , which is only accessible when the cabinet is open. Any exposed portion of fastener 18 is configured to prevent tampering by using, for example, push-in studs as shown in FIG. 8E. Access to the interior of the kiosk housing 10 can be limited by the use of locks or security fasteners 18 , to prevent removal of or tampering with internal hardware components by persons denied access to the necessary tools, keys, or pass cards, according to security arrangements.
[0052] A gasket 26 is interposed between the faceplates 22 and the support members 20 , in order to provide a seal to prevent the entry of contaminants. Gasket 26 is constructed of a material and cross section which provides for spacing of the faceplates 22 relative to each other, allows for manufacturing tolerances, and provides a seal between the modular doors, various frames and the faceplates 22 . This is achieved using a “T” section (as seen in FIG. 8F) and/or an “L” section (as seen in FIG. 8E), as appropriate, and incorporating intermediate parts, which correspond to the divisions of the cabinet face. A ribbed gasket may also be used to provide multiple seals within one length of gasket. Gasket 26 may comprise one large unibody gasket, or multiple smaller gaskets.
[0053] A gasket 27 is also located between face frame 14 and frames 86 , 88 and/or 90 .
[0054] The kiosk shown in FIG. 1 further has a vent and air filter 40 to provide for internal cooling while excluding dust particles and other environmental elements.
[0055] The kiosk also has a phone 30 , which may be configured as a pay telephone, or as a direct access phone to, for example, a user assistance line or a taxi company.
[0056] The kiosk of FIG. 1 has also been provided with a cap 32 which can have multiple functions. Cap 32 protects the kiosk and shelters the kiosk user from rain, snow, sunlight and other environmental elements. Cap 32 can contain a fan (not shown) to facilitate air flow through the kiosk for cooling internal elements, or lighting for the face of the kiosk. In another embodiment of the kiosk, as shown in FIG. 3, the cap 32 can include a top display 80 , which may be used for advertising, lighting, or user instruction. The cap could also be manufactured to allow for natural light to pass through and illuminate the kiosk.
[0057] [0057]FIG. 1 also shows fire suppression system 42 , which integrates a smoke or heat detector with a cooling or extinguishing apparatus such as inert gas or dry chemical for extinguishing any fire caused by internal malfunction.
[0058] Examples of various embodiments of the kiosks are depicted in FIGS. 3, 4, 5 , and 5 . All such configurations are easily constructed and may be subsequently reconfigured using the same underlying kiosk housing system described herein. Thus, the present invention provides for the selection by the end user of any subset of any components, and provides for the accommodation of still others not shown. Components that may be used as desired include printer 58 , printer output 68 , camera 46 , speakers 48 , card readers 52 , keyboard 50 , screen 54 , data ports 56 , touch pad 60 , keypad 76 , instruction panel 66 , data ports 56 , lockable maintenance port 70 , as well as components not shown, such as a microphone, a mouse, key pad, track ball, and other peripherals, such as those set out in Table 1. The screen 54 can be standard, resistive touch or surface acoustic wave touch. The card reader can be a push/pull magnetic strip reader or a power loader. The camera may come equipped with a vandal shutter. The components can be connected to remote information sources by wire or wireless means. The kiosks of the invention can thus be designed to perform a wide variety of tasks, including e-mail, videoconferencing and database access. This allows the same set of housing components to accommodate hardware permitting an extremely broad range of applications, including those contemplated in Table 2 and a wide range of functions, including those contemplated in Table 3 .
[0059] When installed, kiosk housing 10 may be mounted directly to a vertical surface, or to a support frame 82 which is in turn fastened to the vertical surface, as shown in FIG. 8. As shown in FIG. 5, with little modification, kiosk housing 10 may also be constructed so as to extend to the ground on a free standing support stand 78 . As shown in FIG. 6, kiosk housing 10 may be supported against a wall and also extent to the ground, via a lower frame 90 . In this embodiment, lower frame 90 is suitable for housing computer unit 34 , UPS system 38 , and any other components not requiring user interface.
[0060] The invention described herein may provide all or some of the following benefits.
[0061] Firstly, for manufacturing, the rear housing, face frame and faceplate elements can be manufactured prior to the receipt of an order for a specific configuration and assembled in the requested configuration immediately prior to shipment. This reduces the time necessary to customize the configuration.
[0062] Secondly, the cost and time necessary to create and test new kiosk designs is severely reduced, allowing for more unique customized configurations, and allowing small orders to be filled.
[0063] The hardware components can be removed and replaced in the field with different sized components, or with a completely different manner of components, with minimal cost and mechanical work. The kiosk no longer has to be removed and returned to the supplier for major machining such as cutting, drilling, tapping, or otherwise altering the mountings necessary to remove a device and replace it with one having a different physical configuration. Such work can be occasioned by obsolescence of the device, a change in intended use of the configuration or other reason. Thus the kiosk housing does not have to be replaced should a component require replacement for any reason, and so has a longer useful lifespan.
[0064] The mentioned benefits are achieved without reducing the ability of the enclosure to exclude contaminants by positioning of the gasket shown in FIG. 8 and 8 A to 8 H. Furthermore the interchangeable faceplates are provided with projecting studs, bosses or hooks which prevent removal of parts other than by a person with the ability to access the rear of the door, when the cabinet is open.
[0065] The present invention also provides modular components supported on a service door, such that, upon opening the service door, the components are readily accessible for servicing (i.e. are no longer contained within the body of the kiosk, but are projecting from the inner face of the service door and thus are more readily accessible for servicing).
[0066] The present invention thus provides modular fascia, each fascia attached to a corresponding modular component (e.g. monitor, keyboard, printer, card reader), with the components configured and sized to project inwards from its corresponding faceplate such that the components can be more readily removed and replaced with an updated component, a different component, or a faceplate without a component. This also allows for various combinations of components to be readily installed in the basic unit, either at the time of manufacture or later.
[0067] The kiosk also resists tampering, the elements, and provides access for maintenance and the replenishment of consumable supplies.
[0068] Thus the present kiosk housing provides for a wider range of selection of hardware components without replacing the fascia of the kiosk housing. The present kiosk housing also allows for clear access to internal hardware components for servicing. The kiosk is also lightweight, compact, easily movable, structurally rugged, and economical to manufacture. The kiosk provides a method of mounting the faceplate components to a housing in a manner which is tamper resistant. The kiosk provides a method of mounting the faceplate components to a housing in a manner which provides for protection from the elements.
[0069] The kiosk housing system may be used for many different purposes and many different hardware sets, without requiring re-design of the basic housing. The kiosk housing may be configured for its intended use at the time of its assembly. The kiosk housing may be altered subsequent to its assembly, without the need for re-working. The invention thus also teaches a fabrication method which can be applied to kiosk housings of different forms, utilizing the principles described herein.
[0070] While the present invention has been illustrated and described in detail in the drawings and foregoing description, it should be recognized that other embodiments will be apparent to those skilled in the art. It is therefore intended that the following claims cover any such embodiments as fall within the scope of the invention.
TABLE 1 Modular Kiosk Component Examples Device Options 1 17″ Monitor Flat 2 Touch screen overlay SAW Technology 3 Large capacity high speed printer Thermal, Roll Fed 4 Computer P.C. in Compact Config. 5 Network device On Board P.C. 6 UPS 7 Fan With Filter 8 Thermostatic switch Thermistor 9 Refrigeration Semiconductor Heat Pump 10 Heating Above, Polarity Reversed 11 Back-lit graphic Fluorescent Lamp Lit 12 USB Webcam With Vandal Shutter 13 TTL handset 14 Smart card reader/loader Push/Pull or Power 15 Mag-stripe reader Same 16 Wide bed color printer Dye Sub. 17 Keyboard Vandal Resistant 18 Pin Pad Vandal Resistant 19 Bill acceptor 20 Speakers 2 21 Audio Amplifier 22 Microphone 23 Remote Monitoring Device RS 232 24 Fire Suppression System Automatic 25 Data Ports Telecom, Infrared, Serial 26 Pointing Device Trackball, Touchpad
[0071] [0071] TABLE 2 Examples of Component Subsets Plain Paper Card or Facility Type/ Large Main Display Swipe or Colour Micro- Push Tele- Kiosk Use Graphic Panel (CRT, LCD) Additional Display Touch Screen POS pad Bill Acceptor Keyboard Thermal printer Printer phone Camera Speakers Buttons phone Non-Reserved Ticketing, e.g. Theatre Reserved Seat Ticketing, e.g. Theatre, Sports Reserved Seat Ticketing, e.g. Travel Single Program Ticketing, e.g. Parking Facility Orientation, Utility e.g. Office Facility Orientation, ADA e.g. Institutional STD Facility Orientation, ADA e.g. Mall STD Add - bridal registry, gift certificate, vending STD Photo Kiosk E-mail Kiosk Product Information Kiosk VR Game Legend: STD = standard OPT = optional
[0072] [0072] TABLE 3 Typical Functional Requirements FUNCTION OPTIONS Web Surfing White listing Black listing “Canned” Database Search Large Memory (prob. remote), Online updating Debit/Credit Card Payment Smart Card Payment/Cross Load Cash Payment Receipt Printing Page Printing Colour Black and White Phone Call TTL Video Conferencing Photo Booth Scanning E-mail Attachment Reading with Plug-ins Audio Output Speech Input Remote Monitoring Remote Device Control Shut Down Boot Scrolling Ads Multiple Video Cards Temperature Control −40° C. + 55° C. ambient or Surface Temperature Weather resistance Condensing Humidity Rain, Driving Rain Blowing Snow Dust, EMI Neither produces nor is affected by
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An automated kiosk has (a) a cabinet; (b) a face frame releasably securable to the cabinet; (c) a plurality of cross members secured to the face frame; and (d) a plurality of hardware components releasably secured to the cross members. The hardware components may be sized and configured such that they project substantially directly inward into the cabinet when the face frame is secured to the cabinet. A method of modifying a kiosk of the invention, comprises (a) removing a hardware component or a faceplate from the kiosk; (b) repositioning a cross member on the kiosk; and (c) installing a new hardware component on the kiosk. A method of constructing a kiosk of the invention comprises (a) assembling a cabinet to a face frame; (b) receiving an order which designates the hardware components required for the kiosk; (c) securing a plurality of cross members to the face frame in a configuration suitable for receiving the designated hardware components; and (d) securing the designated hardware components to the cross members.
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BACKGROUND OF THE INVENTION
The present invention relates to tubular elements and joints for their mutual articulated connection both at their upper and lower ends, to form a partition wall which is self-supporting and can be positioned so as to assume a desired curved pattern according to the requirements.
It is known that, following the present architectural trend, a so-called "open space" arrangement is adopted in the public and private offices, that is without a wall partition of the available space into separate rooms, but with the desks or each clerk's places of work being located near one another. However it is frequently required to separate certain working areas from others where a distinct and independent activity is carried on, while trying all the same to avoid permanently installed dividing structures, e.g. of masonry.
The need of modifying these separating structures in case of re-arrangement of the available space has brought to date to the use of mobile panels, such as made of laminate, which however require a supporting frame and means for the anchoring to the floor and possibly to the ceiling. Should it be necessary to modify the position of these panels, a laborious disassembly and re-assembly of the structures will be required, with consequent use of implements such as screwdrivers, wrenches, etc. It should also be appreciated the considerable cost of those partition panels and of the associate clamping means, usually made of metal as well as the limitations of varying the perimeter defined by these mobile walls which will be necessarily of the polygonal type.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a structural assembly to form a partition wall which is self-supporting and consequently does not require means for its anchoring to the floor or to the ceiling, but only junction means for mutually connecting the tubular bodies forming the assembly, all of easily mouldable plastic material, thus of low cost, which can be disassembled and re-assembled manually, without using tools.
Another important advantage of the structural assembly according to the invention resides in the possibility of placing the partition wall along the desired curved pattern to meet any various architectural requirement, being capable of immediate displacements with no need of disassembling the junction elements.
It is also possible to obtain branches of these walls, two of which can divert at an angle from a third one, thus forming e.g. a Y-shaped configuration.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a plan view, irrespective whether from above or from below, of a wall length according to the invention in one embodiment comprising some joints of the invention itself;
FIG. 2 shows a partial, diagrammatic front view of another embodiment of partition wall, with a sectioned particular;
FIG. 3 shows a cross-section view of one of the upright tubular elements forming the partition wall assembly of the invention;
FIGS. 4a, 4b show respectively a view from above and a front view, the latter in the direction of arrow A, of a so-called "plug" member as used in the partition wall according to the invention;
FIGS. 5a, 5b show respectively a view from above and a sectional view along B--B of a first joining member according to the invention;
FIGS. 6a, 6b show respectively a view from above and a sectional view along B--B of a second joining member according to the invention; and
FIG. 7 shows a view below of a special embodiment of the second joining member of FIGS. 6a and 6b.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
With reference to the drawings, the assembly forming the partition wall of the invention substantially comprises a plurality of tubular elements 1 placed side by side, generally cylindrical and having a cross-sectional shape as shown in FIG. 3. Each tubular element 1 is closed at both ends by a head "plug" 2, shown in FIGS. 4a and 4b, with a central hole 20 in which one of two hollow, bored pins 10 of a plate 3 can fit as well as, at the inside of pin 10, one of two joining pins 11 formed in a second link plate 4, as is better shown in the partial section of a particular of FIG. 2.
Each vertical tubular element 1 is formed in a longitudinally extending concave lateral portion 5 shaped as a circular arc in cross-section, having the same bending radius as the radius of the remainder, convex cylindrical portion 6 and is capable of rotation with such a concave portion 5 around portion 6 of the adjacent element 1'.
The distance between the axis of hole 20 and the centre of concave arc 5, corresponding to the centre of the convex portion 6 of the adjacent element 1', in other words the distance between the centres of holes 20 in plugs 2 fitted on contiguous vertical elements 1, 1' is equal to the distance between the centres of pins 10 and 11 of each link plate 3, 4, respectively.
The assembly of the structure according to the invention will now be described with a more detailed reference to the particulars of the various members by which it is composed.
The main component 1, as shown in cross-section FIG. 3 can be made of whichever light material such as aluminium, wood and preferably a resistant plastic material, having a certain elasticity and adapted to be shaped as illustrated (e.g. advantageously by extrusion), with recesses 21, 22 and 23 formed in the concave portion 5 to reinforce the structure and at the same time to impart a greater elasticity thereto. These recesses 21, 22 and 23 are symmetrically arranged to the median plane X--X of element 1 and in the represented embodiment show all an inner portion having a substantially circular cross-section which is connected to the outer periphery 5 through two facing parallel lengths of wall. The central recess 23 has a greater size than the other two recesses and extends itself to the inside of the element so that the centre of its inner circular portion coincides with the centre of the convex portion 6. The extension of portion 6 is substantially greater than the portion 5 extension. Stiffening radial ribs 24, 24a are provided to join said recess 23 to the inner wall of portion 6. Elements 1, 1' etc. are placed side by side so that the concave portion 5 of each of them is against the convex portion 6 of the adjacent element and so on, the mutual matching being provided by the above-indicated relationship between the respective radii.
At the upper and lower ends of each element 1 a head plug is applied as represented with 2 in FIGS. 4a, 4b. It should be appreciated that the outer profile of plug 2 is substantially coincident with that of element 1, except for recesses 21, 22, 23. The snap fitting is made easier by radial ribs 25 which not only stiffen the assembly, but also have a guide function during the coupling, as they slide with their outer ends along the inner wall of element 1. At the same time a central cylindrical bore pin 13 with through hole 20 fits along a short length at the inside of the central cylindrical passage formed by recess 23.
The plug 2 is also provided, at its upper face 14, with upraised zones 15, 15a being symmetrically positioned to median line X'--X', which define with their upper, co-planar surfaces a plane parallel to the surface 14 and suitable to form the base of the whole assembly, as will be explained later on. These two raised portions, as seen in FIGS. 4a, 4b, are extended from the two peripheral zones of plug 2 where the concave portion, corresponding to portion 5 of element 1, touches the convex circumferential portion corresponding to portion 6 of the element and each of them is defined in addition to these two outer zones, by a generally upright shoulder which for a length 16a is substantially parallel to the median line X'--X' and for a length 16 is at an acute angle therewith.
Thereafter the plugs 2, and thereby also the elements 1 already clamped to them, are connected each other in pairs by means of linking joint plates 3, 4 as respectively shown in FIGS. 5a, 5b and 6a, 6b. This occurs by fitting first in each hole 20 one pin 10 with through hole 30 of plate 3 and then, in the hole 30, one pin 11 of plate 4, the inner cavity of which is blind. The diameters of holes 20 and 30, as well as of pins 10 and 11 are so sized to allow the assembly and disassembly of the various members merely by hand, the snap fits being aided by the elastic material of the pins and by their shape with longitudinal slits 26, 26a and protruding edges 27, 27a.
The plate 3 shows in its central zone a planar raised portion 17 which is defined externally by the plate contour itself and, at the inner sides, by a shoulder with a concave profile having its bending centre coincident with the centre of hole 30 faced by said profile and a bending radius at least equal to the radius R of the rounded end 28 of plate 3. The height of the raising is such as to reach the level of raised portions 15, 15a when plate 3 rests with its lower surface of face 14 of plug 2 and pin 10 fitted in the hole 30.
The plate 4, on the other hand similar to plate 3 as far as the overall outline is concerned, is instead planar at its upper side and is formed with a spacing member 18 on its lower side. Spacer 18 has a profile substantially corresponding to the raising 17 and such a thickness to rest with its lower edge on the surface 14 of plug 2 when the "upper" plate 4 is fitted therein through a hole 30 of a "lower" plate 3. The overall thickness of both plates 3 and 4 in the generally circular zone where they are over lapping having the same radius R and being complementary both to the upraised portion 17 of plate 3 and to the lower spacer 18 of plate 4, is the same as the thickness of plate 3 alone in the raised portion 17, of the plate 4 alone as measured at the lower edge of spacer 18 and of the raised portions 15, 15a of plug 2. Thereby, upon assembly, the upper surfaces of the portions 15, 15a, 17 and the entire upper face of plate 4 are co-planar, so that the whole assembly can rest firmly on the floor and also the upper end has a planar profile.
It appears clearly that each element 1 (and also both the lower and upper plugs 2 associated therewith) can pivot about the adjacent element 1' faced by its concave portion 5 with a rotation axis passing through the co-axial centres of hole 20 and recess 23 and with a rotation radius corresponding to the center-to-center distance between holes 30 or pins 11.
The link connection between each element 1 and the adjacent one is provided by a plate 3 and a plate 4 alternatively, as in the hole 20 of each plug 2 there are inserted every time two plates 3 and 4 respectively, directed to opposite sides, except only for the elements at the ends of the assembly. The shoulders 16, 16a, by which the raised portions 15, 15a are defined, set a limit both to the range of mutual rotation of elements, with respect to each other, and to the rotation of each element about its own axis. The two opposite shoulders 16a are spaced apart a distance at least corresponding to the width of a plate 3 or 4. At a limit position of maximum relative rotation of two adjacent elements, the shoulder 16 of one element is aligned with the shoulder 16a of the other and such a continuous shoulder forms an abutment for a side of the plate 3 or 4 involved, as shown in FIG. 1.
It is also provided, according to the present invention, instead of an "upper" plate 4, the use of an angular junction plate 7, substantially formed as two plates 4 integrally combined together at right angles in a L-shape with three pins 11, one at each vertex thereof, and with a lower spacer 18 having the configuration shown in FIG. 7. As indicated, the spacer 18 also in this embodiment is such as to surround, with a bending radius R, the areas designed to the rotation of the underlying associated plates 3, to form a seat for such a rotation. Plate 7 will be utilized, at the base and the top of the assembly, when a Y-shaped branching of the partition wall is desired or more commonly, at a corner when partition walls of the invention should be arranged traditionally at right angles, whereas the main characteristics of the present invention is the possibility of defining areas, by means of a single partition wall having a polygonal shape, or forming a continuous or broken curved line, substantially according to any desired pattern with the provision that no such discontinuities are involved to require a relative pivoting of two adjacent elements, for an angle greater than the range allowed by the abutments 15, 15a.
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A self-supporting wall is formed by assembling tubular elements with a longitudinal portion having a concave arc-shaped cross-section by means of joints being link plates of two different types. One type, with a central raised portion and two bored pins, and the other, with a lower spacer member and two dead-end hole pins, alternately link together the elements placed side by side, through plug members adapted to fit into a central passage of each element and to be coupled to said pins of the plates. The partition wall can thus assume a variety of polygonal or arc-shaped patterns with no need of being anchored to the floor or to the ceiling.
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This application is a division of Ser. No. 194,118 filed Oct. 6, 1980, now U.S. Pat. No. 4,348,343, issued Sept. 7, 1982.
BACKGROUND OF THE INVENTION
This application relates in general to a method for forming a resin binder system and more preferably to a method for forming a resin binder system of a furfural-phenolic resin system.
Furan modified phenolics have found great favor recently, largely because of their capability of providing high carbon content, high strength and thermosetting characteristics. However, because of the liquid nature of such furan phenolics, difficulties in their use were presented. For example, mixing with sand to form a foundry shape produced a heavy, sticky or viscous mix which was hard to work with. Mixing with carbon for subsequent molding or extrusion produced a sticky mix with little green strength.
Attempts to solve the above problem to render furan modified phenolics more acceptable for use with refractory materials in forming desired shapes and articles, as typified by U.S. Pat. No. 4,051,301 to Laitar, have resulted in a solid thermoplastic resin which, when added to a refractory material such as sand, had to be heated or otherwise dissolved to result in a free-flowing particulate mix that can be converted to a hard rigid thermoset article. However, this desirable end result is achievable only through the use of an expensive formulation procedure, thereby putting the resin in an unfavorable economic position with traditional phenolic novolaks.
SUMMARY OF THE INVENTION
An object of the present invention is a free-flowing non-sticky particulate mixture of a high furfural content binder and a solid particulate material.
An additional object of this present invention is an economical free-flowing particulate mixture having a binder of a furan-modified phenolic.
An object of the subject invention is a furan-modified phenolic binder which has a long storage life.
Another additional object of the present invention is a solid non-sticky thermoplastic furan-modified phenolic binder which can be handled and processed at room temperatures and yet is thermosetting at moderate temperatures.
A still further object of the present invention is a catalyzed, long bench life coated particulate mixture capable of being converted to an integral mass by warming or pressure.
These and other objects of the present invention are provided by the method and composition for forming a free-flowing stable particulate mix having a binder of a high furfural content system, such as, for example, a furfural-phenolic resin system. A preferred binder system is generally formed by admixing a liquid blend of a solid non-sticky novolak resin and furfural to a particulate material having a small amount of the liquid amine uniformly dispersed thereon. Mixing is continued until the entire mass breaks into a free-flowing particulate mixture. The resulting particulate material may be shaped, extruded, or compression molded, depending upon the desired end product, and is converted to an integral mass by warmth or compression.
Consider broadly, the objects of this invention are achieved by dissolving a solid non-sticky resin in furfural monomer in an amount sufficient to reduce the viscosity of the solution to a level at which the solution can be uniformly admixed with a particulate solid material such as carbon, sand, glass fibers, other refractory materials, and the like. Upon addition of the resulting solution to particulate material containing the amine the resulting mass is transformed to a "dry" (i.e. no liquid) free-flowing particulate mass. The amines which are used are of the class which are liquid at ambient room temperatures, and capable of forming a reaction product with furfural.
DETAILED DESCRIPTION OF THE INVENTION
In a preferred embodiment of the subject invention a phenolic novolak resin is mixed with furfural so as to achieve a desired viscosity as will be discussed. Generally speaking, as used herein, the term "novolak" and "novolak resin" denote a condensation product such as is obtained by causing a phenol to condense with less than an equimolar portion of an aldehyde or a ketone, in an acidic environment. Structurally the molecules of a novolak consist essentially of alkyl-substituted or unsubstituted phenyl nuclei connected together by methylene or substituted methylene links.
To form a preferred novolak suitable for use in the subject invention a mixture of phenol and aqueous formaldehyde is prepared at a ratio of 1.15 moles phenol to 1.00 moles of formaldehyde. A sufficient quantity of oxalic acid is admixed therewith to provide a pH of about 1.0 and the reaction mixture is allowed to react under atmospheric reflux temperature conditions until all of the formaldehyde disappears. Thereafter, a sufficient quantity of aqueous sodium hydroxide is added to the reaction mixture to elevate the pH of the reaction mixture to approximately 6.3. Thereafter the refluxing condensor is removed and most of the water and unreacted phenol is allowed to be removed from the reaction mixture in the conventional reduced pressure distillation stripping step. The resulting resin is a solid at room temperature. While reference is made herein to a specific manner of preparing a solid novolak, other methods as are known and accepted in the art may be utilized.
To the novolak prepared as indicated above, furfural is added in sufficient quantities to achieve a desired viscosity. The furfural may be either added to the novolak while still in melted condition in the novolak reactor or solid novolak may be added to the furfural. For long term storage stability the pH of the resulting furfural solution should preferably be adjusted to 3.5-4.0. However a pH value of 1-7 is useful. The following table indicates approximate amounts of furfural as percentages of the whole mixture which may be added to the novolak to obtain a given viscosity.
TABLE I______________________________________% Furfural Viscosity (cps)______________________________________44% 300048% 90053% 40057% 25069% 18074% 65______________________________________
The furfural-novolak solution thus prepared has a long shelf life at room temperature and, though liquid and completely adjustable in viscosity, is completely reactive, all components becoming a part of the solids of the cured resin. However, inclusion of the reactive amine with this solution, in accordance with the present invention, converts it to an uncured but solid, non-sticky condition. The resulting solid is thermoplastic. However, because the amine can convert the system into a thermoset condition, the amine-containing admixture is a catalyzed binder system when dispersed on a particulate solid in accordance with the present invention.
Although the particulate solids coated in accordance with this invention contain the amines, they are essentially uncured and are capable of becoming plastic or semi-liquid on heating. This allows the particulate solids to be molded or extruded. When furfural is added to the novolak in an amount more than double that of the novolak by weight the excess would appear to be wasteful. The minimum amount of furfural to be added to the novolak is that which is sufficient to liquify the novolak. Furfural to novolak ratios of 0.6:1.0 to 2.0:1.0 are preferred.
Preferably the amines of the subject invention are liquid mono- or poly-amines having two or more free hydrogens on the amine nitrogen and a boiling point over 150° C. However lower boiling amines such as ammonia or ethylene diamine may be used. The most preferred amine is triethylenetetramine (TETA).
As a result of the six free hydrogens available in TETA for reaction with furfural molecules, a relatively small amount of the TETA will bind up at room temperature the liquid furfural in the furfural novolak mixture, transforming such a mixture into a thermoplastic solid. Thus when the TETA is initially dispersed on an aggregate such as sand or carbon, and the furfural-novolak resin blend added, the resin system essentially coats the sand or carbon particles, as will be discussed in greater detail hereinafter, with no free furfural, as evidenced by the absence of the pungent furfural odor. The result is a dry free-flowing particulate solid which has good bench life, and, while being thermoplastic, can be completely thermoset by baking at moderate temperatures. Alternatively the binder system can be cured at room temperature over a long period of time. The curing rate of the resin binder system can be adjusted by increasing or decreasing the amount of the amine. For instance the amount of 4 percent TETA based on the furfural present will provide greater shelf life at room temperature, while increasing the amount of TETA up to a maximum of 30 percent will increase the curing rate. The minimum amount of amine which can be used in accordance with this invention is the amount which will react with the furfural in the novolak-furfural solution to convert it at room temperature to an uncured solid. Mixing of the amine with the furfural resin solution is carred out at room temperature with cooling if the mixing conditions require cooling. Preferably the amine is added to the solid particulate substrate prior to addition of the furfural resin solution.
As stated above, the resin binder system of the subject invention is useful in forming articles and shapes from a wide variety of particulate solid material. The following examples illustrate some of those uses and are not to be taken as limiting in any respect. All parts and percentages, unless expressly stated to be otherwise, are by weight.
EXAMPLE I
Approximately 2 percent of triethylenetetramine (TETA) and 70-75 percent carbon particles are thoroughly blended. To this dry amine-carbon mixture is added 16-23 percent of a liquid mixture of the furfural-novolak resin, prepared as described above to have a viscosity of 2500 cps. The mixing apparatus was cooled throughout the blending of the ingredients. Within 10 minutes of the addition of the resin binder system, the temperature of the resulting mixture started dropping gradually from a peak of 50°-60° C. Mixing of the ingredients was continued for a total of twenty minutes when a dry, free-flowing particulate solid was obtained. No furfural fumes were observed to be emitted during the mixing procedure.
The free-flowing powder was later placed into a preheated (60°-65° C.) extruder and extruded through a die into rods. The resulting rods, upon being cooled to room temperature, were found to be very hard and solid, with good green strength. The green carbon rods were baked and thoroughly carbonized by baking in a reducing atmosphere with a programmed temperature rise to 650° C. and holding at that temperature for 48 hours. When carbonized, the rods had satisfactory density and resistivity for use as electrodes. No bleeding or cracking was observed. The stack gases from the carbonization furnace were reduced in objectionable gases.
In practice the carbon particle portion of the mix may be formed from a variety of carbon sources, the percentages of which may vary, according to availability and other considerations. An actual formulation may contain carbon in the form of baked scrap, i.e. that scrap already baked and subsequently rejected for reasons such as quality control, and green scrap or that scrap which has been extruded yet not baked. A petroleum product such as a high viscosity (1500 cps) oil, may also be added for lubrication purposes. The following formulations are set forth to show the range of ingredient compositions yielding satisfactory carbon rods.
TABLE II______________________________________ Formulation No.Ingredients I II III IV V______________________________________Coarse Calcined 44.8% 38.5% 40.1% 43% 36%Petroleum CokeBaked Scrap 29.8 26.0 26.6 20.0 32Green Scrap -- 13.0 13.3 10.0 12.0Oil (1500 cps) 0.9 0.8 0.9 2.8 2.8Furfural-Phenolic Resin 23.3 20.3 17.8 22.0 15.7System (2500 cps)TETA 1.2 1.0 1.3 2.2 1.5______________________________________
EXAMPLE II
92.3 parts coke particles of one-quarter inch mesh or smaller were mixed with 0.7 parts TETA and 7 parts of the furfural phenolic resin blend (3000 cps) was added; the mixing action was continued for twenty minutes with cooling until a free-flowing granulated solid resulted. The free-flowing solid was compression molded into five inch cubes useful as a source of carbon when added to molten iron as a cupola melt ingredient.
EXAMPLE III
83.8 parts silicon carbide aggregate were mixed with 1.2 parts TETA. Fifteen parts of the furfural phenolic resin blend (3000 cps) was added to the dry silicon carbide and TETA; the mixing action was continued with cooling until a free-flowing granulated solid was attained. The granulated solid was formed into a crucible one foot in diameter by two feet in depth through a shaping mold having a conventional rotating scribe. The resulting green crucible shape was separated from the mold and cured at 65° C. for 24 hours. The cured crucible was then carbonized at 800° C. under a reducing atmosphere.
EXAMPLE IV
91.7 parts grated aggregate of calcined dead-burned magnesite having a particle size of no greater than one-quarter inch mesh and 3 parts fine carbon powder was blended with 0.3 parts TETA. Five parts of the furfural phenolic resin mixture (3000 cps) described above was added to the magnesite, carbon and TETA; mixing was continued until a dry free-flowing granulated solid resulted. The granulated solid was compression molded in the shape of a large brick at 145° C. A higher temperature is required to cure refractory bricks in this application because of the large size of the brick and its poor heat conductivity. Alternatively the brick may be cold-molded and then baked at 95° C. for 24 hours. The resulting refractory brick may be used to form furnace linings and the like.
EXAMPLE V
93.5 parts foundry sand, Wedron 5025, was mixed with 0.3 parts TETA. 3.5 parts of the furfural phenolic resin mixture (3000 cps) described above was added to the sand-TETA blend and mixed until a dry free-flowing solid resulted. A surplus quantity of the above mix is placed against a mold pattern heated to 175° C. for a sufficient time to produce a shell mold of desired thickness, for instance, 60 seconds. The mold was inverted and the surplus mix dropped into a conventional recovery sand unit. The resulting formed sand mold was removed from the pattern.
EXAMPLE VI
89 parts granulated carbon was blended with 1.0 parts hexamethylenetetramine. 10 parts of the furfural-phenolic resin (3000 cps) described previously was added and mixing was continued. A sticky, viscous lumpy mix resulted having a furfural odor. The sticky mix was incapable of being easily molded or handled.
EXAMPLE VII
89 parts granulated carbon was blended with 10 parts triethanolamine. 10 parts of the furfural-phenolic resin (3000 cps) described above was added and mixing continued. A sticky viscous lumpy mix having the distinct odor of furfural resulted. The sticky mix could not be easily molded or handled.
A review of the above examples will show that the use of the liquid aliphatic amine TETA, which has free hydrogens available for interaction with the furfural molecule, was capable of providing dry free-flowing mixtures with the furfural phenolic resins. The failure of both triethanolamine and hexamethylenetetramine to provide a dry free-flowing mix can be explained by their lack of free hydrogens on the amine linkages. The aliphatic structure of TETA and other similar amines provides the necessary free hydrogens for tying up the furfural molecules, resulting in the solid free-flowing mixture observed.
While applicants herein do not wish to be bound by any theory, it is believed that the individual aggregate particles of the particular refractory material used are coated with the furfural-phenolic-TETA resin complex. This solid uncured resin complex, though adhering to the refractory particle, does not cause the coated particles to adhere to each other, thus creating the free-flowing dry powder observed. When advanced to the cured state, for example by a long period of time at room temperature or by low temperatures such as 60° C. Upon heating, the coating on the individual particles becomes initially liquid as in thermoplastic resins, whereby the mass exhibits good molding and extrusion characteristics, the resulting shaped mass exhibiting good green strength, and finally setting to a hard, thermo-set rigid shape.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the cope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims.
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A method and composition for forming a dry free-flowing particulate solid is disclosed which utilizes a novel binder system for bonding particles of carbon, sand and/or other solid particulate materials. The solid, non-sticky binder system comprises furfural, solid resin, (such as a phenolic resin), which is not sticky at room temperature and is soluble in furfural, and a liquid amine having free hydrogens on the amine nitrogen which amine is capable of reacting with furfural. This system is capable of adhering to such particles while retaining the free-flowing characteristics of the particles. The free-flowing particulate solid thus formed may be shaped, extruded or compression molded as necessary to form the desired article. A shaped mass of this particulate material is converted to an integral mass by warming or compressing. While the binder is curable at room temperature over a long period of time, the cure rate may be accelerated by increases in temperature. Carbonization of the resin system yields a high carbon residue.
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This application claims the benefit of Danish Application No. PA 2003 00354 filed Mar. 7, 2003 and PCT/DK2004/000144 filed Mar. 5, 2004, which are hereby incorporated by reference in their entirety.
BACKGROUND OF THE INVENTION
The present invention concerns an apparatus for use in determining the position of and forming of assembling holes in spectacle lenses for rimless spectacles, the assembling holes intended for mounting a bridge and a side bar hinge, and of the type including a holder for the lens and machining means that are movable, preferably in two dimensions, relative to the holder.
The invention furthermore concerns a fixture for spectacle lenses for rimless spectacles and for use in determining the position of and formation of assembling holes in the lens, the assembling holes intended for mounting a bridge and a side bar hinge.
The invention furthermore concerns a packing for use in fixture for spectacle lenses for rimless spectacles and for use in determining position of and formation of assembling holes in the lens, the assembling holes being intended for mounting a bridge and a side bar hinge, the fixture including an opening for fixing the lens at its circumferential edge with the packing disposed between the lens and the fixation opening.
Finally, the invention also concerns a method for fixing spectacle lenses for rimless spectacles by determining position of and formation of assembling holes in the lens, and including:
fixing the lens in a fixture for correct hole centre line orientation; forming the assembling holes; mounting a bridge and a side bar hinge in the assembling holes; and moving machining means, preferably in two dimensions, relative to the holder.
In the industry of spectacle manufacturing, rimless spectacles have hitherto been problematic for the optician to produce. This is due to that tools and methods up till now put great demands on skill and precision on the part of the optician making assembling holes for mounting bridge and hinge fittings/side bars in the lenses. Among these, a difficulty has particularly appeared at correct positioning of the spectacle lenses in relation to the machining means used for forming the assembling holes. Just a very little turning of axis when positioning a lens in relation to the frame of the machining tool has thus caused a very visible skewness when placing assembling holes and thereby also risk of a distinct skewness in the formed spectacle.
With the known systems, one also desires to use as thin glasses as possible due to weight and appearance of the spectacles. When mounting bridge and hinges occurs in such lenses, the thinner the lenses the greater demands are put on precision.
Furthermore, from the user there are demands to placing the assembling holes/slits as close to the edge of the lens as possible with regard to the general appearance and so that fastening members become less visible in the field of vision. This is particularly the case when the models are relatively small.
Usually, when making lenses it is important to be able to place the spectacle lenses with optical centre correctly in relation to the user. Correct positioning is particularly important on small models where progressive lenses are used. In such lenses, a slight displacement and very small axis deflections of 2-3° may produce big sight problems for the user. By known embodiments, assembling holes in the shape of slits or round holes positioning systems are placed by manual marking of the lens. In some cases, this also occurs under use of simple drill jigs or measuring jigs with basis in manual markings on the lens. This puts great demands on skilled measurement, where the precision depends on the care and the ability residing with the individual optician.
When the optician grinds a lens, there will be tolerances on the so-called box dimensions. Box dimensions are the rectangle where the circumference of the lens can be ground in. A datum line will appear at the same time as the centre line of the height of the box dimension.
The optician will typically measure the width in the box. With the tolerances existing for machines used for grinding today, there is risk of tolerance deviation on the height/width of the box dimension. Therefore, there will be a risk of variations in the box dimensions of the lens. This often entails that the optician grinds lenses with undersize, meaning in turn that the lens becomes too small in relation to a template. When the optician is subsequently to place assembling holes in the lens, this occurs by pressing the lens against a sidewall where the hole is to be made. However, this gives rise to uncertainty at the formation of the assembling holes.
SUMMARY OF THE INVENTION
It is the purpose of the invention to relieve the drawbacks hitherto associated with positioning of and formation of assembling holes in lenses and to provide a system and a method whereby rimless spectacle lenses can be produced very accurately without special, skilled qualifications on the part of the optician.
According to the present invention, this is achieved with an apparatus of the kind mentioned in the introduction, which is peculiar in that the holder includes a fixture having an opening for fixing the lens at its circumferential rim and which has at least two first guide means that interact with two corresponding second guide means on the apparatus frame, and which are disposed unambiguously, preferably symmetrically, in relation to a hole centre line for the lens when the latter is placed in the fixation opening.
According to the invention, the fixture forming part of the system will be peculiar in that it includes an opening for fixing the lens at its circumferential edge and at least two first guide means that are arranged for interaction with two corresponding second guide means on a frame in an apparatus in which the fixture will be placed, and which is placed unambiguously, preferably symmetrically, in relation to a hole centre line for the lens when the latter is placed in the fixation opening.
The method indicated according to the present invention is peculiar in that the lens is fixed in a fixture having an opening for fixing the lens at its circumferential edge, that the fixture is fixed in an apparatus via at least two first guide means that are brought to interact with two corresponding second guide means on the apparatus frame, the first guide means being disposed unambiguously, preferably symmetrically, in relation to a hole centre line for the lens, when the latter is placed in the fixation opening.
The packing indicated according to the present invention is peculiar in that the packing is largely rectangular with cut off corners, preferably for forming a largely cross-shaped packing, and that the packing is formed by a resilient material.
In the present invention, by hole centre line is meant a line passing through a centre point for assembling holes or assembling slits and which is parallel with the datum line of the lens. If the assembling holes are disposed at the centre of a lens, the hole centre line and the datum line will coincide.
As the fixture has an opening fixing the lens at its circumferential edge, the risk of axis turning is avoided. The fixing opening will have a position and place in the fixture which is well-defined in relation to the placing of the first guiding means in the fixture. Hereby it becomes possible to perform a precise disposition of the hole centre line of the lens when it is placed in the fixation opening. This is substantially difficult from the prior art where the optician was to fasten the lens according to a visual assessment, with a hole centre line oriented from lines located on a table or a base.
As the fixture has at least two first guide means, two fixation points are achieved which unambiguously can define the position of the hole centre line. Preferably, the two first guide means will be placed as openings or pins which are disposed symmetrically at each their side of the hole centre line. These guide means can interact with corresponding guide means on the apparatus frame. Hereby, the position of the lens will be well defined in relation to the apparatus and thereby also to the machining means of the apparatus. Thus it is possible to perform a very precise positioning and formation of the assembling holes.
The fixture may be used as a negative lens jig so that the optician can ensure that the lens is ground with correct size and shape. Furthermore, marking of the hole centre line in the lens can be aligned with a corresponding marking of the hole centre line in or at the fixation opening in the lens jig, sot that the optician may also ascertain that the lens not only has the correct shape but that the hole centre line of the lens is also oriented entirely correct in relation to the marking placed in immediate vicinity of the fixation opening of the fixture. The control means will thus be disposed symmetrically in relation to the markings of the fixture for the hole centre line as well as the marking of the lens of the hole centre line.
It is preferred that the control means are disposed symmetrically in relation to the hole centre line, but it is possible to place them at other unambiguous positions in relation to the hole centre line.
The packing according to the invention enables placing the lens in the fixation opening. The packing will be squeezed by the lens which is then fixed correctly in the opening with guidance vertically as well as laterally. As the packing is made without corners, either by cutting off corners or by making with cross-shape, problems with folding in corners are avoided, though sufficient guiding of the lens is achieved, as the longitudinal and side faces on the lens are in contact with the packing. It is preferred that with the packing about 80% of the circumference of the lens is covered, however, yet it is possible to have as narrow an extension of the packing material between the cut off corners so that a covering as low as about 60% of the circumference of the lens is attained.
The rubber-elastic material is preferred to have a Shore between 40 and 60. The packing material may be produced of an elastomer, of silicone, a rubber material or other resilient material.
For most practical purposes, the packing will have a thickness in the magnitude of about 1 mm for use in a fixture made with a dimension which is nominally about 9/10 mm over the nominal dimension of the lens. By using such a combination it is possible to compensate for lenses irrespectively whether they are made undersize or slightly oversize relative to the exact dimension of the lens.
As an alternative to making a separate packing for laying in the fixture, it will also be possible to make a fixture having an elastic, flexible edge list in the fixation opening. Such an elastic fixation list in the fixation opening may e.g. be formed of an elastic O-ring which is held in a fixation groove inside the circumference edge of the fixation opening. Such a packing may be used for engaging the circumferential edge of the lens.
According to a further embodiment, the apparatus and the fixture are peculiar in further including an elastic ring for placing in a fixation opening at a position between the lens and the apparatus frame for fixing the position of the lens in direction perpendicularly to the plane of the fixation opening, as the lens is pressed down against the ring which thereby is brought into contact against the frame on which the fixture is placed. Hereby is achieved a possibility for correct positioning of the lens relative to the frame and thereby also relative to a plane perpendicular to the fixation opening. Thus it is possible to fix the lens spatially during machining, which thereby can be performed very accurately, not only in the plane of the lens but also in directions perpendicularly thereto, ensuring that inclining assembling holes for the bridge and side bar hinges are not formed.
According to a further embodiment, the apparatus and fixture are peculiar in that arms projecting from the ring are provided, and that the fixture includes cutouts for accommodating the arms in a fixed engagement. In a simple way is hereby achieved a correct positioning of the ring in the fixation opening, and the optician's work is facilitated by the ring being secured in relation to the fixture.
According to a further embodiment, the apparatus is peculiar in that a pressure pad is supported on the frame and arranged displaceable in a plane largely in parallel with the fixture so that it can be disposed opposite to the lens in the fixation opening and displaceable in direction perpendicularly thereto for pressing and fixing the lens in a contact position in the fixation opening. The bearing of the pressure pad against the lens will occur in the so-called box centre.
According to a further embodiment, the apparatus and fixture are peculiar in that first and second guide means are guide pins and guide holes, respectively. Hereby is achieved technically simple means for positioning the fixture. The fixture will be held in place by the force of gravity when the guide pins are placed in the guide holes. The guide holes will preferably be placed in the fixture.
If the fixture is a moulded plastic article, the guide holes and the fixation opening may be formed at the moulding, so that the fixture can be moulded in large series with exact shape which the optician can use without any need for machining or adaptation.
Alternatively, the guide holes and fixation opening can be formed by machining a pre-form or blank.
According to a further embodiment, the apparatus and fixture are peculiar in that the fixture has opposing side faces, and that the fixation opening is a through-going opening between these side faces, and that there is provided first control means on both side faces. Hereby, there will only be need for one fixture for a right and a left spectacle lens, irrespectively if the two spectacle lenses are identical or not.
According to a further embodiment, the fixture is peculiar in that it includes a packing for disposition between the lens circumferential edge and the fixation opening which is oversized in relation to the lens. Hereby, the need for tolerances in the lens box dimensions and risk of imprecise positioning of the assembling holes is reduced. The dimensions for the fixation opening may nominally be greater than the lens dimension, e.g. with 9/10 mm over the lens dimension. It may be said that the packing acts as compensating means for the oversize of the fixation opening.
The optician turns the fixture with one side facing the apparatus frame when machining one lens and with the other side face facing the frame when machining the other lens. This is possible as spectacle lenses will normally always be symmetrical, irrespectively whether they are identical or not. By using one fixture for both lenses, it is particularly ensured that the formed, rimless spectacle will be symmetrical, without demanding special skilled abilities on the part of the optician.
With the method according to the invention, there will always be a secure positioning of the lens so that the hole centre line is placed correctly when the lens is placed in the fixation opening. The guide means of the apparatus interacting with the guide means on the fixture will ensure the correct position for the subsequent formation of the assembling holes.
If by the method a separate packing is used, this will be disposed over the fixation opening before the lens is pressed in. Hereby, the lens is pressed into the fixation opening simultaneously with the packing being clamped between the circumferential edge of the lens and the inner side of the fixation opening of the fixture. The fixture is then placed in the apparatus, and assembling holes are formed in the way which is analogous to the way by which the assembling holes are formed in a lens mounted in the fixture without using the packing.
DESCRIPTION OF THE DRAWINGS
The invention will now be explained more closely with reference to the accompanying drawing, where:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a perspective view of a fixture according to the invention;
FIG. 2 shows a cross-section through the fixture shown in FIG. 1 ,
FIG. 3 shows a perspective view of an apparatus according to the invention for use together with the fixture shown FIGS. 1 and 2 ;
FIG. 4 shows a perspective view corresponding to FIG. 3 but with the fixture placed on the frame of the apparatus;
FIG. 5 shows a schematic, partial view of a detail in the apparatus shown in FIG. 4 for illustrating securing of a lens in the fixture;
FIG. 6 shows a perspective view corresponding to FIG. 4 for illustrating the apparatus under formation of assembling holes in the lens;
FIG. 7 shows a perspective view of the apparatus during turning the fixture for forming additional assembling holes in the lens;
FIG. 8 shows perspective views for illustrating turning the fixture in order to fix another symmetric spectacle lens in which assembling holes are to be formed subsequently;
FIG. 9 shows a perspective view through an assembling hole in a lens and a plan view of the assembling hole with a U-shaped bracket placed therein; and
FIGS. 10-16 show views corresponding to FIGS. 1-7 for illustrating the method for forming assembling holes during use of a packing in the fixture.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the following, identical or corresponding elements in different FIGS. will be provided the same designations, and therefore no explicit explanation to all elements in each FIG. will be given. Also, there will not be given any specific explanation to the parallel elements in FIGS. 10-16 . Also here will be given an explanation to the difference occurring by using a packing together with the fixture in contrast to using a fixture without a packing, as illustrated in FIGS. 1-7 .
In FIG. 1 is seen a fixture 1 with a fixation opening 2 for fixing a spectacle lens 3 by bringing the circumferential edge 4 of the lens in contact with the inner circumferential edge 5 of the fixation opening 2 . The fixture is provided with guide means in the form of guide holes 6 . The guide holes 6 are provided in pairs symmetrically about a hole centre line 7 for the lens when the latter is placed in the fixation opening 2 . By being placed in the fixation opening 2 , the hole centre line 7 will be located opposite to a marking 8 that indicates where the hole centre line is to be when the lens is placed in the fixture.
An elastic ring 9 is provided with two projecting arms 10 . The fixture 1 is provided with cutouts 11 for accommodating the arms 10 so that the elastic ring is located in the fixation opening.
By placing the ring 9 in the fixation opening, the lens 3 can be disposed correctly as illustrated in the cross-section shown in FIG. 2 . The arrow 12 illustrates how the lens 3 is displaced into the fixation opening 2 until it is bearing against the ring 9 . The ring 9 will be secured in relation to the fixture, as the arms 10 will be of an elastic material and have a size which is slightly greater than the cutouts 11 so that they are elastically secured in relation to the fixture.
FIG. 3 shows how the fixture 1 with the lens located therein is placed in an apparatus which is generally designated 13 and which includes a frame 14 on which the fixture 1 is placed. The frame 14 is provided with guide pins 15 that interact with the guide holes 6 in the fixture 1 . The fixture and thereby also the lens are hereby disposed correctly in relation to machining means in the shape of a drilling machine 15 which is provided with a drill 16 used for forming assembling holes 17 (see FIG. 9 ) in the lens. The assembling holes 17 are, as it appears from FIG. 9 , intended for receiving a U-shaped bracket 18 which in a known way is fastened in the assembling hole 17 due to the elastic force in the bracket that is used for mounting of use and side bar hinges. Thus assembling holes are 17 are provided at each side of a lens.
The machining apparatus shown in FIG. 3 includes an operating handle 19 which is used for moving the drill 16 up and down. Furthermore, the drill is suspended in a pivotable column 20 . The pivotability for the drill 16 is limited as the drilling machine only can be displaced between two adjustable stops 21 (only one is visible in FIG. 3 ). By forming an assembling hole, the drill diameter determines the width of an assembling hole 17 , and the setting of the stops 21 defines the length of the assembling hole. When the fixture 1 is placed on the apparatus frame 14 , the elastic ring 9 will bear against the frame 14 . In order to secure the lens 3 in correct position in the fixation opening 2 , the apparatus is provided with a pressure pad 22 . This is supported in a support holder 23 mounted displacing in a groove 24 in the apparatus 13 .
As indicated by an arrow 25 in FIG. 4 , the pressure support holder 3 is arranged on a pivoting pressure pad, from a neutral position where the fixture is readily placed on the frame 14 , to a position where the pressure pad 22 is situated opposite to the ring 9 . By pivoting the support holder 23 the arm 26 is thus brought from a position where the arm 14 is free, to a position in over the fixture when the latter is placed on the frame, as shown in FIG. 4 . Then an axial displacement of the pressure pad 22 is performed down against the lens 2 by turning a screw-threaded head 27 in the support holder 23 . Hereby, the pressure pad 22 is pressed down against the lens 3 so that it is secured between the pressure pad 22 and the ring 9 in a correct position. The correct position for the pressure pad 22 will be a bearing against the lens in the box centre.
As it appears from FIG. 5 , the pressure pad 22 and the ring 9 will be placed around a common axis 28 so that a skew pressure on the lens 3 will not occur. In this position, the table 16 will be positioned opposite to the intended position for an assembling hole.
FIG. 6 illustrates formation of an assembling hole 17 in the lens 2 . An arrow 29 indicates that the user presses the handle forward whereby the drill 16 is displaced downwards and drills a hole in the lens 2 . Since the drilling machine 15 can be swung between two extreme positions defined by the stops 21 , the side of the drill 16 will cut an oblong slit in the lens when the user pivots the drilling machine 15 from side to side. This operation is indicated by the arrows 30 where it appears that up- and downward motions 31 are performed with the drill and a lateral movement 32 in relation thereto.
As alternative to a slit-shaped assembling hole 17 , it is possible to form two juxtaposed, round assembling holes (not shown). Fastening bridge and hinges may hereby be effected with two holes or one hole and a groove in the circumferential edge of the lens. It is necessary to have two holes at each fastening element for the sake of absorbing moment. The formation of a slit is thus just a possible design of the assembling hole 17 for interacting with the above mentioned U-shaped bracket 18 .
FIG. 7 illustrates that the pressure pad 22 is released and that the support holder 23 is pivoted to its position outside the frame 14 . The fixture 1 may hereby be lifted free of the frame 14 as indicated by the arrow 33 . Then the fixture is turned as indicated by the arrow 34 . In this way, a side face 35 of the fixture will still face up against the tool, whereas a side face 36 will be placed against the frame 14 .
It is here remarked that the fixture advantageously is formed with four guide holes 6 for interaction with the guide pins 15 . By forming the first assembling hole 17 in the lens, the guide holes 6 disposed at a first longitudinal edge 37 will engage the guide pins 15 . After the turning according to the arrow 34 , the guide holes 6 at an opposite longitudinal edge 38 will be brought into engagement with the guide pins 15 . In this position, the lens 2 will be placed correctly for forming the second assembling hole in the lens when the fixture, as indicated by the arrow 39 , is placed on the arm 14 .
It is noted that in the above explanation, reference is made to guide holes 6 , and that in the shown illustration these are placed at the side face 35 of the fixture. In reality, it will be guide pins 6 which are placed at the side face 36 of the fixture which is brought into engagement with the guide pins. However, the guide pins 6 will be provided as through-going holes, but may alternatively be provided as various bottom holes at the side faces 35 , 36 of the fixture 2 .
After the above mentioned turning of the fixture, the above described operations with the intention of clamping the lens and forming the assembling hole are repeated. Then the lens is released again, and the fixture 1 is lifted off the frame. The lens will now be provided with the two assembling holes for mounting bridge and side bar hinge.
The fixture is formed with a through-going fixation opening 2 . This means that a symmetrical spectacle lens together with the first mentioned lens are to be used for making a spectacle also can be provided with assembling holes by using the same fixture. It is only necessary to remove the ring 9 from the cutout 11 at the side face 36 and as indicated by the 39 in FIG. 8 move the ring 9 to the opposing side face 35 and place the arms 10 in the cutouts 11 at the side faces 35 . Then the lens is turned 180° as indicated by the arrow 40 . Then the side face 36 will face upwards against the machining tool, and a lens, which is symmetrical relative to the first lens, can now be placed in the fixation opening 2 by a method as described above. Then assembling holes can be formed in a way corresponding to that described above.
By correct positioning of the spectacles, not only a situation without risk of turning the axis can be achieved. Furthermore, a very certain position of the assembling holes is achieved. Hereby, it becomes possible to make the assembling holes 17 and place them very close to the circumferential edge 4 of a spectacle lens, in the way appearing from FIG. 9 . Thus there will be no risk of the assembling hole 17 being placed inadvertently close to the circumferential edge 5 so that there is risk that the lens 3 does not have the required strength properties at the subsequent mounting of the U-shaped bracket 18 .
FIG. 10 corresponds to FIG. 1 , but it is shown here how a packing 41 is placed between the lens 3 and the fixture 1 . In FIG. 11 is illustrated how the packing 41 is displaced according to the arrow 42 into the fixation opening 2 when the lens 3 according to the arrow 12 is placed against the top side of the packing 41 and pressed into the fixation opening 2 .
The packing 41 is cut off at the corners 43 so that cross-shaped arms 44 are formed. The cruciform arms will cover about 80% of the circumferential edge 4 of the lens. The cruciform arms 44 will bear on the longitudinal edges 45 of the lens and the side edges 46 of the lens, respectively.
After the lens 3 has been placed in the fixture 1 , as illustrated in FIG. 11 , the fixture 1 is placed in the apparatus 13 as illustrated in FIG. 12 . Subsequently, the pressure pad 22 is swung in and fixes the lens, as illustrated in FIGS. 13 and 14 . After that, the assembling holes 17 are formed as illustrated in FIGS. 15 and 16 by turning the fixture as described above.
By using the packing 41 as illustrated in FIGS. 10-16 , it is possible to secure the lens 3 in the fixation opening 2 in a fixture in a resilient way, where the fixation opening 2 is oversized and where there will be reduced requirements to tolerances for the fixation opening 2 and the lens 3 .
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There is described an apparatus and a fixture used in determining position and for producing assembling holes in a spectacle lens for rimless spectacles. The assembling holes are intended for receiving a U-shaped bracket which is used in fastening bridge and side bar hinge. The apparatus and fixture includes interacting guide pins and guide holes. These guide holes/pins are unambiguously disposed. The guide holes will preferably be placed symmetrically in relation to a hole center line for the lens, when this is placed in the fixation opening of the fixture with the hole center line disposed opposite to markings at the fixation opening. The assembling holes are thus placed symmetrically in relation to the marking. By such a system it is possible to make rimless spectacles that appear very accurate, without special skilled qualifications on the part of the optician to make assembling holes in the lenses.
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CROSS-REFERENCE TO RELATED PATENT APPLICATION
[0001] This application is a continuation of international application number PCT/EP2014/073575 filed on Nov. 3, 2014.
[0002] This patent application claims the benefit of International application No. PCT/EP2014/073575 of Nov. 3, 2014 and German application No. 10 2013 112 670.7 of Nov. 18, 2013, the teachings and disclosure of which are hereby incorporated in their entirety by reference thereto.
BACKGROUND OF THE INVENTION
[0003] The invention relates to a cooling circuit comprising a refrigerant compressor incorporating a suction port and a pressure chamber incorporating a pressure port, a condenser which is arranged in the cooling circuit downstream of the pressure port and comprises a fluid collecting chamber in which a reservoir of refrigerant is formed, an evaporator which is located in the cooling circuit between the condenser and the suction port, a feed unit which is connected at one side to the refrigerant reservoir and to the pressure chamber at the other side and which serves for supplying refrigerant from the refrigerant reservoir to the pressure chamber and which incorporates a pumping unit for the refrigerant.
[0004] Cooling circuits of this type are known from the state of the art such as DE 43 38 939 C1 for example.
[0005] In these known cooling circuits however, complex pumping units were provided for the feed unit and this has led to economically non-realizable solutions.
[0006] Consequently, the object of the invention is to improve a cooling circuit of the type indicated in the preamble of the main Claim in such a way that it is realizable in an economically more meaningful manner.
[0007] In accordance with the invention, this object is achieved in the case of a cooling circuit of the type described hereinabove in that the pumping unit comprises a pressure-tight closed housing which is provided with only one inlet and one outlet as access points, and a pumping element which is movable for pumping the refrigerant is arranged in the pumping chamber thereof.
SUMMARY OF THE INVENTION
[0008] The advantage of the solution in accordance with the invention is to be seen in that it is then possible to utilise simply built pumps having a very low handling capacity which will suffice for the application in accordance with the invention, such pumps having a very low leakage rate for the pressurised refrigerant in keeping with their permanently closed construction and being producible economically and operable economically.
[0009] A low leakage rate in keeping with the permanently closed devices of this type amounts to 3 g/year or less per connection port under a pressure of at least 0.25 times the maximally permissible pressure.
[0010] In consequence, a cooling circuit of the type described in the preamble of the main Claim can be operated efficiently when using the solution in accordance with the invention.
[0011] In the context of the present invention, liquefaction of the refrigerant is effected in a condenser in the event of a subcritical mode of operation as is the case in the usual commercially used refrigerants, but in the event of a supercritical mode of operation however, only cooling of the refrigerant without liquefaction thereof occurs.
[0012] Consequently, liquid refrigerant collects in the fluid collecting chamber in a subcritical mode of operation, but a cooled gaseous refrigerant collects in the event of a supercritical mode of operation.
[0013] It is particularly advantageous hereby for the pumping chamber to be arranged in a pressure-tight closed pumping chamber housing.
[0014] In the case of a solution of this type, the pumping chamber is thus arranged directly in a pressure-tight housing.
[0015] Furthermore, it is advantageously envisaged in this solution that the pumping element be driven by an electromagnetic or magnetic force that is effective through the pumping chamber housing.
[0016] A solution of this type is particularly advantageous since the pumping chamber housing can then be of very small volume and consequently this very small volume can be closed in pressure-tight manner in a simple manner and with simple means so that the constructional realization of the solution in accordance with the invention is thereby particularly simple in regard to the cost thereof.
[0017] A pressure-tight termination in the sense of the solution in accordance with the invention is to be understood in particular as a termination which is free of a mechanical feed-through for a drive of the pumping element, i.e. all the complex sealing measures that are necessary in the region of a mechanical feed-through for a drive but which nevertheless lead to leakages at the requisite pressures of more than 15 bar for example, preferably of more than 20 bar and still better of more than 25 bar can be avoided.
[0018] The most varied of possibilities are conceivable in regard to the construction of the pumping element.
[0019] Hereby, one particularly simple and economically realizable solution envisages that the pumping element be in the form of a piston.
[0020] A piston of this type could, for example, be a conventional piston of a piston pump. However, a particularly simple and expedient solution envisages that the piston be constructed in the form of a spring-loaded oscillating piston so that it can then move in oscillatory manner due to the spring loading thereof.
[0021] In particular, a oscillating piston of this type can easily be driven in oscillatory manner by means of a solenoid coil.
[0022] To this end, an alternative solution envisages that the pumping element be in the form of a pumping element which rotates about an axis and is thus, in particular, also driven in rotary manner.
[0023] A rotary pumping element of this type permits of a multiplicity of simply realizable forms of pump having a rotary pumping element.
[0024] For example hereby, provision is made for the rotary pumping element to be a gear wheel in a set of gear wheels in a gear pump.
[0025] A particularly expedient solution envisages that the pumping unit be controlled by a refrigerant supply control unit.
[0026] With the aid of the refrigerant supply control unit, there is then the possibility of not only controlling the processes of switching on and switching off the pumping unit but, by controlling the delivery rate of the pumping unit, it is also possible to control the cooling of the pressure chamber and thus of regulating the temperature of the pressure chamber in order to hold the temperature within a range about a given threshold value.
[0027] As an alternative or in addition to the initially described solution in accordance with the invention, a further solution of the object specified hereinabove envisages that a gas discharge unit be associated with the pumping unit, wherein said unit comprises a gas discharge line which conducts away gaseous refrigerant from the feed unit.
[0028] The advantage of this solution is to be seen in that it is then possible to remove a gas cushion of refrigerant which is formed during the switching off periods in the region of the pumping unit and in particular at the inlet side of the pumping unit and which, in the case of pumping units having a low flow rate, leads to them only beginning to pump liquid refrigerant after at least a long start-up time or only occasionally pumping liquid refrigerant or not pumping any liquid refrigerant at all during the envisaged run time since, once a build-up of a gas of the refrigerant at the inlet side of the pumping unit has occurred, the low delivery rate of the pumping unit is insufficient to pump away quickly enough the gas that has been formed by the input of heat so that eventually, the pumping unit is unable to reliably pump liquid refrigerant, this being something that is essential for the solution in accordance with the invention because the envisaged low delivery rates of the pumping unit in accordance with the invention then only lead to a meaningful cooling process in the pressure chamber if they are delivering liquid refrigerant which can then evaporate in the pressure chamber and thereby absorb heat.
[0029] For example hereby, the gas discharge line could lead to a refrigerant path at an intermediate pressure level, to an intermediate pressure port of the compressor for example.
[0030] A particularly expedient solution envisages that the gas discharge line lead into a refrigerant path of the cooling circuit which is at suction-side pressure so that there is a large pressure difference available for discharging the gaseous refrigerant from the feed unit and it can thus be rapidly removed.
[0031] Herein, the refrigerant path of the cooling circuit which is at suction-side pressure is to be understood as the entire refrigerant path running from the evaporator to the suction chamber of the compressor.
[0032] It is particularly expedient if the gas discharge line leads into the refrigerant path which is at suction-side pressure prior to the suction port of the compressor so that, in the event of liquid refrigerant being supplied by way of the gas discharge line to this refrigerant path, there is an opportunity for it to evaporate before reaching the suction chamber.
[0033] In particular, it is expedient if the refrigerant path which is at suction-side pressure runs from the suction port of the compressor in the compressor housing through a motor compartment of the compressor in order to cool it so that evaporation of any liquid refrigerant that is being supplied can be assisted by joining the gas discharge line prior to the motor compartment or into the motor compartment.
[0034] Furthermore, one expedient solution envisages that the gas discharge unit be connected to a supply line section of the feed unit leading to the inlet of the pumping unit.
[0035] However, the supply of refrigerant over the gas discharge line to the refrigerant path which is at suction-side pressure can also be used to good effect for cooling the compressor.
[0036] To this end, a throttle or an expansion unit is preferably provided in the gas discharge line, for example, prior to the junction thereof into the refrigerant path which is at suction-side pressure, said throttle or expansion unit expanding and thus cooling the refrigerant before it enters the refrigerant path which is at suction-side pressure so that this cooled refrigerant can be supplied to the compressor at the suction-side.
[0037] Another advantageous solution envisages that the gas discharge unit be connected to a discharge line section of the feed unit leading to the pressure chamber.
[0038] A particularly expedient solution envisages that the gas discharge unit be connected to an inlet of the pumping unit and/or to an outlet of the pumping unit in order to enable the pumping unit to be supplied with liquid refrigerant insofar as possible before it starts or immediately after it has started so that it will pump liquid refrigerant to the pressure chamber.
[0039] In order to be able to activate and deactivate the gas discharge unit, provision is preferably made for an on-off valve to be associated with the gas discharge unit and in particular, for it to be provided in the gas discharge line.
[0040] Preferably hereby, the on-off valve is controllable by a refrigerant supply control unit in such a way that the gas discharge unit is activated thereby either before or when switching-on the pumping unit and firstly, during a definable time period for example, gaseous refrigerant and possibly some of the liquid refrigerant flowing after it is conducted away until such time as only liquid refrigerant is present at the pumping unit for the purposes of pumping it to the pressure chamber.
[0041] Hereby for example, a length of time is selected in such a way that at the end of this period it is ensured that liquid refrigerant is present at the inlet of the pumping unit in every operational state of the cooling circuit.
[0042] A further advantageous solution, which reduces the supply of liquid refrigerant to the suction-pressure-side of the refrigerant path, envisages that the length of time be adjustable so as to be variable in correspondence with the actual operational state of the cooling circuit wherein the operational state of the cooling circuit is detected by sensors such as temperature and/or pressure sensors for example.
[0043] However, as an alternative thereto, there is also the possibility of detecting whether liquid refrigerant is already present in the supply line section and/or in the discharge line section and/or in the gas discharge unit by means of a liquid sensor for example, and then, if this is the case, to deactivate the gas discharge unit.
[0044] As an alternative or in addition to the previously described mode of operation, the conveyance of liquid refrigerant in the gas discharge line can also be detected by the provision of a throttle in the gas discharge line so that when refrigerant flows therethrough the temperature of the refrigerant is reduced due to the expansion process and this reduction of temperature is detectable by a sensor located downstream of the throttle and/or a sensor located upstream of the throttle so that, upon the occurrence of a reduction of temperature corresponding to the expansion of liquid refrigerant, the gas discharge unit is deactivated.
[0045] Furthermore, the invention relates to a method of operating a cooling circuit comprising a refrigerant compressor incorporating a suction port and a pressure chamber incorporating a pressure port, a condenser which is arranged in the cooling circuit downstream of the pressure port and comprises a fluid collecting chamber in which a refrigerant reservoir of refrigerant is formed, an evaporator located in the cooling circuit between the condenser and the suction port, a feed unit which is connected at one side to the refrigerant reservoir and to the pressure chamber at the other side and serves for supplying refrigerant from the refrigerant reservoir to the pressure chamber which incorporates a pumping unit for the refrigerant and with the aid of which refrigerant is supplied by means of the feed unit to the pressure chamber for the purposes of cooling it, wherein gaseous refrigerant is conducted away from the feed unit by means of a gas discharge unit.
[0046] Further features of the invention form the subject matter of the following description and the graphical illustration of some exemplary embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0047] FIG. 1 , shows a schematic illustration of a first exemplary embodiment of a cooling circuit in accordance with the invention;
[0048] FIG. 2 , a schematic illustration similar to FIG. 1 of a second exemplary embodiment of a cooling circuit in accordance with the invention;
[0049] FIG. 3 , a schematic illustration of a first exemplary embodiment of a pumping unit provided in accordance with the invention;
[0050] FIG. 4 , a schematic illustration of a second exemplary embodiment of a pumping unit in accordance with the invention and
[0051] FIG. 5 , a schematic illustration of a variant of the second exemplary embodiment of the pumping unit in accordance with the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0052] A first exemplary embodiment of a cooling circuit 10 employing a circulating refrigerant in accordance with the invention which is illustrated in FIG. 1 comprises a compressor for the refrigerant which may be in the form of a piston compressor for example and bears the general reference 12 .
[0053] However, the compressor 12 could also be implemented in the form of a scroll compressor, a rotary piston compressor, a vane compressor or a rotary screw compressor.
[0054] In the case of a piston compressor 12 , a drive motor 16 is arranged in a compressor housing 14 and it drives pistons 18 in one or more cylinders 22 which are arranged in a cylinder block 24 of the compressor housing 14 and are closed off by at least one cylinder head 26 , wherein the at least one cylinder head 26 comprises a suction chamber 32 and a pressure chamber 34 , wherein refrigerant that is to be sucked-in is supplied to the suction chamber 32 , supplied therefrom to the one or the plurality of cylinders 22 and then, after being compressed by the cylinders 22 , is delivered to the pressure chamber 34 .
[0055] The pressure chamber 34 is provided with a pressure port 38 for compressed refrigerant and a pressure line 42 leads from the pressure port 38 to a condenser 44 which liquefies the pressurised refrigerant in the case of a subcritical mode of operation, or cools it in the case of a supercritical mode of operation, and then supplies it to a fluid collecting chamber 46 in which a refrigerant reservoir 48 consisting of refrigerant, liquid refrigerant in a subcritical mode of operation, is formed.
[0056] Hereby, the fluid collecting chamber 46 can be integrated into the condenser 44 . However, as illustrated in FIG. 1 , the fluid collecting chamber 46 could also be arranged in a collector vessel 52 which forms the fluid collecting chamber and is arranged in the refrigerant circulation path 10 between the condenser 44 and an evaporator 54 .
[0057] However, the fluid collecting chamber could also be arranged in a supply line which leads to the evaporator 54 and has been widened-out in correspondence with the volume required.
[0058] For example, a supply line 56 leads from the condenser 44 to the collector vessel 52 in order to supply the liquefied refrigerant thereto and an evaporator supply line 58 leads from the collector vessel 52 to the evaporator 54 , wherein the evaporator supply line 58 is arranged relative to the fluid collecting chamber 46 in such a way as to take liquid refrigerant from the refrigerant reservoir 48 but not vaporous refrigerant.
[0059] For its part, the evaporator 54 is additionally provided with a control valve 62 which controls the inflow of refrigerant to the evaporator 54 , wherein the refrigerant in the form of a liquid refrigerant then evaporates in the evaporator 54 in a subcritical mode of operation under given pressure conditions and, in a supercritical mode of operation, cools down due to the expansion process and thereby absorbs heat.
[0060] The refrigerant that has been evaporated in the evaporator 54 is then fed back to the compressor 12 through a suction line 64 of the refrigerant circulation path 10 which is at suction pressure, wherein for example, a suction port 66 of the compressor 12 is arranged in such a way that the evaporated refrigerant coming from the suction line 64 firstly flows round a drive motor 16 which is arranged at the suction end, cools it and then enters the suction chamber 32 of the cylinder head 26 .
[0061] Since, in particular, refrigerants having a high compression index such as the refrigerants R407A, R407F, CO 2 , NH 3 for example reach high compression end temperatures, there is substantial heating of the cylinders 22 and the cylinder head 26 in the case of high pressure conditions, especially in the region of the pressure chamber 34 and overall, this then leads to heating of the compressor housing 14 so that the efficiency of the compressor 12 is impaired due to heat transfer losses.
[0062] The heating in the region of the pressure chamber can also lead to chemical decomposition of a lubricant being conveyed by the refrigerant mass flow and thus, as a consequence thereof, to the breakdown of the compressor and to contamination of the system.
[0063] For this reason, there is provided a feed unit bearing the general reference 70 for the supply of liquid refrigerant from the refrigerant reservoir 48 into the pressure chamber 34 of the at least one cylinder head 26 so that cooling of the pressure chamber 34 is achieved by evaporation of the supplied liquid refrigerant in the pressure chamber 34 .
[0064] Herein, the feed unit 70 comprises a supply line 72 which either opens out directly into the refrigerant reservoir 48 or branches off from the evaporator supply line 58 and opens out into the pressure chamber 34 of the at least one cylinder head 26 .
[0065] However, as the pressure in the fluid collecting chamber 46 is lower than the pressure in the pressure chamber 34 due to pressure losses in the pressure line 42 and in the condenser 44 , it is in a range of between 0.5 and 5 bar for example in the case of the refrigerants R407A and R407F or refrigerants having similar working pressures and is still lower in the case of high pressure refrigerants such as CO 2 for example, there is provided in the supply line 72 a pumping unit 74 for liquid refrigerant which raises the liquid refrigerant from the pressure level in the fluid collecting chamber 46 to at least slightly above the pressure level in the pressure chamber 34 or at most to 5 bar above the pressure level in the pressure chamber and moreover, there is provided in the supply line 72 between the pumping unit 74 and the point of entry thereof into the pressure chamber 34 a check valve 86 which permits the pumping unit 74 to be switched off at any desired time point.
[0066] Hereby, the pumping unit 74 comprises an inlet 76 which is connected to a supply line section 78 of the supply line 72 and also an outlet 82 which is connected to a discharge line section 84 of the supply line 72 , wherein the discharge line section 84 leads from the outlet 82 to the pressure chamber 34 .
[0067] In particular, a check valve 86 is arranged in the discharge line section 84 , said valve permitting the pumping unit 74 to be switched off if a high temperature above a desired value does not occur in the pressure chamber 34 and only allowing it to switch on when a temperature above a desired value occurs in the pressure chamber 34 of the cylinder head 26 .
[0068] In order to operate the pumping unit 74 , there is provided a refrigerant supply control unit 90 which detects the temperature in the pressure chamber 34 or in a region of the at least one cylinder head 26 bordering the pressure chamber 34 by means of a temperature sensor 92 and then always switches on the pumping unit 74 when the temperature in the pressure chamber 34 or in a region of the cylinder head 26 bordering the pressure chamber 34 exceeds a predetermined threshold value so that the supply of refrigerant to the pressure chamber 34 only occurs in a sub-critical mode of operation when the threshold value is exceeded, whereby the refrigerant then evaporates in the pressure chamber 34 and thereby absorbs heat and thus cools the gaseous refrigerant present in the pressure chamber 34 as well as the cylinders 22 and the compressor housing 14 .
[0069] In the case of a drive motor of the compressor which is arranged at the pressure end, cooling of the drive motor by the supply of liquid refrigerant is also possible if the refrigerant emerging from the pressure chamber 34 flows around this motor.
[0070] The threshold value lies within a range of 80° C. to 150° C. for example, preferably within a range of 110° C. to 130° C., and in particular, in a range of between 115° C. and 125° C.
[0071] Furthermore, there is preferably provided a safety cut-out which switches off the compressor 12 in the event that a maximum temperature in the pressure chamber 34 is exceeded, wherein the maximum temperature lies within a range of 130° C. to 150° C., preferably within a range of 135° C. to 145° C.
[0072] In order to additionally ensure that the threshold value is not significantly exceeded, the refrigerant supply control unit 90 controls the pumping unit 74 in such a way that the quantity of material being delivered by the pumping unit 74 is regulated, wherein the pumping unit 74 is designed such that a maximum delivery rate thereof is sufficient to meet the envisaged working conditions in order to prevent the threshold value from being permanently exceeded.
[0073] The additional refrigerant being supplied to the pressure chamber 34 by way of the supply line 72 then flows to the condenser 44 through the pressure line 42 in addition to the refrigerant that was compressed by the at least one cylinder 22 , and it is liquefied in the condenser 44 .
[0074] In particular, the supply of refrigerant to the pressure chamber 34 is effected until such time as the temperature measured by the temperature sensor 92 drops back below the threshold value.
[0075] In order to ensure that the pumping unit 74 conveys substantially only liquid refrigerant, there is associated with the supply line 72 a gas discharge unit 100 which comprises a gas discharge line 102 that branches off from the supply line section 78 in the first exemplary embodiment illustrated in FIG. 1 , wherein said gas discharge line may join the cooling circuit 10 between the evaporator 54 and the at least one cylinder 22 which represents a flow path of the refrigerant that is at suction pressure.
[0076] This means that the gas discharge line 102 can, for example, open out into the suction line 64 or into the suction port 66 , or, it can open out in the compressor housing 14 into the flow path running therethrough for the refrigerant that is being sucked in and is flowing to the suction chamber 32 or, it could also open out directly into the suction chamber 32 as is illustrated in FIG. 1 .
[0077] For the purposes of activating the gas discharge line 102 , there is provided therein a gas discharge valve 104 which is controllable by the refrigerant supply control unit 90 .
[0078] For example, activation of the gas discharge line 102 is effected by opening the gas discharge valve 104 when switching on the pumping unit 74 or before switching it on so that, due to the large pressure gradient between the pressure in the supply line section 78 of the supply line 72 and the suction pressure of the compressor 12 , the gas that collects in the supply line section 78 as a result of the heating process occurring when the pumping unit 74 is switched off is supplied to the compressor 12 at the suction end via the gas discharge line 102 and in consequence liquid refrigerant flows thereafter from the refrigerant reservoir 48 into the supply line 72 .
[0079] If liquid refrigerant is present at the inlet 76 of the pumping unit 74 , the refrigerant supply control unit 90 can close the gas discharge valve 104 and thus deactivate the gas discharge line 102 since the pumping unit 74 can then convey the liquid refrigerant present at the inlet 76 thereof and bring the pressure up to a level such that this refrigerant will flow into the pressure chamber 34 of the at least one cylinder head 26 in order to be evaporated in the pressure chamber 34 and thus—as described—to cool down in the pressure chamber 34 .
[0080] The presence of liquid refrigerant at the inlet 76 of the pumping unit 74 can be ensured in the most varied of manners.
[0081] A first possibility envisages the opening of the gas discharge valve 204 for a time period that is definable in regard to the length of time thereof, wherein the length of time is measured in such a way as to ensure that liquid refrigerant will definitely be available at the inlet 76 of the pumping unit 74 at the end of the period under all the usual operating conditions.
[0082] Hereby, the length of time can be fixed in accordance with the maximum length of time that is necessary under all possible operating conditions.
[0083] However, it is also possible to detect the operating conditions occurring at different positions of the cooling circuit by means of sensors such as sensors for the ambient temperature and/or sensors for the temperatures in the evaporator and/or pressure sensors for example and to set the length of time in a variable manner in accord with the particular operating conditions that have been detected.
[0084] A second possibility envisages that the presence of liquid refrigerant be detected by means of at least one liquid sensor 106 . Hereby, this liquid sensor 106 can be arranged in the supply line section 78 such as directly before the inlet 76 of the pumping unit 74 for example and/or in the gas discharge line 102 such as at the point of branching from the supply line section 78 and/or at the point of entry into the refrigerant path which is at suction-side pressure for example.
[0085] As soon as the temperature in the pressure chamber 34 or in the part of the cylinder head 26 bordering the pressure chamber 34 has dropped again to such an extent that it is under the threshold value, the refrigerant supply control unit 90 switches off the pumping unit 74 so that the feed unit 70 will be inactive until such time as the threshold value for the temperature in the pressure chamber 34 or in the part of the cylinder head 26 bordering the pressure chamber 34 is exceeded once again.
[0086] In the first exemplary embodiment, the gas discharge line 102 branches from the supply line section 78 of the supply line 72 as directly as possible before the inlet 76 , preferably at the inlet 76 , in order to conduct away all the gas from the supply line section 78 before the inlet 76 of the pumping unit 74 so that the pumping unit 74 sucks in as little as possible or, if possible, no gaseous refrigerant at all, but rather, when it is switched on, it can directly pump out liquid refrigerant.
[0087] As an alternative thereto, provision is made in a second exemplary embodiment of a cooling circuit 10 ′ in accordance with the invention that is illustrated in FIG. 2 for the gas discharge line 102 ′ to branch out from the pressure port 38 or from the supply line 72 , for example, between the outlet 82 of the pumping unit 74 and the check valve 86 in the discharge line section 84 so that, upon activating the gas discharge line 102 , there will be a pressure gradient through the pumping unit 74 which permits certain flooding of the pumping unit 74 with liquid refrigerant so that, after deactivating the gas discharge line 102 by closing the gas discharge valve 104 , the pumping unit 74 as a whole is flooded with liquid refrigerant and thus immediately begins to pump liquid refrigerant.
[0088] Hereby, the check valve 86 prevents the process of conducting away the gaseous refrigerant from negatively affecting the pressure in the pressure chamber 34 .
[0089] This solution is attractive in particular if the pumping unit 74 is constructed in such a way that a pressure gradient occurring therein in the pumping direction can assist the conveyance of gaseous refrigerant.
[0090] In all other respects, the second exemplary embodiment of the cooling circuit in accordance with the invention in accord with FIG. 2 is constructed in the same way as the first exemplary embodiment so that the same parts are provided with the same reference symbols and reference can be made to the full extent of the remarks relating to the first exemplary embodiment in regard to the description thereof.
[0091] In regard to the construction of the pumping unit 74 , no detailed indications have as yet been given.
[0092] A first exemplary embodiment of a pumping unit 74 in accordance with the invention which is illustrated in FIG. 3 is constructed in the form of a piston pump 110 which comprises a piston 112 that moves in a reciprocating linear manner in an oscillation direction 114 .
[0093] To this end, an outer piston surface 116 of the piston 112 is guided in a pumping chamber 118 such as to be moveable in the direction of oscillation 114 and, for example, it is arranged between two springs 122 and 124 so that the piston 112 can move in the pumping chamber 118 in the direction of oscillation 114 due to the compression of one of the springs 122 , 124 and the relaxation of the other one of the springs 122 , 124 .
[0094] For example, the piston 112 is provided with a passage 126 so that the medium that is to be conveyed can flow therethrough.
[0095] Furthermore, a first variable volume 134 is formed between a first end face 132 of the piston 112 and the inlet 76 and a second variable volume 138 is formed between a second end face 136 of the piston 112 and the outlet 82 .
[0096] Moreover, an inlet valve 142 is arranged between the inlet 76 and the first volume 134 , an outlet valve 144 is arranged between the second volume 138 and the outlet 82 and yet another piston valve 146 which is arranged in the passage 126 for example is associated with the piston 112 .
[0097] If the piston 112 moves in such a way that the second volume 138 becomes smaller whilst the first volume 134 grows larger, then the outlet valve 144 opens and the liquid refrigerant flows out of the piston chamber due to the reduction of the second volume 138 . At the same time, the inlet valve 142 opens since the first volume 134 has become larger so that liquid refrigerant can enter the pumping chamber 118 via the inlet 76 .
[0098] The piston valve 146 remains closed hereby.
[0099] If then the piston 112 moves in such a way that the first volume 134 becomes smaller and the second volume 138 grows larger, then both the inlet valve 142 and the outlet valve 144 close whilst the piston valve 146 opens and liquid refrigerant can thus be transferred from the first volume 134 through the passage 126 into the second volume 138 , whereupon the piston valve 146 opens.
[0100] The movements of the piston 112 in the direction of oscillation 114 are enabled by an electromagnet 152 which is arranged outside the pumping chamber 118 , the magnetic field thereof being effective on the piston 112 in such a manner that the latter is moved in reciprocating manner in the direction of oscillation 114 .
[0101] For example, this is made possible by virtue of the magnetic field of the electromagnet moving the piston 112 in a direction leading to a reduction of the second volume 138 , and removal of the magnetic field of the electromagnet 152 leads to the piston 112 moving in a direction producing a reduction of the first volume 134 due to the effect of the springs 122 and 124 , and a renewed activation of the electromagnet 152 again leads to a movement of the piston 112 in a direction producing a reduction of the second volume 138 .
[0102] Since the piston pump 110 works at pressures in a range of over 15 bar, preferably in a range of over 20 bar and still better in a range of over 25 bar, the piston pump 110 is constructed in such a way that a pumping chamber housing 154 forming the pumping chamber 118 is hermetically sealed and in particular is also connected to the inlet 76 and to the outlet 82 in hermetically sealed manner, wherein in this case, the electromagnet 152 does not have to be arranged in a hermetically sealed housing 156 , but rather, the field effect thereof is effective on the piston 112 through the pumping chamber housing 154 .
[0103] Another solution envisages that the piston pump 110 comprise a hermetically sealed outer housing 156 which encompasses the pumping chamber housing 154 and which is connected to the inlet 76 and to the outlet 82 in hermetically sealed manner, wherein the electromagnet 152 is also located within the outer housing 156 at a pressure level lying above 15 bar, preferably above 20 bar and still better above 25 bar.
[0104] In both cases it is thus possible to hold the liquid refrigerant that is to be conveyed in a housing which encloses it hermetically and in particular one which is free of mechanical feed-throughs for the drive for the piston 112 .
[0105] A second exemplary embodiment of a pumping unit 74 ′ in accordance with the invention is illustrated in FIG. 4 . This pumping unit is in the form of a rotary pump 170 which comprises a pumping element 172 that is driven in rotary manner about an axis 174 .
[0106] For example, the pumping element 172 is a gear wheel of a gear pump which cooperates with a further gear wheel that is not visible in FIG. 4 .
[0107] Here, liquid refrigerant is advanced from the inlet 76 to the outlet 82 , wherein the pumping element 172 is arranged in a pumping chamber 176 which is connected to both the inlet 76 and the outlet 82 .
[0108] The pumping chamber 176 here is arranged in a pumping chamber housing 178 which does not comprise any sort of mechanical feed-throughs for the drive means for the pumping element 172 .
[0109] Rather, the drive for the pumping element 172 is effected by means of magnetic coupling between a rotor 184 of a drive motor 182 , wherein the rotor 184 is arranged in an interior space 186 of a motor housing 188 adjoining the pumping chamber housing 178 such that it is coaxial with the pumping element 172 so that the reciprocally acting magnetic interaction between the rotor 184 and the pumping element 172 is effected through the motor housing 188 and the pumping chamber housing 178 .
[0110] Furthermore, a stator 192 which encloses the rotor 184 and is effective for the rotary motion of the rotor 184 is arranged in the interior of the motor housing 188 .
[0111] In this exemplary embodiment, in which the pumping element 172 in the pumping chamber 176 does not comprise any sort of mechanical feed-throughs for the operation of the pumping element 172 , the pumping chamber 176 is connected exclusively to the inlet 76 and the outlet 82 whilst the drive means for the pumping element 172 is provided by means of a reciprocally acting magnetic interaction between the pumping element and the rotor 184 .
[0112] In a variant of the second exemplary embodiment of the pumping unit 74 ′ which is constructed in the form of a rotary pump 170 ′ and is illustrated in FIG. 5 , the pumping chamber housing 178 ′ and the motor housing 188 form a hermetically sealed unit so that the interior 186 of the motor housing 188 accommodating the rotor 184 and the stator 192 can adopt the same pressure level as the pumping chamber 176 .
[0113] In this case, it is thus also possible for the pumping element 172 to be coupled to the rotor 184 by means of a mechanical shaft 194 so that the rotor 184 together with the shaft 194 and the pumping element 172 represent a mutually non-rotationally connected unit which rotates about the axis 174 .
[0114] Consequently, in this exemplary embodiment too, there also arises the possibility of working with the pumping element 172 at a very high pressure level of over 15 bar for example, still better, a level of over 20 bar and even better of over 25 bar without leakage losses due to mechanical feed-throughs for the drive means.
[0115] With regard to the maximum delivery rate of the compressor 12 in all of the preceding exemplary embodiments, the delivery rate envisaged for the feed unit 70 amounts to less than 100%, still better less than 50% and preferably less than 30% of this maximum delivery rate of the compressor 12 .
[0116] In the case of the two embodiments of the pumping units 74 and 74 ′ in accordance with the invention, the dimensioning thereof is effected such that the maximum handling capacity of a pumping unit of this type amounts to 100 litres or less per hour so that one or possibly more parallel-working, very small pumping units having a very low power consumption can be used.
[0117] Preferably hereby, the handling capacity of one of the pumping units 74 , 74 ′ of this type that are to be used is at least 0.3 litres per hour, still better at least 0.3 litres per hour [sic], or more.
[0118] Furthermore, in both embodiments of the pumping units 74 , 74 ′, additional regulation of the handling capacity of the pumping units 74 , 74 ′ can be effected by means of the refrigerant supply control unit 90 so that the handling capacity of the pumping units 74 , 74 ′ can be adapted to the requisite cooling performance in the pressure chamber 34 by the supplied refrigerant.
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In a cooling circuit which comprises a refrigerant compressor incorporating a suction port and a pressure chamber incorporating a pressure port, a condenser which is arranged in the cooling circuit downstream of the pressure port and comprises a fluid collecting chamber in which a reservoir of refrigerant is formed, an evaporator which is located in the cooling circuit between the condenser and the suction port, a feed unit which is connected at one side to the refrigerant reservoir and to the pressure chamber at the other side and which serves for supplying refrigerant from the refrigerant reservoir to the pressure chamber which incorporates a pumping unit for the refrigerant, it is proposed that in order improve this cooling circuit in such a manner that it is realizable in an economically meaningful manner that the pumping unit comprise a pressure-tight closed housing which is provided with only one inlet and one outlet as access points and a pumping element which is movable for pumping the refrigerant be arranged in the pumping chamber thereof.
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This is a continuation of application Ser. No. 08/854,952, filed May 13, 1997 now U.S. Pat. No. 6,249,972.
BACKGROUND AND SUMMARY OF THE INVENTION
This invention relates to the manufacture of wooden roof trusses, of the kind including a bottom chord and at least one upper chord obliquely disposed in relation to the bottom chord, webs being connected between these chords.
In the manufacture of a set of such roof trusses it is customary to calculate, with the aid of a computer program, the composition of each truss according to span and loading, in the course of which the length and end cut geometry of each web, and its position in a truss, are determined. In a given set of trusses for a roofing job, there will be a great number of different webs which must be cut and correctly located during assembly.
We have found that it is possible to produce structurally satisfactory trusses in the varying sizes and types required in roofing construction, in which the webs are selected from a set of standard stock web lengths, with the panel points being determined by the successive selection of web lengths from stock lengths, and in which the ends of the webs are provided with a standard shape, set without regard to the geometry of the particular joints at which the ends are actually to be used.
In this way webs may be manufactured in advance of use and drawn from stock according to the specifications of a given job, with resultant cost savings.
In the preferred form of such webs, the ends are formed as semi-circles with a diameter substantially corresponding to the width of the web and their centres on the axis of the web.
U.S. Pat. No. 3,867,803 discloses a parallel chord joist truss in which the webs have such standardised end shapes. Unlike parallel chord trusses, however, the production of gable trusses and other roof trusses having oblique chords by the use of known procedures requires the production of webs of many specific lengths for a given job.
In its second aspect, the present invention provides methods of choosing a satisfactory web combination using the stock web lengths available, to achieve the desired structural performance. Whereas in the conventional approach, the panel points of the truss have been determined by the geometry of the chords (for example, where, in a so-called Fink truss, the panel lengths of the top chords are equalised, as are the panel lengths of the bottom chord, thus specifying the position of the panel points), in accordance with the present invention the actual panel points are determined by choosing webs from the stock lengths according to a predetermined scheme. The preferred schemes described herein relate the actual panel points defined by web selection to the panel points defined by panel length equalisation, for example by choosing a web length which will locate the actual panel point most closely on a predetermined side of the relevant notional panel point or by choosing webs which will contact the chords within provisionally determined panel point zones on the chords of the truss, the panel point zones being chosen on the basis of structural considerations.
In one such approach the invention provides a method of manufacturing wooden roof trusses of the kind having a bottom chord and at least one upper chord obliquely disposed relative to the bottom chord, the upper and bottom chords being connected by webs by means of nail-plated joints, characterised in that at least some of the webs are selected from a set of standard stock web lengths, and in that the ends of those webs are provided with a standard shape, set without regard to the geometry of the joints at which the ends are to be used.
Preferably the stock of webs comprises a set of web lengths which increase by equal increments between minimum and maximum lengths.
Preferably also the panel points of the truss are determined by the successive selection of web lengths from said stock.
In a particularly preferred form of the methods of the invention, the method includes the steps of
a) determining notional panel points on the chords said panel points being joined by notional web lines;
b) choosing a starting point on a chord, said chord being a starting chord; and,
c) using successive webs of lengths chosen from said set of web lengths to form two alternating sets of webs, such that:
(i) in the case of one set of alternate webs, each web has its length chosen from said set of web lengths as the length the longest not greater than the length of a notional web having said predetermined end shape and fitting the distance from the joint of the web with the starting chord to the notional panel point for that web on the chord opposite the starting chord; and,
(ii) in the case of the other set of alternate webs, each web has its length chosen from said set of web lengths as the length the shortest which is at least the length of a notional web having said predetermined end shape and fitting the distance from the connection of said web with the said opposite chord to the intersection with the starting chord of a line passing through said connect ion and parallel to the notional line of the web.
Preferably in such a method where the length thus determined of a web of said other set of alternate webs is greater than the said distance from the connection of said web with said opposite chord to the intersection with the starting chord of said line, the joint of the second web with the starting chord is located on the side of said intersection remote from the starting point.
Preferably also the starting point is the apex of the truss, and the notional panel points of an upper chord are determined by dividing the chord into panels, preferably equal panels, and the notional panel points of the bottom chord are at the intersection with the bottom chord of lines, preferably normal to the upper chord, intersecting the upper chord at the notional panel points thereof.
In another approach to the criteria for web selection, target panel point zones are established on structural principles, and alternative methods used to determine an efficient web layout within the constraints of such zones. Such a method may include the steps of
a) determining the maximum allowable panel lengths for each chord of the truss
b) determining the minimum number of overlapping maximum panel lengths in each chord, the regions of overlap thereof being referred to herein as panel point zones
c) selecting webs from the stock range on the basis of chosen criteria including the requirement that the chosen web will connect with the chord within a target panel point zone previously determined for the next web-to-chord joint.
Each of these alternative methods is characterised by a stepwise procedure reiterated where necessary, in which, starting at a chosen point on the truss, preferably either
(a) starting at the apex (or other point where the angle of the chord changes) and working toward the heels of the truss, or
(b) starting at the heels and working toward the apex, or
(c) starting with the provision of a king post and starting other web selection
from the foot of the king post and working toward the heels webs are selected from the stock range on the basis of chosen criteria including the requirement that the chosen web will connect with the chord within a target panel point zone previously determined for the next web-to-chord joint.
One of these alternative methods begins by establishing all possible combinations of webs satisfying the requirement that they begin and end in a panel point zone. A choice is then made between these combinations on the basis of a pre-determined criterion or set of criteria. Suitable criteria for this purpose include
(a) the sum of the individual departures of the panel points from the location of corresponding panel points in a standard solution, and
(b) timber usage.
Other criteria may be adopted.
In the second of the alternative methods, webs are chosen on the basis of a parameter extreme, for example,
(a) the web which hits the target panel point zone at a position within that zone closest to the starting point (eg. the apex or centre of the truss),
(b) the shortest stock length which will reach the target panel point zone,
c) the longest stock length which will reach the target panel point zone.
Other possible bases for web choice include choosing the web for which the included angle between the web and the chord is closest to a preferred angle for the panel point in question.
As a matter of convenience, the invention will be described primarily in its application to symmetrical trusses having a pair of upper chords meeting at a centrally located apex, but it is to be borne in mind that the invention may be applied, with appropriate modifications, to other types of trusses. Also as a matter of convenience, the trusses will be dealt with in the description of assembly methods in terms of single dimension line drawings, thereby avoiding the need to be concerned with web width and end shape, and with the choice of measurement conventions, for example the choice between the use of internal or external triangles. As is well known, various conventions are used in defining truss dimensions, particularly chord length. Providing the structural implications of the convention employed are taken into account, however, the choice of convention is of no relevance to the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings,
FIG. 1 illustrates a web for use in the practice of the invention.
FIGS. 2 to 4 show three common forms of truss, respectively having two, four and six webs on each side, configured conventionally with equal panels in the upper chords and equal panels in the lower chords;
FIGS. 5 and 6 illustrate web to chord joints employing webs of the kind illustrated in FIG. 1;
FIGS. 7 to 9 illustrate web to chord joints employing alternative web end shapes;
FIGS. 10 to 14 schematically illustrate a method of web selection according to one embodiment of the invention;
FIGS. 15 to 19 schematically illustrate a method of web selection according to another embodiment of the invention; and
FIG. 20 schematically illustrates a method of web selection according to another embodiment of the invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Illustrated in FIG. 1 is a web 50 made for the purposes of the invention, provided with semi-circular ends 49 the radius of which is one half of the web width. While end shapes other than a semicircle may be used, as described below, this is the preferred form.
In accordance with the invention, either at the mill or in the truss factory, webs are cut with such ends, in a standard range of lengths. The optimum length range and the optimum increment by which web length increases from one standard length to the next will to some extent depend on the range of truss types and sizes being manufactured, but as a guide, in the manufacture of roof trusses for housing in Sydney Australia, lengths in 150 mm increments between 150 and 3600 mm have been found suitable. The increments by which the length of the webs increase need not be equal, and benefit may be found in some applications in adopting a scheme whereby the length increments as a function of length, for example geometrically or logarithmically, or indeed random predetermined lengths may be employed.
FIG. 5 illustrates a typical joint between a single web 50 and a chord 51 , effected by means of a conventional nail plate 52 , while FIG. 6 shows a joint involving two such webs. The use of nail plates in the fabrication of wooden trusses is well known, and conventional nail plates may be used in conjunction with the present invention.
FIG. 7 shows a joint in which the web ends instead of being semi-circular are formed with a radiused end and a tapering section 53 on one side. FIG. 8 shows a joint in which the web ends have a taper 53 on both sides and a radiused end of consequently smaller radius. An extreme example is shown in FIG. 9, which shows a joint in which the web ends are simply cut to form oblique faces 54 .
Alternative end formations may be employed, for example the standard end may consist of a series of cuts at successive angles, or a combination of such cuts with radiused portions.
What all such shapes including the preferred semicircular shape have in common is the provision of some form of taper, which reduces the gap which will be produced between the ends of the webs and the chord, and between abutting web ends. Of these tapering shapes, the semicircular shape is preferred for the reason that the gap between the chord and a pair of web ends, or between a single web and a chord, is constant for varying web angles.
The web selection methods of the invention for such truss types will now be described. As a matter of convenience, and because it may best introduce the reader to the concepts involved, the alternative methods of web choice will be described first, followed by the most preferred method.
The first methods to be described make use of the concept of panel point zones which are chosen by first determining in accordance with criteria adopted for the purpose, the maximum allowable panel lengths for the chords, for a given choice of factors which may include chord section and grade, web configuration, chord length and truss loading.
The maximum allowable panel lengths may be determined from first principles, based on the allowable loading of the timber sections in question. The maximum allowable panel lengths determined in this way may differ for the different panels of each chord.
Other methods may be employed for the determination of the allowable panel lengths. For example, the lengths may be determined by examining the panel lengths in a conventionally designed truss for the maximum span allowed for that truss type for the timber section and quality to be employed. In such a conventionally designed truss, the equal panel lengths will not be equally stressed, so deriving the maximum allowable panel length in this way will give a conservative figure.
In the preferred practice of the invention, panel point zones, or at least the panel point zones after the first zone in the sequence of web placement, are determined initially as provisional zones, by providing the minimum number of substantially equally overlapping maximum allowable panel lengths in each chord. The provisional panel point zones are the regions of overlap of these panel lengths. The panel point zones after the first from the starting point are revised upon the determination of the location of the preceding panel point on the chord in question, again by reference to the maximum allowable panel length or by calculation. The webs are then chosen, either by the method of establishing all possible combinations and then choosing the combination which best satisfies the chosen criteria, or by choosing successive webs according to one of the other methods described above.
In the case where web lengths are determined progressively, it may occur that there is no available web length between the last located panel point and any point in the next panel point zone. In such a case the previous web is replaced by an alternative, preferably the next incremental web length away from the starting extreme, and the next web selection reiterated. If again no web length is suitable, the previous web is again replaced, by the next length again away from the extreme, and so on. Where this procedure does not produce a result, then the web preceding this immediately preceding web is substituted in the same way, until a fit is found. Where no fit can be found in this way, the number of webs is increased and the procedure repeated until a fit is found.
The application of this approach to the design of a symmetrical truss with four webs per side will now be described.
The truss design will normally take place within the context of the parameters of truss sizes, chord materials and loadings standardised for normal production for the plant. A typical set of such parameters may be as follows:
Span range: To 10000 mm
Pitch range: 18 to 26 degrees
Preferred top chord material: F5 JD5 90×35 mm kiln dried pine
Preferred bottom chord material: F5 JD5 90×35 mm kiln dried pine
Roof Loadings: Terra Cotta tiles
Ceiling Loadings: Plasterboard 13 mm
Design wind speed: 41 m/sec
Top Chord bracing: Tile battens@ 300 mm ctrs
Bottom Chord bracing: Bracing at 1800 mm ctrs
For these parameters a suitable top chord maximum allowable panel length may be for the truss in question 2100 mm, and for bottom chords 2700 mm.
The span and pitch of the truss and the material section determine the internal or external triangle of the truss and the dimensions of the chords. Once this is determined, the next step is to locate the panel point zones, by locating substantially equally overlapping units of the maximum allowable panel lengths 11 and 12 along the respective chords from the apex and from the heels as shown in FIG. 10 .
In the present example two such zones 14 and 15 are determined on each of the top chords 11 and 12 , while the bottom chord 13 has two pairs of zones 16 and 17 .
The preferred starting point for the web selection is the apex of the truss, since this is a fixed location. While it is possible to work from the heel towards the apex, this has the difficulty that the end point of the process is inflexible, unless one is prepared to tolerate a truss in which the central webs do not meet the upper chords at the apex.
In the following description, the choice of webs will be discussed in relation only to the left-hand side of the truss as viewed in FIG. 10, since the truss is symmetrical and the same results will be obtained on the other side.
Where the truss design is to be solved by determining all possible web combinations which satisfy the available stock lengths and the panel point zones, the possible choices of first web 18 (FIG. 11) are determined, shown in this example as 18 a , 18 b and 18 c.
For each of these solutions for the first web 18 , the family of webs 19 meeting the target panel point zone 14 is then determined. In the example shown in FIG. 12, for the case of web 18 a , the possible family is 19 aa , 19 ab , 19 ac (FIG. 12 ). It is to be observed that a web may be capable of meeting a panel point zone in two places. In such a case, both possibilities will preferably be used.
For each of the possible webs 18 a , 18 b and 18 c (FIG. 11 ), the target panel point zone 17 is re-calculated by measuring out the relevant maximum allowable panel length from each of the panel points of these possible webs, producing a family of overlapping zones 17 a , 17 b , 17 c . Similarly for each member of the family of possible webs 19 , such as 19 aa , 19 ab , 19 ac (FIG. 12 ), a family of target panel point zones 15 a , 15 b , 15 c , . . . is calculated.
This procedure is repeated along the truss until all web families have been determined. At this point a large family of trusses will have been generated, each of which could be manufactured from the available stock.
Preferably, each of these truss designs is examined to identify those which incorporate web geometry which is undesirable, for example, where the minimum included angle between a web and the chord to which it is attached is not reached for unopposed joints of webs which are to act in, or may go into, compression. In such cases the truss may be deleted, or the joint modified to provide opposition for the web, for example by adding a block attached to the chord or by adding a further web.
Once such exceptions have been taken care of, a choice is made between the remaining truss solutions, on the basis of a predetermined criterion or set of criteria. Preferably, this is done by comparing each of the trusses with a truss which would have been manufactured using prior art techniques. The preferred method of comparison is to take one truss at a time, and measure the distance between each panel point of the truss and the corresponding panel point of the prior art truss. Each of these distances is then totalled for each truss. The chosen truss will be the one which has the smallest total, indicating close correspondence with the prior art solution.
As indicated above, some other basis of choice may be made, for example based on the quantity of timber used by each truss solution.
An example will now be described of the way in which the truss may be determined by the sequential selection of webs by the adoption of webs which satisfy a parameter extreme, in this example, the web which lands at a point in the target panel point zone which is closest to the starting point of web selection.
The first web 18 (FIG. 13) is chosen as that web from the stock lengths of web which will extend from the apex and contact the bottom chord within the zone 16 at the point closest to the centre of the truss. With the selection of this web, the panel point zone 17 can now be determined by measuring out the relevant maximum allowable panel length from the panel pont of the web 17 towards the heel.
The next web to be chosen, web 19 , is that having the stock length which will extend from a joint at the lower chord adjacent the web 18 , and strike the upper chord 11 within the provisional panel point zone 14 , closest to the apex of the truss. The selection of web 19 then allows the determination of panel point zone 15 . Similarly, the next web 20 is chosen as the stock length which will extend from the joint with web 19 on the upper chord 11 and contact the lower chord 13 within the panel point zone 17 and closest to the centre of the truss.
Finally the web 21 is chosen as the stock length which will extend from the joint with web 20 on the lower chord 13 and contact the upper chord 11 within the provisional panel point zone 15 , closest to the apex.
Before the web layout thus arrived at can be considered complete, the angle of contact between compression webs (or tension webs which may go into compression, for example under wind uplift) and the chord at an unopposed joint (i.e. a joint comprising a chord and only one web), should be checked to ensure that it is not so small as to be unacceptable for the nail plate fixing employed. It will be found convenient to adopt a minimum angle based on testing of such joints, and to reject designs which produce an angle at an unopposed joint which is less than this minimum angle. With the parameters employed in the present examples, such a minimum angle may be found to be in the region of 10 to 30 degrees.
Where the web angle is found to be less than the minimum, it will be necessary either to revise the preceding web choice, or to use other expedients such as the use of a block attached to the chord to provide opposition for the web, or add a further web to provide this opposition.
FIG. 14 illustrates a case in which web length selection must be reiterated to achieve the truss design. Here it is shown that after the initial choice of the web 18 , in seeking the correct length for the next web it is found that while the web length 119 is too short to reach the zone 14 , the next longest web 219 is too long. In this case the web 18 is replaced by the next greater stock length landing in the target panel point zone 16 , i.e. the next stock length web landing away from the apex of the truss. This will generate a new starting point for the next web, whereupon it may be found that the web 119 or a web of another stock length reaches the provisional zone 14 .
Should this reiteration of the procedure not produce a workable choice for the next web, the first web length is again incremented, and a fit for the second web sought afresh.
It will be understood that this procedure will be used to overcome the absence of a suitable web length at any of the successive web locations along the truss. In an extreme case it may be necessary to carry the reiteration of length determination back for more than one web in the sequence.
In the case where the first web choices are exhausted without finding a suitable truss, or without finding an available web length for a given web, then the configuration of the truss must be revised, increasing the number of webs.
In most cases it will be found that more than one set of webs can be found for a given truss, if the designer experiments with different starting web lengths or substitutes intermediate webs. In such cases, even where the method of determining webs successively is employed, the manufacturer may prefer to generate a family of possible web choices for a given truss, and choose from among these the pattern of webs which best suits the application, for example by providing room for air-conditioning ducts, or for personnel access in the roof. Indeed, the designer conscious of such additional design parameters will modify his choices of web length at the appropriate part of the truss to take these into account, choosing, for example, a longer web at a particular point than would otherwise be suggested by the simplest form of the method described above.
In conjunction with the approach to truss design thus described, a further modification to normal practice can be of advantage. In this modified approach, joints comprising more than one web end are modified so that the web ends are spaced along the chord (or, at an apex, their respective chords). Preferably a standard spacing is adopted which is compatible with the structural requirements of the truss, but the spacing may be varied within a given truss, and not all joints may be designed in this way. A typical spacing of the web ends in roof trusses may be 200 mm.
The use of open joints of this kind provides several advantages in the method of the present invention. The panel point zone may be extended, and consequently the number of web lengths in the stock family may be reduced, by increasing the length increment between successive stock lengths. This approach will also enable some trusses to be constructed with less webs than otherwise. For example, a truss which had to be constructed with six webs per side because a web length/zone fit could not be found for the case of four webs per side may, with spaced joints, have four webs per side.
The methods thus described may be implemented by computer or conducted manually. Computer implementation will be of particular benefit where it is desired to generate a family of web solutions.
FIGS. 15 to 19 illustrate another approach to the web selection process, foreshadowed above and having the advantage of starting with a clearly defined chord geometry. In this method, as shown in FIG. 15 there is first provided a king post 22 cut to the correct length if necessary, descending vertically from the apex of the web. By fixing such a web in position before fixing the remaining webs the chords are now fixed in position with an accurately defined apex height, whereas in the methods previously described the truss triangle was not fixed until web installation was substantially complete.
The subsequent webs may now be selected according to the method and criteria described above, leading to the development of trusses as shown in FIGS. 16 to 19
A preferred method of web selection, which is particularly well adapted to embodiment in computer software, will now be described.
In the truss illustrated in FIG. 20, each of the upper chords is, as is conventional, divided into equal panel lengths to define upper chord notional panel points 23 and 24 . Parallel lines 25 and 26 are then drawn intersecting the upper chords at each of the notional panels points to define at their intersections with the bottom chord, notional panel points 27 and 28 . The angle between the relevant upper chord and the lines 25 and 26 , which may be regarded as notional web lines, is suitably 90 degrees, but other angles may be used and chosen on structural principles or by experiment In the example illustrated, an angle of 90 degrees will be used.
Lines 29 and 30 are shown as the notional web lines joining the apex and panel point 27 , and panel points 23 and 28 .
The object of the web selection method now employed is to select webs which determine panel points on the bottom chord having a close correspondence with the notional panel points. This is done by starting (preferably) at the apex of the truss, and choosing for each side of the truss the greatest web length 30 a which will produce a joint at or on the near side of the notional panel point 27 . In other words, the web length chosen is the longest in the stock of lengths which is not greater than the distance between the apex and the notional panel point 27 .
From the actual panel point 27 a thus established on the lower chord 13 , a line 25 a is drawn parallel to the line 25 intersecting the upper chord 11 . The next web 31 is chosen as the web with the shortest stock length which is not less than the distance between the panel point 27 a and the intersection of the line 25 a with the upper chord 11 .
Except in the rare case that there is a stock length equal to this distance, the web 31 can form a joint with the upper chord in either of two locations, one on each side of the line 25 a . Preferably the web is positioned with its joint on the upper chord on the side of the line 25 a remote from the apex, since in this way the resultant web layout will most closely approximate the notional layout. The location of the resulting panel point 25 b relative to the notional panel point 23 will depend on the length of the web 31 and the other relevant parameters of the web, but it will be found that for a practical choice of web length increments as discussed above, the point 25 b will be quite close to the notional point 23 .
This process is repeated, with the web 32 being chosen for the greatest length from the stock lengths which will produce a joint at or on the near side of the notional point 28 , and the web 33 as the shortest stock length which is not less than the distance between the panel point 28 a and the intersection of the line 26 a with the upper chord 11 . As in the case of the web 31 , the web 33 is positioned with its upper panel point on the side of the line 26 a remote from the apex (i.e. closest to the notional panel point 24 ). The effect of this methodology will be seen to be to group the actual panel points as closely as possible to the notional points, with a simple, unambiguous basis for web length choice in each case. It may also be observed that by choosing the angle between the upper chord 11 and the notional web lines 26 as 90 degrees, the likelihood that an unopposed web to chord joint such as that of the web 33 , will be made at an angle less than the minimum web angle discussed above, is very small, since such a large departure from parallelism between the actual web line and the line 26 a is unlikely.
This last described method may be varied, if desired, for example by reversing the sides of the lines 25 and 26 and/or 25 a and 26 a on which the respective web ends fall.
As in the methods previously described, the web layout thus arrived at will be checked for compliance with the predetermined minimum web angle, and if this requirement is not satisfied, then either a block will be added to the chord to oppose the web at the offending joint, or a further web added for this purpose. Alternatively, the designer may choose to repeat the web selection process for a truss with an additional web on each side.
Preferably, the truss will also be checked to ensure that the panel points established by this process of web selection satisfy the structural requirements of the truss application. This can be done by checking the truss by first principles, or by determining that the panel points land within the panel point zones determined as described above. If this is not the case, then one or more webs should be added to the design and the web selection process repeated.
While this last methodology has been described in terms of working from the apex (or other point of chord angle change) it is to be appreciated that this method also may be practiced by starting elsewhere, for example at the notional panel point closest to the heel of the truss, with choices of the alternative actual upper panel point locations being made, as above, preferably in a way which results in a web layout approximating the notional layout. Other starting points may be chosen, for example on the notional panel points on either chord, or any point within any panel point zone, or at a panel point determined by prior art methods.
The invention may be applied to trusses other than the simple end-supported gable trusses discussed so far. Examples of other trusses to which the invention may be applied are cantilevered trusses where differing panel lengths may apply in the cantilevered portion of the truss, or trusses with additional supports, truncated trusses, mono and cut-off mono trusses, cut-off gable trusses and valley trusses. In all these and other cases not listed here the same basic procedures described above may be practised.
It will be understood that there may be instances where, because of the type of truss, or the need to include an extreme web to truss angle, one or more conventionally cut webs of non-standard length may have to be incorporated in a particular truss. The invention extends to such mixed trusses, where the time and labour saving offered by the use of the invention will still largely be obtained.
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A plurality of wooden roof trusses for constructing a roof includes first and second wooden roof trusses. Each of the first and second wooden roof trusses includes a bottom chord and at least one upper chord obliquely disposed relative to the bottom chord. A first web is provided to the first wooden roof truss and a second web is provided to the second wooden roof truss. Each of the first and second webs has a tapered web end shape set without regard to a shape of a first and second joint, respectively, into which said tapered web end shapes of the first and second webs fit. The first and second webs are substantially identical in length and web end shape. The first and second webs are located at different positions in their respective first and second wooden roof trusses.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to systems for covering the external surface of a building construction; and more particularly to an improved system for shielding openings left between portions of siding systems.
2. Description of the Related Art
The use of siding to protect the outside of a house is commonplace in new construction as well as renovation of existing structures. Such siding is generally made of aluminum, vinyl or steel and is attached to the external building surface. In order to complete the exterior covering of the building, various types of accessory moldings are required. For example, various types of moldings are needed at the corners, edges, adjacent the roof, and at various other interconnecting locations.
Typically, when finishing off a building opening, a J-channel is utilized. The J-channel is first secured around the opening with one portion of the channel being fastened directly to the exterior building surface. The joint left between the J-channel and the frame placed in the opening is then filled with a weatherproofing caulk. The joint then presents a continuous maintenance item as well as an aesthetically compromised appearance.
U.S. Pat. No. 4,341,048 discloses a technique for covering the peripheral gap between a frame placed in the building opening and the exterior surface of the building. The patent teaches a facia having two portions which are oriented orthogonal to one another. The outward edges of the portions are inserted into respective grooves. A first groove in the frame and a second groove in a receptor placed on the external building surface. A resilience imparted to the facia by the structure of the second groove maintains engagement of the facia in the first groove. The engagement of the facia in the first groove may be enhanced by application of a bead of caulk. Over the passage of time, weathering impairs the resilience of the system as well as the integrity of the caulk bead leading to possible leakage.
Therefore, there exists a need for a system for providing a shield for the periphery of a building opening which is resistant to weathering and does not require a caulk bead.
SUMMARY OF THE INVENTION
An exemplary embodiment of the present invention includes a facia system for shielding the periphery of the framework of a building opening adjacent a building surface including a first channel extending orthogonal to the building surface, a second channel extending parallel to the building surface and a facia having first and second planar portions joined together to define an L-shaped cross-section; wherein the facia has edges for insertion into the first and second channels. The second channel is formed as a utility combined with a J-channel.
The invention further includes a system for shielding an opening left between portions of a system covering the external surfaces of a building including a first member which defines an elongated linearly extending first channel. The first member has a closed interior portion defining part of the first channel and an elongated slotted opening which communicates with the first channel. The first member further includes a flange for maintaining the first channel in fixed relation to the framework in which the first channel is oriented in a predetermined manner with respect to the building surface. One manner of orientation is one in which the first channel is oriented substantially orthogonal to the building. The system further includes a second member which defines an elongated linearly extending second channel. The second member has a closed interior portion defining part of the second channel and an elongated slotted opening which communicates with the second channel. The second member further includes a flange for attaching the second member to the building surface thereby maintaining the second channel in fixed relation to the framework in which the second channel is oriented in a predetermined manner with respect to the building surface. The second member may be oriented substantially parallel to the building surface. Finally, the system includes a facia member having first and second planar portions. The first portion has an edge for slidable insertion into the slotted opening of the first member and the second portion has an edge for slidable insertion into the slotted opening of the second member. The facia thereby spans the periphery of the framework between the first and second members to provide a weather resistant cover. Further, the facia member having first and second planar portions joined together may define a generally L-shaped cross-section. In addition, the invention includes a third member which defines an elongated linearly extending third channel. The third member has a closed interior portion defining part of the third channel and an elongated slotted opening which communicates with the third channel. The third member further includes a flange means for maintaining the third channel in fixed relation to the framework in which the third channel is substantially orthogonal to the building surface and in which the elongated slotted openings of the first and third members converge at a predefined angle. The system further includes a fourth member which defines an elongated linearly extending fourth channel. The fourth member has a closed interior portion defining part of the fourth channel and an elongated slotted opening which communicates with the fourth channel. The fourth member further is secured to the building surface thereby maintaining the fourth channel in fixed relation to the framework in which the fourth channel is substantially parallel to the building surface and in which the elongated slotted openings of the second and fourth members converge at said predefined angle. The system also includes a second facia member having third and fourth planar portions joined together. The third portion has an edge for slidable insertion into the slotted opening of the third member and the fourth has an edge for slidable insertion into the slotted opening of the fourth member wherein the second and fourth planar portions overlap one another and the second facia member spans the periphery of the framework between the third and fourth members to provide a weather resistant cover. It is to be noted that the facia member having first and second planar portions joined together may define a generally L-shaped cross-section. The invention further includes a system wherein the second channel lies generally in a plane parallel to and outwardly of the building surface and wherein the slotted opening of the second member defines a gap. The second portion is sufficiently deformable such that the facia member will articulate about the slotted opening sufficiently to permit the slidable engagement of the first portion with the slotted opening of the first member. Further, the system, as described, features a first member having a closed end wherein the edge of the first portion of the facia member is spaced apart to permit thermal expansion. In addition, the closed end of the second member and the edge of the second portion of the facia member are spaced apart to permit thermal expansion. In addition, the system may include a first portion of the generally L-shaped cross-section including raised portions providing an enlarged cross-section which cooperates with the first channel to achieve mechanical interlock therebetween. In addition, the system includes a second member having an elongated linearly extending third channel wherein the second member has a closed interior portion defining part of the third channel and an elongated slotted opening which communicates with the third channel and the third channel is substantially parallel to the second channel and oriented in an opposing direction therefrom for receiving siding placed on the exterior surface of the building. The system may feature a first member which is separate from the framework and attachable thereto for retrofitting the existing building structures.
These and other aspects of the present invention will become more readily apparent by reference to the following detailed description of the embodiments as shown in the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a building opening incorporating the facia of the present invention;
FIG. 2 is a cross-section of the facia system of the present invention taken along lines 2--2 of FIG. 1;
FIG. 3 is a cross-section of the facia system shown in FIG. 2 for use on buildings without siding;
FIG. 4 is an exploded perspective view of the present invention;
FIG. 5 is a cross-section of the facia system of the present invention incorporating rolled channels for interlocking the elements of the facia system;
FIG. 6 is a cross-section of the facia system shown in FIG. 5 for use on buildings without siding;
FIG. 7 is a cross-section of the facia system of the present invention incorporating frictionally interlocking channels for interlocking the elements of the facia system;
FIG. 8 is a cross-section of the facia system shown in FIG. 7 for use on buildings without siding;
FIG. 9 is a cross-section of the facia system of the present invention incorporating inverted frictionally interlocking channels for interlocking the elements of the facia system; and
FIG. 10 is a cross-section of another embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The preferred embodiment of the present invention is shown in FIG. 4 including a finned window 10 having a first receptor 12 integrally formed therewith. The first receptor incorporates an open channel 14. A second receptor 16 secured to the outermost building surface 18 incorporates an open channel 20. A facia 22, including a first portion 100 featuring edge 102 and a second portion 104 featuring edge 106, is received in the channels 14, 20. Siding 28 covering the building surface 18 is received in opening 24 of receptor 16.
A NHPI Snaplock punch may be used to provide raised cross-sectional portions 26 in facia 22 to cooperate with channel 14 to retain the facia 22 therein.
The steps of assembly include;
(a) installing the finned window 10 including the first receptor 12;
(b) installing the second receptor 16 on the building surface 18;
(c) inserting a first edge of facia 22 into receptor 16; and
(d) articulating facia 22 into locking engagement between raised cross-sectional portions 26 and receptor 12.
FIG. 2 illustrates the present invention as a retrofit to an existing window. That is, receptor 12 is shown as a separate member secured to the window 10 by conventional means including adhesive or equivalent fasteners (not shown).
FIG. 3 also represents the present invention as adapted to an existing window; however, receptor 16 is modified for installation abutting a building surface 18 which is not covered by siding.
FIGS. 5, 7 and 9 feature subsequent embodiments in which the channels 14, 20 are formed in a manner which cooperates with respective portions of facia 22 to complete mechanical interlock therebetween. The second embodiment disclosed in FIG. 5 includes a first receptor 12 having open channel 14 formed in a generally circular cross-sectional shape offering an opening less than 180 degrees wide. Facia 22 has a first portion 100 including an edge 102 which is rolled to present an outside diameter slightly greater than the width of the opening offered by channel 14. In this manner, facia 22 may be snapped into engagement with receptor 12 forming a strong mechanical connection therebetween as well as a weathertight, continuous seal. The opposite end of facia 22 includes a portion 104 which is also formed in a generally circular cross-sectional shape offering an opening less than 180 degrees wide. This opening is slightly smaller than the external dimension of portion 20 of receptor 16. Portion 20 is preferably of a circular shape.
The embodiment disclosed in FIG. 5 is assembled by first installing portion 106 of facia 22 over portion 20 of receptor 16. This achieves a strong mechanical interconnection therebetween which offers a weathertight continuous seal. Subsequently, facia 22 may be articulated about the axis of portion 20 thereby bringing portion 102 thereof into mechanical interlocking relation to channel 14. In this manner, a strong mechanical interlock may be achieved while providing a continuous weatherproof seal. A modification of this embodiment for use on buildings which do not incorporate siding on the external buildings surface is shown in FIG. 6.
The third embodiment disclosed in FIG. 7 incudes a receptors 12, 16 having an open chain 14, 20 offering constant width openings. Facia 22 having a first portion 100 with sawtooth shaped protrusions formed thereon provides ease of installation while resisting removal. In this manner, the facia 22 may be snapped into engagement with receptor 12 forming a strong mechanical connection therebetween as well as a weathertight, continuous seal. The opposite end of facia 22 includes a portion 104 which also features sawtooth shaped protrusions formed thereon.
The embodiment disclosed in FIG. 7 is assembled by first installing portion 106 of facia 22 into channel 20 of receptor 16. This achieves a strong mechanical interconnection therebetween which offers a weathertight continuous seal. Subsequently, facia 22 may be articulated about the axis of portion 20 thereby bringing portion 102 into engagement which channel 14.
In this manner, a strong mechanical interlock may be achieved while providing a continuous weatherproof seal. A modification of this embodiment for use on buildings which do not incorporate siding on the external building surface is shown in FIG. 8.
A modification to the third embodiment is shown in FIG. 9 including a receptor 16 having an open channel 20 including resiliently deformable portion 108 engaging the chip making portion of sawtooth shaped protrusions formed on facia 22. Assembly techniques are identical to that previously described with the exception that channel 20 imparts a continuous force which supplements the mechanical interlock of portion 102 of facia 22 in channel 14.
The embodiment disclosed in FIG. 10 includes a first receptor 12 having open channel 14. A second receptor 16 incorporates open channel 20. A facia 22 including edge 102, 106 is received in channels 14, 20. Siding 28 covering building surface 18 may be received in opening 24 of receptor 16. The embodiment disclosed in FIG. 10 is assembled by first installing edge 102 in channel 14. Next, facia 22 is elastically deformed permitting edge 106 to be installed in channel 20 of receptor 16.
One skilled in the art will readily recognize that certain specific details shown in the foregoing specification and drawings are exemplary in nature and subject to modification without departing from the teachings of the disclosure. Various modifications of the invention discussed in the foregoing description will become apparent to those skilled in the art. All such variations that basically rely on the teachings through which the invention has advanced the art are properly considered within the spirit and scope of the invention.
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A facia system for shielding the periphery of the framework of a building opening adjacent a building surface including a first channel extending orthogonal to the building surface, a second channel extending parallel to the building surface and a facia having first and second planar portions joined together to define an L-shaped cross-section; wherein the facia has edges for insertion into the first and second channels.
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BACKGROUND OF THE INVENTION
It is highly desirable for tires to exhibit good traction characteristics on both dry and wet surfaces. However, it has traditionally been very difficult to improve the traction characteristics of a tire without compromising its rolling resistance and tread wear. Low rolling resistance is important because good fuel economy is virtually always an important consideration. Good tread wear is also an important consideration because it is generally the most important factor that determines the life of the tire.
The traction, tread wear and rolling resistance of a tire is dependent to a large extent on the dynamic viscoelastic properties of the elastomers utilized in making the tire tread. In order to reduce the rolling resistance of a tire, rubbers having a high rebound have traditionally been utilized in making the tire's tread. On the other hand, in order to increase the wet skid resistance of a tire, rubbers which undergo a large energy loss have generally been utilized in the tire's tread. In order to balance these two viscoelastically inconsistent properties, mixtures of various types of synthetic and natural rubber are normally utilized in tire treads. For instance, various mixtures of styrene-butadiene rubber and polybutadiene rubber are commonly used as a rubber material for automobile tire treads. However, such blends are not totally satisfactory for all purposes.
The inclusion of styrene-butadiene rubber (SBR) in tire tread formulations can significantly improve the traction characteristics of tires made therewith. However, styrene is a relatively expensive monomer and the inclusion of SBR in tire tread formulations leads to increased costs.
Carbon black is generally included in rubber compositions which are employed in making tires and most other rubber articles. It is desirable to attain the best possible dispersion of the carbon black throughout the rubber to attain optimized properties. It is also highly desirable to improve the interaction between the carbon black and the rubber. By improving the affinity of the rubber compound to the carbon black, physical properties can be improved. Silica can also be included in tire tread formulations to improve rolling resistance.
U.S. Pat. No. 4,843,120 discloses that tires having improved performance characteristics can be prepared by utilizing rubbery polymers having multiple glass transition temperatures as the tread rubber. These rubbery polymers having multiple glass transition temperatures exhibit a first glass transition temperature which is within the range of about −110° C. to −20° C. and exhibit a second glass transition temperature which is within the range of about −50° C. to 0° C. According to U.S. Pat. No. 4,843,120, these polymers are made by polymerizing at least one conjugated diolefin monomer in a first reaction zone at a temperature and under conditions sufficient to produce a first polymeric segment having a glass transition temperature which is between −110° C. and −20° C. and subsequently continuing said polymerization in a second reaction zone at a temperature and under conditions sufficient to produce a second polymeric segment having a glass transition temperature which is between −20° C. and 20° C. Such polymerizations are normally catalyzed with an organolithium catalyst and are normally carried out in an inert organic solvent.
U.S. Pat. No. 5,137,998 discloses a process for preparing a rubbery terpolymer of styrene, isoprene and butadiene having multiple glass transition temperatures and having an excellent combination of properties for use in making tire treads which comprises: terpolymerizing styrene, isoprene and 1,3-butadiene in an organic solvent at a temperature of no more than about 40° C. in the presence of (a) at least one member selected from the group consisting of tripiperidino phosphine oxide and alkali metal alkoxides and (b) an organolithium compound.
U.S. Pat. No. 5,047,483 discloses a pneumatic tire having an outer circumferential tread where said tread is a sulfur-cured rubber composition comprised of, based on 100 parts by weight rubber (phr), (A) about 10 to about 90 parts by weight of a styrene-isoprene-butadiene terpolymer rubber (SIBR) and (B) about 70 to about 30 weight percent of at least one of cis 1,4-polyisoprene rubber and cis 1,4-polybutadiene rubber wherein said SIBR rubber is comprised of (1) about 10 to about 35 weight percent bound styrene, (2) about 30 to about 50 weight percent bound isoprene and (3) about 30 to about 40 weight percent bound butadiene and is characterized by having a single glass transition temperature (Tg) which is in the range of about −10° C. to about −40° C. and, further, the said bound butadiene structure contains about 30 to about 40 percent 1,2-vinyl units, the said bound isoprene structure contains about 10 to about 30 percent 3,4-units and the sum of the percent 1,2-vinyl units of the bound butadiene and the percent 3,4-units of the bound isoprene is in the range of about 40 to about 70 percent.
U.S. Pat. No. 5,272,220 discloses a styrene-isoprene-butadiene rubber which is particularly valuable for use in making truck tire treads which exhibit improved rolling resistance and tread wear characteristics, said rubber being comprised of repeat units which are derived from about 5 weight percent to about 20 weight percent styrene, from about 7 weight percent to about 35 weight percent isoprene and from about 55 weight percent to about 88 weight percent 1,3-butadiene, wherein the repeat units derived from styrene, isoprene and 1,3-butadiene are in essentially random order, wherein from about 25 percent to about 40 percent of the repeat units derived from the 1,3-butadiene are of the cis-microstructure, wherein from about 40 percent to about 60 percent of the repeat units derived from the 1,3-butadiene are of the trans-microstructure, wherein from about 5 percent to about 25 percent of the repeat units derived from the 1,3-butadiene are of the vinyl-microstructure, wherein from about 75 percent to about 90 percent of the repeat units derived from the isoprene are of the 1,4-microstructure, wherein from about 10 percent to about 25 percent of the repeat units derived from the isoprene are of the 3,4-microstructure, wherein the rubber has a glass transition temperature which is within the range of about −90° C. to about −70° C., wherein the rubber has a number average molecular weight which is within the range of about 150,000 to about 400,000, wherein the rubber has a weight average molecular weight of about 300,000 to about 800,000 and wherein the rubber has an inhomogeneity which is within the range of about 0.5 to about 1.5.
U.S. Pat. No. 5,239,009 reveals a process for preparing a rubbery polymer which comprises: (a) polymerizing a conjugated diene monomer with a lithium initiator in the substantial absence of polar modifiers at a temperature which is within the range of about 5° C. to about 100° C. to produce a living polydiene segment having a number average molecular weight which is within the range of about 25,000 to about 350,000; and (b) utilizing the living polydiene segment to initiate the terpolymerization of 1,3-butadiene, isoprene and styrene, wherein the terpolymerization is conducted in the presence of at least one polar modifier at a temperature which is within the range of about 5° C. to about 70° C. to produce a final segment which is comprised of repeat units which are derived from 1,3-butadiene, isoprene and styrene, wherein the final segment has a number average molecular weight which is within the range of about 25,000 to about 350,000. The rubbery polymer made by this process is reported to be useful for improving the wet skid resistance and traction characteristics of tires without sacrificing tread wear or rolling resistance.
U.S. Pat. No. 5,061,765 discloses isoprene-butadiene copolymers having high vinyl contents which can reportedly be employed in building tires which have improved traction, rolling resistance and abrasion resistance. These high vinyl isoprene-butadiene rubbers are synthesized by copolymerizing 1,3-butadiene monomer and isoprene monomer in an organic solvent at a temperature which is within the range of about −10° C. to about 100° C. in the presence of a catalyst system which is comprised of (a) an organoiron compound, (b) an organoaluminum compound, (c) a chelating aromatic amine and (d) a protonic compound; wherein the molar ratio of the chelating amine to the organoiron compound is within the range of about 0.1:1 to about 1:1, wherein the molar ratio of the organoaluminum compound to the organoiron compound is within the range of about 5:1 to about 200:1 and herein the molar ratio of the protonic compound to the organoaluminum compound is within the range of about 0.001:1 to about 0.2:1.
U.S. Pat. No. 5,405,927 discloses an isoprene-butadiene rubber which is particularly valuable for use in making truck tire treads, said rubber being comprised of repeat units which are derived from about 20 weight percent to about 50 weight percent isoprene and from about 50 weight percent to about 80 weight percent 1,3-butadiene, wherein the repeat units derived from isoprene and 1,3-butadiene are in essentially random order, wherein from about 3 percent to about 10 percent of the repeat units in said rubber are 1,2-polybutadiene units, wherein from about 50 percent to about 70 percent of the repeat units in said rubber are 1,4-polybutadiene units, wherein from about 1 percent to about 4 percent of the repeat units in said rubber are 3,4-polyisoprene units, wherein from about 25 percent to about 40 percent of the repeat units in the polymer are 1,4-polyisoprene units, wherein the rubber has a glass transition temperature which is within the range of about −90° C. to about −75° C. and wherein the rubber has a Mooney viscosity which is within the range of about 55 to about 140.
U.S. Pat. No. 5,654,384 discloses a process for preparing high vinyl polybutadiene rubber which comprises polymerizing 1,3-butadiene monomer with a lithium initiator at a temperature which is within the range of about 5° C. to about 100° C. in the presence of a sodium alkoxide and a polar modifier, wherein the molar ratio of the sodium alkoxide to the polar modifier is within the range of about 0.1:1 to about 10:1; and wherein the molar ratio of the sodium alkoxide to the lithium initiator is within the range of about 0.05:1 to about 10:1. By utilizing a combination of sodium alkoxide and a conventional polar modifier, such as an amine or an ether, the rate of polymerization initiated with organolithium compounds can be greatly increased with the glass transition temperature of the polymer produced also being substantially increased. The rubbers synthesized using such catalyst systems also exhibit excellent traction properties when compounded into tire tread formulations. This is attributable to the unique macrostructure (random branching) of the rubbers made with such catalyst systems.
U.S. Pat. No. 5,620,939, U.S. Pat. No. 5,627,237 and U.S. Pat. No. 5,677,402 also disclose the use of sodium salts of saturated aliphatic alcohols as modifiers for lithium-initiated solution polymerizations. Sodium t-amylate is reported to be a preferred sodium alkoxide by virtue of its exceptional solubility in non-polar aliphatic hydrocarbon solvents, such as hexane, which are employed as the medium for such solution polymerizations.
Numerous solutions have been proposed in order to decrease the rolling resistance of tires, in particular, by modifying the rubber compositions used for the treads of the tires. Thus, for rubber compositions that are reinforced with carbon black, it was initially proposed to reduce the content of carbon black. For instance, U.S. Pat. No. 4,822,844 proposes to use carbon black having specific characteristics expressed by a specific iodine absorption surface (IA) and nitrogen absorption surface (N 2 SA), as well as by an average size of well-defined carbon particles. Another solution described in U.S. Pat. No. 4,866,131 proposes a tire tread composition which is comprised of a low molecular weight copolymer of butadiene and styrene (SBR) prepared in solution in mixture with another conventional copolymer prepared in solution or emulsion. U.S. Pat. No. 4,894,420 proposes to use a tread formed of a blend of cis 1,4-polyisoprene and a diene/acrylonitrile copolymer. However, none of the solutions proposed up to now have proven to be totally satisfactory since the improvement in the rolling resistance is accompanied by a decrease in one or more essential properties, such as the reduction of adherence on wet and/or snow-covered surfaces or a reduction in the resistance to wear. It has also been proposed to use white fillers, such as silica, bentonite, clay, titanium oxide, talc, and the like, as reinforcing fillers. Such white fillers have the advantage of not being obtained from petroleum and decreasing the rolling resistance of tire treads manufactured therewith. However, in view of the resultant decline in the properties, in particular the decline in the resistance to wear, the use of silica in tread compositions is still an exception and frequently represented only a minority fraction of the total filler as described in U.S. Pat. No. 4,894,420 and U.S. Pat. No. 4,820,751. In order to remedy this situation, European Patent Application 299,074 proposes a rubber composition comprising silica, as reinforcing filler, in very large proportions and which is based on a polymer which is functionalized by means of a special alkoxy silane compound having a non-hydrolyzable alkoxy group. However, this solution is restrictive in that it permits the use only of a very specific family of silanes, which constitutes a handicap for industrial use.
U.S. Pat. No. 5,227,425 discloses a sulfur-vulcanizable rubber composition obtained by thermomechanical working of a conjugated diene compound and an aromatic vinyl compound prepared by solution polymerization in a hydrocarbon solvent having a total content of aromatic vinyl compound of between 5 percent and 50 percent and a glass transition temperature (Tg) of between 0° C. and −80° C. with 30 to 150 parts by weight per 100 parts by weight of elastomer of a silica having a BET surface area of between 100 and 250 m 2 /g, a CTAB surface area of between 100 and 250 m 2 /g, an oil absorption measured in DBP of between 150 and 250 ml/100 g and an average projected area of the aggregates greater than 8500 nm 2 before use and between 7000 and 8400 nm2 after thermomechanical mixing as well as the additives conventionally employed, with the exception of the sulfur vulcanization system, comprising at least one heat step reaching a temperature of between 130° C. and 180° C. for a suitable period of time of between 10 seconds and 20 minutes which is a function of the temperature selected in order to carry out the mechanical work and of the nature and volume of the components subjected to the mechanical work, followed by a finishing step consisting of the incorporating of the vulcanization system by mechanical work at a temperature below the vulcanization temperature. However, it is essential to utilize a rubbery polymer containing a vinyl aromatic monomer made by solution polymerization, such as solution SBR, in such tire tread compositions.
SUMMARY OF THE INVENTION
The present invention relates to a tire tread compound that is highly loaded with silica. This compound offers the advantages of silica compounding without the need for solution SBR. More specifically, the tire tread rubber formulations of this invention offer an excellent combination of traction, treadwear and rolling resistance characteristics. The highly silica-loaded tread rubber formulations of this invention are comprised of (1) high vinyl polybutadiene rubber and (2) tin-coupled isoprene-butadiene rubber.
The present invention reveals a rubber formulation which is comprised of (1) 10 phr to 35 phr of high vinyl polybutadiene rubber having a glass transition temperature which is within the range of −40° C. to 10° C., (2) 65 phr to 90 phr of tin-coupled isoprene-butadiene rubber having a glass transition temperature which is within the range of−90° C. to −70° C., (3) 30 phr to 90 phr of silica, (4) 5 phr to 50 phr of carbon black, (5) 2 phr to 50 phr of processing oil and (6) 0.5 phr to 15 phr of a silica coupling agent.
The subject invention further discloses a tire which is comprised of a generally toroidal-shaped carcass with an outer circumferential tread, two spaced beads, at least one ply extending from bead to bead and sidewalls extending radially from and connecting said tread to said beads; wherein said tread is adapted to be ground-contacting; wherein the tread is comprised of (1) 10 phr to 35 phr of high vinyl polybutadiene rubber having a glass transition temperature which is within the range of −40° C. to 10° C., (2) 65 phr to 90 phr of tin-coupled isoprene-butadiene rubber having a glass transition temperature which is within the range of −90° C. to −70° C., (3) 30 phr to 90 phr of silica, (4) 5 phr to 50 phr of carbon black, (5) 2 phr to 50 phr of processing oil and (6) 0.5 phr to 15 phr of a silica coupling agent.
DETAILED DESCRIPTION OF THE INVENTION
The tire tread formulations of this invention are made by blending (1) 10 phr (parts by weight per 100 parts by weight of rubber) to 35 phr of high vinyl polybutadiene rubber having a glass transition temperature which is within the range of −40° C. to 10° C., (2) 65 phr to 90 phr of tin-coupled isoprene-butadiene rubber having a glass transition temperature which is within the range of −90° C. to −70° C., (3) 30 phr to 90 phr of silica, (4) 5 phr to 50 phr of carbon black, (5) 2 phr to 50 phr of processing oil and (6) 0.5 phr to 15 phr of a silica coupling agent. The tire tread formulations of this invention will normally contain 20 phr to 35 phr of the high vinyl polybutadiene rubber and 65 phr to 80 phr of the tin-coupled isoprene-butadiene rubber. It is normally preferred for the tire tread formulations of this invention will normally 25 phr to 35 phr of the high vinyl polybutadiene rubber and 65 phr to 75 phr of the tin coupled isoprene-butadiene rubber.
The rubber blends of this invention can be compounded utilizing conventional ingredients and standard techniques. For instance, the tread rubber blends of this invention will typically be mixed with sulfur, accelerators, waxes, scorch inhibiting agents and processing aids. In most cases, the tread rubber blends will be compounded with sulfur and/or a sulfur containing compound, at least one accelerator, at least one antidegradant, zinc oxide, optionally a tackifier resin, optionally a reinforcing resin, optionally one or more fatty acids, optionally a peptizer and optionally one or more scorch inhibiting agents. Such blends will normally contain from about 0.5 to 5 phr (parts per hundred parts of rubber by weight) of sulfur and/or a sulfur containing compound with 1 phr to 2.5 phr being preferred. It may be desirable to utilize insoluble sulfur in cases where bloom is a problem.
Silica and carbon black will both be included as fillers in the tread formulations of this invention. From 30 phr to 90 phr of silica will be included in the blend. At high silica loading, it is only necessary to include a small amount of carbon black in the blend to give the tire a traditional black color. For instance, at high silica loadings, it is only necessary to include about 5 phr of carbon black in the rubber compound. Normally, from 40 phr to 80 phr of silica will be included in the blend to attain the desired tire performance characteristics. In most cases, it is preferred to include 50 phr to 75 phr of silica in the tread rubber compound. The amount of carbon black included in the blend will typically be within the range of 5 phr to 50 phr. In cases where at least 40 phr of silica are included in the blend, it will be desirable to limit the amount of carbon black in the blend to no more than 20 phr. In cases where at least 50 phr of silica are included in the blend, it will be desirable to limit the amount of carbon black in the blend to no more than 10 phr. Clays and/or talc can be included in the filler to reduce cost.
The blend will also normally include from 0.1 to 2.5 phr of at least one accelerator with 0.2 to 1.5 phr being preferred. Antidegradants, such as antioxidants and antiozonants, will generally be included in the tread compound blend in amounts ranging from 0.25 to 10 phr with amounts in the range of 1 to 5 phr being preferred. Processing oils will be included in the blend in amounts ranging from 2 to 50 phr with amounts ranging from 5 to 20 phr being preferred. The tread rubber blends of this invention will also normally contain from 0.5 to 10 phr of zinc oxide with 1 to 5 phr being preferred. These blends can optionally contain from 0 to 10 phr of tackifier resins, 0 to 10 phr of reinforcing resins, 1 to 10 phr of fatty acids, 0 to 2.5 phr of peptizers and 0 to 1 phr of scorch inhibiting agents.
To fully realize the advantages of the tread rubber formulations of this invention, it is critical to include a silica coupling agent therein. More specifically, the processing of the tread rubber compound is conducted in the presence of a sulfur containing organosilicon compound to realize maximum benefits. Examples of suitable sulfur containing organosilicon compounds are of the formula:
Z—Alk—Sn—Alk—Z (I)
in which Z is selected from the group consisting of
wherein R 1 is an alkyl group containing from 1 to 4 carbon atoms, a cyclohexyl group or a phenyl group; wherein R 2 is alkoxy group containing from 1 to 8 carbon atoms or a cycloalkoxy group containing from 5 to 8 carbon atoms; wherein Alk represents a divalent hydrocarbon containing from 1 to 18 carbon atoms; and wherein n represents an integer from 2 to 8.
Specific examples of sulfur containing organosilicon compounds which may be used in accordance with the present invention include: 3,3′-bis(trimethoxysilylpropyl) disulfide, 3,3′-bis(triethoxysilylpropyl) tetrasulfide, 3,3′-bis(triethoxysilylpropyl) octasulfide, 3,3′--bis(trimethoxysilylpropyl) tetrasulfide, 2,2′-bis(triethoxysilylethyl) tetrasulfide, 3,3′--bis(trimethoxysilylpropyl) trisulfide, 3,3′-bis(triethoxysilylpropyl) trisulfide, 3,3′--bis(tributoxysilylpropyl) disulfide, 3,3′-bis(trimethoxysilylpropyl) hexasulfide, 3,3′-bis(trimethoxysilylpropyl) octasulfide, 3,3′-bis(trioctoxysilylpropyl) tetrasulfide, 3,3′-bis(trihexoxysilylpropyl) disulfide, 3,3′-bis(tri-2″-ethylhexoxysilyipropyl) trisulfide, 3,3′-bis(triisooctoxysilylpropyl) tetrasulfide, 3,3′-bis(tri-t-butoxysilylpropyl) disulfide, 2,2′-bis(methoxy diethoxy silyl ethyl) tetrasulfide, 2,2′-bis(tripropoxysilylethyl) pentasulfide, 3,3′-bis(tricyclonexoxysilylpropyl) tetrasulfide, 3,3′-bis(tricyclopentoxysilylpropyl) trisulfide, 2,2′-bis(tri-2″-methylcyclohexoxysilylethyl) tetrasulfide, bis(trimethoxysilylmethyl) tetrasulfide, 3-methoxy ethoxy propoxysilyl 3′-diethoxybutoxy-silylpropyltetrasulfide, 2,2′-bis(dimethyl methoxysilylethyl) disulfide, 2,2′-bis(dimethyl sec.butoxysilylethyl) trisulfide, 3,3′-bis(methyl butylethoxysilylpropyl) tetrasulfide, 3,3′-bis(di t-butylmethoxysilylpropyl) tetrasulfide, 2,2′-bis(phenyl methyl methoxysilylethyl) trisulfide, 3,3′-bis(diphenyl isopropoxysilylpropyl) tetrasulfide, 3,3′-bis(diphenyl cyclohexoxysilylpropyl) disulfide, 3,3′-bis(dimethyl ethylmercaptosilylpropyl) tetrasulfide, 2,2′-bis(methyl dimethoxysilylethyl) trisulfide, 2,2′-bis(methyl ethoxypropoxysilylethyl) tetrasulfide, 3,3′-bis(diethyl methoxysilylpropyl) tetrasulfide, 3,3′-bis(ethyl di-sec. butoxysilylpropyl) disulfide, 3,3′-bis(propyl diethoxysilylpropyl) disulfide, 3,3′-bis(butyl dimethoxysilylpropyl) trisulfide, 3,3′-bis(phenyl dimethoxysilylpropyl) tetrasulfide, 3-phenyl ethoxybutoxysilyl 3′-trimethoxysilylpropyl tetrasulfide, 4,4′-bis(trimethoxysilylbutyl) tetrasulfide, 6,6′-bis(triethoxysilylhexyl) tetrasulfide, 12,12′-bis(triisopropoxysilyl dodecyl) disulfide, 18,18′-bis(trimethoxysilyloctadecyl) tetrasulfide, 18,18′-bis(tripropoxysilyloctadecenyl) tetrasulfide, 4,4′-bis(trimethoxysilyl-buten-2-yl) tetrasulfide, 4,4′-bis(trimethoxysilylcyclohexylene) tetrasulfide, 5,5′-bis(dimethoxymethylsilylpentyl) trisulfide, 3,3′-bis(trimethoxysilyl-2-methylpropyl) tetrasulfide and 3,3′-bis(dimethoxyphenylsilyl-2-methylpropyl) disulfide.
The preferred sulfur containing organosilicon compounds are the 3,3′-bis(trimethoxy or triethoxy silylpropyl) sulfides. The most preferred compound is 3,3′-bis(triethoxysilylpropyl) tetrasulfide. Therefore, as to Formula I, preferably Z is
wherein R 2 represents an alkoxy group containing from 2 to 4 carbon atoms, with 2 carbon atoms being particularly preferred; wherein Alk represents a divalent hydrocarbon containing from 2 to 4 carbon atoms with 3 carbon atoms being particularly preferred; and wherein n represents an integer from 3 to 5 with 4 being particularly preferred.
The amount of the sulfur containing organosilicon compound of Formula I in a rubber composition will vary depending on the level of silica that is used. Generally speaking, the amount of the compound of Formula I will range from about 0.01 to about 1.0 parts by weight per part by weight of the silica. Preferably, the amount will range from about 0.02 to about 0.4 parts by weight per part by weight of the silica. More preferably, the. amount of the compound of Formula I will range from about 0.05 to about 0.25 parts by weight per part by weight of the silica.
It is to be appreciated that the silica coupler may be used in conjunction with a carbon black; namely, pre-mixed with a carbon black prior to addition to the rubber composition, and such carbon black is to be included in the aforesaid amount of carbon black for the rubber composition formulation. In any case, the total quantity of silica and carbon black will be at least about 30 phr. The combined weight of the silica and carbon black may be as low as about 30 phr but is preferably from about 45 to about 130 phr.
The commonly employed siliceous pigments used in rubber compounding applications can be used as the silica. For instance, the silica can include pyrogenic and precipitated siliceous pigments (silica), although precipitate silicas are preferred. The siliceous pigments preferably employed in this invention are precipitated silicas such as, for example, those obtained by the acidification of a soluble silicate, e.g., sodium silicate.
Such silicas might be characterized, for example, by having a BET surface area, as measured using nitrogen gas, preferably in the range of about 40 to about 600, and more usually in a range of about 50 to about 300 square meters per gram. The BET method of measuring surface area is described in the Journal of the American Chemical Society, Volume 60, page 304 (1930).
The silica may also be typically characterized by having a dibutylphthalate (DBP) absorption value in a range of about 100 to about 400, and more usually about 150 to about 300. The silica might be expected to have an average ultimate particle size, for example, in the range of 0.01 to 0.05 micron as determined by the electron microscope, although the silica particles may be even smaller, or possibly larger, in size.
Various commercially available silicas may be considered for use in this invention such as, only for example herein, and without limitation, silicas commercially available from PPG Industries under the Hi-Sil trademark with designations 210, 243, etc; silicas available from Rhone-Poulenc, with, for example, designations of Z1165MP and Z165GR and silicas available from Degussa AG with, for example, designations VN2 and VN3.
Tire tread formulations which include silica and an organosilicon compound will typically be mixed utilizing a thermomechanical mixing technique. The mixing of the tire tread rubber formulation can be accomplished by methods known to those having skill in the rubber mixing art. For example, the ingredients are typically mixed in at least two stages; namely, at least one non-productive stage followed by a productive mix stage. The final curatives including sulfur vulcanizing agents are typically mixed in the final stage which is conventionally called the “productive” mix stage in which the mixing typically occurs at a temperature, or ultimate temperature, lower than the mix temperature(s) than the preceding non-productive mix stage(s). The rubber, silica and sulfur containing organosilicon, and carbon black if used, are mixed in one or more non-productive mix stages. The terms “non-productive” and “productive” mix stages are well known to those having skill in the rubber mixing art. The sulfur vulcanizable rubber composition containing the sulfur containing organosilicon compound, vulcanizable rubber and generally at least part of the silica should be subjected to a thermomechanical mixing step. The thermomechanical mixing step generally comprises a mechanical working in a mixer or extruder for a period of time suitable in order to produce a rubber temperature between 140° C. and 190° C. The appropriate duration of the thermomechanical working varies as a function of the operating conditions and the volume and nature of the components. For example, the thermomechanical working may be for a duration of time which is within the range of about 2 minutes to about 20 minutes. It will normally be preferred for the rubber to reach a temperature which is within the range of about 145° C. to about 180° C. and to be maintained at said temperature for a period of time which is within the range of about 4 minutes to about 12 minutes. It will normally be more preferred for the rubber to reach a temperature which is within the range of about 155° C. to about 170° C. and to be maintained at said temperature for a period of time which is within the range of about 5 minutes to about 10 minutes.
Tire tread compounds made using the tread rubber compounds of this invention can be used in tire treads in conjunction with ordinary tire manufacturing techniques. Tires are built utilizing standard procedures with the rubber compounds of this invention simply being substituted for the rubber compounds typically used as the tread rubber. After the tire has been built with the rubber compounds of this invention, it can be vulcanized using a normal tire cure cycle. Tires made in accordance with this invention can be cured over a wide temperature range. However, it is generally preferred for the tires to be cured at a temperature ranging from about 132° C. (270° F.) to about 166° C. (330° F.). It is more typical for the tires of this invention to be cured at a temperature ranging from about 143° C. (290° F.) to about 154° C. (310° F.). It is generally preferred for the cure cycle used to vulcanize the tires to have a duration of about 10 to about 20 minutes with a cure cycle of about 12 to about 18 minutes being most preferred.
Synthesis of the High Vinyl Polybutadiene Rubber
U.S. patent application Ser. No. 09/227,367, filed on Jan. 8, 1999, discloses a process for preparing high vinyl polybutadiene rubber that can be utilized in the tire tread rubber formulations of this invention. The teachings of U.S. patent application Ser. No. 09/227,367 are incorporated herein by reference in their entirety. The technique disclosed therein involves polymerizing 1,3-butadiene monomer with a lithium initiator at a temperature which is within the range of about 5° C. to about 100° C. in the presence of a metal salt of a cyclic alcohol and a polar modifier, wherein the molar ratio of the metal salt of the cyclic alcohol to the polar modifier is within the range of about 0.1:1 to about 10:1; and wherein the molar ratio of the metal salt of the cyclic alcohol to the lithium initiator is within the range of about 0.05:1 to about 10:1.
The polymerization used in synthesizing the high vinyl polybutadiene rubber is normally carried out as a solution polymerization in an inert organic medium utilizing a lithium catalyst. However, metal salts of cyclic alcohols can also be employed as modifiers for bulk polymerizations or vapor phase polymerizations. The vinyl content of the polybutadiene rubber made is controlled by the amount of modifier present during the polymerization.
In solution polymerizations, the inert organic medium which is utilized as the solvent will typically be a hydrocarbon which is liquid at ambient temperatures which can be one or more aromatic, paraffinic or cycloparaffinic compounds. These solvents will normally contain from 4 to 10 carbon atoms per molecule and will be liquids under the conditions of the polymerization. It is, of course, important for the solvent selected to be inert. The term “inert” as used herein means that the solvent does not interfere with the polymerization reaction or react with the polymers made thereby. Some representative examples of suitable organic solvents include pentane, isooctane, cyclohexane, normal hexane, benzene, toluene, xylene, ethylbenzene and the like, alone or in admixture. Saturated aliphatic solvents, such as cyclohexane and normal hexane, are most preferred.
The lithium catalysts which can be used are typically organolithium compounds. The organolithium compounds which are preferred can be represented by the formula R-Li, wherein R represents a hydrocarbyl radical containing from 1 to about 20 carbon atoms. Generally, such monofunctional organolithium compounds will contain from 1 to about 10 carbon atoms. Some representative examples of organolithium compounds which can be employed include methyllithium, ethyllithium, isopropyllithium, n-butyllithium, sec-butyllithium, n-octyllithium, tert-octyllithium, n-decyllithium, phenyllithium, 1-napthyllithium, 4-butylphenyllithium, p-tolyllithium, 1-naphthyllithium, 4-butylphenyllithium, p-tolyllithium, 4-phenylbutyllithium, cyclohexyllithium, 4-butylcyclohexyllithium and 4-cyclohexylbutyllithium. Organo monolithium compounds, such as alkyllithium compounds and aryllithium compounds, are usually employed. Some representative examples of preferred organo monolithium compounds that can be utilized include ethylaluminum, isopropylaluminum, n-butyllithium, secondary-butyllithium, normal-hexyllithium, tertiary-octyllithium, phenyllithium, 2-napthyllithium, 4-butylphenyllithium, 4-phenylbutyllithium, cyclohexyllithium, and the like. Normal-butyllithium and secondary-butyllithium are highly preferred lithium initiators.
The amount of lithium catalyst utilized will vary from one organolithium compound to another and with the molecular weight that is desired for the high vinyl polybutadiene rubber being synthesized. As a general rule in all anionic polymerizations, the molecular weight (Mooney viscosity) of the polymer produced is inversely proportional to the amount of catalyst utilized. As a general rule, from about 0.01 phm (parts per hundred parts by weight of monomer) to 1 phm of the lithium catalyst will be employed. In most cases, from 0.01 phm to 0.1 phm of the lithium catalyst will be employed with it being preferred to utilize 0.025 phm to 0.07 phm of the lithium catalyst.
Normally, from about 5 weight percent to about 35 weight percent of the 1,3-butadiene monomer will be charged into the polymerization medium (based upon the total weight of the polymerization medium including the organic solvent and monomer). In most cases, it will be preferred for the polymerization medium to contain from about 10 weight percent to about 30 weight percent monomer. It is typically more preferred for the polymerization medium to contain from about 20 weight percent to about 25 weight percent monomer.
The polymerization temperature will normally be within the range of about 5° C. to about 100° C. For practical reasons and to attain the desired microstructure, the polymerization temperature will preferably be within the range of about 40° C. to about 90° C. Polymerization temperatures within the range of about 60° C. to about 90° C. are most preferred. The microstructure of the high vinyl polybutadiene is somewhat dependent upon the polymerization temperature.
The polymerization is allowed to continue until essentially all of the 1,3-butadiene monomer has been exhausted. In other words, the polymerization is allowed to run to completion. Since a lithium catalyst is employed to polymerize the 1,3-butadiene monomer, a living polymer is produced. The living polymer synthesized will have a number average molecular weight that is within the range of about 25,000 to about 700,000; The rubber synthesized will more typically have a number average molecular weight that is within the range of about 150,000 to about 400,000.
To increase the level of vinyl content, the polymerization is carried out in the presence of at least one polar modifier. Ethers and tertiary amines which act as Lewis bases are representative examples of polar modifiers that can be utilized. Some specific examples of typical polar modifiers include diethyl ether, di-n-propyl ether, diisopropyl ether, di-n-butyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, triethylene glycol dimethyl ether, trimethylamine, triethylamine, N,N,N′,N′-tetramethylethylenediamine, N-methyl morpholine, N-ethyl morpholine, N-phenyl morpholine and the like.
The modifier can also be a 1,2,3-trialkoxybenzene or a 1,2,4-trialkoxybenzene. Some representative examples of 1,2,3-trialkoxybenzenes that can be used include 1,2,3-trimethoxybenzene, 1,2,3-triethoxybenzene, 1,2,3-tributoxybenzene, 1,2,3-trihexoxybenzene, 4,5,6-trimethyl-1,2,3-trimethoxybenzene, 4,5,6-tri-n-pentyl-1,2,3-triethoxybenzene, 5-methyl-1,2,3-trimethoxybenzene and 5-propyl-1,2,3-trimethoxybenzene. Some representative examples of 1,2,4-trialkoxybenzenes that can be used include 1,2,4-trimethoxybenzene, 1,2,4-triethoxybenzene, 1,2,4-tributoxybenzene, 1,2,4-tripentoxybenzene, 3,5,6-trimethyl-1,2,4-trimethoxybenzene, 5-propyl-1,2,4-trimethoxybenzene, and 3,5-dimethyl-1,2,4-trimethoxybenzene. Dipiperidinoethane, dipyrrolidinoethane, tetramethylethylene diamine, diethylene glycol, dimethyl ether and tetrahydrofuran are representative of highly preferred modifiers. U.S. Pat. No. 4,022,959 describes the use of ethers and tertiary amines as polar modifiers in greater detail.
The utilization of 1,2,3-trialkoxybenzenes and 1,2,4-trialkoxybenzenes as modifiers is described in greater detail in U.S. Pat. No. 4,696,986. The teachings of U.S. Pat. No. 4,022,959 and U.S. Pat. No. 4,696,986 are incorporated herein by reference in their entirety. The microstructure of the repeat units that are derived from butadiene monomer is a function of the polymerization temperature and the amount of polar modifier present. For example, it is known that higher temperatures result in lower vinyl contents (lower levels of 1,2-microstructure). Accordingly, the polymerization temperature, quantity of modifier and specific modifier selected will be determined with the ultimate desired microstructure of the polybutadiene rubber being synthesized being kept in mind.
It has been found that a combination of a metal salt of a cyclic alcohol and a polar modifier act synergistically to increase the vinyl content of rubbery polymer synthesized in their presence. The utilization of this synergistic modifier system can also be employed advantageously in the synthesis of the high vinyl polybutadiene rubber.
The metal salt of the cyclic alcohol will typically be a Group Ia metal salt. Lithium, sodium, potassium, rubidium, and cesium salts are representative examples of such salts with lithium, sodium and potassium salts being preferred. Sodium salts are typically the most preferred. The cyclic alcohol can be mono-cyclic, bi-cyclic or tri-cyclic and can be aliphatic or aromatic. They can be substituted with 1 to 5 hydrocarbon moieties and can also optionally contain hetero-atoms. For instance, the metal salt of the cyclic alcohol can be a metal salt of a di-alkylated cyclohexanol, such as 2-isopropyl-5-methylcyclohexanol or 2-t-butyl-5-methylcyclohexanol. These salts are preferred because they are soluble in hexane. Metal salts of disubstituted cyclohexanol are highly preferred because they are soluble in hexane and provide similar modification efficiencies to sodium t-amylate. Sodium mentholate is the most highly preferred metal salt of a cyclic alcohol that can be employed in the practice of this invention. Metal salts of thymol can also be utilized. The metal salt of the cyclic alcohol can be prepared by reacting the cyclic alcohol directly with the metal or another metal source, such as sodium hydride, in an aliphatic or aromatic solvent.
The molar ratio of the metal salt of the cyclic alcohol to the polar modifier will normally be within the range of about 0.1:1 to about 10:1 and the molar ratio of the metal salt of the cyclic alcohol to the lithium initiator will normally be within the range of about 0.01:1 to about 20:1. It is generally preferred for the molar ratio of the metal salt of the cyclic alcohol to the polar modifier to be within the range of about 0.2:1 to about 5:1 and for the molar ratio of the metal salt of the cyclic alcohol to the lithium initiator to be within the range of about 0.05:1 to about 10:1. It is generally more preferred for the molar ratio of the metal salt of the cyclic alcohol to the polar modifier to be within the range of about 0.5:1 to about 1:1 and for the molar ratio of the metal salt of the cyclic alcohol to the lithium initiator to be within the range of about 0.2:1 to about 3:1.
After the polymerization has been completed, the living high vinyl polybutadiene rubber can optionally be coupled with a suitable coupling agent, such as a tin tetrahalide or a silicon tetrahalide. The high vinyl polybutadiene rubber is then recovered from the organic solvent. The high vinyl polybutadiene rubber can be recovered from the organic solvent and residue by any means, such as decantation, filtration, centrification and the like. It is often desirable to precipitate the high vinyl polybutadiene rubber from the organic solvent by the addition of lower alcohols containing from about 1 to about 4 carbon atoms to the polymer solution. Suitable lower alcohols for precipitation of the high vinyl polybutadiene rubber from the polymer cement include methanol, ethanol, isopropyl alcohol, normal-propyl alcohol and t-butyl alcohol. The utilization of lower alcohols to precipitate the high vinyl polybutadiene rubber from the polymer cement also “kills” the living polymer by inactivating lithium end groups. After the high vinyl polybutadiene rubber is recovered from the solution, steam-stripping can be employed to reduce the level of volatile organic compounds in the polymer. The inert solvent and residual monomer can then be recycled for subsequent polymerization.
Synthesis of the Tin-Coupled Isoprene-Butadiene Rubber
The tin-coupled isoprene-butadiene rubber will typically have a Mooney ML 1+4 viscosity which is within the range of about 5 to about 40 before coupling and a Mooney ML 1+4 viscosity of about 60 to about 120 after coupling. The tin-coupled isoprene-butadiene rubber will preferably have a Mooney ML 1+4 viscosity that is within the range of about 5 to about 35 before coupling and a Mooney ML 1+4 viscosity of about 75 to about 110 after coupling. The tin-coupled isoprene-butadiene will most preferably have a Mooney ML 1+4 viscosity that is within the range of about 10 to about 30 before coupling and a Mooney ML 1+4 viscosity of about 80 to about 100 after coupling.
The tin-coupled isoprene-butadiene rubber will typically be prepared by reacting “living” isoprene-butadiene rubber having lithium end groups with a tin halide, such as tin tetrachloride. This coupling step will normally be carried out as a batch process. However, it is generally preferred to tin-couple the isoprene-butadiene rubber in a continuous process that results in the formation of asymmetrically tin-coupled isoprene-butadiene rubber. A technique for producing asymmetrically tin-coupled isoprene-butadiene rubber is disclosed in U.S. Provisional Patent Application Ser. No. 60/037,929, filed on February 14, 1997. The teachings of U.S. Provisional Patent Application Ser. No. 60/037,929 are hereby incorporated herein by reference in their entirety.
The tin coupling agent employed in making asymmetrically tin-coupled isoprene-butadiene rubber will normally be a tin tetrahalide, such as tin tetrachloride, tin tetrabromide, tin tetrafluoride or tin tetraiodide. However, tin trihalides can also optionally be used. In cases where tin trihalides are utilized, a coupled polymer having a maximum of three arms results. To induce a higher level of branching, tin tetrahalides are normally preferred. As a general rule, tin tetrachloride is most preferred.
Broadly, and exemplary, a range of about 0.01 to 4.5 milliequivalents of tin coupling agent is employed per 100 grams of the rubbery polymer. It is normally preferred to utilize about 0.01 to about 1.5 milliequivalents of the tin coupling agent per 100 grams of polymer to obtain the desired Mooney viscosity. The larger quantities tend to result in production of polymers containing terminally reactive groups or insufficient coupling. One equivalent of tin coupling agent per equivalent of lithium is considered an optimum amount for maximum branching. For instance, if a tin tetrahalide is used as the coupling agent, one mole of the tin tetrahalide would be utilized per four moles of live lithium ends. In cases where a tin trihalide is used as the coupling agent, one mole of the tin trihalide will optimally be utilized for every three moles of live lithium ends. The tin coupling agent can be added in a hydrocarbon solution (e.g., in cyclohexane) to the polymerization admixture in the reactor with suitable mixing for distribution and reaction.
After the tin coupling has been completed, a tertiary chelating alkyl 1,2-ethylene diamine can optionally be added to the polymer cement to stabilize the tin-coupled rubbery polymer. This technique for stabilization of the tin-coupled rubber is more fully described in U.S. Pat. No. 5,739,182. The teachings of U.S. Pat. No. 5,739,182 are incorporated herein by reference in their entirety. The tertiary chelating amines that can be used for stabilization are normally chelating alkyl diamines of the structural formula:
wherein n represents an integer from 1 to about 6, wherein A represents an alkane group containing from 1 to about 6 carbon atoms and wherein R 1 , R 2 , R 3 and R 4 can be the same or different and represent alkane groups containing from 1 to about 6 carbon atoms. The alkane group A is the formula CH 2 m wherein m is an integer from 1 to about 6. The alkane group will typically contain from 1 to 4 carbon atoms (m will be 1 to 4) and will preferably contain 2 carbon atoms. In most cases, n will be an integer from 1 to about 3 with it being preferred for n to be 1. It is preferred for R 1 , R 2 , R 3 and R 4 to represent alkane groups which contain from 1 to 3 carbon atoms. In most cases, R 1 , R 2 , R 3 and R 4 will represent methyl groups.
A sufficient amount of the chelating amine should be added to complex with any residual tin coupling agent remaining after completion of the coupling reaction. In most cases, from about 0.01 phr (parts by weight per 100 parts by weight of dry rubber) to about 2 phr of the chelating alkyl 1,2-ethylene diamine will be added to the polymer cement to stabilize the rubbery polymer. Typically, from about 0.05 phr to about 1 phr of the chelating alkyl 1,2-ethylene diamine will be added. More typically, from about 0.1 phr to about 0.6 phr of the chelating alkyl 1,2-ethylene diamine will be added to the polymer cement to stabilize the rubbery polymer.
After the polymerization, asymmetrical tin coupling and optionally the stabilization step has been completed, the tin-coupled isoprene-butadiene rubber can be recovered from the organic solvent utilized in the solution polymerization. The tin-coupled rubbery polymer can be recovered from the organic solvent and residue by means such as decantation, filtration, centrification and the like. It is often desirable to precipitate the tin-coupled rubbery polymer from the organic solvent by the addition of lower alcohols containing from about 1 to about 4 carbon atoms to the polymer solution. Suitable lower alcohols for precipitation of the rubber from the polymer cement include methanol, ethanol, isopropyl alcohol, normal-propyl alcohol and t-butyl alcohol. The utilization of lower alcohols to precipitate the tin-coupled rubbery polymer from the polymer cement also “kills” any remaining living polymer by inactivating lithium end groups. After the tin-coupled rubbery polymer is recovered from the solution, steam-stripping can be employed to reduce the level of volatile organic compounds in the tin-coupled rubbery polymer.
The asymmetrical tin-coupled isoprene-butadiene rubber that can be employed in the blends of this invention are comprised of a tin atom having at least three isoprene-butadiene arms covalently bonded thereto. At least one of the isoprene-butadiene arms bonded to the tin atom has a number average molecular weight of less than about 40,000 and at least one of the isoprene-butadiene arms bonded to the tin atom has a number average molecular weight of at least about 80,000. The ratio of the weight average molecular weight to the number average molecular weight of the asymmetrical tin-coupled isoprene-butadiene rubber will also normally be within the range of about 2 to about 2.5.
The asymmetrical tin-coupled isoprene-butadiene rubber that can be utilized in the blends of this invention is typically of the structural formula:
wherein R 1 , R 2 , R 3 and R 4 can be the same or different and are selected from the group consisting of alkyl groups and isoprene-butadiene arms (isoprene-butadiene rubber chains), with the proviso that at least three members selected from the group consisting of R 1 , R 2 , R 3 and R 4 are isoprene-butadiene arms, with the proviso that at least one member selected from the group consisting of R 1 , R 2 , R 3 and R 4 is a low molecular weight isoprene-butadiene arm having a number average molecular weight of less than about 40,000, with the proviso that at least one member selected from the group consisting of R 1 , R 2 , R 3 and R 4 is a high molecular weight isoprene-butadiene arm having a number average molecular weight of greater than about 80,000, and with the proviso that the ratio of the weight average molecular weight to the number average molecular weight of the asymmetrical tin-coupled isoprene-butadiene rubber is within the range of about 2 to about 2.5. It should be noted that R 1 , R 2 , R 3 and R 4 can be alkyl groups because it is possible for the tin halide coupling agent to react directly with alkyl lithium compounds which are used as the polymerization initiator.
In most cases, four isoprene-butadiene arms will be covalently bonded to the tin atom in the asymmetrical tin-coupled isoprene-butadiene rubber. In such cases, R 1 , R 2 , R 3 and R 4 will all be isoprene-butadiene arms. The asymmetrical tin-coupled isoprene-butadiene rubber will often contain an isoprene-butadiene arm of intermediate molecular weight as well as the low molecular weight arm and the high molecular weight arm. Such intermediate molecular weight arms will have a molecular weight which is within the range of about 45,000 to about 75,000. It is normally preferred for the low molecular isoprene-butadiene arm to have a molecular weight of less than about 30,000, with it being most preferred for the low molecular weight arm to have a molecular weight of less than about 25,000. It is normally preferred for the high molecular isoprene-butadiene arm to have a molecular weight of greater than about 90,000, with it being most preferred for the high molecular weight arm to have a molecular weight of greater than about 100,000.
This invention is illustrated by the following examples which are merely for the purpose of illustration and are not to be regarded as limiting the scope of the invention or the manner in which it can be practiced. Unless specifically indicated otherwise, all parts and percentages are given by weight.
EXAMPLE 1
In this experiment, 2300 g of a silica/alumina/molecular sieve dried premix containing 11.0 weight percent 1,3-butadiene was charged into a one-gallon (3.8 liters) reactor. After the impurity of 1.5 ppm was determined, 7.42 ml of 1 M solution of N,N,N′,N′-tetramethylethylene diamine (TMEDA) in hexanes, 0.21 ml of 1.12 M solution of sodium mentholate (SMT) in hexanes and 1.1 ml of a 1.03 M solution of n-butyllithium (n-BuLi) in hexanes (0.9 ml for initiation and 0.2 ml for scavenging the premix) were added to the reactor. The molar ratio of SMT to TMEDA and to n-BuLi was 0.25:8:1.
The polymerization was carried out at 65° C. for 10 minutes. The GC analysis of the residual monomer contained in the polymerization mixture indicated that the polymerization was complete at this time. Then one ml of 1 M ethanol solution in hexanes was added to shortstop the polymerization and polymer was removed from the reactor and stabilized with 1 phm of antioxidant. After evaporating hexanes, the resulting polymer was dried in a vacuum oven at 50° C.
The high vinyl polybutadiene produced was determined to have a glass transition temperature (Tg) at 25° C. It was then determined to have a microstructure which contained 85 percent 1,2-polybutadiene units and 15 percent 1,4-polybutadiene units. The Mooney ML-4 viscosity at 100° C. was 83 for this polybutadiene.
EXAMPLES 2-8
The procedure described in Example 1 was utilized in these examples except that the SMT/TMEDA/n-BuLi ratio was varied. The Tgs and ML-4s of the resulting polybutadienes are listed in Table I.
TABLE I
Example
SMT/TMEDS/n-BuLi Ratio
Tg (° C.)
ML-4
1
0.25:8:1
−25.4
83
2
0.25:5:1
−26.9
81
3
0.25:3:1
−28.9
87
4
0.25:1:1
−35.6
88
5
0.25:0.5:1
−49.2
88
6
0.15:3:1
−26.9
7
0.5:3:1
−26.5
81
8
1:3:1
−26.1
EXAMPLE 9 AND COMPARATIVE EXAMPLES 10 AND 11
In this experiment, a tire tread compound was made by blending 30 phr of high vinyl polybutadiene rubber having a glass transition temperature of −28° C., 70 phr of tin-coupled isoprene-butadiene rubber, 70 phr of silica, 11 phr of processing oil and 11 phr of a 50 percent/50 percent mixture of Si-69 silica coupling agent and carbon black. It was cured and physical properties were determined and compared to two control compounds. The first control compound (Comparative Example 10) contained 30 phr of high vinyl polybutadiene rubber having a glass transition temperature of −28° C., 70 phr of linear isoprene-butadiene rubber (IBR) having a glass transition temperature of−83° C. and a Mooney ML 1+4 viscosity of 85, 70 phr of silica, 11 phr processing oil and 11 phr of a 50 percent/50 percent mixture of Si-69 silica coupling agent and carbon black. The second control (Comparative Example 11) contained 30 phr of Budene7 1207 high cis-1,4-polybutadiene rubber, 70 phr of solution SBR having a glass transition temperature of −43° C., 70 phr of silica, 11 phr processing oil and 11 phr of a 50 percent/50 percent mixture of Si-69 silica coupling agent and carbon black. The physical properties of the blends are shown in Table II.
TABLE II
Comp
Comp
Ex 9
Ex 10
Ex. 11
high-cis-1,4-PBD-
30
solution SBR
—
70
high vinyl PBD
30
30
—
tin coupled IBR
70
—
linear IBR (Tg = −83° C.)
70
HiSil 210 silica
70
70
70
processing oil
11
11
11
silica coupling agent/
11
11
11
carbon black blend
Zwick Rebound @ 0° C.
30.0
28.2
26.2
Zwick Rebound @ 22° C.
48.4
48.5
46.7
tan delta @ 100□C & 11 Hz
0.117
0.112
0.111
DIN abrasion (2.5 N/10 N)
66/54
72/63
88/76
RPA G’ uncured @ 100° C.
214
366
353
& .333 Hz
Rheometer ML @ 150° C.
11.2
18
18
As can be seen from Table II, the tire tread formulation of this invention exhibited a lower level of DIN abrasion than did either of the controls. The lower level of DIN abrasion observed means that the tire tread composition of this invention can be used in making tire tread compounds that have improved tread wear characteristics. The tread compound of this invention had a Zwick rebound at 23° C. and tan delta at 100° C. which was essentially equivalent to the controls. This means that tire treads made with the compounds of this invention will exhibit rolling resistance which is equivalent to the controls. However, the tread rubber compound made in this example had a Zwick rebound at 0° C. which was slightly higher than was observed in the controls. This is indicative of a reduction in wet traction characteristics. Table II also shows that the tire tread formulation of this invention processed better than did the control formulations.
The tin coupled IBR containing tire tread compound made in this example offers outstanding tread wear and rolling resistance characteristics. It also offers superior processing with a slight reduction in wet traction characteristics. However, wet traction characteristics can be improved by increasing the ratio of high vinyl polybutadiene rubber to tin coupled IBR in the compound.
Variations in the present invention are possible in light of the description of it provided herein. It is, therefore, to be understood that changes can be made in the particular embodiments described which will be within the full intended scope of the invention as defined by the following appended claims.
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The present invention relates to a tire tread compound that is highly loaded with silica. This compound offers the advantages of silica compounding without the need for solution SBR. More specifically, the tire tread rubber formulations of this invention offer an excellent combination of traction, treadwear and rolling resistance characteristics. The subject invention discloses a tire which is comprised of a generally toroidal-shaped carcass with an outer circumferential tread, two spaced beads, at least one ply extending from bead to bead and sidewalls extending radially from and connecting said tread to said beads; wherein said tread is adapted to be ground-contacting; wherein the tread is comprised of (1) 10 phr to 35 phr of high vinyl polybutadiene rubber having a glass transition temperature which is within the range of −40° C. to 10° C., (2) 65 phr to 90 phr of tin-coupled isoprene-butadiene rubber having a glass transition temperature which is within the range of −90° C. to −70° C., (3) 30 phr to 90 phr of silica, (4) 5 phr to 50 phr of carbon black, (5) 2 phr to 50 phr of processing oil and (6) 0.5 phr to 15 phr of a silica coupling agent.
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BACKGROUND AND SUMMARY OF THE INVENTION
This invention relates in general to the broad field of shotgun cartridges and, more particularly, to cartridges provided with a quantity of germinative seeds. This is a continuation-in-part of my co-pending application Ser. No. 488,169 filed July 12, 1974 now abandoned.
Heretofore various efforts have been undertaken in the general field of horticulture to utilize the propellant charge of a shotshell or shotgun cartridge for distribution of plant nutrients, and pollen for fertilization of fruit and nut bearing trees, and the like. However, each of such attempts have replaced the normal shot charge of the cartridge with such nutrients or pollen so that the resultant cartridge is useful for but its single intended horticultural purpose. Reference may be made to the Farley Patents, U.S. Pat. Nos. 2,660,002 and 2,660,003 wherein the disclosed cartridge incorporates the pollinating charge within that portion of the shell which would normally contain the shot charge. In each instance the pollen is intermixed with a suitable quantity of an appropriate carrier which conduces to the distribution and constitutes the major portion of the particular charge. Another earlier effort is demonstrated by the Simmons U.S. Pat. No. 3,069,809 wherein the normally shot-containing chamber of the shell is filled with the particular plant nutrient or combination of nutrients which may be of solid or particulate character and wherein it was asserted that the power of the explosion of the propellant would tend to force the nutrients into plants without damage to such plants. Simmons also suggested nutrients in liquid form as encased within a tissue-thin rubber sack which was intended to rupture to allow the contained liquid to penetrate the plant. In each of the prior art efforts, there has been the necessity of incorporating a ballast for the particular charge. But to the present time, one has not developed a shotgun cartridge which concurrently is capable of being used for its intended purpose, as for hunting game, as well as for botanical purposes.
Therefore, it is an object of the present invention to provide a shot shell which incorporates a conventional shot charge, as well as a predetermined load of seed, whereby the shell may be used for customary hunting purposes as well as for simultaneously discharging seed for germinating purposes.
It is another object of the present invention to provide a shot shell of the character stated which may be of conventional character and readily loaded with a predetermined quantity of seed by the individual reloader.
It is another object of the present invention to provide a shot shell of the character stated wherein the components are so arranged that the discharged seed is in no way damaged or adversely affected by the burning of the powder or gases of explosion so that the same are capable of germination.
It is a further object of the present invention to provide a shot shell of the character stated wherein the seeds are retained within a water soluble sack or capsule so as to be restrained against indiscriminate dispersal upon firing and thereby be maintained for ultimate effective plant growth.
It is a still further object of the present invention to provide a shot shell incorporating a seed charge which may be most economically produced; does not entail modification of the shotgun cartridge embodying the normal components thereof; and which shell in usage is fully capable of accomplishing its dual purpose.
DESCRIPTION OF THE DRAWING
The FIGURE is a vertical sectional view of a shot shell constructed in accordance with and embodying the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now by reference characters to the drawing which illustrates the preferred embodiment of the present invention, A designates a shotgun shell or cartridge having the usual tubular body 1 fabricated of paper, plastic, metal or the like and having a suitably encased base, as at 2. Mounted within the base is a conventional primer 3 received within a base wad 4 which may, if desired, incorporate a base wad overlay 5; it being recognized that the latter is not critical to the present invention.
Provided above primer 3 is a propellant charge 6 and in immediate overlying relationship to said latter is an obturating wad 7 which is shown as incorporating a peripheral skirt 8. Provided above obturating wad 7 may be one or more filler or separator wads 9, fabricated of any suitable material, such as felt, pulp, or the like. Disposed upon filler wad 9 is a predetermined quantity or load of seed 10 encased within a thin-walled container or capsule 11 fabricated of a water soluble or moisture-rupturable material, such as gelatin, of the type which has found wide usage for medicinal capsules. Superimposed upon seed load 10 is a top filler wad 12, as of like character as wad 9, and with said wad 12 cooperating with the upper portion of body 1 to define a chamber 13 for a shot charge 14, as of multi-missile character, and being the usual type of shot for customary shotgun usage. A sealing or card wad 15 defines the upper limit of chamber 13 and with the upper end of shell A being closed in any well known manner, as by infolding of body 1, crimping, etc.
Although not of extreme criticality, it has been found that the seed load 10 may be of substantially like volume as the shot charge 14. However, it is recognized that the amount of seed may be obviously varied, as well as that of the shot charge and the amount of propellant charge depending upon the individual requirements of the reloaders.
The present invention is adapted for shotgun shell casings having gages extending throughout the gamut of gages presently available. With larger gages a single complementary seed load 10 could be utilized or, if desired, the seed load may be provided within a plurality of discrete, capsule units.
It is to be observed that seed load 10 is sandwiched between the shot charge and the propellant and being separated therefrom by one or more wads on either side. The number of wads utilized will, of course, be dependent upon the available types and the characteristics of the selected loading of the cartridge.
In actual practice, it has been clearly established that upon firing of cartridge A, seed load 10 has been sufficiently insulated so as not to be damaged or destroyed by the combustion of the powder charge, nor caused any interference with the dispersal of the shot so that the same may effect its designed pattern.
In usage, it will be seen that upon firing of cartridge A seed load 10 and shot charge 14 will be moved down the barrel of the firearm toward the muzzle and with the gases of explosion, on expanding, exerting an outward pressure upon skirt 8 to force same into sealing engagement with the gun barrel and thereby preventing gas leakage and concurrently coacting with filler wad 9 to prevent contact of such gases with seed load 10.
As stated above, shot 14 will upon emission from the firearm muzzle expand into its predetermined pattern and seed load 10 will follow its intended trajectory in fully integrated unitary character, with the gelatinous casing 11 unbroken. Thus, while the shot 14 travels toward the particular target of the firearm operator, seed load 10 will ultimately come to rest upon the ground for ultimate dissolution of casing 11 whereby the seeds 10 will be brought into contact with the soil for germination and ultimate plant growth. Experience has demonstrated conclusively that seed load 10 retains its germinating potential despite the firing of cartridge A. The loads 10 within their casing 11 have been retrieved, opened, and the seeds planted in an ordinary flower pot permitting of continual inspection. Within approximately one week such seeds germinated and growth of the plant commenced. Thus, the unique manner of disposing of the seed load within cartridge A has preserved the germinative potential of the seeds while simultaneously permitting the user to fire at any selected target, such as game or the like.
Therefore, the present invention brings about a duality of objects in permitting retention of the usual shotgun purpose, as well as providing for distribution of seed charges for ultimate plant replenishment as well as, conceivably, providing a limited source of nourishment to animals.
Seeds of all types may be utilized within the load 10 and evidentiary of this is the fact that milo seeds, cereal grass seeds, such as millet, sunflower seeds, and wheat seeds have all been utilized in actual practice and have been demonstrated to retain their viability.
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A cartridge for both hunting and seed distributing purposes comprising a cylindrical casing having a primer, a propellant charge ignitable upon firing of said primer, spaced-apart wads above said propellant charge defining a load-receiving volume therebetween, a load of plant seeds received within a capsule disposed within said volume; a multi-missile shot charge provided above said volume and means for enclosing the normally forward end of said cartridge.
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This Application is a continuation of application Ser. No. 08/371,282 filed Jan. 11, 1995 now abandoned, which application Ser. No. 08/371,282 is a Continuation-in-Part of application Ser. No. 08/225,375 filed Apr. 8, 1994 now abandoned for LINE HEAD FOR FLEXIBLE LINE TRIMMER, being incorporated herein for all purposes by reference.
FIELD OF INVENTION
The invention relates generally to vegetation cutters and more particularly to line heads for flexible line trimmers.
BACKGROUND OF THE INVENTION
To overcome what is generally perceived to be the major deficiency of flexible line trimmers, a great deal of effort has been directed in the past to methods of making replenishing broken cutting line more convenient for users without substantially complicating and increasing the cost of a line trimmer. A standard approach is to sell a supply of replacement line on a spool and have the user mount it in a line head that is coupled to the motor of the line trimmer. A line head typically includes a hub, coupled to the output shaft of a motor, and a housing or shroud extending outwardly from the hub and down around the spool to protect the spool from dirt and debris. The user places the spool on the hub, feeds a small length of line through an opening in the housing, and places a cover over the spool to retain and protect the spool within the line head. The spool is locked to the hub so that rapid spinning of the line head flails the line. When line breaks, the spool is unlocked and spun on the hub to unwind line through the opening.
Several methods have been used to lock and unlock the spool against the hub. Early line heads used a manual release mechanism. To replace line, the trimmer was stopped and turned upside down. The locking mechanism was released manually and the spool turned to unwind and feed line. To avoid having to stop and turn the trimmer upside to feed line, most current line heads have a "bump-feed" mechanism that indexes the spool through a predetermined angle of rotation each time it is bumped against the ground, thus allowing the user to feed a predetermined amount of line while the trimmer is running. There also exist line heads which automatically index the spool without any intervention of the user. Generally, these heads sense a change in the centrifugal force acting on a component of the spinning head or on the flailing line to release the spool for rotation and pay-out line when the line becomes short.
Though bump-feed and automatic line heads provide a great deal of convenience for the user, once a supply of flexible line on a spool is exhausted, the line trimmer must be turned on its side or upside down and held in an unwieldy position to replace the empty spool with another spool pre-wound with line and reattach the cover. Covers of line heads are often attached to the line head in a manner that demands such dexterity and strength to unfasten and remove that many users become frustrated by the task of replacing a spool.
One approach to make spool replacement easier is to locate the spool in the handle of the trimmer, near the user. Examples of these configurations are illustrated in U.S. Pat. No. 4,369,577 of Gise, et al. and U.S. Pat. No. 4,285,128 of Schnell, et al. However, the line must then be fed through the handle shaft of the trimmer motor and then through line head, replacing one potentially frustrating task with another. U.S. Pat. No. 4,633,588 to Pittinger, Jr., on the other hand, retains the spool in the line head, but attempts to provide for an improved spool fastening mechanism that does not require removal of a cover. Instead, its fastening mechanism is released through a pin extending through the bottom of the spool. This pin-actuated release mechanism has, however, several disadvantages. It has several moving parts and is relatively complicated. It thus tends to be more expensive to manufacture and is more susceptible to sticking or interference from accumulation of dirt and debris around the pin and the fastening mechanism. The spool could thus be prematurely released during use or the pin become very difficult to push to release the spool.
SUMMARY OF THE INVENTION
The invention is a line head for a flexible line trimmer having a spool retention mechanism that allows a spool to be removed from a line head in a single movement by a user simply pulling down on the spool. The spool may also be replaced in a single movement by pushing the spool into the line head. No fasteners need to be released or covers removed. Furthermore, the spool mechanism is simple, inexpensive to manufacture and assemble, and is less susceptible to the adverse effects of dirt and debris.
According to one aspect of the invention, a line head includes a retention member mounted within a downwardly facing socket defined within a hub in the center of the line head without extra fasteners. The retention member extends radially outwardly from the hub under the spool and engages the bottom of the spool. The spool is thus free to rotate and to move upwardly on the hub. Manually pushing a spool onto or pulling the spool off of the hub pushes the retention member radially inwardly, permitting the spool to be mounted and released in a single movement. The retention member is inserted through the bottom of the hub and snapped into place in a single movement, thus securing it against movement without separate fasteners such as screws.
In accordance with another aspect of the invention, the socket in the hub electrically insulates the retention member from the drive shaft of an AC electric motor to which the line head is attached. A metal arbor extending through the plastic injection molded hub is not necessary for attaching the retention member to the line head as no separate fastener is required to attach the retention member within the socket. The AC motor is thereby double insulated for safety.
In accordance with yet another aspect of the invention, a spool for a line head, which includes a hub formed around the spool's axis of rotation and disk-shaped flanges located on opposite ends of the hub extending perpendicularly to the axis of rotation, is specially adapted to reduce the tendency of line to "nest." A line "nests" when it becomes entangled in a manner that resembles a bird's nest. Nesting is a nuisance to a user. It interferes with replacing the spool in the line head and the line feeding operation of the line head. When the line is being wound, nesting will also tend to spread the flanges of the spool, which interferes with spool replacement and feeding line from the line head. To help to overcome this problem, a spool is formed with a series of grooves or ridges formed around the outer circumference of the hub, parallel to the flanges. The grooves or ridges tend to reduce lateral movement of inner layers of line as additional layers of line are wound and unwound over inner layers of line.
In a preferred embodiment, a retention member is a form of a spring which includes four legs extending downwardly when mounted within a socket of the hub. Two of the opposed legs flare outwardly through slots in a side wall of the hub and then back inwardly to form knob-shaped tabs depressible by application of pressure to the surfaces of the tabs in either direction parallel to the axis of the hub. When the spool is fully mounted on the hub, the bottom of the spool clears the tabs, allowing the tabs to spring outwardly and thereby retain the spool on the hub. Pushing a spool onto or pulling it from the hub depresses the tabs of the spring, releasing the spool. To retain the spring within the hub without the need for fasteners, the other two opposed legs of the spring are bent outwardly to form retaining tabs for fitting into slots within the sides of the socket. The spring is easily fabricated and installed in the hub of the line head by inserting the retention member into the socket, the retaining tabs snapping into the slots within the hub. It also has a minimal number of moving parts or surfaces, thus lessening the adverse effects of dirt and debris generated by using the line trimmer.
These and other features and advantages invention are described in or will be apparent from the following detailed description of the preferred embodiment of the invention as illustrated in the accompanying drawings.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a cross-section through a motor housing section of a flexible line trimmer and a line head, the line head split along its axis of rotation to show a spool in two axially displaced operating positions.
FIG. 2A is a cross-section of the line head of FIG. 1, illustrating the spool and button assembly fully removed from the line head.
FIG. 2B is a cross-section of the line head of FIG. 1 that illustrates the position of the spool and button assembly as it is being removed from or inserted into the line head.
FIG. 2C is a cross-section of the line head of FIGS. 1 and 3 with the spool and button assembly fully mounted within the line head.
FIG. 3 is a bottom plan view of the line head of FIG. 1 with a portion of a bottom wall of the spool partly removed.
FIG. 4 is a section of the line head illustrated in FIG. 3, taken along Section line 4--4.
FIG. 5 is an exploded view of a spool retention assembly portion in the line head of FIG. 1.
FIG. 6 is a section of an alternative embodiment of the line head.
FIG. 7 is an exploded perspective view of an alternative embodiment of the spool retention assembly in the line head of FIG. 6.
DESCRIPTION OF PREFERRED EMBODIMENTS
Like numbers refer to like parts in the following description.
Referring now to FIG. 1, an electric flexible line trimmer 100 includes an electric motor 102 mounted within motor housing 104. The motor housing is manufactured in two halves, the right half being removed for purposes of illustration. The motor's output shaft 103 is generally vertical with respect to the ground when the flexible line trimmer is held in a normal operating position. Tubular handle support tube 106 is attached to the upper end of the housing 104. The housing includes an integrally formed shield 107. Though not shown, mounted to the upper end of the handle support tube 106 is a handle with a trigger switch for turning on and off a flow of current to the motor. The trimmer may also include an auxiliary handle to assist in holding and maneuvering the trimmer. The electric flexible line trimmer illustrated is just one example of flexible line trimmers generally other types include those powered by internal combustion engines. Heavier engines are usually located at the opposite end of the support tube 106 for better balance and are coupled to the line head through a shaft extending through the middle of the support tube 106.
The output shaft 103 of motor 102 is coupled to a line head 108 through a metal arbor 110. The arbor includes a socket that receives the end of the output shaft 103 of the motor. The arbor is attached to a hub 114 of the line head for transmitting torque from the shaft 103 to the hub. Integrally formed with hub 114 is line head housing 112, formed from a circular skirt extending outwardly from the hub and then down around the hub. This cup-shaped housing defines a cavity in which a reel or spool 116 is mounted for rotation about the hub. The spool includes a hollow, cylindrical hub section 117 for mounting the spool on the hub 114 for rotation. The spool thus rotates on the hub about the same axis of rotation as the line head. The spool is normally wound with a supply of flexible, monofilament line (not shown). Bottom side wall 128 and top side wall 134 of the spool are integrally formed with the spool's hub 117 and assist in retaining line wound on the spool. Bottom side wall 128 is solid and also forms a bottom wall of the line head housing.
Referring to FIGS. 1 and 5 together, the cylindrically-shaped line head hub 114 has a hollow center or bore, into which the arbor extends and in which a retention spring 118 is mounted. Retention spring 118 is a generally U-shaped leaf spring. It has a relatively flat mid section 118a, with a hole through which a screw 120 extends to attach the spring to the arbor. It also has two downwardly extending legs 118b. The bottom portion of each leg is bent to form a knob 122. Each knob extends outwardly through slots 124 formed through the side of the hub 114. The spring 118 is compressed by the inside walls of the hubs 114, providing a bias to the knobs in their fully extended position as shown. Each knob has two exterior surfaces 122a and 122b exposed when fully extended through a slot. Each surface is slanted or angled obliquely with respect to the axis of rotation of the hub, which axis indicated by dashed line 123. A force applied to either surface that is substantially parallel to the axis of rotation of the hub generates, when combined with the ramp offered by the surfaces 122a and 122b, a force perpendicular to the axis of the hub which has a magnitude sufficient to overcome the biasing force of spring 118 tends to deflect the knobs inwardly to the point that the peak of each knob lies within the radius of the hub of the spool. The spool is thus able to be pulled off of or pushed onto the hub 114 in a single movement.
Referring now only to FIG. 1, line head 108 is illustrated split along the axis of rotation of the spool, indicated by line 123, to show it in two operating positions. Side 126 of the line shows the spool in a first normal operating position and side 127 shows it in a second, axially displaced operating position. The spool 116 is biased to its first operating position by compressed coiled spring 129. The knobs 122 abut the bottom edge of the spool hub 117 when it is in the first operating position to hold or retain the spool on the hub. Swiftly hitting or bumping button 130 against the ground axially displaces the spool to its second operating position.
The spool 116 and the button 130 are formed by separate injection molding processes and then permanently joined in a single movement. A circular ridge or rim 136 is formed on the bottom side of the spool surrounding the center of the spool. The ridge has an undercut formed on its outer circumference or surface. The radius of the ridge with respect to the axis of rotation of the hub, is large enough to accommodate the knobs 122 when fully extended below the spool. The button is circular and is generally shaped like a bowl, with a cavity 137 formed by side walls 138 extending perpendicularly upward from a bottom wall or surface 139 of the button. The bottom of the button has a convex outer surface that assists in bumping the line head when the surface of the ground is uneven or the trimmer is being held at an angle and also reduces the friction when bumped on a hard, flat surface. On the inside of the rim of the sides 138 of the button is formed an undercut that complements and mates with the undercut on the ridge 136 of the spool. During factory assembly, the spool and button are pushed together so that the undercuts on the spool and undercut on the button hook each other, thus securely attaching the spool and button in a single movement without fasteners. The hooked rims of the button and spool also seal the inside surfaces of the spool's hub, helping to prevent dirt and debris kicked up during use from interfering with rotation of the spool in the line head and its removal. The radius of the cavity 137 is greater than the radius of the hub, permitting the knobs 122 of the spring to extend radially outward beneath the spool. The depth of the cavity 137 in the button is also large enough to accommodate the knobs when the spool is displaced upwardly to the second operating position, thus permitting the spool to rotate freely. Also, if the head is used with electrically powered units as shown in FIG. 1, fins 144 are molded at the top of the hub. These fins create an air flow that cools the electric motor. Also if debris wraps around the head, it may create problems if it reaches the motor shaft. To avoid this problem, the hub is extended in such a way that shields the motor output shaft and bearing.
Referring now to FIGS. 2A, 2B and 2C, these figures illustrate spool 116, assembled with button 130, being mounted onto the hub 114 in a single movement. In FIG. 2A, the assembly is fully removed. To mount the assembly, an operator grasps the button 130, aligns the hub of the spool with the hub of the line head, and pushes the top edge of the spool's hub against the lower surface 122a of the knobs 122. The angle of the lower surface 122a, which angle is taken with respect a lever arm extending roughly between the screw 120 (about which each leg of the retention spring bends to be compressed) and the knob, is less than that of the upper surface 122b, creating greater leverage to compress the retention spring. This makes mounting the spool easier than removing it. The tab angles and the biasing force of the spring is set so that most persons have the strength to comfortably overcome the biasing force of the spring to deflect the knobs inwardly.
In FIG. 2B, knobs 122 have been fully deflected, creating sufficient clearance to permit the spool to slide on or off of the hub 114 of the line head.
In FIG. 2C, once the spool 116 is slide past the knobs 122, the knobs spring back under the biasing force of the retention spring. As previously indicated, the knobs retain the spool and button assembly in the line head during normal operation. The biasing force applied by the retention spring, as well as centrifugal forces acting on the retention spring and its knobs when the line head is rapidly spinning, are sufficient to counteract forces experienced during normal operation that would tend to move the spool downward with respect to the line head.
The assembly of the spool 116 and button 130 is removed from the line head (after the line has been depleted for example) in a single movement similar to that used to slide the spool and button assembly on to the hub. A user grasps the button 130 and, assisted by ledge 134 on the outer circumference of the button, pulls down, causing the bottom edge of the spool's hub 117 to deflect the knobs inwardly to the point shown in FIG. 2B. The spool is then free to be pulled off the hub by the user. The user may then replace the spool, if depleted of line, with a spool wound with line. Replacement spool and button assemblies are sold as a unit and wound with a full supply of line so that replenishing line is very easily and quickly accomplished.
Referring now to FIGS. 1, 3 and 4, line head 108 includes an indexing mechanism comprised of a set of stepped detentes that function to pay out a predetermined amount of line in response to the bottom 130 being bumped swiftly against the ground.
In the first operation position, shown on side 126 of line 123 (FIG. 1), spool 116 is held against line head 108 for rotation with the line head by the cooperation of series of tab-like stops 140 projecting radially inwardly from the inner surface of housing 112 and ears 142 projecting radially outwardly from the edge of the upper side wall 134 of the spool 116. When the head starts spinning, the centrifugal force acting over the line outside of the spool moves the ears of the spool 142 against the stops 140. Rotation of the line head causes the stops 140 to engage ears 142, and thus rotate the spool with the line head. Stops 140 are equally spaced apart and integrally formed with the line head hub 114 and housing 112 during an injection molding process. Openings 141 are caused by the insertion into and retraction from the mold of pins that define the top edge of each stop during the injection molding process. Ears 142 are spaced apart at intervals equal to those of the stops. The ears are integrally formed on the spool during the injection molding process.
To feed or pay out a predetermined length of line from the line head 108 during operation, button 130 is hit swiftly against the ground, moving the spool 116 axially upward from the first operating position to the second or displaced operating position, shown on side 128 of line 123 in FIG. 1. Each ear 142 moves upward and over the top of stop 140, against which it had been held, thus releasing the spool 116 and allowing it to slip on hub 114 as the line head spins. A set of protuberances 145, stepped upwardly and displaced circumferentially from the stops 140, project inwardly from the line head housing in the plane of rotation of the ears when the spool is displaced. Each protuberance is spaced midway between adjacent stops 140. The protuberances stop rotation of the spool while the tap button is held against the ground when it is in the second displaced position, and assist in deflecting the ears 142 downwardly, under the urging of compressed spring 129 (FIG. 1) once the ears have moved past the stops 140. The spool then continues to slip in the first operating position until the ears engage the stops 140. The surfaces of the protuberances 145 are angled and face downwardly to assist in deflecting the ears downwardly toward the first operating position.
Referring now to FIG. 6, the illustrated line head is specially adapted to be driven by an alternating current electric motor 179. The end of the motor's output shaft 180 is formed with self-tapping threads 197 so that it can be screwed into hole 189. Hole 189 is formed in the top of plastic hub 190 during a conventional plastic injecting molding process and is coaxial with the axis of rotation of the line head housing 192. A plurality of fins 193 on the upper surface of housing 192 cool the electric motor 179. Housing 192 includes a circular skirt extending around the housing hub 190 that defines a cavity in which a spool 194 is mounted for rotation on hub 190 about an axis common with line head 186. Spool 194 includes upper and lower flanges 194a and 194b integrally formed with and extending radially from spool hub 194c. Integrally formed on the outer surface of the spool hub 194c is a groove 194d that wraps around the circumference of the hub in a spiral fashion. The groove has a semi-circular cross section with a radius approximately the same or slightly larger than the radius of flexible monofilament line (not shown) that is normally wound around the spool hub. The groove, or the ridges formed between adjacent turns of the groove, tends to hold the line in place and reduce the tendency of the line to move laterally on the spool's hub, in the direction of its axis of rotation, as additional layers of line are wound around or unwound from the hub. Within a lower section of the hub 190 is defined during the injection molding process a socket 196 having a downward facing opening for receiving metal retention spring 182. The retention spring is electrically insulated from the output shaft 180 by wall 198.
Referring now to FIGS. 6 and 7 together, the retention spring 182 is a generally cross-shaped piece of metal bent to form a four-leg leaf spring. It has a relatively flat midsection 206a, with four downwardly extending legs (206b, 206c, 206d, 206e). A bottom edge of each of a first opposed pair of legs (206b, 206d) are bent outward to form a flat tab 208 that fits into a slot 210 defined on opposite sides of the wall of the hub 190. Positioning the tabs 208 within the slots 210 secures the spring 182 against movement and twisting within socket 196. During assembly of the line head, retention spring is inserted into opening of the socket and mounted in a single movement. The first opposed pair of legs deflect inwardly during insertion until the tabs 208 align with and snap into slots 210. Each leg acts as a compressed spring that applies force sufficient to maintain registration of the tab with the slot and thereby essentially locks the retention spring into the socket. Mounting the spring 182 in this manner not only simplifies assembly of the line head, but it also makes possible elimination of a metal arbor or other metal components conventionally found within the line hub to which a fastener, such as a screw, would attach to retain the spring.
A second opposed pair of legs (206c, 206e) have bottom portions bent to form a knob 212. Each knob 212 extends outwardly through slots 213 formed through the side of hub 190. The spring 182 is slightly compressed by the inside wall of socket 196 providing a bias to the knobs 212 in their fully extended position as shown. Each knob 212 has two exterior surfaces 212a and 212b exposed when fully extended through a slot 213. Each exterior surface (212a, 212b) is slanted or angled obliquely with respect to the axis of rotation of the hub 190. A portion of a force applied to either exterior surface (212a, 212b) that is substantially parallel to the axis of rotation of the hub 190 is directed by the ramp formed by the surfaces into a direction generally perpendicular to the axis of the hub, tending to cause the knobs to deflect inwardly against the biasing force of the spring, to the point that the peak of each knob lies within the radius of the hub section 202 of the spool 194. The spool 194 is thus able to be pulled off or pushed onto the hub in a single movement.
The invention has been described in connection with a preferred embodiment. Alterations, modifications, rearrangements, substitutions and omissions may be made in the preferred embodiment without departing from the spirit and scope of the invention as set forth in the appended claims.
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A "bump-feed" type line head (108) and replaceable spool (116) for a flexible line trimmer are specially adapted for removing and mounting the spool in a single manual movement to the line head to facilitate spool and line replacement. A U-shaped retention spring (118) is snap-fitted without separate fasteners within a hub in the line head on which the spool is journalled. The spring includes knob-shaped sections (122) protruding through the hub, beneath the spool, for retaining the spool on the hub without interfering with a bump-feed indexing mechanism. Pulling the spool from or pushing the spool onto the hub tends to deflect the knobs inwardly, allowing removal of the spool from the hub. The spool includes an integrally formed reel (116) and an integrally formed button (130) connected in a single movement to the bottom of the reel using undercut surfaces (136)(138), forming a cavity having a radius sufficient to accommodate extension of the knobs beneath the spool.
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BACKGROUND OF THE INVENTION
This invention generally relates to an hydraulic apparatus having means for automatically adjusting the positions of the headlights of a motor vehicle as a dependent function of the load on the axles of the motor vehicle and more particularly an apparatus in which the movement of the front and rear axles relative to the sprung motor vehicle body are oppositely sensed by means of a metering piston of a level sensor that is installed in proximity to each of the axles and the reactions of which are transmitted by means of positioning elements to the headlight housings.
Such an apparatus is generally known by the disclosure in DT-AS No. 2,014,280. In this apparatus, the level sensors and the positioning elements lie within a continuous conduit and the positioning elements are arranged in series. In such an apparatus it is not possible to incorporate thereinto additional elements that will permit manual operation of the headlight adjusting members.
On the other hand and by virtue of DT-OS No. 2,503,834, an apparatus with a hydraulic and manually effected adjustment is known in which a mechanically actuatable sensor is connected by way of two separate hydraulic lines that extend to the positioning elements of the headlight housings. However, such an apparatus is not adapted for automatic and load dependent operation.
There is also known by virtue of DT-OS No. 1,455,748 (see FIG. 2), an automatic and load dependent hydraulic apparatus in which, however, the rear axle level sensor requires a special converter.
OBJECT AND SUMMARY OF THE INVENTION
Accordingly, the primary object of this invention is to provide an apparatus for hydraulically adjusting the headlights of a motor vehicle through level sensors that are automatically and load dependently actuated and into which is further incorporated a mechanically actuatable manual adjustment means.
Another object of this invention is to provide an apparatus of the aforesaid type in which the level sensors are constructed identically thus making the apparatus considerably cheaper to manufacture.
Still another object of the invention is that this concept provides the advantage of providing separate circuits for the left headlight as well as for the right headlight. Thus in this way positioning of the headlights is thereby simplified, and a leak in a conduit is made less problematic thereby.
A further object of this invention is to provide an assembly in which the line connections at the sensors and at the positioning elements are embodied as removable push-pull couplings that are suitably sealed against loss of hydraulic fluid.
Yet another object of this invention is to provide a valve provided with a special sealing means that is adapted to guard the interconnection of the two hydraulic circuits at one sensor.
The invention will be better understood and further objects and advantages will become apparent from the ensuing detailed specification of preferred but merely exemplary embodiments taken in conjunction with the drawings.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 shows in a highly schematical view a hydraulic system, according to the invention, for automatically adjusting the position of the headlights of an automobile, and
FIG. 2 is a cross sectional view of a level sensor.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Turning now to the drawings, a motor vehicle front axle 1 as well as the rear axle 2 thereof are supported by spring means, not shown, relative to a vehicle body 3. As shown, levers 4 and 5 are arranged to cooperate with a level sensor 6 located in proximity to the front axle 1 and upon a level sensor 7 that is supported adjacent to the rear axle 2. Thus, the motions of the axles 1 and 2 are transmitted to its respective sensor means.
The two level sensors 6 and 7 are essentially identical in their construction and dimensions. In FIG. 2 there is shown an enlarged cross-sectional view of the rear axle sensor 7. It is to be noted that the lever 5 is attached on a shaft 8 with the aid of a toothed rim 9 and the end portion of the lever 10 touches the foot 11 of an elongated shank that terminates in a plunger 12. The plunger 12 has a head 13 that is provided with a keying surface 14. A metering piston 15 includes a hollow axially extending sleeve portion 16 that is provided with a narrow bore 17 that is complemental to the shank that supports the head 13 with its keying surface 14. A spring 19 is interposed between the foot 11 and an outer shoulder portion 18 of the metering piston 15 so that after inserting the head through the bore 17 and rotating it 90 degrees the assembly can be held together by the spring.
The metering piston 15 includes a fork piece 15' which provide two integral positioning pistons 20 and 21, respectively, these pistons being arranged to act on the diaphragms 22 and 23. The pistons 20 and 21 are arranged to extend through dual oppositely spaced apertures in member 16' and rest against portions of diaphragms 22 and 23, as shown. The pistons 20 and 21 together with diaphragms 22 and 23, as shown in FIG. 2, thus form two working chambers 24 and 25. An apertured cover 40 is provided with dual depressions that coincide with the bulged area created by the pistons 20 and 21 and the corresponding diaphragms 22 and 23. The depressions in the cover 40 extend to apertures into each of which are inserted pipe couplings or nipples 28 and 29 preferably in the form of latchable push couplings that are retained in said apertures by means of seal-type O-rings 26 and 27, respectively. The working chambers 24 and 25 each communicate with parallel bores 32 and 33 provided in the cover 40 so as to connect the working chambers 24 and 25 to a chamber 34 that is located in a bore 40' provided in the cover and closed toward the outside by means of a plug 35 which has a bayonet lock 36. An O-ring 37 that rests against a shoulder 38 of the plug 35 serves to seal the chamber 34 toward the atmosphere. The O-ring 37 is pressed by means of the locking plug 35 against an annular rim 39 situated in the bore 40' of cover 40 and disposed between the two axially parallel bores 32 and 33. In this manner the O-ring 37 and the annular rim 39 thus form a valve 60. The plug 35 needs only to be lifted slightly to disconnect the bayonet lock function to interconnect the two working chambers 24 and 25. Accordingly the O-ring 37 will then lift off the annular rim 39. However, the O-ring 37 still continues to remain effective as a seal toward the atmosphere.
The aforesaid elements 32 to 39 as well as 40' and 60 are present only in the rear axle level sensor 7. However, although the front axle level sensor 6 does also include a cover element 41, the plug 35 and the valve 60 are not included in this sensor. On the other hand, four push couplings or nipples 42, 43, 44, and 45 are disposed in apertures in the cover 41, of which two (42 and 43) are provided for the lines 30 and 31 that extend from the rear axle level sensor 7 and are attached to working chambers 46 and 47. Hydraulic lines 48 and 49 also extend from the same working chambers 46 and 47 and lead separately via the push couplings or nipples 44 and 45 to the positioning elements 50 and 51 located adjacent to the headlights as will be explained later herein.
The two positioning elements 50 and 51 comprise an assembly of identical elements (FIG. 1). They each have working chambers 52, 53 that are bounded by diaphragm pistons 54, 55 which are acted upon by a spring means 54', 55'. A piston rod 56, 57 of each piston 54, 55 is linked to a housing 58, 59 of a headlight that is swivably supported on the vehicle.
A manual positioning device 61 is shown by means of dashed lines in FIG. 1, and includes a threaded element 62 or other suitable positioning means which acts via a yoke 62 that in turn is arranged to cooperate with a pair of pistons 64 and 65. The pistons 64 and 65 comprise the working chambers 66 and 67 that are connected via the lines 68 and 69 to the lines 48 and 49. The manual positioning assembly 61 except for the actuator 62 has the same dimensions, type of couplings, or nipples and construction as do the level sensors 6 and 7. Accordingly, the manual positioning assembly 61 can be substituted for the level sensors 6 and 7, when the headlights are to be actuated manually. Conversely, the conversion of a manual to an automatic and load dependent actuation is also possible without difficulty due to the identical dimensions of the hydraulic chambers 6, 7, and 61.
OPERATION
The hydraulic system shown in FIG. 1 is a static system in which a static pressure prevails that is dependent on its magnitude upon the pre-tensioning of the springs 54' and 55' in the positioning elements 50 and 51.
During a uniformly increasing or uniformly decreasing load upon the axles of the motor vehicle, the system remains at rest due to the counteracting deflections of the levers 4 and 5, except that the level sensors 6 and 7 exchange fluid via the lines 30 and 31. Consequently the total fluid capacity of the four working chambers 24, 25, 46, and 47 remains unchanged.
However, when either of the motor vehicle axles 1 or 2 are loaded more than the other, then the total fluid capacity of the four working chambers 24, 25, 46, and 47 changes and the pistons 54 and 55 of the positioning elements re-position the housings 58 and 59 of the headlights equally and in the same direction via the separate lines 48 and 49 within separate fluid circuits. Also, it is to be understood that like re-positioning of the housings 58 and 59 is possible with the aid of the manual positioning device 61, when the apparatus is to be manually actuated.
The apparatus is filled at the level sensor 7 by means of the valve 60 (better shown in detail in FIG. 2), and the fluid can transfer from one circuit to the other when the valve 60 is lifted. In addition, a relief valve is provided at an elevated location.
The described apparatus is substantially the same for automatic positioning and for manual positioning, so that a simple changeover is made possible. In addition, simple and identical positioning elements and pistons are used at the hydraulic chambers 6, 7, and 61. Each headlight has its own separate hydraulic circuit.
Furthermore, the positioning elements 50 and 51 at the headlights are also identical, and the housings of the hydraulic chambers 6, 7, and 61 are likewise substantially identical. Roll diaphragms, fabric diaphragms and foils can also be used as diaphragms for the pistons 20 and 21 as well as 54 and 55 and also for 64 and 65. The interconnection of the housing components of the level sensors and of the positioning elements, as well as the actuation excursion of the valve 60, are produced by means of bayonet couplings which are simply and rapidly loosened and joined.
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What follows is the description of an improved hydraulic apparatus for the automatic adjustment of the inclination of the headlights of a motor vehicle, the adjustment being a dependent function of the axle load. The apparatus has a level sensor at each axle and each level sensor contains one metering piston and two positioning pistons. The rear axle level sensor is connected via two separate hydraulic lines to the front axle sensor, and the front axle sensor is in turn connected via two separate hydraulic lines to the positioning elements of the headlight housings. The internal construction of the two level sensors is substantially identical and is chosen such that the system is also suitable for manual adjustment.
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FIELD OF THE INVENTION
[0001] The present invention relates generally to a method and apparatus for repairing a defective tube, and more particularly to a method, apparatus, and prefabricated replacement tube for partial tube replacement in a heat exchanger to which access is restricted.
BACKGROUND OF THE INVENTION
[0002] Various types of heat exchangers, such as boilers and waterwalls, are commonly used in hoods and stacks for cooling and/or treating industrial exhaust, for example from steelmaking furnaces, and by utilities (electric companies) to produce electrical energy and/or to cool power generating equipment.
[0003] One problem with the operation of heat exchangers is that the heat, gases, dust and substances or fluids to which they are exposed frequently leads to increased rates of corrosion resulting in damage or defects in the tubes of the heat exchanger and subsequent leakage.
[0004] A conventional approach to repairing the heat exchanger is to remove a section of the damaged tube, including the defect, over some length, and to install a new replacement tube in its place. The ends of the replacement tube and the stubs of the existing tube are prepared for welding by fitting and beveling surfaces at which they will be joined. Typically, the joining is done manually using shielded metal arc welding (SMAW).
[0005] One problem with this approach is that because the weld is performed completely from the outer diameter (OD) of the tube, access is required to all sides of the tube, which is not possible for all heat exchanger designs, particularly boilers such as waterwalls. For example, tubes in a waterwall are frequently connected together along the length of their sides by a metal-webbing or membrane to give added rigidity and strength to the waterwall. Moreover, the waterwall is usually positioned abutting or in close proximity to an outer wall of the boiler (the cold-side). Thus, access is limited to more than half of the outer surface of the tube. This limited accessibility makes it difficult for the welder to achieve good weld tie-in/penetration and often results in less than desirable weld quality and may create problems in the future.
[0006] Yet another problem with the above tube replacement method is manual welds performed from the OD are prone to weld defects such as reinforcement or excessive build-up of material on the inner diameter (ID) that lead to restricted fluid flow and accelerated corrosion or erosion at the weld locations.
[0007] Another generally known approach for partial replacement of a tube in a heat exchanger, which avoids some of the problems of the above approach, is described, for example, in U.S. Pat. No. 4,047,659, to Drago (DRAGO). DRAGO discloses accessing the ID of the tube by cutting windows at each end of the replacement tube, the windows intersecting the ends of the replacement tube, and manually welding a portion of the attachment weld from the ID through the window. Covers for the windows are fabricated and welded over the windows from the OD completing the repair.
[0008] While a significant improvement over the above approach, this approach is also not wholly satisfactory. A major shortcoming of the approach disclosed in DRAGO is the time required for measuring the section cut from the tube to be repaired, cutting a replacement tube to the correct length, cutting out the windows, preparing the ends of the replacement tube for welding, fabricating covers for the windows and welding the covers over the windows. Another problem with the approach in DRAGO is that all welds are performed manually using a SMAW process. Since the SMAW welds are full penetration, i.e., through the entire thickness of the tube, build-up on the ID for that portion of the welding done from the OD, such as the window covers, can still be a problem. Moreover, because the welds are performed manually weld quality is inconsistent, not-reproducible and can vary from weld to weld.
[0009] Accordingly, there is a need for a method and apparatus for repairing a defective tube that provides a weld quality similar to that of a new installation or original fabrication. It is desirable that the method and apparatus eliminate excessive buildup of material from the ID of the repaired tube that can disrupt or reduce fluid flow through the repaired tube and lead to increased erosion/corrosion at the joints. It is also desirable that the method and apparatus enable repairs to be completed quickly with a minimum amount of down time for the heat exchanger. It is further desirable that the method and apparatus be automatic to reduce the level of skilled labor needed.
[0010] The present invention provides a solution to these and other problems, and offers other advantages over the prior art.
SUMMARY OF THE INVENTION
[0011] It is an object of the present invention to provide a method, apparatus and prefabricated replacement tube for partial tube replacement in a heat exchanger to which access is restricted.
[0012] According to one aspect, the present invention provides a method for repairing a defect in a tube using an apparatus including a rotatable torch assembly, a wire feeder for supplying wire to the rotatable torch assembly, and a rotational drive assembly for supporting and rotating the rotatable torch assembly. Generally, the method involves steps of: (i) removing a section of the tube having the defect therein; (ii) fabricating a replacement tube having a wall with an opening extending through a portion thereof, and first and second ends prepared for joining to stubs of the tube formed by removal of the section of the tube having the defect therein; (iii) positioning the replacement tube between the stubs of the tube; (iv) inserting the rotatable torch assembly into the replacement tube through the opening, the rotatable torch assembly configured to align with a joint between the first end of the replacement tube and a stub; and (v) joining the first end of the replacement tube to the stub entirely along a joint therewith by rotating the rotatable torch assembly within the replacement tube. Optionally, slip rings in sliding engagement with the outer surface of the replacement tube hold it in position before it is joined to the stubs. In this embodiment, following the positioning of the replacement tube between the stubs, the slip rings slide up or down to cover the joints. The slip rings have the further advantage of serving as backing rings strengthening the joint when the replacement tube is joined to the stubs, typically by welding.
[0013] In one embodiment, the replacement tube is prefabricated having a first end and a second end separated by a predetermined length, and the step of removing a section of the tube having the defect therein involves removing a length of the tube substantially equal to the predetermined length of the prefabricated replacement tube.
[0014] In another embodiment, the opening is centrally located between the first and second ends, and the method further includes the steps of: (i) removing the rotatable torch assembly from the opening; (ii) reorienting the rotatable torch assembly; (iii) re-inserting the rotatable torch assembly into the replacement tube through the opening, the rotatable torch assembly configured to align with a joint between the second end of the replacement tube and another one of the stubs; and (iv) joining the second end of the replacement tube to one of the stubs substantially entirely along or around a joint formed there between by rotating the rotatable torch assembly within the replacement tube. The repair of the tube is completed by removing the rotatable torch assembly from the opening, and sealing the opening with a prefabricated cover. Typically, the cover is cover-welded or welded to the opening.
[0015] As noted above, the replacement tube is joined to the stubs by welding. Preferably, the replacement tube is joined to the stubs by butt-welding or welding the first and second ends of the replacement tube to the stubs using the rotatable torch assembly. In one version of this embodiment, the apparatus is a Gas Metal Arc Welding (GMAW) apparatus, or a Gas Tungsten Arc Welding (GTAW) apparatus, and the step of welding includes providing a shield gas to the rotatable torch assembly through a rotatable coupling in the rotational drive assembly.
[0016] Whichever method for joining is used, preferably, the apparatus further includes a controller for controlling power supplied to the rotatable torch assembly, and operating the rotational drive assembly, and the step of joining the replacement tube to the stubs is performed automatically once the torch is aligned with a joint. The controller controls or adjusts power supplied to the rotatable torch assembly and operates the rotational drive assembly to rotate the torch at a speed that substantially eliminates an excessive build up of material on the inner diameter (ID) of the tube at the joint. Thus, restriction in fluid flow through the repaired tube and corrosion of the joint is reduced.
[0017] In another aspect, the present invention is directed to an apparatus for joining a replacement tube to stubs of a tube from which a section of the tube having a defect therein has been removed. The apparatus includes a rotatable torch assembly capable of being inserted into the replacement tube through a window in the replacement tube, to join first and second ends of the replacement tube to the stubs. Wire for joining the replacement tube to the stubs is fed to the rotatable torch assembly by a wire feeder having a wire drive assembly and a wire supply. A rotational drive assembly supports the rotatable torch assembly and rotates it within the replacement tube to join the first and second ends of the replacement tube to the stubs substantially entirely along joints therewith. Generally, the apparatus according further includes a mount to which the rotational drive assembly and the wire feeder are attached, and a latching mechanism for securing the mount to position the rotatable torch assembly within the replacement tube. In one embodiment, the latching mechanism is adapted to be partially inserted into the window to secure the mount to the replacement tube.
[0018] In one embodiment, the window in the replacement tube is a centralized window centrally located between the first and the second ends. The rotatable torch assembly is adapted to be inserted into the replacement tube through the centralized window to align with the joint between the first end of the replacement tube and one of the stubs to join the first end to the stub, and to be removed from the replacement tube, reoriented, and reinserted through the centralized window to align with and join the second end to the other stub.
[0019] Alternatively, the replacement tube has a number of windows including: (i) a first window located a predetermined distance from the first end of the replacement tube and through which the rotatable torch assembly can be inserted into the replacement tube to join the first end of the replacement tube to one of the stubs; and (ii) a second window located the same predetermined distance from the second end of the replacement tube and through which the rotatable torch assembly can be inserted into the replacement tube to join the second end of the replacement tube to one of the stubs.
[0020] In another embodiment, the rotatable torch assembly is adapted to weld the first and second ends of the replacement tube to the stubs. In one version of this embodiment, the apparatus is a gas metal arc welding apparatus (GMAW), and the rotational drive assembly further includes a rotatable coupling through which shield gas is supplied to the rotatable torch assembly. The rotational drive assembly is adapted to rotate the rotatable torch assembly at predetermined rate based on power supplied to the rotatable torch assembly and materials of the wire, the replacement tube and the tube.
[0021] In still another embodiment, the apparatus further includes a controller for automatically supplying power to the rotatable torch assembly, and operating the rotational drive assembly. The controller controls or adjusts power supplied to the rotatable torch assembly and operates the rotational drive assembly to rotate the torch at a speed that substantially eliminates a build up of material on the inner diameter (ID) of the tube at the joint. Thus, restriction in fluid flow through the repaired tube and corrosion of the joint is reduced.
[0022] In yet another aspect, the present invention is directed to a prefabricated replacement tube for use in repairing a tube having a defect therein. Generally, the replacement tube has a wall with a central opening extending through a portion thereof, and first and second ends separated by a predetermined length. The ends are prepared for joining to stubs of the tube from which a section of the tube having the defect therein has been removed. The central opening is centrally located between the ends, and adapted to enable a rotatable torch to be inserted into the replacement tube through the central opening to join the ends of the replacement tube to the stubs.
[0023] Preferably, the central opening is adapted to accommodate the rotatable torch of an automated gas metal arc welding apparatus, which is inserted into the replacement tube to weld the ends thereof to the stubs of the tube substantially without a build up of material at joints. More preferably, the central opening is also adapted to enable an automated welding apparatus to weld a prefabricated cover over the central opening, thereby completing repair of the tube.
[0024] Optionally, the prefabricated replacement tube further includes at least one slip ring in sliding engagement with an outer surface of the wall to maintain the replacement tube in alignment with the stub while it is joined to the stubs. The slip ring is adapted to be positioned over the joint between one of the ends of replacement tube and one of the stubs.
[0025] Advantages of the method, apparatus and prefabricated replacement tube of the present invention include any one or all of the following:
[0026] (i) a weld quality similar to that of a new installation or original fabrication;
[0027] (ii) welding is performed from the inner diameter (ID) eliminating excessive buildup or reinforcement typical of outer diameter (OD) welding processes, which can disrupt or reduce fluid flow through the repaired tube and lead to increased erosion/corrosion at the joints;
[0028] (iii) weld quality is reproducible and consistent compared to manual applications;
[0029] (iv) weld defects associated with manual repair methods are eliminated;
[0030] (v) repair is completed entirely from one side of the tubing, for example, fire-side of a waterwall, eliminating access problems associated with welding from both sides; and
[0031] (vi) prefabricated replacement tubes having standardized lengths and window configurations can be made available on demand or stocked on site eliminating delays for fabricating replacement tubes.
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] These and various other features and advantages of the present invention will be apparent upon reading of the following detailed description in conjunction with the accompanying drawings, where:
[0033] [0033]FIG. 1 (prior art) is a perspective view of a portion of a waterwall for which a method and apparatus according to an embodiment of the present invention is particularly useful;
[0034] [0034]FIG. 2 is a perspective view of a prefabricated replacement tube having a central opening or window according to an embodiment of the present invention;
[0035] [0035]FIG. 3 is a perspective view of a prefabricated cover for the central opening in the prefabricated replacement tube of FIG. 2 according to an embodiment of the present invention;
[0036] [0036]FIG. 4 is a perspective view of an alternative embodiment of a prefabricated replacement tube having multiple openings or windows according to an embodiment of the present invention;
[0037] [0037]FIG. 5 is a sectional side view of an apparatus for welding a replacement tube to a tube from which a section of damaged tube has been removed according to an embodiment of the present invention;
[0038] [0038]FIG. 6 is a top view of the apparatus of FIG. 5;
[0039] [0039]FIG. 7 is a bottom view of the apparatus of FIG. 5;
[0040] [0040]FIG. 8 is a partial sectional view of a rotational drive assembly of the apparatus of FIG. 5; and
[0041] [0041]FIG. 9 is a flow chart showing steps of a method for repairing a defect in a tube according to an embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0042] The present invention is directed to a method, apparatus, and prefabricated replacement tube for partial tube replacement in a heat exchanger to which access is restricted.
[0043] In general, the method involves the steps of: (i) providing a prefabricated repair or replacement tube having wall with an opening extending through a portion thereof, and first and second ends separated by a predetermined length and prepared for joining to stubs of a tube formed by removal of a section of the tube having a defect therein; (ii) removing the section of tube with the defect, the section having a length substantially equal to the predetermined length of the replacement tube; (iii) inserting a rotatable torch assembly of the apparatus into the replacement tube through the opening to align with a joint between the first end of the replacement tube and a stub; (iv) joining one end of the replacement tube to the stub entirely along a joint therewith by rotating the rotatable torch assembly within the replacement tube; and (v) removing, reorienting and reinserting the rotatable torch assembly to join the remaining end of the replacement tube to the remaining stub. Preferably, the opening is centrally located between the first and second ends. More preferably, the opening and the rotatable torch assembly are configured to enable the rotatable torch assembly to align correctly with either end of the replacement tube, thereby enabling the joining process to be automated. The repair of the tube is completed by removing the rotatable torch assembly from the opening, and sealing the opening with a prefabricated cover.
[0044] Heat exchangers generally include a number of tubes through which a heat transfer fluid is passed. Usually, the tubes are cylindrically shaped with a diameter much less than their length, and have open ends that are sealed or coupled to a larger tube or plenum (not shown) through which the heat transfer fluid is passed. The heat transfer fluid can include a gas, such as air, nitrogen, helium, argon and carbon dioxide, a liquid, such as water, deionized water, distilled water, oil, alcohol, ethylene glycol, or a liquid metal, such as sodium. To increase the efficiency of thermal transfer the heat transfer fluid may be contained within a closed pressurized system of which the heat exchanger is but one component.
[0045] [0045]FIG. 1 is a perspective view of a portion of a particular type of heat exchanger, a waterwall 100 , for which a method and apparatus (not shown in this figure) according to an embodiment of the present invention is particularly useful. Waterwalls 100 are commonly used in, for example, gas, oil and coal-fired boilers (not shown) of electric power or utility plants. For purposes of clarity, many of the details of waterwalls 100 that are widely known and are not relevant to the present invention have been omitted. Referring to FIG. 1, a waterwall 100 typically includes a number of parallel tubes 102 through which a heat transfer fluid is passed. As fuel is burned in a boiler's interior, heat is transferred into the waterwall 100 to heat water contained therein and produce steam to turn a turbine and generate electricity. Optionally, the heat transfer fluid in the waterwall 100 is pressurized to raise the boiling point reducing or eliminating boiling, and the heated heat transfer fluid, water, is coupled to second heat exchanger, a steam generator (not shown), in which water heated by the heat transfer fluid is boiled to produce steam. This embodiment has the advantage of enabling use of heat transfer fluids having greater heat transfer capacities or corrosion inhibiting properties. It should be noted that in this embodiment the method and apparatus of the present invention can be used to repair defective tubes 102 in both the waterwall 100 and the steam generator.
[0046] Because the tubes 102 of the waterwall 100 have thin walls 104 relative to their cross-section, they are often joined to one another along the sides thereof by a mesh or webbing 106 to improve the strength of the waterwall. To improve heat transfer, strength and tolerance to elevated temperatures the tubes 102 and the webbing 106 are made of a metal, such as steel, copper, zinc, nickel and/or alloys thereof. As noted above, the tubes 102 are cylindrically shaped having a diameter much less than their length, and open ends that are sealed or coupled to a larger tube or plenum (not shown) through which the heat transfer fluid is passed. For example, a typical waterwall used a utility plant can include over 1,000 tubes, each having a length of up to 200 meters, and a diameter of from 2 to 10 centimeters.
[0047] An embodiment according to the present invention of a replacement tube 108 for repairing a tube 102 in a waterwall 100 from which a section 110 having a damage or defect 112 therein will now be described with reference to FIGS. 1, 2 and 3 . FIG. 2 is a perspective view of a prefabricated replacement tube 108 having a window or opening 114 according to an embodiment of the present invention. Generally, the replacement tube 108 has a cylindrical wall 116 with a diameter or radius substantially the same as that of a tube 102 in the waterwall 100 , an opening 114 extending through a portion of the wall, and first and second ends 118 , 120 , separated by a predetermined length. Preferably, for reasons described below, the opening 114 is a central opening centrally located between the first and second ends 118 , 120 . The opening 114 is sized and shaped to accommodate a rotatable torch assembly (not shown in this figure) of the apparatus of the present invention. In the embodiment shown, the opening 114 has an oval shape with a long axis parallel with that of the replacement tube 108 . By predetermined length it is meant any one of several lengths ranging from a length little longer than that of the opening to a length nearly equal to that of a tube in a waterwall for which it is prefabricated as a replacement tube. In a preferred embodiment of the method a number of prefabricated replacement tubes 108 having diameters equal to those of tubes in a waterwall and various predetermined lengths are maintained in inventory near where they are to be used to expedite the repair process and minimize downtime of the waterwall.
[0048] Edges of the first and second ends 118 , 120 , are prepared for joining to stubs 126 , 128 , formed by removal of the damaged section 110 of the tube 102 in the waterwall 100 having the defect 112 therein. For example, the edges of the first and second ends 118 , 120 , can be beveled to self-align and fit flush with edges 130 , 132 , of the stubs 126 , 128 , which are beveled or slanted in a complementary direction when the replacement tube 108 is positioned between the stubs. Similarly, an edge 134 , or edges, surrounding and defining the opening 114 can be prepared or beveled for joining to an edge, or edges, of a prefabricated cover 138 , described in detail below.
[0049] The replacement tube 108 can be joined to the stubs 126 , 128 , by soldering, brazing or welding. Preferably, the replacement tube 108 is joined to the stubs 126 , 128 , using a Gas Metal Arc Welding (GMAW) process. Alternatively, the replacement tube 108 is joined to the stubs 126 , 128 , by a butt-weld using a Gas Tungsten Arc Welding (GTAW) process that penetrates the full thickness of the wall 116 of the replacement tube and tube 102 undergoing repair.
[0050] It will be appreciated, that the replacement tube 108 need not be made from the same metal or material as the tubes 102 of the waterwall 100 it is used to repair. Rather, the replacement tube 108 can be made from a metal or material selected to facilitate joining with the stubs 126 , 128 , of the tube 102 , or of a material that is resistant to corrosion, and electrochemical corrosion, and is suitable for use in a wide range of environments or applications. For example, high-temperature nickel alloys, stainless-steel, or other steel alloys. Preferably, the metal or material of the replacement tube 108 has a coefficient of thermal expansion similar to that of the metal or material of tubes 102 in the waterwall 100 . More preferably, the material of the replacement tube 108 also has corrosion properties similar to that of the metal or material of tubes 102 in the waterwall 100 .
[0051] Optionally, the replacement tube 108 further includes one or more slip rings 140 , 142 , in sliding engagement with an outer surface 144 of the wall 116 of the replacement tube. The slip rings 140 , 142 , are configured to be positioned over joints formed between the first and second ends 118 , 120 , of the replacement tube 108 and the stubs 126 , 128 , thereby maintaining the replacement tube in alignment or position between the stubs prior to the replacement tube being joined to the stubs. In addition, in a preferred embodiment wherein the replacement tube 108 is joined to the stubs 126 , 128 , by a weld fully penetrating thicknesses of the replacement tube and the stubs, the slip rings 140 , 142 .
[0052] [0052]FIG. 3 is a perspective view of a prefabricated cover 138 for the opening 114 in the prefabricated replacement tube 108 of FIG. 2. Generally, the cover 138 has a size and shape substantially the same as those of the opening 114 and an edge (not shown) prepared for joining to the edge 134 of the opening 114 . For example, the edge 146 of the cover 138 can be beveled to fit flush with the edge 134 of the opening 114 . In one embodiment, the cover 138 is a piece of the wall 116 of the replacement tube 108 cut from the replacement tube. Alternatively, the cover 138 can be prefabricated from a separate tube or piece of metal having an inner and/or an outer surface with a radius similar to that of the replacement tube. The prefabricated cover 138 need not be made from the same metal or material as the replacement tube 108 or the tube 102 being repaired. Rather, the cover 138 can be made from a metal or material selected to facilitate sealing the opening 114 therewith. Preferably, the material of the cover 138 , if made from a separate tube or piece of metal, has a coefficient of thermal expansion similar to that of the metal or material of the replacement tube 108 . More preferably, the material of the cover 138 also has corrosion properties similar to those of the metal or material of the replacement tube and the tube being repaired. The cover 138 can be cover-welded or welded over or into the opening 114 .
[0053] An alternative embodiment of a prefabricated replacement tube 108 having multiple openings or windows through which the rotatable torch assembly (not shown in this figure) can be inserted into the replacement tube. The windows, include a first window 114 A located a first predetermined distance from the first end 118 of the replacement tube 108 , and a second window 114 B located a second predetermined distance from the second end of the replacement tube. Generally, the first window 114 A is sized, shaped and located so that the rotatable torch assembly can be inserted into the replacement tube 108 to join the first end 118 of the replacement tube to one of the stubs 126 , and the second window 114 B is sized, shaped and located so that the rotatable torch assembly can be inserted into the replacement tube to join the second end 120 of the replacement tube to the other stub 128 . Preferably, the first predetermined distance from the first window 114 A and the first end 118 of the replacement tube 108 , and the second predetermined distance from the second window 114 B and the second end 120 of the replacement tube are substantially the same. This embodiment particularly useful for relatively long replacement tubes 108 for which a centralized window 114 would result in an impractically long rotatable torch assembly. This embodiment is also useful for situations in which the rotatable torch assembly must be kept relatively short. For example, in repairing boilers or waterwalls 100 to which access is severely limited.
[0054] An embodiment of an apparatus according to the present invention for repairing a tube 102 in a waterwall 100 will now be described with reference to FIGS. 5 through 8.
[0055] [0055]FIG. 5 is a sectional side view of an apparatus 150 according to an embodiment of the present invention for welding a replacement tube 108 to stubs 126 , 128 , of a tube 102 from which a damaged or defective section 110 has been removed. Generally, the apparatus 150 includes: (i) a rotatable torch assembly 152 configured to be inserted into the replacement tube 108 through the opening 114 and to weld the first and second ends 118 , 120 , of the replacement tube 108 to the stubs 126 , 128 ; (ii) a wirefeed mechanism or wire feeder 156 having a wire drive assembly 158 and a wire supply 160 configured to feed filler wire or wire 162 , such as welding wire, to the rotatable torch assembly 152 to join first and second ends 118 , 120 , of the replacement tube 108 to the stubs 126 , 128 ; (iii) a rotational drive assembly 164 supports the rotatable torch assembly 152 and rotates it within the replacement tube 108 to join the first and second ends 118 , 120 , of the replacement tube to the stubs 126 , 128 , substantially entirely along joints formed therewith; (iv) a mount 166 to which the rotational drive assembly 164 and the wire feeder 156 are attached; and (v) a latching mechanism 168 for securing the mount 166 to position the rotatable torch assembly 152 within the replacement tube 108 .
[0056] Optionally, the apparatus 150 further includes a controller 170 that can be operated or programmed to automatically provide power and filler wire 162 to the rotatable torch assembly 152 , and to control the rotational drive assembly 164 , thereby providing a uniform and defect-free joint between the first and second ends 118 , 120 , and the stubs 126 , 128 . In addition, performing the joining process from inside the replacement tube 108 and automating the process, substantially eliminates build up of material at joints between the replacement tube and tube 102 , thereby reducing restriction in fluid flow through the tube and corrosion/erosion of the joints after the tube has been repaired.
[0057] The latching mechanism 168 can include any suitable means for temporarily attaching the mount 166 to the replacement tube 108 and/or the tube 102 undergoing repair. In a preferred embodiment, the latching mechanism 168 is adapted to be partially inserted into the opening 114 to secure the mount 166 to the replacement tube 108 . In a preferred embodiment, the latching mechanism 168 is integrally formed with the mount 166 . That is, a portion of the mount 166 is also part of the latching mechanism 168 that is inserted into the opening 114 . In one version of this embodiment, as shown, the latching mechanism 168 further includes a latch-and-release trigger 172 and a spring 174 that forces the trigger against one end or edge of the opening 114 , and, through the mount 166 and a housing frame 176 , forces the rotational drive assembly 164 against the opposing or facing end or edge.
[0058] Typically, the wire feeder 156 includes an electric motor 178 driving one or more gears or drive rollers 180 that engage the filler wire 162 forcing it through a wire conduit 182 to the rotatable torch assembly 152 . The wire feeder 156 can be operated manually by an operator controlling power to the electric motor 178 , or automatically by the controller 170 to synchronize feeding of the filler wire 162 to the rotation of the rotatable torch assembly 152 .
[0059] In a preferred embodiment, the apparatus 150 is a welding apparatus and the rotatable torch assembly 152 is adapted to weld or butt-weld the first and second ends 118 , 120 , of the replacement tube 108 to the stubs 126 , 128 . For purposes of clarity, many of the details of welding systems that are widely known and are not relevant to the present invention have been omitted. Generally, in this embodiment the apparatus 150 includes a power input terminal 184 to which power from a welding power supply 186 is applied, and a lead 188 electrically coupling the terminal to the tip 154 of the rotatable torch assembly 152 . The electrical coupling is accomplished using a power brush and a rotating contact ring in the rotational drive assembly 164 , described in greater detail below. Welding is accomplished using the concentrated heat from an electric arc formed between the welding wire 162 and the replacement tube 108 and/or the tube 102 being repaired, which is electrically connected by a ground cable (not shown) to the welding power supply 186 .
[0060] In a preferred embodiment, the apparatus 150 is a Gas Metal Arc Welding (GMAW) apparatus or a Gas Tungsten Arc Welding (GTAW) apparatus, and the rotational drive assembly 164 further includes a gas inlet 190 and a rotatable coupling 192 through which shield gas is supplied to the rotatable torch assembly 152 .
[0061] [0061]FIG. 6 is a top view of the apparatus 150 of FIG. 5 showing the rotational drive assembly 164 and the latching mechanism 168 inserted in the replacement tube 108 .
[0062] [0062]FIG. 7 is a bottom view of the apparatus 150 of FIG. 5 showing the gas inlet 190 and a rotatable coupling 192 for supplying shield gas to the rotatable torch assembly 152 .
[0063] [0063]FIG. 8 is a partial sectional view of a rotational drive assembly 164 of the apparatus 150 of FIG. 5 showing the power input terminal 184 , lead 188 , power brush 194 and a rotating contact ring 196 through which power from welding power supply 186 is electrically coupled to the tip 154 of the rotatable torch assembly 152 . Power brush 194 and contact ring 196 are electrically insulated from the housing frame 176 by insulator 198 . Spring 200 forces power brush 194 against contact ring 196 , thereby ensuring good electrical coupling therebetween.
[0064] An embodiment of a method for operating the apparatus 150 according to the present invention will now be described with reference to FIG. 9. FIG. 9 is a flow chart showing steps of a method for repairing a defect in a tube 102 according to an embodiment of the present invention. Generally, the method involves:removing a section 110 of the tube 102 having the defect 112 therein (step 202 ); fabricating a replacement tube 108 having a wall 116 with an opening 114 extending through a portion thereof, and first and second ends 118 , 120 , prepared for joining to stubs 126 , 128 , of the tube 102 formed by removal of the section 110 of the tube 102 having the defect 112 therein (step 204 ); positioning the replacement tube 108 between the stubs 126 , 128 , of the tube 102 (step 206 ); (iv) inserting the rotatable torch assembly 152 into the replacement tube 108 through the opening 114 , the rotatable torch assembly configured to align with a joint between the first end 118 of the replacement tube 108 and a stub 126 (step 208 ); and joining the first end 118 of the replacement tube 108 to the stub 126 entirely along a joint therewith by rotating the rotatable torch assembly 152 within the replacement tube 108 (step 210 ). Preferably, the opening 114 is centrally located between the first and second ends 118 , 120 , and the method involves the further steps of: removing the rotatable torch assembly 152 from the opening 114 (step 212 ); reorienting the rotatable torch assembly 152 (step 214 ); re-inserting the rotatable torch assembly 152 into the replacement tube 108 through the opening 114 , the rotatable torch assembly 152 configured to align with a joint between the second end 120 of the replacement tube 108 and another one of the stubs 128 (step 216 ); and joining the second end 120 of the replacement tube 108 to one of the stubs 128 substantially entirely along or around a joint formed there between by rotating the rotatable torch assembly 152 within the replacement tube (step 217 ). The repair of the tube 102 is completed by removing the rotatable torch assembly 152 from the opening 114 (step 218 ), and sealing the opening 114 with a prefabricated cover 138 (step 220 ). Typically, the cover 138 is welded to the opening.
[0065] Optionally, the step of positioning the replacement tube 108 between the stubs 126 , 128 , of the tube 102 , step 204 , includes the step of positioning slip rings 140 , 142 , in sliding engagement with the outer surface 144 of the replacement tube 108 over joints between the ends 118 , 120 , of the replacement tube 108 and the stubs 126 , 128 , thereby maintaining alignment of the replacement tube with the stubs while they are joined.
[0066] As noted above, the apparatus 150 can be configured to join the replacement tube 108 with the stub, steps 210 , 217 , by welding. Whichever method is used for joining, preferably, the apparatus 150 further includes a controller 170 for controlling power supplied to the rotatable torch assembly 152 , and operating the rotational drive assembly 164 , and the steps of joining the replacement tube to the stubs, steps 210 , 217 , are performed automatically once the tip 154 is aligned with a joint.
[0067] It is to be understood that even though numerous characteristics and advantages of certain embodiments of the present invention have been set forth in the foregoing description, together with details of the structure and function of various embodiments of the invention, this disclosure is illustrative only, and changes may be made in detail, especially in matters of structure and arrangement of parts within the principles of the present invention to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed.
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A method, a apparatus ( 150 ) and a prefabricated replacement tube ( 108 ) are provided for repairing a defect ( 112 ) in a tube ( 102 ), such as in a waterwall ( 100 ). In the method, a replacement tube ( 108 ) is prefabricated having a wall ( 116 ), a central opening ( 114 ) extending through a portion thereof and a predetermined length. A length of the tube ( 102 ), including the defect ( 112 ), equal to the predetermined length is removed. The replacement tube ( 108 ) is positioned between stubs ( 126, 128 ) of the tube ( 102 ), and a rotatable torch ( 152 ) of an automated welding apparatus ( 150 ) inserted through the opening ( 114 ) to align with a joint between an end ( 118, 112 ) of the replacement tube and a stub ( 126, 128 ). The torch ( 152 ) is rotated to join it to the stub ( 126, 128 ) along the entire joint. The torch ( 152 ) is then removed, turned 180 degrees, and reinserted to weld the remaining joint. Optionally, the replacement tube ( 108 ) is held in position before welding by slip rings ( 140, 142 ) which are slid down to cover the joints.
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CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] Pursuant to the provisions of 37 C.F.R. section 1.53(c), this non-provisional patent application claims the benefit of an earlier-filed provisional application. The provisional application was assigned Ser. No. 61/673,389 and it listed the same inventors.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable.
MICROFICHE APPENDIX
[0003] Not Applicable
BACKGROUND OF THE INVENTION
[0004] 1. Field of the Invention
[0005] This invention relates to the field of solar energy. More specifically, the invention comprises a solar collector incorporating multiple parabolic troughs and multiple collector pipes running through the troughs, in which the position of the pipes relative to the troughs is varied in order to keep the collector pipes in the focus of the troughs as the sun moves across the sky.
[0006] 2. Description of the Related Art
[0007] Solar energy collecting devices frequently use focusing lenses or reflectors to intensify the energy of the sun. Some collecting devices directly convert the solar energy to electrical energy using a photovoltaic array. Other collecting devices use the solar energy to heat a circulating working fluid. The present invention may be adapted to either type of collecting devices, as well as other types.
[0008] FIG. 1 shows an elevation view of a prior art solar collector suitable for heating a circulating working fluid. Parabolic trough 10 receives incoming rays 12 . Because the sun may be considered to be an infinite distance away, the incoming rays are effectively parallel. The parabola that is used to define parabolic trough 10 is selected to bring the parallel incoming rays to the same point central focal point 14 . Meeting this limitation produces the maximum collection efficiency.
[0009] The reflecting trough shown extends for any suitable distance in a direction that is perpendicular to the orientation of the view. For this type of collector, a conductive pipe containing the circulating working fluid is run through central focal point 14 , with the pipe running in a direction that is also perpendicular to the view of FIG. 1 .
[0010] Those skilled in the art will quickly realize that focal point 14 lies along the parabola's axis of symmetry 15 , so long as the incoming rays are parallel to the axis of symmetry. Because the reflecting trough actually extends for some distance in a direction that is perpendicular to the view of FIG. 1 , axis of symmetry 15 actually defines a “plane of symmetry” that extends along the length of the trough (the plane of symmetry being perpendicular to the orientation of the view).
[0011] In FIG. 1 , the sun is located directly above the reflector and the rays are coming straight down. Of course, the sun moves across the sky during the course of the day. Parabolic trough 10 must generally be tilted so that the plane of symmetry running through axis of symmetry 15 remains parallel with the incoming rays. This tilting action is generally referred to as an adjustment in “elevation.” It is indicated by the reciprocating arrow labeled tracking pivot 16 .
[0012] Prior art parabolic trough collectors typically include a suitable tilting mechanism in order to adjust the elevation of the collector. This mechanism regulates the elevation of the collector throughout the course of the day. An azimuth tracking mechanism is also frequently included. Such mechanisms tend to be complex and relatively expensive.
[0013] FIG. 5 shows a simplified representation of a prior art solar collector that includes both elevation and azimuth tracking. Three parallel parabolic trough reflectors 10 are contained within housing 46 . The parabolic troughs each have a finite length. The focus of each trough is therefore not a single point but rather an axis that runs through the focal point existing at each section taken through the trough. Thus, as seen in the view, the three trough reflectors have three parallel focus axes 44 .
[0014] In order to keep the housing perfectly perpendicular to the incoming solar rays it must be adjusted in both elevation and azimuth. Elevation adjustment 48 tilts housing 46 as indicated. Azimuth adjustment 50 rotates the housing so that it tracks the sun crossing the sky.
[0015] One may simply set the elevation adjustment to match the latitude of the location and gain a good approximation of the optimum elevation through the middle of the day. Azimuth, however, is not so easy to approximate. A simple visualization exercise demonstrates this fact: If one sets the azimuth of a device such as shown in FIG. 5 so that housing 46 directly faces the sun at sunrise, it is immediately apparent that the trough reflectors will not receive any direct rays by sunset. For this reason, a housing that lacks azimuth tracking is most often set so that the azimuth is correct when the sun is directly overhead.
[0016] This static approach works fairly well for photovoltaic cells but it does not work well for parabolic trough reflectors. FIG. 2 graphically illustrates the focusing error that occurs in the absence of a tracking mechanism. This figure shows a static parabolic trough 10 after the sun has moved away from its zenith position. Incoming rays 12 are no longer parallel to the parabola's axis of symmetry 15 (and plane of symmetry). The result is that the incoming rays are no longer reflected toward central focal point 14 . Instead, they have shifted to the right toward shifted focal zone 42 . The shift is primarily in a direction that is perpendicular to the plane of symmetry running through axis of symmetry 15 . The term “focal zone” is used because a parabola only brings incoming rays into sharp focus when the rays are parallel to the parabola's axis of symmetry. Once the incoming rays are angularly offset from the axis of symmetry, the parabola is no longer able to create a perfect focus. However, over a reasonable range of angular displacement, the parabola is still able to create a good concentration of solar energy and the region of this concentration is therefore referred to as a “focal zone.”
[0017] The reader will thereby appreciate that it is desirable to position a collector pipe within the focal zone even when the focal zone moves away from the trough collector's plane of symmetry. The present invention presents such a solution.
BRIEF SUMMARY OF THE INVENTION
[0018] The present invention comprises a trough collector for solar energy, with multiple parallel troughs preferably being contained within a single unit. The collector does not use conventional azimuth tracking in order to keep the sun's rays directed toward the parabola's focus as the sun moves across the sky. Instead, the relative position between the collecting device (preferably a conductive tube containing a circulating working fluid) and the plane of symmetry for each collector is adjusted so that the collecting device remains within the focal zone of the collector as the sun traverses the sky.
[0019] A trough reflector has only one true focal axis. As the incoming rays become misaligned with the parabola's plane of symmetry, the focus shifts laterally and blurs somewhat. However—over a reasonable range of travel—the blurring does not significantly degrade the collection efficiency.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0020] FIG. 1 is an elevation view, showing the operation of a prior art parabolic trough reflector.
[0021] FIG. 2 is an elevation view, showing the operation of the trough reflector of FIG. 1 as the incoming rays are angularly offset from the parabola's axis of symmetry.
[0022] FIG. 3 is an elevation view, showing how the focus of the trough reflector moves laterally as the sun transits the sky.
[0023] FIG. 4 is a perspective view, showing a depiction of a simple example of the present invention.
[0024] FIG. 5 is a perspective view, showing a prior art collector that is adjustable in both azimuth and elevation.
[0000]
REFERENCE NUMERALS IN THE DRAWINGS
10
parabolic trough
12
incoming ray
14
central focal point
15
axis of symmetry
16
tracking pivot
18
movable focal point
20
receiver pipe
22
inlet
24
outlet
26
serpentine connector pipe
28
movable frame
30
mounting bracket
32
gear rack
34
drive pinion
36
motor
38
chassis
40
mounting rail
42
shifted focal zone
44
focal axis
46
housing
48
elevation adjustment
50
azimuth adjustment
52
frame notch
DETAILED DESCRIPTION OF THE INVENTION
[0025] FIG. 3 shows a parabolic trough 10 with a depiction of a movable focal point 18 . The three positions shown in FIG. 3 represent three of the varying positions of the focal zone as the angle of incidence of the sun's rays on the trough reflector changes. The reader will observe how the translation of the focal zone occurs primarily in a direction that is perpendicular to the trough collector's plane of symmetry. A goal of the present invention is to position a suitable energy collection device in the focal zone and alter the relative position between the collecting device and the trough reflector as necessary to keep the collection device in the focal zone.
[0026] Many different devices could be employed to achieve this goal and the invention is by no means limited to any particular method or device. However, as the description of a few embodiments may aid the reader's understanding, such a description is provided.
[0027] FIG. 4 shows a simplified embodiment of the present invention that is able to achieve this goal. The reader should appreciate that the embodiment of FIG. 4 illustrates the important components of the invention but should not by any means be viewed as an optimized embodiment. An optimized embodiment would likely contain many more parallel reflector troughs and other components. However, the embodiment of FIG. 4 illustrates the important concepts.
[0028] Chassis 38 serves to mount the other components. It is depicted as a flat plate, though it will likely be a more complex structure for most embodiments. Four parallel parabolic troughs 10 are attached to the chassis using one or more supports 40 . The parabolic troughs are fixedly attached to the chassis. That is, in this embodiment the troughs do not move. The positioning of the collecting devices in the focal zones of the troughs is accomplished by moving the collecting devices relative to the stationary troughs. In other embodiments, just the opposite will be done.
[0029] A receiver pipe 20 is provided for each parabolic trough 10 . This receiver pipe is moved laterally with respect to the parabolic trough it lies within so that it remains within the focal zone of the parabolic trough as the sun transverses the sky. In the embodiment of FIG. 4 , the four receiver pipes 20 are joined by serpentine connector pipes 26 to form a serpentine flow path from inlet 22 to outlet 24 . In other words, a given control volume within the working fluid travels through every receiver pipe in the array. Such a flow path is generally referred to as a “series path.” One could also create a parallel flow path by using an inlet manifold, an outlet manifold, and a plurality of receiver pipes flowing therebetween. In such a parallel scheme, a given control volume would flow through only one of the receiver pipes as it travels from the inlet manifold to the outlet manifold.
[0030] In the series-flow scheme of FIG. 4 , all the pipes in the serpentine flow path are connected to movable frame 28 . The connection may assume a wide variety of forms. In this embodiment five mounting brackets 30 are used. The use of these mounting brackets unites movable frame 28 and all the pipes in the serpentine flow path into a single moving unit. The entire assembly therefore moves as one piece.
[0031] Movable frame 28 moves on a pair of mounting rails 40 . Frame notches 52 in movable frame 28 allow movable frame 28 (and the attached piping) to translate in the directions indicated by the reciprocating arrow. Linear bearings may be employed to allow a smooth movement. A low-friction sliding block may also be placed in each frame notch. Such blocks could be made of NYLON, DELRIN, or any other suitable material. The translation required will be quite slow, so a fairly crude sliding connection will suffice in many applications.
[0032] It is, however, preferable to move the frame in a controlled fashion so that the four receiver pipes 20 in this embodiment are accurately maintained in the focal zone of the four parabolic troughs 10 (as the sun transits the sky). In the embodiment of FIG. 4 , gear rack 32 is provided somewhere on the movable frame. Drive pinion 34 engages gear rack 32 on movable frame 28 . The drive pinion is driven by motor 36 (preferably through a set of reduction gears). Motor 36 is attached to chassis 38 .
[0033] Thus, by selectively energizing motor 36 , movable frame 28 can be moved with respect to chassis 38 . The motion may be controlled in any number of suitable ways. One simple approach is to use an open-loop “timetable” that moves the receiver pipes 20 to a predetermined position according to the time of day. One could also employ a closed-loop control system. In this arrangement an energy sensor could be placed at a suitable location on one of the receiver pipes. The control system would then be activated every few minutes during daylight hours and the closed-loop motion control system would adjust the position of the movable frame in order to maximize the energy received by the energy sensor. The energy sensor could be a simple temperature probe or some type of light intensity sensor. Of course, one could also employ a timetable motion controller that is relined by the application of a closed-loop energy sensing function.
[0034] Solar tracking is thus performed by the motion of movable frame 28 along with its attached components. Returning briefly to FIG. 1 , the reader will recall that each parabolic trough reflector includes an axis of symmetry 15 and a plane of symmetry (the plane of symmetry simply being the axis of symmetry projected along the length of the trough). As explained with respect to FIGS. 2 and 3 , the focal zone translates laterally as the sun's angle of incidence on the trough reflector varies. This translation is almost exclusively in a direction that is perpendicular to the axis of symmetry/plane of symmetry. It is therefore apparent that if one can vary the position of the collection device in a direction that is perpendicular to the axis of symmetry/plane of symmetry, one may continually position the collection device in the focal zone.
[0035] The embodiment of FIG. 4 achieves the desired positioning of the collection device(s). By activating motor 36 in a controlled fashion, movable frame 28 and its associated receiver pipes 20 is translated in a direction that is perpendicular to the planes of symmetry of the four parabolic trough collectors. This movable feature allows the device to “track” the azimuth of the sun as it transits the sky. The displacement of the center of each receiver pipe from the axis of symmetry/plane of symmetry is referred to as the “receiver pipe displacement distance.” Using this nomenclature, those skilled in the art will immediately recognize that a value for the “receiver pipe displacement distance” may be positive, negative, or zero. In other words, although the displacement distance is defined, the actual value of that displacement may be zero at a particular point in time.
[0036] Chassis 38 may be set to a fixed elevation setting or elevation tracking may be provided using a conventional mechanism that tilts the entire assembly with respect to the horizontal. If the chassis is static, it is preferable to set the elevation of chassis 38 in order to maximize the efficiency of the collector. The elevation may be set according to latitude. On the equator, the elevation would be zero and chassis 38 would simply be parallel to the ground. At fifteen degrees north latitude, chassis 38 would preferably be set to an elevation of 15 degrees or something slightly less than this to achieve the best approximation of true elevation tracking. For example, the chassis could be mounted so that the side of the chassis proximate motor 36 in the embodiment of FIG. 4 would be lower than the distal side of the chassis (with the upward facing surface of the chassis lying at an angle of 15 degrees to the horizontal).
[0037] Those skilled in the art will realize that many other components beyond those depicted in FIG. 4 are preferred in the creation of an efficient collector. For example, it is preferable to enclose many of the components in an enclosure in order to elevate the internal temperatures. Thus, the chassis would typically include opaque side walls extending up and beyond movable frame 28 . A clear cover would then be placed over the movable frame and joined to the side walls in order to create a “greenhouse effect.” It is also preferable to include mounting bracketry to facilitate the attachment of the chassis to some other structure. All these components are well known to those skilled in the art and they have not been illustrated.
[0038] Those skilled in the art will also realize that many other embodiments are possible within the inventive scope of the present invention. As one example, one could design a collector where the receiver pipes remain fixed but the parabolic troughs move laterally to track the sun. Returning to FIG. 4 , such an embodiment would involve connecting the reflector troughs to movable frame 28 and connecting the receiver pipes to the chassis so that they remain stationary. One could also choose to move both the reflector troughs and the receiver pipes in order to maintain the desired relative position between the two.
[0039] It is also possible to combine the azimuth-accommodating features of the present invention with conventional azimuth-tracking devices. For example, a crude azimuth turntable could be provided that sets the device of FIG. 4 in one of three azimuth positions—morning, noon, and evening. The motion between the receiver pipes and the reflector troughs could then be used to optimize the performance of the device in each of these three stationary azimuth positions.
[0040] Thus, although the preceding descriptions contain significant detail, they should properly be viewed as disclosing examples of the inventions' many possible embodiments rather than disclosing the full scope of the invention itself. The scope of the invention will properly be determined by the claims to follow rather than any specific example provided.
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A trough collector for solar energy, with multiple parallel troughs preferably being contained within a single unit. The collector does not use conventional azimuth tracking in order to keep the sun's rays directed toward the parabola's focus as the sun moves across the sky. Instead, the relative position between the collecting device (preferably a conductive tube containing a circulating working fluid) and the plane of symmetry for each collector is adjusted so that the collecting device remains within the focal zone of the collector as the sun traverses the sky.
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CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
This application is a divisional of U.S. application Ser. No. 13/558,757, filed Jul. 26, 2012, which is a continuation of U.S. application Ser. No. 12/078,955, filed Apr. 8, 2008, which is a divisional of U.S. application Ser. No. 11/603,124, filed Nov. 22, 2006, which is a continuation of U.S. application Ser. No. 10/851,481, filed May 24, 2004, which claims benefit of U.S. Provisional Application Ser. No. 60/472,407, filed on May 22, 2003, the entire contents of which applications are incorporated by reference herein.
FIELD OF THE INVENTION
This invention pertains generally to prostacyclin analogs and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. Through these prostacyclin-mimetic mechanisms, the compounds of the present invention may be used in the treatment of/for: pulmonary hypertension, ischemic diseases (e.g., peripheral vascular disease, Raynaud's phenomenon, Scleroderma, myocardial ischemia, ischemic stroke, renal insufficiency), heart failure (including congestive heart failure), conditions requiring anticoagulation (e.g., post MI, post cardiac surgery), thrombotic microangiopathy, extracorporeal circulation, central retinal vein occlusion, atherosclerosis, inflammatory diseases (e.g., COPD, psoriasis), hypertension (e.g., preeclampsia), reproduction and parturition, cancer or other conditions of unregulated cell growth, cell/tissue preservation and other emerging therapeutic areas where prostacyclin treatment appears to have a beneficial role. These compounds may also demonstrate additive or synergistic benefit in combination with other cardiovascular agents (e.g., calcium channel blockers, phosphodiesterase inhibitors, endothelial antagonists, antiplatelet agents).
BACKGROUND OF THE INVENTION
Many valuable pharmacologically active compounds cannot be effectively administered orally for various reasons and are generally administered via intravenous or intramuscular routes. These routes of administration generally require intervention by a physician or other health care professional, and can entail considerable discomfort as well as potential local trauma to the patient.
One example of such a compound is treprostinil, a chemically stable analog of prostacyclin. Although treprostinil sodium (Remodulin®) is approved by the Food and Drug Administration (FDA) for subcutaneous administration, treprostinil as the free acid has an absolute oral bioavailability of less than 10%. Accordingly, there is clinical interest in providing treprostinil orally.
Thus, there is a need for a safe and effective method for increasing the systemic availability of treprostinil via administration of treprostinil or treprostinil analogs.
SUMMARY OF THE INVENTION
In one embodiment, the present invention provides a compound having structure I:
wherein,
R 1 is independently selected from the group consisting of H, substituted and unsubstituted benzyl groups, and groups wherein OR 1 are substituted or unsubstituted glycolamide esters;
R 2 and R 3 may be the same or different and are independently selected from the group consisting of H, phosphate and groups wherein OR 2 and OR 3 form esters of amino acids or proteins, with the proviso that all of R 1 , R 2 and R 3 are not H;
an enantiomer of the compound;
and pharmaceutically acceptable salts of the compound and polymorphs.
In some of these embodiments, R 1 is a substituted or unsubstituted benzyl group, such as CH 2 C 6 H 5 . In other embodiments, OR 1 is a substituted or unsubstituted glycolamide ester, R 1 is —CH 2 CONR 4 R 5 , R 4 and R 5 may be the same or different and are independently selected from the group consisting of H, OH, substituted and unsubstituted alkyl groups, —(CH 2 ) m CH 3 , —CH 2 OH, and —CH 2 (CH 2 ) n OH, with the proviso that m is 0, 1, 2, 3 or 4, and n is 0, 1, 2, 3 or 4. In certain of these embodiments one or both of R 4 and R 5 are independently selected from the group consisting of H, —OH, —CH 3 , or —CH 2 CH 2 OH. In any of the previously discussed embodiments, one or both of R 2 and R 3 can be H. In some enantiomers of the compound R 1 ═R 2 ═R 3 ═H, or R 2 ═R 3 ═H and R 1 =valinyl amide.
In still further embodiments of the present compounds R 2 and R 3 are independently selected from phosphate and groups wherein OR 2 and OR 3 are esters of amino acids, dipeptides, esters of tripeptides and esters of tetrapeptides. In some compounds only one of R 2 or R 3 is a phosphate group. In other compounds R 2 and R 3 are independently selected from groups wherein OR 2 and OR 3 are esters of amino acids, such as esters of glycine or alanine. In any of the above embodiments, one of R 2 and R 3 are H. In certain of the present compounds, the oral bioavailability of the compound is greater than the oral bioavailability of treprostinil, such as at least 50% or 100% greater than the oral bioavailability of treprostinil. The above compounds can further comprise an inhibitor of p-glycoprotein transport. Any of these compounds can also further comprise a pharmaceutically acceptable excipient.
The present invention also provides a method of using the above compounds therapeutically of/for: pulmonary hypertension, ischemic diseases, heart failure, conditions requiring anticoagulation, thrombotic microangiopathy, extracorporeal circulation, central retinal vein occlusion, atherosclerosis, inflammatory diseases, hypertension, reproduction and parturition, cancer or other conditions of unregulated cell growth, cell/tissue preservation and other emerging therapeutic areas where prostacyclin treatment appears to have a beneficial role. A preferred embodiment is a method of treating pulmonary hypertension and/or peripheral vascular disease in a subject comprising orally administering a pharmaceutically effective amount of a compound of structure II:
wherein,
R 1 is independently selected from the group consisting of H, substituted and unsubstituted alkyl groups, arylalkyl groups and groups wherein OR 1 form a substituted or unsubstituted glycolamide ester;
R 2 and R 3 may be the same or different and are independently selected from the group consisting of H, phosphate and groups wherein OR 2 and OR 3 form esters of amino acids or proteins, with the proviso that all of R 1 , R 2 and R 3 are not H;
an enantiomer of the compound; and
a pharmaceutically acceptable salt or polymorph of the compound.
In some of these methods, when OR 1 forms a substituted or unsubstituted glycolamide ester, R 1 is —CH 2 CONR 4 R 5 , wherein R 4 and R 5 may be the same or different and are independently selected from the group consisting of H, OH, substituted and unsubstituted alkyl groups, —(CH 2 ) m CH 3 , —CH 2 OH, and —CH 2 (CH 2 ) n OH, with the proviso that m is 0, 1, 2, 3 or 4, and n is 0, 1, 2, 3 or 4. In other methods R 1 is a C 1 -C 4 alkyl group, such as methyl, ethyl, propyl or butyl. In the disclosed methods, R 1 can also be a substituted or unsubstituted benzyl group. In other methods, R 1 can be —CH 3 or —CH 2 C 6 H 5 . In still other methods R 4 and R 5 are the same or different and are independently selected from the group consisting of H, OH, —CH 3 , and —CH 2 CH 2 OH. In yet other methods, one or both of R 2 and R 3 are H. Alternatively, one or both of R 2 and R 3 are not H and R 2 and R 3 are independently selected from phosphate and groups wherein OR 2 and OR 3 are esters of amino acids, dipeptides, esters of tripeptides and esters of tetrapeptides. In some methods, only one of R 2 or R 3 is a phosphate group. In additional methods, R 2 and R 3 are independently selected from groups wherein OR 2 and OR 3 are esters of amino acids, such as esters of glycine or alanine. In further methods one of R 1 and R 2 is H. In some methods, enantiomers of the compound where R 1 ═R 2 ═R 3 ═H, or R 2 ═R 3 ═H and R 1 =valinyl amide are used.
In various methods the oral bioavailability of the compound is greater than the oral bioavailability of treprostinil, such as at least 50% or 100% greater than the oral bioavailability of treprostinil. The present methods can also comprise administering pharmaceutically effective amount of a p-glycoprotein inhibitor, simultaneously, sequentially, or prior to administration of the compound of structure II. In some embodiments the p-glycoprotein inhibitor is administered orally or intravenously. The disclosed methods can be used to treat pulmonary hypertension.
The present invention also provides a method of increasing the oral bioavailability of treprostinil or pharmaceutically acceptable salt thereof, comprising administering a pharmaceutically effective amount of a p-glycoprotein inhibitor and orally administering a pharmaceutically effective amount of treprostinil to a subject. In certain of these embodiments the p-glycoprotein inhibitor is administered prior to or simultaneously with the treprostinil. The route of the p-glycoprotein inhibitor administration can vary, such as orally or intravenously. The present invention also provides a composition comprising treprostinil or a pharmaceutically acceptable salt thereof and a p-glycoprotein inhibitor.
The present compound can also be administered topically or transdermally.
Pharmaceutical formulations according to the present invention are provided which include any of the compounds described above in combination with a pharmaceutically acceptable carrier.
The compounds described above can also be used to treat cancer.
Further objects, features and advantages of the invention will be apparent from the following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A and 1B respectively show plasma concentration versus time curves for intravenous and intraportal dosing of treprostinil diethanolamine salt in rats as described in Example 1;
FIGS. 2A , 2 B and 2 C respectively show plasma concentration versus time curves for intraduodenal, intracolonic and oral dosing of treprostinil diethanol amine salt in rats as described in Example 1;
FIG. 3 shows on a logarithmic scale the average plasma concentration versus time curves for the routes of administration described in Example 1;
FIG. 4 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following oral administration in rats of treprostinil methyl ester as described in Example 2;
FIG. 5 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following oral administration in rats of treprostinil benzyl ester as described in Example 2;
FIG. 6 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following oral administration in rats of treprostinil diglycine as described in Example 2;
FIG. 7 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following oral administration in rates of treprostinil benzyl ester (0.5 mg/kg) and treprostinil diglycine (0.5 mg/kg) as described in Example 2 compared to treprostinil (1 mg/per kg).
FIG. 8 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following intraduodenal administration of treprostinil monophosphate (ring) as described in Example 3;
FIG. 9 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following intraduodenal administration of treprostinil monovaline (ring) as described in Example 3;
FIG. 10 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following intraduodenal administration of treprostinil monoalanine (ring) as described in Example 3;
FIG. 11 is a graphical representation of the plasma concentration versus time curve for treprostinil in rat following intraduodenal administration of treprostinil monoalanine (chain) as described in Example 3; and
FIG. 12 is a graphical representation of the average plasma concentration versus time curve for each prodrug compared to treprostinil alone from Example 1, as described in Example 3. Treprostinil was dosed at 1 mg/kg whereas the prodrugs were dosed at 0.5 mg/kg.
FIGS. 13A-13D respectively show doses, administered every two hours for four doses, for either 0.05 mg per dose (total=0.2 mg), 0.125 mg per dose (total=0.5 mg), 0.25 mg per dose (total=1.0 mg), or 0.5 mg per dose (total=2.0 mg).
FIG. 14 shows pharmacokinetic profiles of UT-15C sustained release tablets and sustained release capsules, fasted and fed state.
FIG. 15 shows an X ray powder diffraction spectrum of the polymorph Form A.
FIG. 16 shows an IR spectrum of the polymorph Form A.
FIG. 17 shows a Raman spectrum of the polymorph Form A.
FIG. 18 shows thermal data of the polymorph Form A.
FIG. 19 shows moisture sorption data of the polymorph Form A.
FIG. 20 shows an X ray powder diffraction spectrum of the polymorph Form B.
FIG. 21 shows thermal data of the polymorph Form B.
FIG. 22 shows moisture sorption data of the polymorph Form B.
DETAILED DESCRIPTION OF THE INVENTION
Unless otherwise specified, “a” or “an” means “one or more”. The present invention provides compounds and methods for inducing prostacyclin-like effects in a subject or patient. The compounds provided herein can be formulated into pharmaceutical formulations and medicaments that are useful in the methods of the invention. The invention also provides for the use of the compounds in preparing medicaments and pharmaceutical formulations and for use of the compounds in treating biological conditions related to insufficient prostacyclin activity as outlined in the Field of Invention. The present invention also provides compounds and methods for the treatment of cancer and cancer related disorders.
In some embodiments, the present compounds are chemical derivatives of (+)-treprostinil, which has the following structure:
Treprostinil is a chemically stable analog of prostacyclin, and as such is a potent vasodilator and inhibitor of platelet aggregation. The sodium salt of treprostinil, (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid monosodium salt, is sold as a solution for injection as Remodulin® which has been approved by the Food and Drug Administration (FDA) for treatment of pulmonary hypertension. In some embodiments, the present compounds are derivatives of (−)-treprostinil, the enantiomer of (+)-treprostinil. A preferred embodiment of the present invention is the diethanolamine salt of treprostinil. The present invention further includes polymorphs of the above compounds, with two forms, A and B, being described in the examples below. Of the two forms, B is preferred. A particularly preferred embodiment of the present invention is form B of treprostinil diethanolamine.
In some embodiments, the present compounds are generally classified as prodrugs of treprostinil that convert to treprostinil after administration to a patient, such as through ingestion. In some embodiments, the prodrugs have little or no activity themselves and only show activity after being converted to treprostinil. In some embodiments, the present compounds were produced by chemically derivatizing treprostinil to make stable esters, and in some instances, the compounds were derivatized from the hydroxyl groups. Compounds of the present invention can also be provided by modifying the compounds found in U.S. Pat. Nos. 4,306,075 and 5,153,222 in like manner.
In one embodiment, the present invention provides compounds of structure I:
wherein,
R 1 is independently selected from the group consisting of H, substituted and unsubstituted benzyl groups and groups wherein OR 1 are substituted or unsubstituted glycolamide esters;
R 2 and R 3 may be the same or different and are independently selected from the group consisting of H, phosphate and groups wherein OR 2 and OR 3 form esters of amino acids or proteins, with the proviso that all of R 1 , R 2 and R 3 are not H;
enantiomers of the compound; and
pharmaceutically acceptable salts of the compound.
In some embodiments wherein OR 1 are substituted or unsubstituted glycolamide esters, R 1 is —CH 2 CONR 4 R 5 and R 4 and R 5 may be the same or different and are independently selected from the group consisting of H, OH, substituted and unsubstituted alkyl groups, —(CH 2 ) m CH 3 , —CH 2 OH, and —CH 2 (CH 2 ) n OH, with the proviso that m is 0, 1, 2, 3 or 4, and n is 0, 1, 2, 3 or 4.
One skilled in the art will also readily recognize that where members are grouped together in a common manner, such as in a Markush group or the groups described in the R of structures I and II above and below, the present invention encompasses not only the entire group listed as a whole, but each member of the group individually and all possible subgroups of the main group. Accordingly, for all purposes, the present invention encompasses not only the main group, but also the main group absent one or more of the group members. The present invention also envisages the explicit exclusion of one or more of any of the group members in the claimed invention. For example, R 1 can specifically exclude H, substituted and unsubstituted benzyl groups, or groups wherein OR 1 are substituted or unsubstituted glycolamide esters.
In some embodiments, R 1 is a substituted or unsubstituted benzyl groups, such as —CH 2 C 6 H 5 , —CH 2 C 6 H 4 NO 2 , —CH 2 C 6 H 4 OCH 3 , —CH 2 C 6 H 4 Cl, —CH 2 C 6 H 4 (NO 2 ) 2 , or —CH 2 C 6 H 4 F. The benzyl group can be ortho, meta, para, ortho/para substituted and combinations thereof. Suitable substituents on the aromatic ring include halogens (fluorine, chlorine, bromine, iodine), —NO 2 groups, —OR 16 groups wherein R 16 is H or a C 1 -C 4 alkyl group, and combinations thereof.
Alternatively, when R 1 is —CH 2 CONR 4 R 5 then R 4 and R 5 may be the same or different and are independently selected from the group consisting of H, OH, —CH 3 , and —CH 2 CH 2 OH. In these compounds where R 1 is not H, generally one or both of R 2 and R 3 are H.
In some embodiment one or both of R 2 and R 3 are H and R 1 is —CH 2 CONR 4 R 5 , and one or both of R 4 and R 5 are H, —OH, —CH 3 , —CH 2 CH 2 OH.
In compounds where one or both of R 2 and R 3 are not H, R 2 and R 3 can be independently selected from phosphate and groups wherein OR 2 and OR 3 are esters of amino acids, dipeptides, esters of tripeptides and esters of tetrapeptides. In some embodiments, only one of R 2 or R 3 is a phosphate group. In compounds where at least one of R 2 and R 3 is not H, generally R 1 is H. In additional embodiments, one of R 2 and R 3 are H and thus the compound of structure I is derivatized at only one of R 2 and R 3 . In particular compounds, R 2 is H and R 3 is defined as above. In additional embodiments, R 1 and R 3 are H and R 2 is a group wherein OR 2 is an ester of an amino acid or a dipeptide. In further embodiments, R 1 and R 2 are H and R 3 is a group wherein OR 3 is an ester of an amino acid or a dipeptide.
When one or both of the OR 2 and OR 3 groups form esters of amino acids or peptides, i.e., dipeptides, tripeptides or tetrapeptides, these can be depicted generically as —COCHR 6 NR 7 R 8 wherein R 6 is selected from the group consisting of amino acid side chains, R 7 and R 8 may be the same or different and are independently selected from the group consisting of H, and —COCHR 9 NR 10 R 11 . Generally, reference to amino acids or peptides refers to the naturally occurring, or L-isomer, of the amino acids or peptides. However, the present compounds and methods are not limited thereto and D-isomer amino acid residues can take the place of some or all of L-amino acids. In like manner, mixtures of D- and L-isomers can also be used. In the embodiments wherein the amino acid is proline, R 7 together with R 6 forms a pyrrolidine ring structure. R 6 can be any of the naturally occurring amino acid side chains, for example —CH 3 (alanine), —(CH 2 ) 3 NHCNH 2 NH (arginine), —CH 2 CONH 2 (asparagine), —CH 2 COOH (aspartic acid), —CH 2 SH (cysteine), —(CH 2 ) 2 CONH 2 (glutamine), —(CH 2 ) 2 COOH (glutamic acid), —H (glycine), —CHCH 3 CH 2 CH 3 (isoleucine), —CH 2 CH(CH 3 ) 2 (leucine), —(CH 2 ) 4 NH 2 (lysine), —(CH 2 ) 2 SCH 3 (methionine), —CH 2 Ph (phenylalanine), —CH 2 OH (serine), —CHOHCH 3 (threonine), —CH(CH 3 ) 2 (valine),
—(CH 2 ) 3 NHCONH 2 (citrulline) or —(CH 2 ) 3 NH 2 (ornithine). Ph designates a phenyl group.
In the above compounds, R 7 and R 8 may be the same or different and are selected from the group consisting of H, and —COCHR 9 NR 10 R 11 , wherein R 9 is a side chain of amino acid, R 10 and R 11 may be the same or different and are selected from the group consisting of H, and —COCHR 12 NR 13 R 14 , wherein R 12 is an amino acid side chain, R 13 and R 14 may be the same or different and are independently selected from the group consisting of H, and —COCHR 15 NH 2 . One skilled in the art will realize that the peptide chains can be extended on the following scheme to the desired length and include the desired amino acid residues.
In the embodiments where either or both of OR 2 and OR 3 groups form an ester of a peptide, such as dipeptide, tripeptide, tetrapeptide, etc. the peptides can be either homopeptides, i.e., repeats of the same amino acid, such as arginyl-arginine, or heteropeptides, i.e., made up of different combinations of amino acids. Examples of heterodipeptides include alanyl-glutamine, glycyl-glutamine, lysyl-arginine, etc.
As will be understood by the skilled artisan when only one R 7 and R 8 includes a peptide bond to further amino acid, such as in the di, tri and tetrapeptides, the resulting peptide chain will be linear. When both R 7 and R 8 include a peptide bond, then the peptide can be branched.
In still other embodiments of the present compounds R 1 is H and one of R 2 or R 3 is a phosphate group or H while the other R 2 or R 3 is a group such the OR 2 or OR 3 is an ester of an amino acid, such as an ester of glycine or alanine
Pharmaceutically acceptable salts of these compounds as well as pharmaceutical formulation of these compounds are also provided.
Generally, the compounds described herein have enhanced oral bioavailability compared to the oral bioavailability of treprostinil, either in free acid or salt form. The described compounds can have oral bioavailability that is at least 25%, 50% 100%, 200%, 400% or more compared to the oral bioavailability of treprostinil. The absolute oral bioavailability of these compounds can range between 10%, 15%, 20%, 25%, 30% and 40%, 45%, 50%, 55%, 60% or more when administered orally. For comparison, the absolute oral bioavailability of treprostinil is on the order of 10%, although treprostinil sodium has an absolute bioavailability approximating 100% when administered by subcutaneous infusion.
As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein, and in particular the bioavailability ranges described herein also encompass any and all possible subranges and combinations of subranges thereof. As only one example, a range of 20% to 40%, can be broken down into ranges of 20% to 32.5% and 32.5% to 40%, 20% to 27.5% and 27.5% to 40%, etc. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” “more than” and the like include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. In the same manner, all ratios disclosed herein also include all subratios falling within the broader ratio.
Administration of these compounds can be by any route by which the compound will be bioavailable in effective amounts including oral and parenteral routes. The compounds can be administered intravenously, topically, subcutaneously, intranasally, rectally, intramuscularly, transdermally or by other parenteral routes. When administered orally, the compounds can be administered in any convenient dosage form including, for example, capsule, tablet, liquid, suspension, and the like.
Testing has shown that that treprostinil can be irritating upon skin contact. In contrast, some of the compounds disclosed herein, generally as prodrugs of treprostinil, are not irritating to the skin. Accordingly, the present compounds are well suited for topical or transdermal administration.
When administered to a subject, the above compounds, and in particular the compounds of structure I, are prostacyclin-mimetic and are useful in treating conditions or disorders where vasodilation and/or inhibition of platelet aggregation or other disorders where prostacyclin has shown benefit, such as in treating pulmonary hypertension. Accordingly, the present invention provides methods for inducing prostacyclin-like effects in a subject comprising administering a pharmaceutically effective amount of one or more of the compounds described herein, such as those of structure I above, preferably orally, to a patient in need of such treatment. As an example, the vasodilating effects of the present compounds can be used to treat pulmonary hypertension, which result from various forms of connective tissue disease, such as lupus, scleroderma or mixed connective tissue disease. These compounds are thus useful for the treatment of pulmonary hypertension.
In another embodiment, the present invention also provides methods of promoting prostacyclin-like effect in a subject by administering a pharmaceutically effective amount of a compound of structure II:
wherein,
R 1 is independently selected from the group consisting of H, substituted and unsubstituted alkyl groups, arylalkyl groups and groups wherein OR 1 form a substituted or unsubstituted glycolamide ester;
R 2 and R 3 may be the same or different and are independently selected from the group consisting of H, phosphate and groups wherein OR 2 and OR 3 form esters of amino acids or proteins, with the proviso that all of R 1 , R 2 and R 3 are not H;
an enantiomer of the compound; and
a pharmaceutically acceptable salt of the compound.
In groups wherein OR 1 form a substituted or unsubstituted glycolamide ester, R 1 can be —CH 2 CONR 4 R 5 , wherein R 4 and R 5 may be the same or different and are independently selected from the group consisting of H, OH, substituted and unsubstituted alkyl groups, —(CH 2 ) m CH 3 , —CH 2 OH, and —CH 2 (CH 2 ) n OH, with the proviso that m is 0, 1, 2, 3 or 4, and n is 0, 1, 2, 3 or 4.
In other methods of inducing vasodilation or treating hypertension, R 1 can be a C 1 -C 4 alkyl group, such as methyl, ethyl, propyl or butyl. In other methods R 1 is a substituted or unsubstituted benzyl groups, such as —CH 2 C 6 H 5 , —CH 2 C 6 H 4 NO 2 , —CH 2 C 6 H 4 OCH 3 , —CH 2 C 6 H 4 Cl, —CH 2 C 6 H 4 (NO 2 ) 2 , or —CH 2 C 6 H 4 F. The benzyl group can be ortho, meta, para, ortho/para substituted and combinations thereof. Suitable substituents on the aromatic ring include halogens (fluorine, chlorine, bromine, iodine), —NO 2 groups, —OR 16 groups wherein R 16 is H or a C 1 -C 4 alkyl group, and combinations thereof.
Alternatively, when R 1 is —CH 2 CONR 4 R 5 then R 4 and R 5 may be the same or different and are independently selected from the group consisting of H, OH, —CH 3 , and —CH 2 CH 2 OH. In these methods, where R 1 is not H, generally one or both of R 2 and R 3 are H.
In some methods, one or both of R 2 and R 3 are H and R 1 is —CH 3 , —CH 2 C 6 H 5 . In other methods where one or both of R 2 and R 3 are H, then R 1 is —CH 2 CONR 4 R 5 , and one or both of R 4 and R 5 are H, —OH, —CH 3 , —CH 2 CH 2 OH.
In methods where one or both of R 2 and R 3 are not H, R 2 and R 3 can be independently selected from phosphate and groups wherein OR 2 and OR 3 are esters of amino acids, dipeptides, esters of tripeptides and esters of tetrapeptides. In some embodiments, only one of R 2 or R 3 is a phosphate group. In methods where at least one of R 2 and R 3 is not H, generally R 1 is H. In other methods, one of R 2 or R 3 is H and the other R 2 or R 3 is as defined elsewhere herein. In some methods, R 2 is H and R 3 is not H. In additional embodiments, R 1 and R 3 are H and R 2 is a group wherein OR 2 is an ester of an amino acid or a dipeptide. In further embodiments, R 1 and R 2 are H and R 3 is a group wherein OR 3 is an ester of an amino acid or a dipeptide.
In the methods, where one or both of the OR 2 and OR 3 groups form esters of amino acids or peptides, i.e., dipeptides, tripeptides or tetrapeptides, these can be depicted generically as —COCHR 6 NR 7 R 8 wherein R 6 is selected from the group consisting of amino acid side chains, R 7 and R 8 may be the same or different and are independently selected from the group consisting of H, and —COCHR 9 NR 10 R 11 . In the embodiments wherein the amino acid is proline, R 7 together with R 6 forms a pyrrolidine ring structure. R 6 can be any of the naturally occurring amino acid side chains, for example —CH 3 (alanine), —(CH 2 ) 3 NHCNH 2 NH (arginine), —CH 2 CONH 2 (asparagine), —CH 2 COOH (aspartic acid), —CH 2 SH (cysteine), —(CH 2 ) 2 CONH 2 (glutamine), —(CH 2 ) 2 COOH (glutamic acid), —H (glycine), —CHCH 3 CH 2 CH 3 (isoleucine), —CH 2 CH(CH 3 ) 2 (leucine), —(CH 2 ) 4 NH 2 (lysine), —(CH 2 ) 2 SCH 3 (methionine), —CH2Ph (phenylalanine), —CH 2 OH (serine), —CHOHCH 3 (threonine), —CH(CH 3 ) 2 (valine),
—(CH 2 ) 3 NHCONH 2 (citrulline) or —(CH 2 ) 3 NH 2 (ornithine). Ph designates a phenyl group.
In the above methods, R 7 and R 8 may be the same or different and are selected from the group consisting of H, and —COCHR 9 NR 10 R 11 , wherein R 9 is a side chain of amino acid, R 10 and R 11 may be the same or different and are selected from the group consisting of H, and —COCHR 12 NR 13 R 14 , wherein R 12 is an amino acid side chain, R 13 and R 14 may be the same or different and are independently selected from the group consisting of H, and —COCHR 15 NH 2 . One skilled in the art will realize that the peptide chains can be extended on the following scheme to the desired length and include the desired amino acid residues.
In the embodiments where either or both of OR 2 and OR 3 groups form an ester of a peptide, such as dipeptide, tripeptide, tetrapeptide, etc. the peptides can be either homopeptides, i.e., repeats of the same amino residue, or heteropeptides, i.e., made up of different combinations of amino acids.
As will be understood by the skilled artisan when only one of R 7 and R 8 includes a peptide bond to further amino acid, such as in the di, tri and tetrapeptides, the resulting peptide chain will be linear. When both R 7 and R 8 include a peptide bond, then the peptide can be branched.
In still other methods R 1 is H and one of R 2 or R 3 is a phosphate group or H while the other R 2 or R 3 is a group such the OR 2 or OR 3 is an ester of an amino acid, such as an ester of glycine or alanine.
In some methods, the administered compound can have an oral bioavailability that is at least 25%, 50% 100%, 200%, 400% of the oral bioavailability of treprostinil. It is generally preferred to administer compounds that have higher absolute oral bioavailabilities, such as 15%, 20%, 25%, 30% and 40%, 45%, 50%, 55%, 60% or more when administered orally.
Treprostinil has also been discovered to inhibit metastasis of cancer cells as disclosed in U.S. patent application Ser. No. 10/006,197 filed Dec. 10, 2001 and Ser. No. 10/047,802 filed Jan. 16, 2002, both of which are hereby incorporated into this application. Accordingly, the compounds described above, and in particular those of structure I and II, can also be used in the treatment of cancer and cancer related disorders, and as such the present invention provides pharmaceutical compositions and methods for treating cancer. Suitable formulations and methods of using the present compounds can be achieved by substituting the compounds of the present invention, such as those of structure I and II and in particular prodrugs of treprostinil, for the active compounds disclosed in U.S. patent application Ser. Nos. 10/006,197 and 10/047,802 filed Jan. 16, 2002.
Synthesis of the following compounds of structure I and structure II can be achieved as follows:
Synthesis of Methyl Ester of Treprostinil (2) and Biphosphate Ester of Treprostinil
Synthesis of Methyl Ester of Treprostinil (2)
Methyl ester of treprostinil (2) was prepared by treating 1.087 g (2.8 mmoles) of treprostinil (1) with 50 ml of a saturated solution of dry hydrochloric acid in methanol. After 24 hours at room temperature, the methanol was evaporated to dryness and the residue was taken in 200 ml dichloromethane. The dichloromethane solution was washed with a 10% aqueous potassium carbonate solution, and then with water to a neutral pH, it was dried over sodium sulfate, filtered and the solvent was removed in vacuo affording treprostinil methyl ester (2) in 98% yield as a yellow oil. The crude methyl ester was used as such in subsequent reactions.
Synthesis of Biphosphate Ester of Treprostinil (4)
The procedure was adapted after Steroids, 2(6), 567-603 (1963). The methyl ester of treprostinil (2) (60 mg, 0.15 mmoles) was dissolved in 2 ml dry pyridine and a pyridinium solution of the previously prepared pyridinium solution of 2-cyanoethylphosphate 1M (0.3 ml, 0.3 mmoles) (cf. Methods in Enzymology, 1971, 18(c), 54-57) were concentrated to dryness in vacuo at 40° C. Anhydrous pyridine was added and the reaction mixture was again concentrated; the operation was repeated twice in order to remove water completely. Finally the residue was dissolved in 2 ml anhydrous pyridine and 190 mg (0.9 mmoles) dicyclohexylcarbodiimide were added as a solution in 2 ml anhydrous pyridine. The reaction mixture in a closed flask was stirred magnetically for 48 hours at room temperature. 1 ml water was added and after one hour, the mixture was concentrated to a thick paste in vacuo. The reaction mixture was treated overnight at room temperature with 3 ml of a 1/9 water/methanol solution containing 35 mg sodium hydroxide. The white solid (dicyclohexylurea) formed was removed by filtration and it was washed well with water. The aqueous-methanolic solution was concentrated almost to dryness in vacuo, water was added and the solution was extracted with n-butanol (3×2 ml), then with methylene chloride (1×2 ml). The pH of the solution was adjusted to 9.0 by treatment with a sulfonic acid ion exchange resin (H+ cycle-Dowex), treatment with Dowex resin for a longer time (˜12 hours) lead to both the cleavage of the TBDMS group and the recovery of the free carboxyl group. The resin was filtered and the solution was concentrated to dryness affording the corresponding bisphosphate 4 (43 mg, yield 52%).
Synthesis of 3′-Monophosphate Ester of Treprostinil (8) and 2-Monophosphate Ester of Treprostinil (10)
Synthesis of Monoprotected TBDMS Methyl Ester of Treprostinil (5 and 6)
The procedure was adapted from Org. Synth., 1998, 75, 139-145. The treprostinil methyl ester (2) (305.8 mg, 0.75 mmoles) was dissolved in 15 ml anhydrous dichloromethane and the solution was cooled on an ice bath to 0° C. Imidazole (102 mg, 1.5 mmoles) and tert-butyldimethyl silyl chloride (226.2 mg, 1.5 mmoles) were added and the mixture was maintained under stirring at 0° C. for 30 minutes, then stirred overnight at room temperature. Water (25 ml) was added and the organic layer was separated. The aqueous layer was then extracted with dichloromethane (3×50 ml). The organic layers were dried over Na 2 SO 4 , the solution was filtered and the solvent was removed in vacuo affording 447 mg crude reaction product. The crude reaction product was separated by column chromatography (silica gel, 35% ethyl acetate/hexanes) affording 140 mg bis-TBDMS protected Treprostinil methyl ester, 160 mg 2-TBDMS protected treprostinil methyl ester (6) and 60 mg 3′-TBDMS protected Treprostinil methyl ester (5).
Synthesis of Monophosphate Ester of Treprostinil 8/10
The procedure was adapted after Steroids, 1963, 2(6), 567-603 and is the same for (8) and (10) starting from (6) and (5), respectively. The TBDMS protected methyl ester of treprostinil (6) (46 mg, 0.09 mmoles) was dissolved in 2 ml dry pyridine and a pyridinium solution of the previously prepared pyridinium solution of 2-cyanoethylphosphate 1M (0.2 ml, 0.2 mmoles) (cf. Methods in Enzymology, 1971, 18(c), 54-57) were concentrated to dryness in vacuo at 40° C. Anhydrous pyridine was added and the reaction mixture was again concentrated; the operation was repeated twice in order to remove water completely. Finally the residue was dissolved in 2 ml anhydrous pyridine and 116 mg (0.56 mmoles) dicyclohexylcarbodiimide were added as a solution in 2 ml anhydrous pyridine. The reaction mixture in a closed flask was stirred magnetically for 48 hours at room temperature in the dark. 5 ml water were added and after one hour, the mixture was concentrated to a thick paste in vacuo. The reaction mixture was treated overnight at room temperature with 10 ml of a 1/9 water/methanol solution containing 100 mg sodium hydroxide. The white solid (dicyclohexylurea) formed was removed by filtration and it was washed well with water. The aqueous-methanolic solution was concentrated almost to dryness in vacuo, water was added and the solution was extracted with n-butanol (3×10 ml), then with methylene chloride (1×10 ml). The pH of the solution was adjusted to 9.0 by treatment with a sulfonic acid ion exchange resin (H+ cycle-Dowex); treatment with Dowex resin for a longer time (=˜12 hours) lead to both the cleavage of the TBDMS group and the recovery of the free carboxyl group. The resin was filtered and the solution was concentrated to dryness affording the corresponding monophosphate 8 (33 mg, yield 68%).
Synthesis of Methyl Ester of Treprostinil (2)
(2) (1 g; 2.56 mmol) was added to methanol (50 ml) prior saturated with gaseous hydrochloric acid and the mixture swirled to give a clear solution that was left to stand overnight at room temperature. Solvent was removed in vacuo and the residue was neutralized with a 20% potassium carbonate solution and extracted in dichloromethane. The organic layer was washed with water, dried over anhydrous magnesium sulfate and evaporated to yield the crude product (0.96 g). Purification by preparative tlc (silica gel plate; eluent: 7:3 (v/v) hexane-ethyl acetate) afforded 2 (0.803; 77.5%), colorless oil.
Synthesis of Treprostinil Diethanolamine (UT-15C)
Treprostinil acid is dissolved in a 1:1 molar ratio mixture of ethanol:water and diethanolamine is added and dissolved. The solution is heated and acetone is added as an antisolvent during cooling.
Synthesis of Diglycil Ester of Treprostinil Methyl Ester (12)
To a magnetically stirred solution of (2) methyl ester 2 (0.268 g; 0.66 mmol) in dichloromethane (30 ml) N-carbobenzyloxyglycine p-nitrophenyl ester (0.766 g; 2.32 mmol) and 4-(dimethyamino)pyridine (250 mg; 2.05 mmol) were successively added. The resulted yellow solution was stirred at 20° C. for 24 hrs., then treated with 5% sodium hydroxide solution (20 ml) and stirring continued for 15 mm. Dichloromethane (50 ml) was added, layers separated and the organic phase washed with a 5% sodium hydroxide solution (6×20 ml), water (30 ml), 10% hydrochloric acid (2×40 ml), 5% sodium bicarbonate solution (40 ml) and dried over anhydrous sodium sulfate. Removal of the solvent afforded crude (11) (0.61 g), pale-yellow viscous oil. Purification by flash column chromatography on silica gel eluting with gradient 9/1 to 1/2 (v/v) hexane-ethyl ether afforded 0.445 g (85.3%) of 11, white crystals, m.p. 70-72° C. ′Fl-NMR [CDCl 3 ; δ(ppm)]: 3.786 (s)(3H, COOC H 3 ), 3.875 (d)(2H) and 3.940 (d)(2H)(NH—C H 2 —COO), 4.631(s) (2H, OC H 2 COOCH 3 ), 4.789 (m)(1H, adjacent to 0° C.—CH 2 NHcbz) and 4.903 (m) (1H, adjacent to OOCCH 2 NHcbz), 5.09 (s)(4H, C 6 H 5 C H 2 O), 5.378 (m)(1H) and 5.392 (m)(1H)(NH), 7.295-7.329 (m)(10H, C 6 H 5 ). LR ESI-MS (m/z): 787.1 [M+H] + , 804.1 [M+NH4] + , 809.3 [M+Na] + , 825.2 [M+K] + , 1590.5 [2M+NH4] + , 1595.6 [2M+Na] − .
Methyl Ester, Diglycyl Ester (12)
A solution of ester (11) (0.4 g; 0.51 mmol) in methanol (30 ml) was introduced in the pressure bottle of a Parr hydrogenation apparatus, 10% palladium on charcoal (0.2 g; 0.197 mmol Pd) was added, apparatus closed, purged thrice with hydrogen and loaded with hydrogen at 50 p.s.i. Stirring was started and hydrogenation carried out for 5 hrs. at room temperature. Hydrogen aas removed from the installation by vacuum suction and replaced with argon. The catalyst was filtered off through celite deposited on a fit and the filtrate concentrated in vacuo to give 0.240 g (91%) of 4, white solid m.p. 98-100° C.
Synthesis of Benzyl Ester of Treprostinil (13)
To a stirred solution of (2) (2 g; 5.12 mmol) in anhydrous tetrahydrofuran (20 ml) benzyl bromide (0.95 ml; 7.98 mmol) and freshly distilled triethylamine (1.6 ml; 11.48 mmol) were consecutively added at room temperature and the obtained solution was refluxed with stirring for 12 hrs. A white precipitate was gradually formed. Solvent was distilled off in vacuo and the residue treated with water (30 ml). Upon extraction with methylene chloride emulsion formation occurs. The organic and aqueous layers could be separated only after treatment with 5% hydrochloric acid solution (20 ml). The organic layer was washed with water, dried on anhydrous sodium sulfate, and evaporated, the residue was further dried under reduced pressure over phosphorus pentoxide to give a yellow viscous oil (2.32 g) that was purified by preparative thin layer chromatography (silica gel plate; eluent: 1:2, v/v, hexane/ethyl ether). Yield: 81.2%.
Synthesis of Bis-Glycyl Ester of Treprostinil (15)
Benzy Ester, Di-cbzGly Ester (14)
To a magnetically stirred solution of benzyl ester 13 (1 g; 2.08 mmol) in dichloromethane (50 ml) N-carbobenzyloxyglycine p-nitrophenyl ester (2.41 g; 7.28 mmol) and 4-(dimethyamino) pyridine (788 mg; 6.45 mmol) were added. The resulted yellow solution was stirred at 20° C. for 21 hrs., then successively washed with a 5% sodium hydroxide solution (6×45 ml), 10% hydrochloric acid (2×40 ml), 5% sodium bicarbonate solution (40 ml) and dried over anhydrous sodium sulfate. Removal of the solvent, followed by drying over phosphorus pentoxide under reduced pressure, afforded crude 14 (2.61 g), pale-yellow oil. Purification by flash column chromatography on silica gel eluting with gradient 9:1 to 1:2 (v/v) hexane-ethyl ether gave (14_(1.51 g; 84.1%) as a colorless, very viscous oil.
Diglycyl Ester (15)
A solution of ester (14) (0.4 g; 0.46 mmol) in methanol (30 ml) was hydrogenated over 10% Pd/C as described for ester (12). Work-up and drying over phosphorus pentoxide in vacuo yielded 0.170 g (72.7%) of ester 15, white solid m.p. 155-158° C.
Synthesis of 3′-Glycyl Ester of Treprostinil 19
Benzyl Ester, t-Butyldimethysilyl Monoester (16)
A solution of tert-butyldimethylsilyl chloride (0.45 g; 2.98 mmol) in dichloromethane (8 ml) was added dropwise over 10 min., at room temperature, into a stirred solution of benzyl ester 13 (0.83 g; 1.73 mmol) and imidazole (0.33 g; 4.85 mmol) in dichloromethane (20 ml). Stirring was continued overnight then water (20 ml) was added, the mixture stirred for one hour, layers separated, organic layer dried over anhydrous sodium sulfate and concentrated in vacuo to give a slightly yellow oil (1.15 g). The crude product is a mixture of the mono-TBDMS (16) and di-TBDMS esters ( 1 H-NMR). Column chromatography on silica gel, eluting with a 9:1 (v/v) hexane-ethyl acetate mixture, readily afforded the di-ester (0.618 g) in a first fraction, and ester 16 (0.353 g; yield relative to 13: 34.4%) in subsequent fractions. Analytical tlc on silica gel of the ester 16 showed only one spot (eluent: 3:2 (v/v) hexane-ethyl ether). Consequently, under the above reaction conditions, the other possible isomer (mono-TBDMS ester at the side-chain hydroxyl) was not observed.
Another experiment in which the molar ratio tert-butyldimethylsilyl chloride:ester 13 was lowered to 1.49 (followed by flash column chromatography of the product on silica gel, eluting with gradient 9.5/0.5 to 3/1 (v/v) hexane-ethyl ether) lead to a decreased content (36.5%, as pure isolated material) of the undesired di-OTBDMS by-product. The mono-OTBDMS ester fractions (45.1%; isolated material) consisted of ester 16 (98%) and its side-chain isomer (2%) that could be distinctly separated; the latter was evidenced (tlc, NMR) only in the last of the monoester fractions.
Benzyl Ester, Cbz-Glycyl Monoester (18)
To a magnetically stirred solution of ester 16 (0.340 g; 0.57 mmol) in dichloromethane (15 ml) N-carbobenzyloxyglycine p-nitrophenyl ester (0.445 g; 1.35 mmol) and 4-(dimethyamino) pyridine (150 mg; 1.23 mmol) were successively added. The solution was stirred at 20° C. for 40 hrs. Work-up as described for esters 11 and 14 yielded a crude product (0.63 g) containing 90% 17 and 10% 18 ( 1 H-NMR). To completely remove the protective TBDMS group, this mixture was dissolved in ethanol (30 ml) and subjected to acid hydrolysis (5% HCl, 7 ml) by stirring overnight at room temperature. Solvent was then removed under reduced pressure and the residue extracted in dichloromethane (3×50 ml); the organic layer was separated, washed once with water (50 ml), dried over sodium sulfate and concentrated in vacuo to give crude ester 18 (0.51 g). Purification by flash column chromatography as for esters 11 and 14 afforded ester 18 (0.150 g; overall yield: 39.1%) as a colorless, viscous oil.
Glycyl Monoester (19)
A solution of ester 18 (0.15 g; 0.22 mmol) in methanol (30 ml) was hydrogenated over 10% Pd/C as described for ester 12 and 15. Work-up and drying over phosphorus pentoxide in vacuo yielded ester 10 (0.98 g; 98.0%), white, shiny crystals m.p. 74-76° C. LR ESI-MS (m/z): 448.2 [M+H] + , 446.4 [M−H] − .
Synthesis of 3′-L-Leucyl Ester of Treprostinil 22
Benzyl Ester, t-Butyldimethysilyl Monoester, Cbz-L-Leucyl Monoester (20)
To a stirred solution of ester 16 (0.38 g: 0.64 mmol) and N-carbobenzyloxy-L-leucine N-hydroxysuccinimide ester (0.37 g; 1.02 mmol) in 10 ml dichloromethane 4-(dimethyamino)pyridine (0.17 g; 1.39 mmol) was added, then stirring continued at room temperature for 2 days. The solvent was removed in vacuo and the crude product (0.9 g) subjected to flash column chromatography on silica gel eluting with 9:1 hexane-ethyl acetate; the firstly collected fraction yielded an oil (0.51 g) which, based on the its NMR spectrum and tlc, was proved to be a 2:1 mixture of ester 20 and the starting ester 16. Preparative tlc on silica gel (eluent: ethyl acetate-hexane 1:4) gave pure 20, colorless oil (overall yield based on 7: 62.6%).
Benzyl Ester, Cbz-L-Leucyl Monoester (21)
De-protection of the cyclopentenyl hydroxyl in the t-butyldimethysilyl monoester 20 succeeded by treatment with diluted hydrochloric acid solution as described for 18, with the exception that a 1:5 (v/v) chloroform-ethanol mixture, instead of ethanol alone, was used to ensure homogeneity. Work-up afforded 20, colorless oil, in 87.6% yield.
L-Leucyl Monoesler (22)
Hydrogenolysis of the benzyl and N-carbobenzyloxy groups in 21 was carried out as for 18. Work-up afforded 22 (95.3%), white solid, m.p. 118-120° C.
Synthesis of 2-L-Leucyl Ester of Treprostinil 25
Benzyl Ester, Cbz-L-Ieucyl Monoesters (21, 23) and -Diester (24)
To a stirred solution of ester 13 (0.53 g: 1.10 mmol) and N-carbobenzyloxy-L-leucine N-hydroxysuccinimide ester (0.76 g; 2.05 mmol) in dichloromethane (30 ml) 4-(dimethyamino) pyridine (0.29 g; 2.37 mmol) was added, then stirring continued at room temperature for 1 day. The solution was diluted with dichloromethane (40 mnl), successively washed with a 5% sodium hydroxide solution (4×25 ml), 10% hydrochloric acid (2×30 ml), 5% sodium bicarbonate solution (50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product (0.85 g), as a viscous, yellow oil. Thin layer chromatography revealed a complex mixture in which esters 13 and 21 as well as cbz-L-leucine could be identified through the corresponding r F values, only as minor products. The crude product was flash-chromatographed through a silica gel column eluting with gradient hexane-ethyl ether. At 7:3 (v/v) hexane-ethyl ether, the first fraction gave the cbz-L-leucyl diester 24 (6% of the product subjected to chromatography) while the two subsequent fractions afforded the cbz-L-leucyl monoester 23 (54% of the crude product, as pure isolated 23; 57.6% yield, relative to 2). Purity of both compounds was verified by analytical tlc and NMR. The other isomer, cbz-L-leucyl monoester 21 constituted only about 5% of the crude product and was isolated by preparative tlc of the latter only a 3:1 23/21 mixture.
L-Leucyl Monoester (25)
Hydrogenolysis of 23 to the ester 25 was performed as described for compound 12 but reaction was carried out at 35 p.s.i., overnight. Work-up and drying over phosphorus pentoxide in vacuo afforded 25, white solid m. p. 153-155° C., in quantitative yield.
Synthesis of 3′-L-Alanyl Ester of Treprostinil 30
N-Cbz-L-Alanyl p-Nitro Phenyl Ester (27)
To a stirred solution containing N-carbobenzyloxy-L-alanine (1 g; 4.48 mmol) and p-nitrophenol (1 g; 7.19 mmol) in anhydrous tetrahydrofuran (7 ml) a fine suspension of 1,3-dicyclohexylcarbodiimide (1.11 g; 5.38 mmol) in tetrahydrofuran (5 ml) was added over 30 min. Stirring was continued at room temperature for 18 hrs., glacial acetic acid (0.3 ml) added, 1,3-dicyclohexylurea filtered off and solvent removed in vacuo, at 40° C., to give a viscous, yellow-reddish oil (2.5 g). The 1 H-NMR spectrum showed a mixture consisting of N-carbobenzyloxy-Lalanine p-nitrophenyl ester (27), unreacted p-nitrophenol and a small amount of DCU, which was used as such in the next reaction step.
Benzyl Ester, Cbz-L-Alanyl Monoester (29)
A solution of 4-(dimethylamino)pyridine (0.30 g; 2.49 mmol) in dichloromethane (3 ml) was quickly dropped (over 5 min.) into a magnetically stirred solution of ester 16 (0.37 g; 0.62 mmol) and crude N-carbobenzyloxy-L-alanine p-nitrophenyl ester (0.98 g) in dichloromethane (12 ml). The mixture was stirred overnight at room temperature, then diluted with dichloromethanc (50 ml), and thoroughly washed with a 5% sodium hydroxide solution (7×35 ml), 10% hydrochloric acid (3×35 ml), 5°/a sodium bicarbonate solution (50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude ester 28 (1.1 g). The latter was dissolved in ethanol (30 ml), 5% hydrochloric acid (8 ml) and chloroform (5 ml) were added and the solution stirred overnight. Solvents were removed in vacuo, the residue taken-up in dichloromethane, washed to pH 7 with a 5% sodium hydrogencarbonate solution, dried over anhydrous sodium sulfate and the solvent evaporated affording crude 29 (1.04 g). Purification by column chromatography on silica gel, eluting with gradient hexane-ethyl ether, enabled separation of a fraction (at hexane:ethyl ether=1:1 v/v) of pure 29 as a colorless very viscous oil (0.11 g; 25.8% overall yield, based on 16).
L-Alanyl Monoester (30)
Removal of the benzyl and N-carbobenzyloxy groups in 29 was achieved through catalytic hydrogenation as described for 12. Ester 30 was obtained (yield: 97.2%) as a pale-yellow, partially crystallized, oil.
Synthesis of the 3′-L-Valine Ester of Treprostinil Benzyl Ester 33
Synthesis of the Benzyl Ester of Treprostinil 13
The benzyl ester 11 was synthesized by adapting the method described by J. C. Lee et al. in Organic Prep. and Proc. Intl., 1996, 28(4), 480-483. To a solution of 1 (620 mg, 1.6 mmoles) and cesium carbonate (782.4 mg, 2.4 mmoles) in acetonitrile (30 ml) was added benzyl bromide (0.48 ml, 4 mmoles) and the mixture was stirred at reflux for 1 hour. After cooling at room temperature, the precipitate was filtered off and the filtrate was concentrated in vacuo. The residue was dissolved in chloroform (150 ml) and washed with a 2% aqueous solution of NaHCO 3 (3×30 ml). The organic layer was washed with brine, dried on Na 2 SO 4 , filtered and the solvent was removed in vacuo to afford 750 mg of the crude benzyl ester 13 (yield 98%) as a yellow viscous oil. The crude benzyl ester 13 can be purified by column chromatography (100-0% dichloromethane(methanol) but it can also be used crude in subsequent reactions.
Synthesis of the TBDMS Protected Treprostinil Benzyl Ester 16
The procedure for the synthesis of the TBDMS protected benzyl ester was adapted from Organic Synth., 1998, 75, 139-145. The benzyl ester 13 (679 mg, 1.4 mmoles) was dissolved in anhydrous dichloromethanc (20 ml) and the solution was cooled to 0° C. on an ice bath. Imidazole (192 mg, 2.8 mmoles) and t-butyl-dimethylsilyl chloride (TBDMSC1) (420 mg, 2.8 mmoles) were added and the mixture was maintained under stirring for another half hour on the ice bath and then it was left overnight at room temperature. 40 ml water was added to the reaction mixture and the organic layer was separated. The aqueous layer was extracted with 3×50 ml dichloromethane. The combined organic layers were dried over Na 2 SO 4 , filtered and the solvent was removed in vacuo. This afforded 795 mg of material which proved to be a mixture of the desired mono TBDMS protected 5 benzyl ester with the bis-TBDMS protected benzyl ester. Pure 16 (249 mg) was obtained by column chromatography on silica gel (eluent 35% ethyl acetate/hexane).
Synthesis of N-Cbz-L-Valine Ester of the TBDMS Protected Treprostinil Benzyl Ester 31
The procedure used was adapted from Tetrahedron Lett., 1978, 46, 4475-4478. A solution of NCbz-L-valine (127 mg, 0.5 mmoles), N,N-dicyclohexylcarbodiimide (DCC) (111 mg, 0.5 mmoles), compound 16 (249 mg, 0.4 mmoles) and 4-(dimethylamino)pyridine (DMAP) (6 mg, 0.05 mmoles) in anhydrous dichloromethane (15 ml) was stirred at room temperature until esterification was complete. The solution was filtered and the formed N,N-dicyclohexylurea was filtered. The filtrate was diluted with dichloromethane (80 ml) and washed with water (3×30 ml), a 5% aqueous acetic acid solution (2×30 ml) and then again with water (3×30 ml). The organic layer was dried over Na 2 SO 4 and the solvent was evaporated in vacuo affording 369 mg crude 31. Pure 31 was obtained by chromatography (silica gel, 35% ethyl acetate/hexane).
Synthesis of the 3′-N-Cbz-L-Valine Ester of Treprostinil Benzyl Ester 32
Cleavage of the TBDMS group in compound 31 was achieved using an adaptation of the procedure described in Org. Letters, 2000, 2(26), 4177-4180. The N-Cbz-L-valine ester of the TBDMS protected benzyl ester 31 (33 mg, 0.04 mmoles) was dissolved in methanol (5 ml) and tetrabutylammonium tribromide (TBATB) (2 mg, 0.004 mmoles) was added. The reaction mixture was stirred at room temperature for 24 hrs until the TBDMS deprotection was complete. The methanol was evaporated and the residue was taken in dichloromethane. The dichloromethane solution was washed with brine and then dried over Na 2 SO 4 . After filtering the drying agent the solvent was evaporated to dryness affording 30.2 mg of crude compound 32.
Synthesis of the 3′-L-Valinc Ester of Treprostinil 33
The benzyl and benzyl carboxy groups were removed by catalytic hydrogenation at atmospheric pressure in the presence of palladium 10% wt on activated carbon. The 3′-N-Cbz-L-valine ester of benzyl ester 32 (30.2 mg, 0.04 mmoles) was dissolved in methanol (10 ml) and a catalytic amount of Pd/C was added. Under magnetic stirring the air was removed from the flask and then hydrogen was admitted. The reaction mixture was maintained under hydrogen and stirring at room temperature for 24 hrs, then the hydrogen was removed with vacuum. The reaction mixture was then filtered through a layer of celite and the solvent was removed in vacuo to afford the pure 3′-L-valine ester of Treprostinil 33 (15 mg, 0.03 mmoles).
Synthesis of 2-L-Valine Ester of Treprostinil 36/Bis-L-Valine Ester of Trenrostinil 37
Synthesis of 2-L-Alanine Ester of Treprostinil 36′/Bis-L-Alanine Ester of Treprostinil 37′
Synthesis of 2-N-Cbz-L-Valine Ester of Treprostinil Benzyl Ester 34 and Bis-N-Cbz-L-Valine Ester of Treprostinil Benzyl Ester 35
The procedure used was adapted from Tetrahedron Lett., 1978, 46, 4475-4478. A solution of NCbz-L-valine (186 mg, 0.7 mmoles), N,N-dicyclohexylcarbodiimide (DCC) (167 mg, 0.8 mmoles), compound 13 (367 mg, 0.8 mmoles) and 4-(dimethylamino)pyridine (DMAP) (12 mg, 0.09 mmoles) in anhydrous dichloromethane (15 ml) was stirred at room temperature until esterification was complete. The solution was filtered and the formed N,N-dicyclohexylurea was filtered. The filtrate was diluted with dichloromethane (100 ml) and washed with water (3×50 ml), a 5% aqueous acetic acid solution (2×50 ml) and then again with water (3×50 ml). The organic layer was dried over Na 2 SO 4 and the solvent was evaporated in vacuo affording 556 mg crude product. The product was separated by chromatography (silica gel, 35% ethyl acetate/hexane) yielding 369.4 mg 2-valine ester 34 and 98 mg bis-valine ester 35.
Synthesis of 2 N-Cbz-L-Alanine Ester of Treprostinil Benzyl Ester 34′ and Bis-N-Cbz-L-Alanine Ester of Treprostinil Benzyl Ester 35′
The procedure used was adapted from Tetrahedron Lett., 1978, 46, 4475-4478. A solution of NCbz-L-alanine (187 mg, 0.84 mmoles), N,N-dicyclohexylcarbodiimide (DCC) (175 mg, 0.85 mmoles), compound 13 (401 mg, 0.84 mmoles) and 4-(dimethylamino)pyridine (UMAP) (11.8 mg, 0.1 mmoles) in anhydrous dichloromethane (15 ml) was stirred at room temperature until esterification was complete. The solution was filtered and the formed N,N-dicyclohexylurea was filtered. The filtrate was diluted with dichloromethane (100 ml) and washed with water (3×50 ml), a 5% aqueous acetic acid solution (2×50 ml) and then again with water (3×50 ml). The organic layer was dried over Na 2 SO 4 and the solvent was evaporated in vacuo affording 516 mg crude product. The product was separated by chromatography (silica gel, 35% ethyl acetate/hexane) yielding 93.4 mg 2-alanine ester 34′ and 227 mg bis-alanine ester 35′.
Synthesis of 2-L-Valine Ester of Treprostinil 36/Bis-L-Valine Ester of Treprostinil 37
The benzyl and benzyl carboxy groups were removed by catalytic hydrogenation at atmospheric pressure in the presence of palladium 10% wt on activated carbon. The 2-N-Cbz-L-valine ester of Treprostinil benzyl ester 34 (58.2 mg, 0.08 mmoles)/bis-N-Cbz-L-valine ester of Treprostinil benzyl ester 35 (55.1 mg, 0.06 mmoles) was dissolved in methanol (10 ml) and a catalytic amount of Pd/C was added. Under magnetic stirring the air was removed from the flask and hydrogen was admitted. The reaction mixture was maintained under hydrogen and stirring at room temperature for 20 hrs, then hydrogen was removed with vacuum. The reaction mixture was then filtered through a layer of celite and the solvent was removed in vacuo to afford the pure 2-L-valine ester of Treprostinil 36 (40 mg, 0.078 mmoles)/bis-L-valine ester of Treprostinil 37 (23 mg, 0.04 mmoles).
Synthesis of 2-L-Alanine Ester of Treprostinil 36′/Bis-L-Alanine Ester of Treprostinil 37′
The benzyl and benzyl carboxy groups were removed by catalytic hydrogenation at atmospheric pressure in the presence of palladium 10% wt on activated carbon. The 2-N-Cbz-L-alanine ester of Treprostinil benzyl ester 34′ (87.4 mg, 0.13 mmoles)/bis-N-Cbz-L-alanine ester of Treprostinil benzyl ester 35′ (135 mg, 0.15 mmoles) was dissolved in methanol (15 ml) and a catalytic amount of Pd/C was added. Under magnetic stirring the air was removed from the flask and hydrogen was admitted. The reaction mixture was maintained under hydrogen and stirring at room temperature for 20 hrs, then hydrogen was removed with vacuum. The reaction mixture was then filtered through a layer of celite and the solvent was removed in vacuo to afford the pure 2-L-valine ester of Treprostinil 36′ (57 mg, 0.12 mmoles)/bis-L-alanine ester of Treprostinil 37′ (82 mg, 0.15 mmoles).
Synthesis of Benzyl Esters of Treprostinil 38 a-e
a 4-NO 2 C 6 H 4 CH 2 ; b 4-(CH 3 O)C 6 H 4 CH 2 ; c 2ClC 6 H 4 CH 2 ; d 2,4-(NO 2 ) 2 C 6 H 3 CH 2 ; e 4-FC 6 H 4 CH 2 Synthesis of the benzyl esters of treprostinil 38 a-e was performed using the procedure for the benzyl ester 13.
Enantiomers of these compounds, shown below, can be synthesized using reagents and synthons of enantiomeric chirality of the above reagents.
Briefly, the enantiomer of the commercial drug (+)-Treprostinil was synthesized using the stereoselective intramolecular Pauson Khand reaction as a key step and Mitsunobu inversion of the side-chain hydroxyl group. The absolute configuration of (−)-Treprostinil was confirmed by an X-ray structure of the L-valine amide derivative.
The following procedure was used to make (−)-treprostinil-methyl-L-valine amide: To a stirred solution of (−)-Treprostinil (391 mg, 1 mmol) and L-valine methyl ester hydrochloride (184 mg, 1.1 mmol) in DMF (10 ml) under Ar was sequentially added pyBOP reagent (1.04 g, 2 mmol), diisopropylethyl amine (0.52 ml, 3 mmol). The reaction mixture was stirred at room temperature overnight (15 hrs). Removal of the solvent in vacuo and purification by chromatography yielded white solid 12 (481 mg, 86%), which was recrystallized (10% ethyl acetate in hexane) to give suitable crystals for X-ray.
Various modifications of these synthetic schemes capable of producing additional compounds discussed herein will be readily apparent to one skilled in the art.
There are two major barriers to deliver treprostinil in the circulatory system. One of these barriers is that treprostinil undergoes a large first pass effect. Upon first circulating through the liver, about 60% of treprostinil plasma levels are metabolized, which leaves only about 40% of the absorbed dose. Also, a major barrier to oral delivery for treprostinil is that the compound is susceptible to an efflux mechanism in the gastrointestinal tract. The permeability of treprostinil has been measured across Caco-2 cell monolayers. The apical to basal transport rate was measured to be 1.39×10 6 cm/sec, which is indicative of a highly permeable compound. However, the basal to apical transport rate was 12.3×10 6 cm/sec, which suggests that treprostinil is efficiently effluxed from the serosal to lumenal side of the epithelial cell. These data suggest that treprostinil is susceptible to p-glycoprotein, a membrane bound multidrug transporter. It is believed that the p-glycoprotein efflux pump prevents certain pharmaceutical compounds from traversing the mucosal cells of the small intestine and, therefore, from being absorbed into systemic circulation.
Accordingly, the present invention provides pharmaceutical compositions comprising treprostinil, the compound of structure I or the compound of structure II, or their pharmaceutically acceptable salts and combinations thereof in combination with one or more inhibitors of p-glycoprotein. A number of known non-cytotoxic pharmacological agents have been shown to inhibit p-glycoprotein are disclosed in U.S. Pat. Nos. 6,451,815, 6,469,022, and 6,171,786.
P-glycoprotein inhibitors include water soluble forms of vitamin E, polyethylene glycol, poloxamers including Pluronic F-68, polyethylene oxide, polyoxyethylene castor oil derivatives including Cremophor EL and Cremophor RH 40, Chrysin, (+)-Taxifolin, Naringenin, Diosmin, Quercetin, cyclosporin A (also known as cyclosporine), verapamil, tamoxifen, quinidine, phenothiazines, and 9,10-dihydro-5-methoxy-9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7,-dimethoxy-2-isoquinolinyl)ethyl]phenyl]-4-acridinecarboxamide or a salt thereof.
Polyethylene glycols (PEGs) are liquid and solid polymers of the general formula H(OCH 2 CH 2 ) n OH, where n is greater than or equal to 4, having various average molecular weights ranging from about 200 to about 20,000. PEGs are also known as alpha-hydro-omega-hydroxypoly-(oxy-1,2-ethanediyl)polyethylene glycols. For example, PEG 200 is a polyethylene glycol wherein the average value of n is 4 and the average molecular weight is from about 190 to about 210. PEG 400 is a polyethylene glycol wherein the average value of n is between 8.2 and 9.1 and the average molecular weight is from about 380 to about 420. Likewise, PEG 600, PEG 1500 and PEG 4000 have average values of n of 12.5-13.9, 29-36 and 68-84, respectively, and average molecular weights of 570-630, 1300-1600 and 3000-3700, respectively, and PEG 1000, PEG 6000 and PEG 8000 have average molecular weights of 950-1050, 5400-6600, and 7000-9000, respectively. Polyethylene glycols of varying average molecular weight of from 200 to 20000 are well known and appreciated in the art of pharmaceutical science and are readily available.
The preferred polyethylene glycols for use in the instant invention are polyethylene glycols having an average molecular weight of from about 200 to about 20,000. The more preferred polyethylene glycols have an average molecular weight of from about 200 to about 8000. More specifically, the more preferred polyethylene glycols for use in the present invention are PEG 200, PEG 400, PEG 600, PEG 1000, PEG 1450, PEG 1500, PEG 4000, PEG 4600, and PEG 8000. The most preferred polyethylene glycols for use in the instant invention is PEG 400, PEG 1000, PEG 1450, PEG 4600 and PEG 8000.
Polysorbate 80 is an oleate ester of sorbitol and its anhydrides copolymerized with approximately 20 moles of ethylene oxide for each mole of sorbitol and sorbitol anhydrides. Polysorbate 80 is made up of sorbitan mono-9-octadecanoate poly(oxy-1,2-ethandiyl) derivatives. Polysorbate 80, also known as Tween 80, is well known and appreciated in the pharmaceutical arts and is readily available.
Water-soluble vitamin E, also known as d-alpha-tocopheryl polyethylene glycol 1000 succinate [TPGS], is a water-soluble derivative of natural-source vitamin E. TPGS may be prepared by the esterification of the acid group of crystalline d-alpha-tocopheryl acid succinate by polyethylene glycol 1000. This product is well known and appreciated in the pharmaceutical arts and is readily available. For example, a water-soluble vitamin E product is available commercially from Eastman Corporation as Vitamin E TPGS.
Naringenin is the bioflavonoid compound 2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one and is also known as 4′,5,7-trihydroxyflavanone. Naringenin is the aglucon of naringen which is a natural product found in the fruit and rind of grapefruit. Naringenin is readily available to the public from commercial sources.
Quercetin is the bioflavonoid compound 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one and is also known as 3,3′,4′,5,7-pentahydroxyflavone. Quercetin is the aglucon of quercitrin, of rutin and of other glycosides. Quercetin is readily available to the public from commercial sources.
Diosmin is the naturally occurring flavonic glycoside compound 7-[[6-O-6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl]oxy]-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one. Diosmin can be isolated from various plant sources including citrus fruits. Diosmin is readily available to the public from commercial sources.
Chrysin is the naturally occurring compound 5,7-dihydroxy-2-phenyl-4H-1-benzopyran-4-one which can be isolated from various plant sources. Chrysin is readily available to the public from commercial sources.
Poloxamers are alpha-hydro-omega-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymers. Poloxamers are a series of closely related block copolymers of ethylene oxide and propylene oxide conforming to the general formula HO(C 2 H 4 O) a (C 3 H 6 O) b (C 2 H 4 O) a H. For example, poloxamer 124 is a liquid with “a” being 12, “b” being 20, and having an average molecular weight of from about 2090 to about 2360; poloxamer 188 is a solid with “a” being 80, “b” being 27, and having an average molecular weight of from about 7680 to about 9510; poloxamer 237 is a solid with “a” being 64, “b” being 37, and having an average molecular weight of from about 6840 to about 8830; poloxamer 338 is a solid with “a” being 141, “b” being 44, and having an average molecular weight of from about 12700 to about 17400; and poloxamer 407 is a solid with “a” being 101, “b” being 56, and having an average molecular weight of from about 9840 to about 14600. Poloxamers are well known and appreciated in the pharmaceutical arts and are readily available commercially. For example, Pluronic F-68 is a commercially available poloxamer from BASF Corp. The preferred poloxamers for use in the present invention are those such as poloxamer 188, Pluronic F-68, and the like.
Polyoxyethylene castor oil derivatives are a series of materials obtained by reacting varying amounts of ethylene oxide with either castor oil or hydrogenated castor oil. These polyoxyethylene castor oil derivatives are well known and appreciated in the pharmaceutical arts and several different types of material are commercially available, including the Cremophors available from BASF Corporation. Polyoxyethylene castor oil derivatives are complex mixtures of various hydrophobic and hydrophilic components. For example, in polyoxyl 35 castor oil (also known as Cremophor EL), the hydrophobic constituents comprise about 83% of the total mixture, the main component being glycerol polyethylene glycol ricinoleate. Other hydrophobic constituents include fatty acid esters of polyethylene glycol along with some unchanged castor oil. The hydrophilic part of polyoxyl 35 castor oil (17%) consists of polyethylene glycols and glyceryl ethoxylates.
In polyoxyl 40 hydrogenated castor oil (Cremophor RH 40) approximately 75% of the components of the mixture are hydrophobic. These comprise mainly fatty acid esters of glycerol polyethylene glycol and fatty acid esters of polyethylene glycol. The hydrophilic portion consists of polyethylene glycols and glycerol ethoxylates. The preferred polyoxyethylene castor oil derivatives for use in the present invention are polyoxyl 35 castor oil, such as Cremophor EL, and polyoxyl 40 hydrogenated castor oil, such as Cremophor RH 40. Cremophor EL and Cremophor RH 40 are commercially available from BASF Corporation.
Polyethylene oxide is a nonionic homopolymer of ethylene oxide conforming to the general formula (OCH 2 CH 2 ) n in which n represents the average number of oxyethylene groups. Polyethylene oxides are available in various grades which are well known and appreciated by those in the pharmaceutical arts and several different types of material are commercially available. The preferred grade of polyethylene oxide is NF and the like which are commercially available.
(+)-Taxifolin is (2R-trans)-2-(3,4-dihydroxyphenyl)-2,3-dihydro-3,5,7-trihydroxy-4H-1-benzo pyran-4-one. Other common names for (+)-taxifolin are (+)-dihydroquercetin; 3,3′,4′,5,7-pentahydroxy-flavanone; diquertin; taxifoliol; and distylin. (+)-Taxifolin is well know and appreciated in the art of pharmaceutical arts and is readily available commercially.
The preferred p-glycoprotein inhibitor for use in the present invention are water soluble vitamin E, such as vitamin E TPGS, and the polyethylene glycols. Of the polyethylene glycols, the most preferred p-glycoprotein inhibitors are PEG 400, PEG 1000, PEG 1450, PEG 4600 and PEG 8000.
Administration of a p-glycoprotein inhibitor may be by any route by which the p-glycoprotein inhibitor will be bioavailable in effective amounts including oral and parenteral routes. Although oral administration is preferred, the p-glycoprotein inhibitors may also be administered intravenously, topically, subcutaneously, intranasally, rectally, intramuscularly, or by other parenteral routes. When administered orally, the p-glycoprotein inhibitor may be administered in any convenient dosage form including, for example, capsule, tablet, liquid, suspension, and the like.
Generally, an effective p-glycoprotein inhibiting amount of a p-glycoprotein inhibitor is that amount which is effective in providing inhibition of the activity of the p-glycoprotein mediated active transport system present in the gut. An effective p-glycoprotein inhibiting amount can vary between about 5 mg to about 1000 mg of p-glycoprotein inhibitor as a daily dose depending upon the particular p-glycoprotein inhibitor selected, the species of patient to be treated, the dosage regimen, and other factors which are all well within the abilities of one of ordinary skill in the medical arts to evaluate and assess. A preferred amount however will typically be from about 50 mg to about 500 mg, and a more preferred amount will typically be from about 100 mg to about 500 mg. The above amounts of a p-glycoprotein inhibitor can be administered from once to multiple times per day. Typically for oral dosing, doses will be administered on a regimen requiring one, two or three doses per day.
Where water soluble vitamin E or a polyethylene glycol is selected as the p-glycoprotein inhibitor, a preferred amount will typically be from about 5 mg to about 1000 mg, a more preferred amount will typically be from about 50 mg to about 500 mg, and a further preferred amount will typically be from about 100 mg to about 500 mg. The most preferred amount of water soluble vitamin E or a polyethylene glycol will be from about 200 mg to about 500 mg. The above amounts of water soluble vitamin E or polyethylene glycol can be administered from once to multiple times per day. Typically, doses will be administered on a regimen requiring one, two or three doses per day with one and two being preferred.
As used herein, the term “co-administration” refers to administration to a patient of both a compound that has vasodilating and/or platelet aggregation inhibiting properties, including the compounds described in U.S. Pat. Nos. 4,306,075 and 5,153,222 which include treprostinil and structures I and II described herein, and a p-glycoprotein inhibitor so that the pharmacologic effect of the p-glycoprotein inhibitor in inhibiting p-glycoprotein mediated transport in the gut is manifest at the time at which the compound is being absorbed from the gut. Of course, the compound and the p-glycoprotein inhibitor may be administered at different times or concurrently. For example, the p-glycoprotein inhibitor may be administered to the patient at a time prior to administration of the therapeutic compound so as to pre-treat the patient in preparation for dosing with the vasodilating compound. Furthermore, it may be convenient for a patient to be pre-treated with the p-glycoprotein inhibitor so as to achieve steady state levels of p-glycoprotein inhibitor prior to administration of the first dose of the therapeutic compound. It is also contemplated that the vasodilating and/or platelet aggregation inhibiting compounds and the p-glycoprotein inhibitor may be administered essentially concurrently either in separate dosage forms or in the same oral dosage form.
The present invention further provides that the vasodilating and/or platelet aggregation inhibiting compound and the p-glycoprotein inhibitor may be administered in separate dosage forms or in the same combination oral dosage form. Co-administration of the compound and the p-glycoprotein inhibitor may conveniently be accomplished by oral administration of a combination dosage form containing both the compound and the p-glycoprotein inhibitor.
Thus, an additional embodiment of the present invention is a combination pharmaceutical composition for oral administration comprising an effective vasodilating and/or platelet aggregation inhibiting amount of a compound described herein and an effective p-glycoprotein inhibiting amount of a p-glycoprotein inhibitor. This combination oral dosage form may provide for immediate release of both the vasodilating and/or platelet aggregation inhibiting compound and the p-glycoprotein inhibitor or may provide for sustained release of one or both of the vasodilating and/or platelet aggregation inhibiting compound and the p-glycoprotein inhibitor. One skilled in the art would readily be able to determine the appropriate properties of the combination dosage form so as to achieve the desired effect of co-administration of the vasodilating and/or platelet aggregation inhibiting compound and the p-glycoprotein inhibitor.
Accordingly, the present invention provides for an enhancement of the bioavailability of treprostinil, a drug of structure I or II, and pharmaceutically acceptable salts thereof by co-administration of a p-glycoprotein inhibitor. By co-administration of these compounds and a p-glycoprotein inhibitor, the total amount of the compound can be increased over that which would otherwise circulate in the blood in the absence of the p-glycoprotein inhibitor. Thus, co-administration in accordance with the present invention can cause an increase in the AUC of the present compounds over that seen with administration of the compounds alone.
Typically, bioavailability is assessed by measuring the drug concentration in the blood at various points of time after administration of the drug and then integrating the values obtained over time to yield the total amount of drug circulating in the blood. This measurement, called the Area Under the Curve (AUC), is a direct measurement of the bioavailability of the drug.
Without limiting the scope of the invention, it is believed that in some embodiments derivatizing treprostinil at the R 2 and R 3 hydroxyl groups can help overcome the barriers to oral treprostinil delivery by blocking these sites, and thus the metabolism rate may be reduced to permit the compound to bypass some of the first pass effect. Also, with an exposed amino acid, the prodrug may be actively absorbed from the dipeptide transporter system that exists in the gastrointestinal tract. Accordingly, the present invention provides compounds, such as those found in structures I and II, that reduce the first pass effect of treprostinil and/or reduce the efflux mechanism of the gastrointestinal tract.
In some embodiments of the method of treating hypertension in a subject, the subject is a mammal, and in some embodiments is a human.
Pharmaceutical formulations may include any of the compounds of any of the embodiments described above, either alone or in combination, in combination with a pharmaceutically acceptable carrier such as those described herein.
The instant invention also provides for compositions which may be prepared by mixing one or more compounds of the instant invention, or pharmaceutically acceptable salts thereof, with pharmaceutically acceptable carriers, excipients, binders, diluents or the like, to treat or ameliorate a variety of disorders related vasoconstriction and/or platelet aggregation. A therapeutically effective dose further refers to that amount of one or more compounds of the instant invention sufficient to result in amelioration of symptoms of the disorder. The pharmaceutical compositions of the instant invention can be manufactured by methods well known in the art such as conventional granulating, mixing, dissolving, encapsulating, lyophilizing, emulsifying or levigating processes, among others. The compositions can be in the form of, for example, granules, powders, tablets, capsules, syrup, suppositories, injections, emulsions, elixirs, suspensions or solutions. The instant compositions can be formulated for various routes of administration, for example, by oral administration, by transmucosal administration, by rectal administration, transdermal or subcutaneous administration as well as intrathecal, intravenous, intramuscular, intraperitoneal, intranasal, intraocular or intraventricular injection. The compound or compounds of the instant invention can also be administered by any of the above routes, for example in a local rather than a systemic fashion, such as injection as a sustained release formulation. The following dosage forms are given by way of example and should not be construed as limiting the instant invention.
For oral, buccal, and sublingual administration, powders, suspensions, granules, tablets, pills, capsules, gelcaps, and caplets are acceptable as solid dosage forms. These can be prepared, for example, by mixing one or more compounds of the instant invention, or pharmaceutically acceptable salts thereof, with at least one additive or excipient such as a starch or other additive. Suitable additives or excipients are sucrose, lactose, cellulose sugar, mannitol, maltitol, dextran, sorbitol, starch, agar, alginates, chitins, chitosans, pectins, tragacanth gum, gum arabic, gelatins, collagens, casein, albumin, synthetic or semi-synthetic polymers or glycerides, methyl cellulose, hydroxypropylmethyl-cellulose, and/or polyvinylpyrrolidone. Optionally, oral dosage forms can contain other ingredients to aid in administration, such as an inactive diluent, or lubricants such as magnesium stearate, or preservatives such as paraben or sorbic acid, or anti-oxidants such as ascorbic acid, tocopherol or cysteine, a disintegrating agent, binders, thickeners, buffers, sweeteners, flavoring agents or perfuming agents. Additionally, dyestuffs or pigments may be added for identification. Tablets may be further treated with suitable coating materials known in the art.
Additionally, tests have shown that the present compounds, including treprostinil, and in particular the compounds of structure I and II have increased bioavailability when delivered to the duodenum. Accordingly, one embodiment of the present invention involves preferential delivery of the desired compound to the duodenum as well as pharmaceutical formulations that achieve duodenal delivery. Duodenal administration can be achieved by any means known in the art. In one of these embodiments, the present compounds can be formulated in an enteric-coated dosage form. Generally, enteric-coated dosage forms are usually coated with a polymer that is not soluble at low pH, but dissolves quickly when exposed to pH conditions of 3 or above. This delivery form takes advantage of the difference in pH between the stomach, which is about 1 to 2, and the duodenum, where the pH tends to be greater than 4.
Liquid dosage forms for oral administration may be in the form of pharmaceutically acceptable emulsions, syrups, elixirs, suspensions, slurries and solutions, which may contain an inactive diluent, such as water. Pharmaceutical formulations may be prepared as liquid suspensions or solutions using a sterile liquid, such as, but not limited to, an oil, water, an alcohol, and combinations of these. Pharmaceutically suitable surfactants, suspending agents, emulsifying agents, may be added for oral or parenteral administration.
As noted above, suspensions may include oils. Such oil include, but are not limited to, peanut oil, sesame oil, cottonseed oil, corn oil and olive oil. Suspension preparation may also contain esters of fatty acids such as ethyl oleate, isopropyl myristate, fatty acid glycerides and acetylated fatty acid glycerides. Suspension formulations may include alcohols, such as, but not limited to, ethanol, isopropyl alcohol, hexadecyl alcohol, glycerol and propylene glycol. Ethers, such as but not limited to, poly(ethyleneglycol), petroleum hydrocarbons such as mineral oil and petrolatum; and water may also be used in suspension formulations.
Injectable dosage forms generally include aqueous suspensions or oil suspensions which may be prepared using a suitable dispersant or wetting agent and a suspending agent. Injectable forms may be in solution phase or in the form of a suspension, which is prepared with a solvent or diluent. Acceptable solvents or vehicles include sterilized water, Ringer's solution, or an isotonic aqueous saline solution. Alternatively, sterile oils may be employed as solvents or suspending agents. Preferably, the oil or fatty acid is non-volatile, including natural or synthetic oils, fatty acids, mono-, di- or tri-glycerides.
For injection, the pharmaceutical formulation may be a powder suitable for reconstitution with an appropriate solution as described above. Examples of these include, but are not limited to, freeze dried, rotary dried or spray dried powders, amorphous powders, granules, precipitates, or particulates. For injection, the formulations may optionally contain stabilizers, pH modifiers, surfactants, bioavailability modifiers and combinations of these. The compounds may be formulated for parenteral administration by injection such as by bolus injection or continuous infusion. A unit dosage form for injection may be in ampoules or in multi-dose containers.
Besides those representative dosage forms described above, pharmaceutically acceptable excipients and carries are generally known to those skilled in the art and are thus included in the instant invention. Such excipients and carriers are described, for example, in “Remingtons Pharmaceutical Sciences” Mack Pub. Co., New Jersey (1991), which is incorporated herein by reference.
The formulations of the invention may be designed for to be short-acting, fast-releasing, long-acting, and sustained-releasing as described below. Thus, the pharmaceutical formulations may also be formulated for controlled release or for slow release.
The instant compositions may also comprise, for example, micelles or liposomes, or some other encapsulated form, or may be administered in an extended release form to provide a prolonged storage and/or delivery effect. Therefore, the pharmaceutical formulations may be compressed into pellets or cylinders and implanted intramuscularly or subcutaneously as depot injections or as implants such as stents. Such implants may employ known inert materials such as silicones and biodegradable polymers.
Specific dosages may be adjusted depending on conditions of disease, the age, body weight, general health conditions, sex, and diet of the subject, dose intervals, administration routes, excretion rate, and combinations of drugs. Any of the above dosage forms containing effective amounts are well within the bounds of routine experimentation and therefore, well within the scope of the instant invention.
A therapeutically effective dose may vary depending upon the route of administration and dosage form. The preferred compound or compounds of the instant invention is a formulation that exhibits a high therapeutic index. The therapeutic index is the dose ratio between toxic and therapeutic effects which can be expressed as the ratio between LD 50 and ED 50 . The LD 50 is the dose lethal to 50% of the population and the ED 50 is the dose therapeutically effective in 50% of the population. The LD 50 and ED 50 are determined by standard pharmaceutical procedures in animal cell cultures or experimental animals.
A method of preparing pharmaceutical formulations includes mixing any of the above-described compounds with a pharmaceutically acceptable carrier and water or an aqueous solution.
Pharmaceutical formulations and medicaments according to the invention include any of the compounds of any of the embodiments of compound of structure I, II or pharmaceutically acceptable salts thereof described above in combination with a pharmaceutically acceptable carrier. Thus, the compounds of the invention may be used to prepare medicaments and pharmaceutical formulations. In some such embodiments, the medicaments and pharmaceutical formulations comprise any of the compounds of any of the embodiments of the compounds of structure I or pharmaceutically acceptable salts thereof. The invention also provides for the use of any of the compounds of any of the embodiments of the compounds of structure I, II or pharmaceutically acceptable salts thereof for prostacyclin-like effects. The invention also provides for the use of any of the compounds of any of the embodiments of the compounds of structure I, II or pharmaceutically acceptable salts thereof or for the treatment of pulmonary hypertension.
The invention also pertains to kits comprising one or more of the compounds of structure I or II along with instructions for use of the compounds. In another embodiment, kits having compounds with prostacyclin-like effects described herein in combination with one or more p-glycoprotein inhibitors is provided along with instructions for using the kit.
By way of illustration, a kit of the invention may include one or more tablets, capsules, caplets, gelcaps or liquid formulations containing the bioenhancer of the present invention, and one or more tablets, capsules, caplets, gelcaps or liquid formulations containing a prostacyclin-like effect compound described herein in dosage amounts within the ranges described above. Such kits may be used in hospitals, clinics, physician's offices or in patients' homes to facilitate the co-administration of the enhancing and target agents. The kits should also include as an insert printed dosing information for the co-administration of the enhancing and target agents.
The following abbreviations and definitions are used throughout this application:
Generally, reference to a certain element such as hydrogen or H is meant to include all isotopes of that element. For example, if an R group is defined to include hydrogen or H, it also includes deuterium and tritium.
As used herein, the term “p-glycoprotein inhibitor” refers to organic compounds which inhibit the activity of the p-glycoprotein mediated active transport system present in the gut. This transport system actively transports drugs which have been absorbed from the intestinal lumen and into the gut epithelium back out into the lumen Inhibition of this p-glycoprotein mediated active transport system will cause less drug to be transported back into the lumen and will thus increase the net drug transport across the gut epithelium and will increase the amount of drug ultimately available in the blood.
The phrases “oral bioavailability” and “bioavailability upon oral administration” as used herein refer to the systemic availability (i.e., blood/plasma levels) of a given amount of drug administered orally to a patient.
The phrase “unsubstituted alkyl” refers to alkyl groups that do not contain heteroatoms. Thus the phrase includes straight chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the like. The phrase also includes branched chain isomers of straight chain alkyl groups, including but not limited to, the following which are provided by way of example: —CH(CH 3 ) 2 , —CH(CH 3 )(CH 2 CH 3 ), —CH(CH 2 CH 3 ) 2 , —C(CH 3 ) 3 , —C(CH 2 CH 3 ) 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 CH(CH 3 )(CH 2 CH 3 ), —CH 2 CH(CH 2 CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , —CH 2 C(CH 2 CH 3 ) 3 , —CH(CH 3 )CH(CH 3 )(CH 2 CH 3 ), —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 CH(CH 3 )(CH 2 CH 3 ), —CH 2 CH 2 CH(CH 2 CH 3 ) 2 , —CH 2 CH 2 C(CH 3 ) 3 , —CH 2 CH 2 C(CH 2 CH 3 ) 3 , —CH(CH 3 )CH 2 CH(CH 3 ) 2 , —CH(CH 3 )CH(CH 3 )CH(CH 3 ) 2 , CH(CH 2 CH 3 )CH(CH 3 )CH(CH 3 )(CH 2 CH 3 ), and others. The phrase also includes cyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl and such rings substituted with straight and branched chain alkyl groups as defined above. The phrase also includes polycyclic alkyl groups such as, but not limited to, adamantyl norbornyl, and bicyclo[2.2.2]octyl and such rings substituted with straight and branched chain alkyl groups as defined above. Thus, the phrase unsubstituted alkyl groups includes primary alkyl groups, secondary alkyl groups, and tertiary alkyl groups. Unsubstituted alkyl groups may be bonded to one or more carbon atom(s), oxygen atom(s), nitrogen atom(s), and/or sulfur atom(s) in the parent compound. Preferred unsubstituted alkyl groups include straight and branched chain alkyl groups and cyclic alkyl groups having 1 to 20 carbon atoms. More preferred such unsubstituted alkyl groups have from 1 to 10 carbon atoms while even more preferred such groups have from 1 to 5 carbon atoms. Most preferred unsubstituted alkyl groups include straight and branched chain alkyl groups having from 1 to 3 carbon atoms and include methyl, ethyl, propyl, and —CH(CH 3 ) 2 .
The phrase “substituted alkyl” refers to an unsubstituted alkyl group as defined above in which one or more bonds to a carbon(s) or hydrogen(s) are replaced by a bond to non-hydrogen and non-carbon atoms such as, but not limited to, a halogen atom in halides such as F, Cl, Br, and I; and oxygen atom in groups such as hydroxyl groups, alkoxy groups, aryloxy groups, and ester groups; a sulfur atom in groups such as thiol groups, alkyl and aryl sulfide groups, sulfone groups, sulfonyl groups, and sulfoxide groups; a nitrogen atom in groups such as amines, amides, alkylamines, dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides, imides, and enamines; a silicon atom in groups such as in trialkylsilyl groups, dialkylarylsilyl groups, alkyldiarylsilyl groups, and triarylsilyl groups; and other heteroatoms in various other groups. Substituted alkyl groups also include groups in which one or more bonds to a carbon(s) or hydrogen(s) atom is replaced by a bond to a heteroatom such as oxygen in carbonyl, carboxyl, and ester groups; nitrogen in groups such as imines, oximes, hydrazones, and nitriles. Preferred substituted alkyl groups include, among others, alkyl groups in which one or more bonds to a carbon or hydrogen atom is/are replaced by one or more bonds to fluorine atoms. One example of a substituted alkyl group is the trifluoromethyl group and other alkyl groups that contain the trifluoromethyl group. Other alkyl groups include those in which one or more bonds to a carbon or hydrogen atom is replaced by a bond to an oxygen atom such that the substituted alkyl group contains a hydroxyl, alkoxy, aryloxy group, or heterocyclyloxy group. Still other alkyl groups include alkyl groups that have an amine, alkylamine, dialkylamine, arylamine, (alkyl)(aryl)amine, diarylamine, heterocyclylamine, (alkyl)(heterocyclyl)amine, (aryl)(heterocyclyl)amine, or diheterocyclylamine group.
The phrase “unsubstituted arylalkyl” refers to unsubstituted alkyl groups as defined above in which a hydrogen or carbon bond of the unsubstituted alkyl group is replaced with a bond to an aryl group as defined above. For example, methyl (—CH 3 ) is an unsubstituted alkyl group. If a hydrogen atom of the methyl group is replaced by a bond to a phenyl group, such as if the carbon of the methyl were bonded to a carbon of benzene, then the compound is an unsubstituted arylalkyl group (i.e., a benzyl group). Thus the phrase includes, but is not limited to, groups such as benzyl, diphenylmethyl, and 1-phenylethyl (—CH(C 6 H 5 )(CH 3 )) among others.
The phrase “substituted arylalkyl” has the same meaning with respect to unsubstituted arylalkyl groups that substituted aryl groups had with respect to unsubstituted aryl groups. However, a substituted arylalkyl group also includes groups in which a carbon or hydrogen bond of the alkyl part of the group is replaced by a bond to a non-carbon or a non-hydrogen atom. Examples of substituted arylalkyl groups include, but are not limited to, —CH 2 C(═O)(C 6 H 5 ), and —CH 2 (2-methylphenyl) among others.
A “pharmaceutically acceptable salt” includes a salt with an inorganic base, organic base, inorganic acid, organic acid, or basic or acidic amino acid. As salts of inorganic bases, the invention includes, for example, alkali metals such as sodium or potassium; alkaline earth metals such as calcium and magnesium or aluminum; and ammonia. As salts of organic bases, the invention includes, for example, trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, and triethanolamine. As salts of inorganic acids, the instant invention includes, for example, hydrochloric acid, hydroboric acid, nitric acid, sulfuric acid, and phosphoric acid. As salts of organic acids, the instant invention includes, for example, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, lactic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. As salts of basic amino acids, the instant invention includes, for example, arginine, lysine and ornithine. Acidic amino acids include, for example, aspartic acid and glutamic acid.
“Treating” within the context of the instant invention, means an alleviation of symptoms associated with a biological condition, disorder, or disease, or halt of further progression or worsening of those symptoms, or prevention or prophylaxis of the disease or disorder. For example, within the context of treating patients having pulmonary hypertension, successful treatment may include a reduction direct vasodilation of pulmonary and/or systemic arterial vascular beds and inhibition of platelet aggregation. The result of this vasodilation will generally reduce right and left ventricular afterload and increased cardiac output and stroke volume. Dose-related negative inotropic and lusitropic effects can also result. The outward manifestation of these physical effects can include a decrease in the symptoms of hypertension, such as shortness of breath, and an increase in exercise capacity.
The present invention, thus generally described, will be understood more readily by reference to the following examples, which are provided by way of illustration and are not intended to be limiting of the present invention.
EXAMPLES
Example 1
In this Example, the bioavailability of treprostinil in rats after dosing orally, intraduodenally, intracolonically and via the portal vein was compared to determine possible barriers to bioavailability. In addition to bioavailability, a number of pharmacokinetic parameters were determined.
Animal Dosing
The bioavailability of treprostinil was evaluated in Sprague-Dawley, male rats. Fifteen surgically modified rats were purchased from Hilltop Lab Animals (Scottdale, Pa.). The animals were shipped from Hilltop to Absorption Systems' West Chester University facility (West Chester, Pa.), where they were housed for at least twenty-four hours prior to being used in the study. The animals were fasted for approximately 16 hours prior to dosing. The fifteen rats used in this study were divided into five groups (I, II, III, IV and V).
The weight of the animals and the dosing regimen are presented in Table 1.
TABLE 1
Dose
Weight
Route of
Study
Volume
Dose
Group
Rat #
(g)
Administration
Day
(mL/kg)
(mg/kg)
I
118
327
Intravenous
0
2
1
119
329
Intravenous
0
2
1
120
320
Intravenous
0
2
1
II
121
337
Intraportal Vein
0
2
1
122
319
Intraportal Vein
0
2
1
123
330
Intraportal Vein
0
2
1
III
124
329
Intraduodenal
0
2
1
125
331
Intraduodenal
0
2
1
126
324
Intraduodenal
0
2
1
IV
127
339
Intracolonic
0
2
1
128
333
Intracolonic
0
2
1
129
320
Intracolonic
0
2
1
V
130
293
Oral
0
2
1
131
323
Oral
0
2
1
132
332
Oral
0
2
1
Samples were withdrawn at the following time points.
IV and IPV: 0 (pre-dose) 2, 5, 15, 30, 60, 120, 240, 360, 480 minutes
ID, IC and Oral: 0 (pre-dose), 5, 15, 30, 60, 120, 240, 360, 480 minutes
Approximately 0.50 to 0.75 mL of whole blood was collected from the jugular vein of a cannulated rat. The blood was transferred to heparinized tubes and placed on ice until centrifuged. Following centrifugation the plasma was placed on ice until frozen at −70 C prior to shipment to Absorption Systems
Analysis of Plasma Samples
Samples were analyzed using the following methodology:
Dosing Solution Preparation
The dosing solution was prepared by combining 15.2 mg of treprostinil diethanolamine (12.0 mg of the free acid form) with 24 mL of 5% dextrose. The solution was then sonicated until dissolved for a final concentration of 0.5 mg/mL. The final pH of the dosing solution was 4.6. At the time of dosing, the dosing solution was clear and homogenous.
Standards and Sample Preparation
To determine the concentration of treprostinil in rat plasma samples, standards were prepared with rat plasma collected in heparin obtained from Lampire Biological Laboratories (Lot #021335263) to contain 1000, 300, 100, 30, 10, 3, 1 and 0.3 ng/mL of treprostinil. Plasma standards were treated identically to the plasma samples.
Plasma samples were prepared by solid phase extraction. After an extraction plate was equilibrated, 150 μL of a plasma sample was placed into the well and vacuumed through. The extraction bed was then washed with 600 μL of acetonitrile: deionized water (25:75) with 0.2% formic acid. The compound was eluted with 600 μL of 90% acetonitrile and 10% ammonium acetate. The eluates were collected and evaporated to dryness. The residue was reconstituted with 150 μL of acetonitrile: deionized water (50:50) with 0.5 μg/mL of tolbutamide (used as an internal standard).
HPLC Conditions
Column: Keystone Hypersil BDS C18 30×2 mm i.d., 3 μm.
Mobile Phase Buffer: 25 mM NH 4 OH to pH 3.5 w/85% formic acid.
Reservoir A: 10% buffer and 90% water.
Reservoir B: 10% buffer and 90% acetonitrile.
Mobile Phase Composition:
Gradient Program:
Time
Duration
Grad. Curve
% A
% B
−0.1
0.10
0
80
20
0
3.00
1.0
10
90
3.00
1.00
1.0
0
100
4.00
2.00
0
80
20
Flow Rate: 300 μL/min.
Inj. Vol.: 10 μL
Run Time: 6.0 min.
Retention Time: 2.6 min.
Mass Spectrometer
Instrument: PE SCIEX API 2000
Interface: Electrospray (“Turbo Ion Spray”)
Mode: Multiple Reaction Monitoring (MRM)
Precursor Ion
Product Ion
Treprostinil
389.2
331.2
IS
269.0
170.0
Nebulizing Gas: 25 Drying Gas: 60, 350° C. Curtain Gas: 25 Ion Spray: −5000 V Orifice: −80 V Ring: −350 V Q0: 10 V IQ1: 11 V ST: 15 V R01: 11 V IQ2: 35 V R02: 40 V IQ3: 55 V R03: 45 V CAD Gas: 4
Method Validation
Table 2 lists the average recoveries (n=6) and coefficient of variation (c.v.) for rat plasma spiked with treprostinil. All samples were compared to a standard curve prepared in 50:50 dH 2 O:acetonitrile with 0.5 μg/mL of tolbutamide to determine the percent of treprostinil recovered from the plasma.
TABLE 2 Accuracy and Precision of Method Spiked Concentration Percent Recovered Coefficient of Variation 1000 ng/mL 85.6 5.2 100 ng/mL 89.6 11.6 10 ng/mL 98.8 7.0
Pharmacokinetic Analysis
Pharmacokinetic analysis was performed on the average plasma concentration for each time point.
The data were subjected to non-compartmental analysis using the pharmacokinetic program WinNonlin v. 3.1 (2).
RESULTS
Clinical Observations
Prior to beginning the experiments it was noted that supra-pharmacological doses of treprostinil would be needed to achieve plasma concentrations that could be analyzed with adequate sensitivity. Using the dose of 1 mg/kg some adverse effects were noted in animals dosed intravenously and via the intraportal vein.
All rats dosed intravenously displayed signs of extreme lethargy five minutes after dosing but fully recovered to normal activity thirty minutes post-dosing. In addition, fifteen minutes after dosing all three animals dosed via the portal vein exhibited signs of lethargy. One rat (#123) expired before the thirty-minute sample was drawn. The other rats fully recovered. The remaining animals did not display any adverse reactions after administration of the compound.
Sample Analysis
Average plasma concentrations for each route of administration are shown in Table 3.
TABLE 3
Average (n = 3) plasma concentrations (ng/mL)
Time (min)
Pre-dose
2
5
15
30
60
120
240
360
480
Intravenous
0
1047.96
364.28
130.91
55.56
14.45
4.45
1.09
0.50
0.30
Intraportal Vein*
0
302.28
97.39
47.98
21.94
11.06
3.87
2.51
4.95
5.14
Intraduodenal
0
—
61.76
31.67
18.57
13.55
5.91
1.11
0.89
0.90
Intracolonic
0
—
7.46
3.43
3.52
1.48
0.64
0.36
0.06 λ
0.20 λ
Oral
0
—
4.52
2.90
3.67
2.06
4.52
1.82
0.90
0.96
*n = 2,
λ concentration falls below the limit of quantitation (LOQ) of the analytical method
The plasma concentration versus time curves for intravenous, intraportal, intraduodenal, intracolonic and oral dosing are shown in FIGS. 1 and 2 . FIG. 3 shows the average plasma concentration versus time curves for all five routes of administration. In the experiments shown in these figures, the diethanolamine salt was used. Table 4 shows the pharmacokinetic parameters determined for treprostinil. The individual bioavailabilities of each rat are found in Table 5.
TABLE 4
Average Bioavailability and Pharmacokinetic Parameters of Treprostinil in Rats
Average
Average
Volume of
Route of
AUC 480 min
C max
T max
T 1/2
Bioavailability
Distribution*
CLs
Administration
(min · ng/mL)
(ng/mL)
(min)
(min)
(%) ± SD
(L · kg −1 )
(mL · min −1 · kg −1 )*
Intravenous
11253.49
2120 Ψ
0
94
NA
1.98
88.54
Intraportal Vein
4531.74
302
2
ND
40.3 ± 5.5
ND
ND
Intraduodenal
2712.55
62
5
ND
24.1 ± 0.5
ND
ND
Intracolonic
364.63
8
5
ND
3.2 ± 2.5
ND
ND
Oral
1036.23
5
5
ND
9.2 ± 1.4
ND
ND
*Normalized to the average weight of the rats
ND: Not determined
Ψ Extrapolated Value
TABLE 5
Individual Bioavailabilities of Treprostinil in Rats
Individual
Route of
Individual AUC 480 min
Bioavailability
Administration
Rat #
(min · ng/mL)
(%)
Intravenous
118
10302.85
NA
119
9981.52
NA
120
13510.65
NA
Intraportal Vein
121
4970.67
44.2
122
4093.21
36.4
123
ND
ND
Intraduodenal
124
2725.68
24.2
125
2763.60
24.6
126
2646.05
23.5
Intracolonic
127
72.63
0.7
128
395.08
3.5
129
625.20
5.6
Oral
130
998.70
8.9
131
907.60
8.1
132
1203.73
10.7
NA: Not applicable
ND: Not determined
CONCLUSIONS
Treprostinil has a terminal plasma half-life of 94 minutes. The distribution phase of treprostinil has a half-life of 10.3 minutes and over 90% of the distribution and elimination of the compound occurs by 60 minutes post-dosing. The volume of distribution (Vd=1.98 L/kg) is greater than the total body water of the rat (0.67 L/kg) indicating extensive partitioning into tissues. The systemic clearance of treprostinil (88.54 mL/min/kg) is greater than the hepatic blood flow signifying that extra-hepatic clearance mechanisms are involved in the elimination of the compound.
First pass hepatic elimination of treprostinil results in an average intraportal vein bioavailability of 40.3%. Fast but incomplete absorption is observed after intraduodenal, intracolonic and oral dosing (T max≦ 5 min). By comparing the intraportal vein (40.3%) and intraduodenal bioavailability (24.1%) it appears that approximately 60% of the compound is absorbed in the intestine. The average intraduodenal bioavailibility is almost three times greater than the oral bioavailibility suggesting that degradation of treprostinil in the stomach or gastric emptying may influence the extent of systemic absorption.
Example 2
In this Example, Treprostinil concentrations were determined in male Sprague-Dawley rats following a single oral dose of the following compounds:
EXPERIMENTAL
Dosing Solution Preparation
All dosing vehicles were prepared less than 2 hours prior to dosing.
1. Treprostinil Methyl Ester
A solution of treprostinil methyl ester was prepared by dissolving 2.21 mg of treprostinil methyl ester with 0.85 mL of dimethylacetamide (DMA). This solution was then diluted with 7.65 mL of PEG 400:Polysorbate 80:Water, 40:1:49. The final concentration of the dosing vehicle was 0.26 mg/mL of treprostinil methyl ester equivalent to 0.25 mg/mL of Treprostinil. The dosing vehicle was a clear solution at the time of dosing.
2. Treprostinil Benzyl Ester
A solution of treprostinil benzyl ester was prepared by dissolving 2.58 mg of treprostinil benzyl ester with 0.84 mL of dimethylacetamide (DMA). This solution was then diluted with 7.54 mL of PEG 400:Polysorbate 80:Water, 40:1:49. The final concentration of the dosing vehicle was 0.268 mg/mL of treprostinil benzyl ester equivalent to 0.25 mg/mL of Treprostinil. The dosing vehicle was a clear solution at the time of dosing.
3. Treprostinil Diglycine
A solution of treprostinil diglycine was prepared by dissolving 1.86 mg of compound with 0.58 mL of dimethylacetamide (DMA). This solution was then diluted with 5.18 mL of PEG 400:Polysorbate 80:Water, 40:1:49. The final concentration of the dosing vehicle was 0.323 mg/mL of treprostinil diglycine equivalent to 0.25 mg/mL of Treprostinil. The dosing vehicle was a clear solution at the time of dosing.
Animal Dosing
The plasma concentrations of Treprostinil following administration of each prodrug were evaluated in male Sprague-Dawley rats. Rats were purchased from Hilltop Lab Animals (Scottdale, Pa.). The animals were shipped from Hilltop to Absorption Systems' West Chester University facility (West Chester, Pa.). They were housed for at least twenty-four hours prior to being used in the study. The animals were fasted for approximately 16 hours prior to dosing. The rats used in this study were divided into three groups (I, II and III). Groups I-III were dosed on the same day.
The weight of the animals and the dosing regimen are presented in Table 6.
TABLE 6
Study Design
Route of
Dose
Weight
Adminis-
Compound
Volume
Dose*
Group
Rat #
(kg)
tration
Dosed
(mL/kg)
(mg/kg)
I
638
306
Oral
Treprostinil
2
0.520
639
310
Oral
methyl ester
640
319
Oral
II
641
319
Oral
Treprostinil
2
0.616
642
309
Oral
benzyl ester
643
320
Oral
III
644
318
Oral
Treprostinil
2
0.646
645
313
Oral
diglycine
646
322
Oral
*This dose of prodrug = 0.500 mg/kg of the active, Treprostinil
Animals were dosed via oral gavage. Blood samples were taken from a jugular vein cannula at the following time points:
0 (pre-dose) 5, 15, 30, 60, 120, 240, 360 and 480 minutes
The blood samples were withdrawn and placed into tubes containing 30 μL of a solution of 500 units per mL of heparin in saline, and centrifuged at 13,000 rpm for 10 minutes. Approximately 200 μL of plasma was then removed and dispensed into appropriately labeled polypropylene tubes containing 4 μL of acetic acid in order to stabilize any prodrug remaining in the samples. The plasma samples were frozen at −20° C. and were transported on ice to Absorption Systems Exton Facility. There they were stored in a −80° C. freezer pending analysis.
Analysis of Plasma Samples
Plasma samples were analyzed as described in Example 1. In brief, Treprostinil was extracted from the plasma via liquid-liquid extraction then analyzed by LC/MS/MS. The analytical validation results were reported previously in Example 1. The lower limit of quantification (LLOQ) of the analytical method was 0.01 ng/mL. Samples were not assayed for unchanged prodrug.
Acceptance Criteria for Analytical Runs
Two standard curves, with a minimum of five points per curve, and a minimum of two quality control samples (QCs) were dispersed throughout each run. Each route of administration was bracketed by a standard curve used for back-calculation. The standards and QCs must be within ±15% (20% for the LLOQ) accuracy and precision for the run to be accepted. At least 75% of all standards and QCs must pass the acceptance criteria.
Pharmacokinetic Analysis
Pharmacokinetic analysis was performed on the plasma concentration of Treprostinil for each individual rat at each time point and on the average plasma concentration for all three rats in the group for each time point. The data were subjected to non-compartmental analysis using the pharmacokinetic program WinNonLin v. 3.1 (2).
RESULTS
Study Observations
No adverse reactions were observed following oral administration of treprostinil methyl ester, treprostinil benzyl ester or treprostinil diglycine.
Plasma Stability of Prodrugs in Acidified Rat Plasma
In order to terminate any conversion of prodrug to active after samples were withdrawn the plasma was acidified. Acetic acid (v/v) was added to each plasma sample immediately after centrifugation of the red blood cells to a concentration of 2%. In-vitro plasma stability of each prodrug was performed to insure that the compound was stable in acidified plasma. To perform this assay 2% acetic acid was added to blank rat plasma obtained from Lampire Biological. The acidified rat plasma was equilibrated at 37° C. for three minutes prior to addition of prodrug. The initial concentration of each prodrug was 1000 μg/mL. A 100 μL aliquot of plasma (n=3 per time point) was taken at 0, 60 and 120 minutes. Each aliquot was combined with 20 μL of HCl and vortexed. Liquid-liquid extraction was then performed and the concentration of Treprostinil in each sample determined. The concentration of Treprostinil at each time point in acidified rat plasma is given in Table 7. Small amounts of Treprostinil appear to be present in the neat compound sample of treprostinil methyl ester and treprostinil diglycine. The concentration of Treprostinil remained constant throughout the course of the experiment, indicating that there was no conversion of prodrug into active compound occurring in acidified plasma.
TABLE 7
Plasma Stability of Prodrugs in Acidified Dog Plasma
Treprostinil Concentration (ng/mL) ± SD (n = 3)
Treprostinil
Treprostinil
Treprostinil
Time (min)
methyl ester
benzyl ester
diglycine
0
56.8 ± 9.3
<0.01
54.9 ± 4.3
60
55.1 ± 5.0
<0.01
51.8 ± 5.9
120
53.8 ± 1.3
<0.01
54.5 ± 0.8
Total % Treprostinil
5.7
<0.01
5.5
Average Treprostinil plasma concentrations following administration of treprostinil methyl ester, treprostinil benzyl ester or treprostinil diglycine are shown in Table 8.
TABLE 8
Treprostinil Concentrations (Average ± SD (n = 3) Plasma Concentrations (ng/mL)
Oral Dosing
Pre-
Solution
Dose
5 (min)
15 (min)
30 (min)
60 (min)
120 (min)
240 (min)
360 (min)
480 (min)
Treprostinil
0
<0.01
0.2 ± 0.0
0.3 ± 0.1
0.5 ± 0.1
1.5 ± 0.8
0.2 ± 0.7
<0.01
0.1 ± 0.1
methyl ester
Treprostinil
0
3.1 ± 2.8
1.9 ± 0.8
2.5 ± 1.5
3.2 ± 1.9
7.3 ± 4.9
1.6 ± 1.2
0.4 ± 0.40
0.6 ± 0.9
benzyl ester
Treprostinil
0
<0.01
1.1 ± 1.9
6.6 ± 10.7
0.5 ± 0.3*
40. ± 5.8
9.0 ± 13.5
2.1 ± 2.9
1.3 ± 0.8
diglycine
*Due to insufficient amount of sample collected this time point is the average of n = 2 rats.
FIGS. 4-7 contain graphical representations of the plasma concentration versus time curves for Treprostinil in rat following administration of each prodrug. Table 9 lists each figure and the information displayed.
TABLE 9 List of Figures Figure Description 4 Oral Dose of Treprostinil methyl ester 5 Oral Dose of Treprostinil benzyl ester 6 Oral Dose of Treprostinil diglycine 7 Oral Dose of Treprostinil benzyl ester and Treprostinil diglycine Compared to Treprostinil Alone from Example 1
Pharmacokinetic Analysis
Bioavailability of the prodrug was determined relative to that of the active compound based on Example 1 in which Treprostinil was dosed to rats. The following formula was used to determine relative bioavailability (F):
Relative F =(AUC (Prodrug Dose) /Dose)/(AUC (Treprostinil Dose) /Dose)*100
Bioavailability was also determined relative to an intravenous dose of Treprostinil in rats determined in Example 1. Results are listed in Table 10.
TABLE 10
Average Relative Bioavailability and Pharmacokinetic Parameters of Treprostinil in Rats
Test
Average
Relative
Compound
Dose
AUC 0−t
C max
T max
Bioavailability
Bioavailability
Administered
(mg/kg)
(min · ng/mL)
(ng/mL)
(min)
(%) ± SD (n = 3)
(%) ± SD (n = 3)
Treprostinil
0.5
212
1.50
120
41.0 ± 16
3.8 ± 2
methyl ester
Treprostinil
0.5
1171
7.20
120
226 ± 155
20.8 ± 14
benzyl ester
Treprostinil
0.5
2242
9.04
240
433 ± 631
39.9 ± 58
diglycine
CONCLUSIONS
In this study the relative oral bioavailabilities of prodrugs of Treprostinil were determined in rats. Treprostinil methyl ester resulted in Treprostinil area under the plasma concentration versus time curves (AUCs) less than that after dosing the active compound. Prodrugs treprostinil benzyl ester and treprostinil diglycine both had Treprostinil average AUCs greater than that after dosing of the active compound. Treprostinil diglycine had the highest relative bioavailability of 433% with over 4 times more Treprostinil reaching the systemic circulation. The Cmax of 9 ng/mL of Treprostinil following administration of treprostinil diglycine occurred at 240 minutes post-dosing. The Cmax following dosing of Treprostinil is 5 ng/mL and occurs only 5 minutes post-dosing. Treprostinil benzyl ester had a relative bioavailability of 226±155% with a Cmax of 7.2 ng/mL occurring 120 minutes post-dosing. It should also be noted that the AUCs are not extrapolated to infinity.
REFERENCES
1. WinNonlin User's Guide, version 3.1, 1998-1999, Pharsight Co., Mountain View, Calif. 94040.
Example 3
This example illustrates a pharmacokinetic study of treprostinil following administration of a single duodenal dose of treprostinil and various prodrugs of the present invention.
In this study, the area under the curve of Treprostinil in male Sprague-Dawley rats following a single intraduodenal dose of treprostinil monophosphate (ring), treprostinil monovaline (ring), treprostinil monoalanine (ring) or treprostinil monoalanine (chain), prodrugs of treprostinil was compared. The compounds were as follows:
having the following substituents:
Compound
R 1
R 2
R 3
treprostinil
H
—PO 3 H 3
H
monophosphate
(ring)
treprostinil
H
—COCH(CH(CH 3 ) 2 )NH 2
H
monovaline
(ring)
treprostinil
H
—COCH(CH 3 )NH 2
H
monoalanine
(ring)
treprostinil
H
H
—COCH(CH 3 )NH 2
monoalanine
(chain)
EXPERIMENTAL
Dosing Solution Preparation
All dosing vehicles were prepared less than 2 hours prior to dosing.
1. Treprostinil Monophosphate (Ring)
A dosing solution of treprostinil monophosphate (ring) was prepared by dissolving 1.01 mg of treprostinil monophosphate (ring) in 0.167 mL of dimethylacetamide (DMA) until dissolved. This solution was further diluted with 1.50 mL of PEG 400: Polysorbate 80: Water, 40:1:49. The final concentration of the dosing vehicle was 0.603 mg/mL of prodrug equivalent to 0.5 mg/mL of Treprostinil. The dosing vehicle was a clear solution at the time of dosing.
2. Treprostinil Monovaline (Ring)
A 50 mg/mL solution of treprostinil monovaline (ring) was prepared in dimethylacetamide (DMA). A 25 μL aliquot of the 50 mg/mL stock solution was then diluted with 175 μL of DMA and 1.8 mL of PEG 400:Polysorbate 80:Water, 40:1:49. The final concentration of the dosing vehicle was 0.625 mg/mL of prodrug equivalent to 0.5 mg/mL of Treprostinil. The dosing vehicle was a clear solution at the time of dosing.
3. Treprostinil Monoalanine (Ring)
A solution of treprostinil monoalanine (ring) was prepared by dissolving 1.05 mg of treprostinil monoalanine (ring) in 0.178 mL of dimethylacetamide (DMA) until dissolved. This solution was further diluted with 1.60 mL of PEG 400: Polysorbate 80: Water, 40:1:49. The final concentration of the dosing vehicle was 0.590 mg/mL of treprostinil monoalanine (ring) equivalent to 0.5 mg/mL of Treprostinil. The dosing vehicle was a clear solution at the time of dosing.
4. Treprostinil Monoalanine (Chain)
A solution of treprostinil monoalanine (chain) was prepared by dissolving 0.83 mg of treprostinil monoalanine (chain) in 0.14 mL of dimethylacetamide (DMA) until dissolved. This solution was further diluted with 1.26 mL of PEG 400: Polysorbate 80: Water, 40:1:49. The final concentration of the dosing vehicle was 0.591 mg/mL of treprostinil monoalanine (chain) equivalent to 0.5 mg/mL of Treprostinil. The dosing vehicle was a clear solution at the time of dosing.
Animal Dosing
The plasma concentrations of Treprostinil following oral administration of each prodrug were evaluated in male Sprague-Dawley rats. Twelve rats were purchased from Hilltop Lab Animals (Scottdale, Pa.). The animals were shipped from Hilltop to Absorption Systems' West Chester University facility (West Chester, Pa.). They were housed for at least twenty-four hours prior to being used in the study. The animals were fasted for approximately 16 hours prior to dosing. The twelve rats used in this study were divided into four groups. All groups were dosed on day 1 of the study. The weight of the animals and the dosing regimen are presented in Table 11.
TABLE 11
Dose
Rat
Weight
Volume
Dose*
#
(g)
Compound
(mL/kg)
(mg/kg)
130
327
treprostinil monophosphate (ring)
1
0.603
131
321
treprostinil monophosphate (ring)
1
0.603
132
310
treprostinil monophosphate (ring)
1
0.603
133
328
treprostinil monovaline (ring)
1
0.625
134
326
treprostinil monovaline (ring)
1
0.625
135
346
treprostinil monovaline (ring)
1
0.625
136
321
treprostinil monoalanine (chain)
1
0.591
137
319
treprostinil monoalanine (chain)
1
0.591
138
330
treprostinil monoalanine (chain)
1
0.591
139
316
treprostinil monoalanine (ring)
1
0.590
140
330
treprostinil monoalanine (ring)
1
0.590
141
339
treprostinil monoalanine (ring)
1
0.590
*This dose of prodrug = 0.500 mg/kg of treprostinil
Animals were dosed via an indwelling duodenal cannula. Blood samples were taken from a jugular vein cannula at the following time points:0 (pre-dose) 5, 15, 30, 60, 120, 240, 360 and 480 minutes.
The blood samples were withdrawn and placed into tubes containing 30 μL of a solution of 500 units per mL of heparin in saline, and centrifuged at 13,000 rpm for 10 minutes. Approximately 200 μL of plasma was then removed and dispensed into appropriately labeled polypropylene tubes containing 4 μL of acetic acid in order to stabilize any prodrug remaining in the samples. The plasma samples were frozen at −20° C. and were transported on ice to Absorption Systems Exton Facility. There they were stored in a −80° C. freezer pending analysis.
Analysis of Plasma Samples
Plasma samples were analyzed using the methods described above. In brief, Treprostinil was extracted from the plasma via solid phase extraction then analyzed by LC/MS/MS. The lower limit of quantification (LLOQ) of the analytical method was 0.03 ng/mL.
Acceptance Criteria for Analytical Runs
Four standard curves, with a minimum of five points per curve, and a minimum of two quality control samples (QCs) at 3 concentrations were dispersed throughout each run. Each prodrug set was bracketed by a standard curve used for back-calculation. The standards and QCs must be within ±15% (20% for the LLOQ) accuracy and precision for the run to be accepted. At least 75% of all standards and QCs must pass the acceptance criteria.
Pharmacokinetic Analysis
Pharmacokinetic analysis was performed on the plasma concentration of Treprostinil for each individual rat at each time point and on the average plasma concentration for all three rats in the group for each time point.
The data were subjected to non-compartmental analysis using the pharmacokinetic program WinNonLin v. 3.1 (2).
RESULTS
Study Observations
No adverse reactions were observed following intraduodenal administration of treprostinil monophosphate (ring), treprostinil monovaline (ring), treprostinil monoalanine (ring) or treprostinil monoalanine (chain).
Ex-Vivo Plasma Stability of Prodrugs in Acidified Rat Plasma
In order to terminate any conversion of prodrug to active after samples were withdrawn, the plasma was acidified. Acetic acid (v/v) was added to each plasma sample immediately after separation of the red blood cells to a concentration of 2%. In-vitro plasma stability of each prodrug was performed to insure that the compound was stable in acidified plasma. To perform this assay 2% acetic acid was added to blank rat plasma obtained from Lampire Biological. The acidified rat plasma was brought to room temperature for three minutes prior to addition of prodrug. The initial concentration of each prodrug was 1000 ng/mL. A 100 μL aliquot of plasma (n=3 per time point) was taken at 0, 60 and 120 minutes. Sample preparation of each plasma sample was performed as described above and the concentration of Treprostinil monitored.
Treprostinil concentrations did not increase in any of the acidified plasma samples spiked with prodrug over the two-hour period of the experiment.
Sample Analysis
Average Treprostinil plasma concentrations following administration of treprostinil monophosphate (ring), treprostinil monovaline (ring), treprostinil monoalanine (ring) or treprostinil monoalanine (chain) are shown in Table 12.
TABLE 12
AVERAGE ± SD (N = 3) PLASMA TREPROSTINIL CONCENTRATIONS (NG/ML)
Oral Dosing
Pre-
Solution
dose
5 (min)
15 (min)
30 (min)
60 (min)
120 (min)
240 (min)
360 (min)
480 (min)
treprostinil
0
8.62 ± 3.0
6.57 ± 1.7
3.31 ± 1.2
4.31 ± 0.8
2.07 ± 0.4
0.91 ± 0.5
0.26 ± 0.08
0.3 ± 0.08
monophosphate
(ring)
treprostinil
0
0.76 ± 0.2
0.91 ± 0.7
1.52 ± 0.6
1.53 ± 0.6
1.65 ± 0.7
0.66 ± 0.1
0.15 ± 0.03
0.05 ± 0.02
monovaline
(ring)
treprostinil
0
2.42 ± 0.6
2.52 ± 0.4
2.91 ± 0.6
3.25 ± 1.5
1.69 ± 0.4
0.55 ± 0.2
0.20 ± 0.1
0.22 ± 0.2
monoalanine
(ring)
treprostinil
0
9.53 ± 2.6
3.92 ± 0.6
3.83 ± 0.7
2.74 ± 0.9
0.86 ± 0.4
0.29 ± 0.2
0.08 ± 0.04
0.19 ± 0.3
monoalanine
(chain)
FIGS. 8-12 contain graphical representations of the plasma concentration versus time curves for Treprostinil in rat following administration of each prodrug. Table 13 lists each figure and the information displayed.
TABLE 13 Figure Description 8 Intraduodenal dose of treprostinil monophosphate (ring) 9 Intraduodenal dose of treprostinil monovaline (ring) 10 Intraduodenal dose of treprostinil monoalanine (ring) 11 Intraduodenal dose of treprostinil monoalanine (chain) 12 Intraduodenal dose of each prodrug compared to treprostinil alone from Example 1
Pharmacokinetic Analysis
Bioavailability of the prodrug was determined relative to that of the active compound based on a previous study in which Treprostinil was dosed to rats. The following formula was used to determine relative bioavailability (F):
Relative F =(AUC (ProdrugDose) /Dose)/(AUC (Treprostinil Dose) /Dose)*100
Absolute bioavailability was also estimated using data from an intravenous dose of Treprostinil in rats determined in Example 1. Results are listed in Table 14.
TABLE 14
List of Figures
Figure
Description
8
Intraduodenal Dose of treprostinil monophosphate (ring)
9
Intraduodenal Dose of treprostinil monovaline (ring)
10
Intraduodenal Dose of treprostinil monoalanine (ring)
11
Intraduodenal Dose of treprostinil monoalanine (chain)
12
Intraduodenal Dose of Each Prodrug Compared to
Treprostinil Alone from Example 1
CONCLUSIONS
The relative intraduodenal bioavailabilities of four prodrugs of Treprostinil were determined in rats. All the compounds had relative intraduodenal bioavailabilities less than that of the active compound. treprostinil monophosphate (ring) and treprostinil monoalanine (ring) had the highest relative intraduodenal bioavailability at 56% and 38% respectively. The T max for treprostinil monophosphate (ring) and treprostinil monoalanine (chain) occurred 5 minutes post-dosing. treprostinil monovaline (ring) and treprostinil monoalanine (ring) had longer absorption times with T max values of 120 and 60 minutes respectively. Maximum Treprostinil concentrations were highest following treprostinil monophosphate (ring) and treprostinil monoalanine (chain) dosing. They reached approximately 9 ng/mL 5 minutes post-dosing. The bioavailabilities are much greater when dosed intraduodenally than when dosed orally as measured by treprostinil plasma levels.
REFERENCES
1. WinNonlin User's Guide, version 3.1, 1998-1999, Pharsight Co., Mountain View, Calif. 94040.
Example 4
In this Example, Treprostinil concentrations will be determined in male Sprague-Dawley rats following a single oral or intraduodenal dose of the following compounds of structure II:
having the following substituents:
Cpd.
R 1
R 2
R 3
A
—CH 2 CONH 2
H
H
B
—CH 2 CON(CH 2 ) 2 OH
H
H
C
—CH 2 CON(CH 3 ) 2
H
H
D
—CH 2 CONHOH
H
H
E
—CH 2 C 6 H 4 NO 2 (p)*
H
H
F
—CH 2 C 6 H 4 OCH 3 (p)*
H
H
G
—CH 2 C 6 H 4 Cl (o)*
H
H
H
—CH 2 C 6 H 4 (NO 2 ) 2
H
H
(o, p)*
I
—CH 2 C 6 H 4 F (p)*
H
H
J
H
—PO 3 H 3
H
K
H
H
—PO 3 H 3
L
H
—COCH 2 NH 2
H
M
H
H
—COCH 2 NH 2
N
H
—COCH(CH 3 )NH 2
H
O
H
H
—COCH(CH 3 )NH 2
P
H
—COCH(CH 3 )NH 2
—COCH(CH 3 )NH 2
*o denotes ortho substitution, m denotes meta substitution and p denotes para substitution.
Examples of these compounds include:
Prodrug preparation and analysis will take place as described in Examples 1 and 2 above. Additionally, the oral bioavailability of treprostinil, treprostinil sodium and the compounds shown in Example 2 and this Example will be administered in close proximity to or simultaneously with various different p-glycoprotein inhibiting compounds at varying concentrations and tested to determine the effect of the p-glycoprotein inhibitors on the oral bioavailability of the compounds. The p-glycoprotein inhibitors will be administered both intravenously and orally.
Example 5
Clinical Studies with Treprostinil Diethanolamine
Introduction
Prior to proceeding directly into clinical studies with a sustained release (SR) solid dosage form of UT-15C (treprostinil diethanolamine), a determination of the pharmacokinetics of an oral “immediate release” solution was performed. The first clinical study (01-101) evaluated the ability of escalating doses of an oral solution of UT-15C to reach detectable levels in plasma, potential dose-plasma concentration relationship, bioavailability and the overall safety of UT-15C. Volunteers were dosed with the solutions in a manner that simulated a sustained release formulation releasing drug over approximately 8 hours.
The second clinical study (01-102) assessed the ability of two SR solid dosage form prototypes (i.e., 1. microparticulate beads in a capsule and, 2. tablet) to reach detectable levels in plasma and the potential influence of food on these plasma drug concentrations. The SR prototypes were designed to release UT-15C over approximately an 8 hour time period.
Details of the two clinical studies are described below.
Clinical Study 01-101
A Safety, Tolerability, and Pharmacokinetic Study of Multiple Escalating Doses of UT-15C (Treprostinil Diethanolamine) Administered as an Oral Solution in Healthy Adult Volunteers (Including Study of Bioavailability).
The oral solution of UT-15C was administered to 24 healthy volunteers to assess the safety and pharmacokinetic profile of UT-15C as well as its bioavailability. To mimic a SR release profile, doses were administered every two hours for four doses at either 0.05 mg per dose (total=0.2 mg), 0.125 mg per dose (total=0.5 mg), 0.25 mg per dose (total=1.0 mg), or 0.5 mg per dose (total=2.0 mg). Study endpoints included standard safety assessments (adverse events, vital signs, laboratory parameters, physical examinations, and electrocardiograms) as well as pharmacokinetic parameters.
All subjects received all four scheduled doses and completed the study in its entirety. Treprostinil plasma concentrations were detectable in all subjects following administration of an oral solution dose of UT-15C. Both AUC inf and C max increased in a linear fashion with dose for each of the four dose aliquots. The highest concentration observed in this study was 5.51 ng/mL after the third 0.25 mg solution dose aliquot of the 2.0 mg UT-15C total dose. Based on historical intravenous treprostinil sodium data, the mean absolute bioavailability values for the 0.2 mg, 0.5 mg, 1.0 mg and 2.0 mg doses of UT-15C were estimated to be 21%, 23%, 24% and 25%, respectively. The results of this study are respectively shown in FIGS. 13A-13D .
UT-15C was well tolerated by the majority of subjects at all doses given. There were no clinically significant, treatment emergent changes in hematology, clinical chemistry, urinalysis, vital signs, physical exams, and ECGs. The most frequently reported adverse events were flushing, headache, and dizziness. This safety profile with UT-15C (treprostinil diethanolamine) is consistent with the reported safety profile and product labeling of Remodulin (treprostinil sodium) and other prostacyclin analogs. Thus, changing the salt form of treprostinil did not result in any unexpected safety issues following the protocol specified dosing regimen (i.e. single dose every 2 hours for four total doses on a single day).
Clinical Study 01-102
A Safety, Tolerability, and Pharmacokinetic Study Comparing a Single Dose of a Sustained Release Capsule and Tablet Formulation of UT-15C (Treprostinil Diethanolamine) Administered to Healthy Adult Volunteers in the Fasted and Fed State
The 01-102 study was designed to evaluate and compare the safety and pharmacokinetic profiles of a (1) UT-15C SR tablet prototype and, (2) UT-15C SR capsule prototype (microparticulate beads in a capsule) in both the fasted and fed state. Each of the SR dosage forms were designed to release UT-15C (1 mg) over an approximate 8-hour time period. Fourteen healthy adult volunteers were assigned to receive the SR tablet formulation while an additional fourteen volunteers were assigned to receive the SR capsule formulation. Subjects were randomized to receive a single dose (1 mg) of their assigned SR prototype in both the fasted and fed state. A crossover design was employed with a seven day wash-out period separating the fed/fasted states. For the fed portion of the study, subjects received a high calorie, high fat meal. Study endpoints included standard safety assessments (adverse events, vital signs, laboratory parameters, physical examinations, and electrocardiograms) as well as pharmacokinetic parameters.
All subjects administered UT-15C SR tablets and capsules had detectable treprostinil plasma concentrations. Calculations of area under the curve from zero to twenty-four hours (AUC 0-24 ) indicate that total exposure to UT-15C SR occurred in the following order: Tablet Fed>Capsule Fasted>Tablet Fasted>Capsule Fed. FIG. 14 displays the pharmacokinetic profiles of the two formulations in the fasted and fed states.
UT-15C SR tablets and capsules were tolerated by the majority of subjects. All adverse events were mild to moderate in severity and were similar to those described in Study 01-101 and in Remodulin's product labeling. Additionally, there were no treatment-emergent changes in vital signs, laboratory parameters, physical examinations, or electrocardiograms throughout the study.
These results demonstrate that detectable and potentially therapeutic drug concentrations can be obtained from a solid dosage form of UT-15C and that these concentrations can be maintained over an extended period of time through sustained release formulation technology.
Polymorphs of Treprostinil Diethanolamine
Two crystalline forms of UT-15C were identified as well as an amorphous form. The first, which is metastable, is termed Form A. The second, which is thermodynamically more stable, is Form B. Each form was characterized and interconversion studies were conducted to demonstrate which form was thermodynamically stable. Form A is made according to the methods in Table 15. Form B is made from Form A, in accordance with the procedures of Table 16.
TABLE 15
Condi-
XRPD
Sample
Solvent
tions a
Habit/Description
Result b
ID
tetrahydro-
FE
opaque white solids;
A
1440-
furan
morphology unknown,
72-02
birefringent
SE
glassy transparent solids
A (PO)
1440-
72-03
SC (60°
translucent, colorless
A
1440-
C.)
glassy sheets of material,
72-16
birefringent
Toluene
slurry
white solids; opaque
A + B
1440-
(RT),
masses of smaller
72-01
6 d
particles
toluene:IPA
SC (60°
white solids; spherical
A
1480-
(11.4:1)
C.)
clusters of fibers,
21-03
birefringent
Water
FE
opaque white solids;
A
1440-
morphology unknowm,
72-07
birefringent
SE
opaque ring of solids,
A + B
1440-
birefringent
72-08
freeze
white, glassy transparent
A + B
1480-
dry
solids
58-02
water:ethanol
FE
opaque white solids;
A +
1440-
(1:1)
morphology unknown,
11.5 pk
72-09
birefringent
FE
clear and oily substance
B
1480-
with some opaque solids
79-02
SE
glassy opaque ring of
A
1440-
solid
72-10
a FE = fast evaporation; SE = slow evaporation; SC = slow cool
b IS = insufficient sample; PO = preferred orientation; LC = low crystallinity; pk = peak
c XRPD = X-ray powder diffraction
TABLE 16 XRPD Solvent Conditions Habit/Description Result Sample ID ethanol/water FE glassy appearing solids of — b 1519-68-01 (1:1) unknown morphology; birefringent 1,4-dioxane slurry(50° C.), 6 d white solids; opaque masses of B 1519-73-02 a material; morphology unknown slurry(50° C.), 2 d small grainy solids; with B 1557-12-01 birefringence subsample of — B 1557-15-01 1557-12-01 subsample of white solids B 1557-15-02 1557-12-01 slurry(50° C.), 2 d — B 1557-17-01 isopropanol slurry(RT), 1 d white solids — b 1519-96-03 tetrahydrofuran slurry(RT), 1 d — — b 1519-96-02 toluene slurry(50° C.), 6 d white solids B 1519-73-01 a Seeds of sample #1480-58-01 (A + B) added b Samples not analyzed c XRPD = X-ray powder diffraction
Characterization of Crystal Forms:
Form A
The initial material synthesized (termed Form A) was characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetry (TG), hot stage microscopy, infrared (IR) and Raman spectroscopy, and moisture sorption. Representative XRPD of Form A is shown in FIG. 15 . The IR and Raman spectra for Form A are shown in FIGS. 16 and 17 , respectively. The thermal data for Form A are shown in FIG. 18 . The DSC thermogram shows an endotherm at 103° C. that is consistent with melting (from hot stage microscopy). The sample was observed to recrystallize to needles on cooling from the melt. The TG data shows no measurable weight loss up to 100° C., indicating that the material is not solvated. The moisture sorption data are shown graphically in FIG. 19 . Form A material shows significant weight gain (>33%) during the course of the experiment (beginning between 65 to 75% RH), indicating that the material is hygroscopic. In addition, hygroscopicity of treprostinil diethanolamine was evaluated in humidity chambers at approximately 52% RH and 68% RH. The materials were observed to gain 4.9% and 28% weight after 23 days in the −52% RH and −68% RH chambers, respectively.
Based on the above characterization data, Form A is a crystalline, anhydrous material which is hygroscopic and melts at 103° C.
Form B
Treprostinil diethanolamine Form B was made from heated slurries (50° C.) of Form A in 1,4 dioxane and toluene, as shown in Table 16. Material isolated from 1,4-dioxane was used to fully characterize Form B. A representative XRPD pattern of Form B is shown in FIG. 20 . Form A and Form B XRPD patterns are similar, however, significant differences are observed in the range of approximately 12-17 °2 θ ( FIG. 20 ).
The thermal data for Form B are shown in FIG. 21 . The DSC thermogram (Sample ID 1557-17-01) shows a single endotherm at 107° C. that is consistent with a melting event (as determined by hotstage microscopy). The TG shows minimal weight loss up to 100° C.
The moisture sorption/desorption data for Form B are shown in FIG. 22 . There is minimal weight loss at 5% RH and the material absorbs approximately 49% water at 95% RH. Upon desorption from 95% down to 5% RH, the sample loses approximately 47%.
Form A and Form B can easily be detected in the DSC curve. Based on the above characterization data, Form B appears to be a crystalline material which melts at 107° C.
Thermodynamic Properties:
Inter-conversion experiments were carried out in order to determine the thermodynamically most stable form at various temperatures. These studies were performed in two different solvents, using Forms A and B material, and the data are summarized in Table 17. Experiments in isopropanol exhibit full conversion to Form B at ambient, 15° C., and 30° C. after 7 days, 11 days, and 1 day, respectively. Experiments in tetrahydrofuran also exhibit conversion to Form B at ambient, 15° C., and 30° C. conditions. Full conversion was obtained after 11 days at 15° C., and 1 day at 30° C. At ambient conditions, however, a minor amount of Form A remained after 7 days based on XRPD data obtained. Full conversion would likely occur upon extended slurry time. Based on these slurry inter-conversion experiments, Form B appears to be the most thermodynamically stable form. Form A and Form B appear to be related monotropically with Form B being more thermodynamically stable.
TABLE 17
Interconversion Studies of Treprostinil Diethanolamine
Experiment/
Sample
Starting
Temper-
No.
Forms
Solvent
Materials
ature
Time
1557-
A vs. B
isopropanol
solid mixture
ambient
7
days
22-01
# 1557-20-01 a
1557-
A vs. B
solid mixture
15° C.
11
days
47-02
# 1557-35-01 d
1557-
A vs. B
solid mixture
30° C.
1
day
33-02
# 1557-35-01 d
1557-
A vs. B
solid mixture
50° C.
—
21-02 e
# 1557-20-01 b
1557-
A vs. B
tetrahydro-
solid mixture
ambient
7
days
20-03
furan
# 1557-20-01 c
1557-
A vs. B
solid mixture
15° C.
11
days
47-01
# 1557-35-01 d
1557-
A vs. B
solid mixture
30° C.
1
day
33-01
# 1557-35-01 d
1557-
A vs. B
solid mixture
50° C.
—
21-01 e
# 1557-20-01 c
a saturated solution Sample ID 1557-21-03
b saturated solution Sample ID 1519-96-03
c saturated solution Sample ID 1519-96-02
d saturated solution prepared just prior to addition of solids
e samples not analyzed as solubility (at 50° C.) of treprostinil diethanolamine was very high and solutions became discolored.
All references disclosed herein are specifically incorporated by reference thereto.
While preferred embodiments have been illustrated and described, it should be understood that changes and modifications can be made therein in accordance with ordinary skill in the art without departing from the invention in its broader aspects as defined herein.
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This invention pertains generally to prostacyclin analogs and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. Generally, the compounds and methods of the present invention increase the oral bioavailability and circulating concentrations of treprostinil when administered orally. Compounds of the present invention have the following formula:
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PRIORITY CLAIM
This application claims the benefit of Romanian Patent Application No. A/00010/2014, filed Jan. 10, 2014; the disclosure of which is incorporated herein by reference in its entirety.
TECHNICAL FIELD
The subject matter described herein relates to testing Ethernet bridges. More particularly, the subject matter described herein relates to methods, systems, and computer readable media for handling unexpected virtual station interface (VSI) discovery and configuration protocol (VDP) packets received by a VSI.
BACKGROUND
Virtual machines are software implementations of physical machines. Virtual machines are often used so that the resources of a single physical computer can be shared among many virtual computers. Each virtual machine may include virtual hardware resources, such as virtual disks, virtual processing resources, and virtual network interface cards. When multiple virtual machines share the same physical Ethernet port, this is referred to as virtual Ethernet port aggregation or VEPA. VEPA has been standardized as IEEE 802.1Qbg—Edge Virtual Bridging, Draft 2.2, 28 Mar. 2012 (hereinafter, “EVB Standard”), the disclosure of which is incorporated herein by reference in its entirety. According to the EVB Standard, an edge relay (ER) is virtual layer 2 switch used by multiple virtual machines to share the same physical Ethernet port. An edge relay can operate in VEPA mode or virtual Ethernet bridging (VEB) mode. Each virtual machine includes a virtual station interface (VSI) that connects the virtual machine to an ER. If a VM connected to an ER operating in VEPA mode desires to send packets to another VM connected to the same ER, the EVB Standard requires that the packet be sent out of the physical Ethernet port, to an adjacent bridge, and back to the VM via the ER. The adjacent bridge is required to build VEPA forwarding tables so that packets will be transmitted correctly between VMs. If the ER is operating in VEB mode, packets can be sent between VSIs connected to the same ER without requiring that the packets be sent to the adjacent bridge.
It is desirable to test the functionality of Ethernet bridges that implement VEPA. One aspect of testing the functionality of VEPA Ethernet bridges is testing the Ethernet bridges' implementation of the VDP protocol. The VDP protocol is used to discover and configure a VSI instance. It has been determined that in some instances, the VEPA Ethernet bridge sends unexpected packets to ERs. These unexpected packets can cause the state machines of the VSIs to crash or enter unexpected states. For example, when a user instructs a VEPA Ethernet bridge to clear all existing sessions, the bridge may initiate transmission of de-associate messages for all sessions. Transmission of some of the de-associate messages may be delayed due to finite resources of the bridge or buffering mechanisms. While waiting to transmit a de-associate message for a session, the bridge may receive a keep-alive message for the same session from one of the VSIs. The bridge may incorrectly interpret the keep-alive message as a message for a new session and may send subsequent messages for the session that the bridge incorrectly interprets as a new session to the VSI. The VSI may subsequently receive the de-associate message, clear the session, and place the session in a retry queue to wait behind other sessions and attempt reestablishment of the session. While waiting to retry establishment of the session, the VSI does not expect to receive new session messages from the bridge. Receipt of such messages while waiting to retry the session causes the station, i.e., the VSI, to enter an indeterminate state.
Accordingly, there exists a need for methods, systems, and computer readable media for handling unexpected VDP packets received by a VSI.
SUMMARY
Methods, systems, and computer readable media for handling unexpected virtual station interface (VSI) discovery and configuration protocol (VDP) packets received by an edge relay (ER) are disclosed. One method includes, at a network equipment test device, emulating an ER and a plurality of VSIs located behind the ER. The method further includes transmitting a keep-alive message from one of the VSIs to a virtual Ethernet port aggregation (VEPA) bridge under test. The method further includes receiving a de-associate message from the bridge, tearing down the session, and attempting to re-establish the session with the bridge. The method further includes, while waiting to initiate the attempt to re-establish the session with the bridge, receiving an unexpected message from the bridge and intercepting and logging receipt of the at least one unexpected message.
The subject matter described herein can be implemented in hardware or hardware in combination with software and/or firmware. For example, the subject matter described herein can be implemented in software executed by a processor. In one exemplary implementation, the subject matter described herein can be implemented using a non-transitory computer readable medium having stored thereon computer executable instructions that when executed by the processor of a computer control the computer to perform steps. Exemplary computer readable media suitable for implementing the subject matter described herein include non-transitory computer-readable media, such as disk memory devices, chip memory devices, programmable logic devices, and application specific integrated circuits. In addition, a computer readable medium that implements the subject matter described herein may be located on a single device or computing platform or may be distributed across multiple devices or computing platforms.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a network diagram illustrating a network equipment test device emulating an ER and plural VSI sessions to test the functionality of a VEPA Ethernet bridge according to an embodiment of the subject matter described herein;
FIG. 2 is a state diagram illustrating the 802.1Qbg station VDP state machine, as specified by the EVB standard;
FIG. 3 is a network diagram illustrating exemplary traffic exchanged between VSIs and a VEPA Ethernet bridge;
FIG. 4 is a network diagram illustrating receipt of unexpected messages by an emulated VSI according to an embodiment of the subject matter described herein;
FIG. 5 is a block diagram illustrating an emulated VSI configured to intercept and process unexpected traffic from a VEPA bridge under test according to an embodiment of the subject matter described herein;
FIG. 6 is a state diagram illustrating modifications to the 802.1Qbg station VDP state machine to facilitate intercepting and logging of unexpected messages received by a VSI according to an embodiment of the subject matter described herein; and
FIG. 7 is a flow chart illustrating an exemplary process for handling unexpected VDP traffic by a VSI according to an embodiment of the subject matter described herein.
DETAILED DESCRIPTION
Methods, systems, and computer readable media for handling unexpected VDP packets received by an ER are disclosed. FIG. 1 is a network diagram illustrating a network equipment test device emulating an ER and plural VSIs for testing a VEPA Ethernet bridge according to an embodiment of the subject matter described herein. Referring to FIG. 1 , network equipment test device 100 communicates with a VEPA bridge 102 over one or more VSI sessions. In the illustrated example, network equipment test device 100 emulates virtual station interfaces 104 A, 104 B, and 104 C and edge relay (ER) 106 . ER 106 forwards packets between VSIs 104 A- 104 C and to DUT 102 via physical network interface 108 . ER 106 may operate in VEPA mode or VEB mode, as described above. Although in the illustrated example, one ER, three VSI interfaces and three corresponding sessions are illustrated, in practice, network equipment test device 100 may emulate more than one ER, hundreds of VSIs and thousands of simultaneous sessions to test the performance of VEPA Ethernet bridge 102 . Each virtual station interface 104 A, 104 B, and 104 C may implement the VDP state machine as specified by the EVB Standard.
FIG. 2 illustrates the 802.1Qbg station VDP state machine. In FIG. 2 , a VSI begins the VDP processing in the INIT state 200 . In the INIT state, if the station receives or issues a new command, the state machine proceeds to the STATION_PROCESSING state 202 . If the station receives an unexpected command in the STATION_PROCESSING state 202 , there is no mechanism in the present state machine for intercepting the command, even if the command is not an expected command. In addition, there is no mechanism in the current state machine for logging receipt of the command. Improvements to the state machine will be described in detail below.
FIG. 3 is a network diagram illustrating a problem that can occur with the 802.1Qbg bridge implementation. In FIG. 3 , bridge 102 receives a clear all sessions command from the user. The result of the clear all sessions command is for the bridge to transmit de-associate messages to network equipment test device 100 . However, the process of transmitting de-associate messages involves placing the messages in a transmit queue of bridge 102 to be transmitted to ER 106 and ultimately to the VSIs located behind ER 106 . Because there may be some delay in transmitting these messages, other messages for the sessions may be transmitted by the VSIs behind ER 106 before the VSIs receive the de-associate message. In the illustrated example, VSI 104 B located behind ER 106 transmits a VDP keep-alive message 300 to bridge 102 . The de-associate message 302 generated by bridge 102 is eventually transmitted to VSI 104 B. The de-associate message 302 transmitted by bridge 102 and the keep-alive message 300 transmitted by VSI 104 B located behind ER 106 cross in the air between bridge 102 and ER 106 .
Referring to FIG. 4 , when bridge 102 receives the keep-alive message, bridge 102 incorrectly interprets the keep-alive message as being associated with a new session. VSI 104 B receives the de-associate message and interprets the de-associate message as being a session termination message 300 . Accordingly, VSI 104 B enters the INIT state and the session is torn down. Because the retry mechanism is active, the session goes into the outstanding queue and waits for other sessions to negotiate so it can also reinitiate the negotiation process.
After one to three seconds from the initial session clear command, because of buffering and temporization features on bridge 102 , bridge 102 replies to the keep-alive message with an associate message 400 for a new session. As set forth in the preceding paragraph, VSI 104 B is in the INIT state where the session is in the outstanding queue still waiting to transmit an associate message when VSI 104 B receives associate message 400 transmitted in error by bridge 102 . Associate message 400 received from bridge 102 is unexpected. In response to receiving the unexpected associate packet, VSI 104 B may go into an indeterminate state and may remain in that state. However, according to improvement herein, VSI 104 B continues to wait to send its associate message but this wait may take longer than a configured session timeout, typically a number of seconds, because of a slow renegotiation rate caused by buffering or throttling mechanisms. After configured session timeout of seconds expires, a timeout occurs on bridge 102 for the pseudo active session, so bridge 102 terminates the connection by sending a de-associate message. In response to receiving the de-associate packet, VSI 104 B goes into an indeterminate state and may remain in that state.
Rather than acting on unexpected messages transmitted by bridge 102 in response to a keep-alive message, virtual station interfaces 104 A through 104 C may intercept and log such messages so that the performance of bridge 102 can be accurately recorded and tested. FIG. 5 is a diagram illustrating an exemplary network equipment test device with the capability of intercepting and logging unexpected VDP messages received in response to a keep-alive message according to an embodiment of the subject matter described herein. In FIG. 5 , VSI 104 B is shown for simplicity. It is understood that multiple VSIs may be implemented as shown and described herein. Referring to FIG. 5 , VSI 104 B implements or includes a VSI session manager 500 that implements a modified version 501 of the VDP state machine illustrated in FIG. 2 , which intercepts unexpected messages and logs the occurrence of unexpected messages in a log 502 .
FIG. 6 illustrates a portion of modified VDP state machine 501 that may be implemented by VSI session manager 500 . VSI session manager 500 may implement the modified states illustrated in FIG. 6 and the remaining states illustrated in FIG. 2 of the VDP state machine. Referring to FIG. 6 , in INIT state 200 , a Boolean variable called newSessionFlag is set to TRUE. In STATION_PROCESSING state 202 , the newSessionFlag variable is checked to determine whether it is set to TRUE. If the newSessionFlag is set to TRUE, the STATION_PROCESSING state 202 executes a new function, invalidRxCount.start( ) that intercepts and logs receipt of unexpected messages while waiting for VSI 104 B to transmit a command to bridge 102 . VSI 104 B may transmit a command to bridge 102 , for example, upon receiving notification that its associated VM has data to send to bridge 102 . Once VSI 104 B transmits the command to bridge 102 , the counting stops and the newSessionFlag is set to FALSE. The pseudo code shown below illustrates the changes in the INIT and STATION PROCESSING states.
INIT state changes to:
operCmd=NULL vsiState=DEASSOC newSessionFlag=TRUE
STATION_PROCESSING state changes to:
rxResp = NULL
if (newSessionFlag == TRUE)
invalidRxCount.Start( )
TxTLV(sysCmd)
if (newSessionFlag == TRUE)
{
invalidRxCount.Stop( )
newSessionFlag = FALSE
}
waitWhile = respWaitDelay
Thus, in FIG. 5 , when the keep-alive message sent by VSI 104 B is improperly interpreted as being associated with a new session by bridge 102 and bridge 102 transmits one or more invalid responses to VSI 104 B, the invalid responses may be intercepted, counted, and records of receipt of the invalid responses may be stored in log 502 . Thus, the invalid responses do not cause the state machine of VSI 104 B to enter an invalid state or stay hung in a particular state.
FIG. 7 is a flow chart illustrating exemplary steps for handling unexpected packets by a VSI's VDP state machine in response to transmission of such packets by a bridge. The flow chart in FIG. 7 is divided into two parts. The left-hand side of the flow chart illustrates steps performed by the VSI's VDP state machine. The right-hand side of the flow chart illustrates steps performed by the bridge. Referring to FIG. 7 , in step 700 , the VSIs exchange VDP packets with the bridge over VSI sessions. For example, network equipment test device 100 may emulate hundreds or thousands of VSIs to test the functionality of bridge 102 . The VSIs establish sessions with the bridge and sends VDP traffic over the sessions.
In step 702 , the user issues a clear session command to the bridge to clear all existing sessions. The clear session command results in the transmission of de-associate messages to the VSIs, as indicated in step 704 . However, there may be some delay in transmitting the de-associate messages to the VSIs. While the bridge is waiting for responses to the de-associate messages, the station sends a keep-alive message to the bridge, as indicated by step 706 . In step 708 , the bridge receives the keep-alive message and wrongly interprets the keep-alive message as a new session. Meanwhile, in step 710 , the station is still waiting for a response to the keep-alive message. In step 712 , the station receives the de-associate message, interprets the de-associate message as a response to the keep-alive message and tears down the session. The station places the session in the outstanding queue and waits for other sessions to negotiate so the station can also renegotiate the session.
In step 714 , the bridge sends an associate message to the station. The associate message is sent in response to the keep-alive message transmitted to the bridge in step 706 . From the station's viewpoint, the associate message is unexpected because the session is in the outstanding queue still waiting to transmit the associate message to the bridge. However, rather than entering an indeterminate state as before, as illustrated in the pseudo code above and in FIG. 6 , from the INIT state, a flag called newSessionFlag is set to TRUE and the state machine transitions to the STATION PROCESSING state. In the STATION_PROCESSING state, the function invalidRxCount( ) starts intercepting and counting unexpected messages (step 716 ). The VSI transmits an associate message to the bridge in an attempt to reestablish the session. While waiting for the associate command to be transmitted from the station, any invalid messages received from the bridge are intercepted and counted. Once the associate message has been transmitted, as indicated by step 718 , the station stops counting unexpected packets and resets the newSessionFlag variable. Thus, using the modified station VDP state machine illustrated in FIG. 6 and the pseudo code above, a network equipment test device that emulates ERs and associated VSIs is prevented from being put in an unexpected state due to some errors in bridge state machine implementations.
It will be understood that various details of the subject matter described herein may be changed without departing from the scope of the subject matter described herein. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation, as the subject matter described herein is defined by the claims as set forth hereinafter.
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Methods, systems, and computer readable media for handling unexpected virtual station interface (VSI) discovery and configuration protocol (VDP) packets received by a VSI are disclosed. One method includes, at a network equipment test device, emulating an ER and VSIs behind the ER. The method further includes transmitting a keep-alive message for a session from one of the VSIs to a virtual Ethernet port aggregation (VEPA) bridge under test. The method further includes receiving a de-associate message from the bridge, tearing down the session, and attempting to re-establish the session with the bridge. The method further includes, while waiting to initiate the attempt to re-establish the session with the bridge, receiving an unexpected message from the bridge and intercepting and logging receipt of the at least one unexpected message.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of priority of U.S. Serial No. 06/295,106, filed May 31, 2001, pursuant to 35 U.S.C. §119, and the entire disclosure of which is incorporated in its entirety by reference herein.
FIELD OF THE INVENTION
[0002] The present invention relates generally to surface maintenance or conditioning machines, and particularly those machines employing one or more surface maintenance or conditioning appliances or tools that perform one or more tasks including, among others, scrubbing, sweeping, and vacuuming. More specifically, the present invention is particularly directed to a combination high-pressure spray cleaning system and a spent-solution recovery system.
BACKGROUND OF THE INVENTION
[0003] Brush-type scrubbing systems and appliances are of course well known for surface maintenance, particularly floor surfaces. However, in some high demand or difficult surface maintenance applications and environments, brush-type-scrubbing systems may be inadequate. Examples of high demand or difficult cleaning applications include, among others, parking lots, airport runways, gas stations, and the like.
[0004] Pressure washers or water blasting or jetting systems are of course well known and commercially available. Manufacturers of such water blasting systems and pressure washers include, among others, Vactor, Jetstream, Gardener Denver Water Jetting, Aqua-Dyne, Hammelmann, and Imperial Industries.
SUMMARY OF THE INVENTION
[0005] An object of the present invention is to provide a high-pressure spray cleaning system.
[0006] Another object of the invention is to provide a combination high-pressure spray cleaning system and solution recovery system.
[0007] Another object of the invention is to provide a combination high-pressure spray cleaning system and solution recovery system intended to be coupled to a transport vehicle.
[0008] Yet, another object of the invention is to provide a combination high-pressure spray cleaning system and solution recovery system intended to be coupled to a transport vehicle with a solution recycling system for solution reuse.
[0009] In accordance with the present invention, a brushless scrub head for cleaning a surface comprises a spraying head system having one or more spraying nozzles from which a high-pressure solution exits therefrom and a solution recovery chamber for removing solution and debris from a surface. In an exemplary embodiment, a hydraulic motor is employed for driving the a rotary spraying head system and controlling the speed of rotation thereof, independent of the pressure of the solution exiting the nozzles. A high-pressure fluid solution pump may be provided for independently controlling the solution spray pressure exiting the nozzles.
[0010] Further, in accordance with the present invention, the brushless scrub head is constructed to include a highly efficient solution recovery system.
[0011] Further, in accordance with an exemplary embodiment of the present invention, the combination brushless scrub head and recovery system is coupled to a transport vehicle including a self contained, solution tank system, solution recovery tank system and/or solution recycling system.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] [0012]FIG. 1 a block diagram of the brushless scrub head system in accordance with present invention.
[0013] [0013]FIG. 2 is a side view of a surface maintenance vehicle employing a brushless cleaning head system in accordance with the present invention.
[0014] [0014]FIG. 3 is a partial perspective view of one exemplary embodiment of the brushless cleaning head system assembly in accordance with the present invention.
[0015] [0015]FIG. 4 is a top view of the brushless cleaning head system assembly of FIG. 3.
[0016] [0016]FIG. 5 is a cross sectional-view taken along lines 5 - 5 of FIG. 4.
[0017] [0017]FIG. 6 is a perspective bottom view of the brushless cleaning head system assembly of FIG. 3.
[0018] [0018]FIG. 7 is a perspective top view of the brushless cleaning head system assembly of FIG. 3.
DETAILED DESCRIPTION OF THE INVENTION
[0019] Illustrated in FIG. 1 is a block diagram of a scrubless head cleaning system 5 in accordance with the present invention and further employing a scrubless cleaning head 200 embodying further several aspects of the present invention. More specifically, a rotatable solution spraying wand system 80 includes a fluid carrying shaft 82 coupled to fluid carrying wands 84 a and 84 b , each terminating with a nozzle 222 . Nozzle 222 and wands 84 a and 84 b are configured to have a selected spraying pattern for directing a solution at a selected angle relative to a horizontal surface 90 . Shaft 82 is coupled to drive motor 10 for causing shaft 82 to spin at a selected spin rate. Drive motor 10 may be a hydraulic motor, an electric motor, an air motor or combinations thereof.
[0020] In one embodiment of the invention, scrubless cleaning head 200 is constructed to form an open ended spraying chamber 206 and an open ended vacuum chamber 208 , each chamber 206 , 208 being open to the surface to be cleaned. It is intended that spinning wands 84 a , 84 b spin and solution spray exits nozzles 222 within spraying chamber 206 . Vacuum chamber 208 is intended to be coupled to spraying chamber 206 so as to follow chamber 208 when the scrubless cleaning head 200 is moving in the forward direction as illustrated in the drawings.
[0021] A vacuum system 114 is coupled to vacuum chamber 208 through a conduit 40 for collecting spent solution exiting from nozzles 222 after being directed toward surface 90 . In turn the collected solution may be transferred to a recovery/recycling tank system 20 . For a recycling tank system, collected solution may be recycled and used as the cleaning solution as depicted by the dotted line conduit 50 coupled to the cleaning solution tank 15 . A variety of known recycling technologies may be utilized to recycle the collected solution, including but not limited to mesh media filters, porous filters, hydrocyclones, or combinations thereof. Alternatively, as illustrate in the drawing, cleaning solution tank 15 may be coupled to a source 17 of solution, e.g., water, or alternatively to a solvent or detergent that may be added to an aqueous solution as is well known in the art.
[0022] Illustrated in FIG. 2 is a surface maintenance vehicle, generally indicated by numeral 100 . Surface maintenance vehicle 100 may include, among other components and systems, a solution inlet 102 , a solvent inlet 106 , a solution tank 104 , a solvent tank 108 , a recovery tank 110 , a solution recycling system 112 . Further, surface maintenance vehicle 100 may also include: a vacuum system 114 , a pumping system 116 for a pressurized spray cleaning system, a solution deliver system 118 , a recovered solution transport system 120 , brushless scrub head 200 , a hydraulic system 123 , and requisite piping and valves, well known in the art and not shown, to enable a variety of system configurations. Alternative embodiments of surface maintenance vehicles may also be used to practice aspects of the present invention.
[0023] An exemplary embodiment of scrubless brush head 200 in accordance with the present invention is particularly described with reference to FIGS. 3 - 7 . FIG. 3 is a perspective view of brushless scrub head 200 including a rigid deck generally indicated by numeral 216 . Deck 216 includes a downwardly depending shroud member 217 , at least in part, for securing a resilient skirt 232 . The combination of deck 216 , shroud 217 and resilient skirt 232 forms an open ended chamber 206 , herein referred to as spraying chamber 206 —the open end of chamber 206 being in communication with the surface intended to be cleaned.
[0024] Associated with a rearward section of deck 216 is a second open-ended chamber 208 . Chamber 208 is formed in part by a resilient skirt 235 attached to shroud member 217 , a chamber dividing portion resilient skirt 232 indicated by numeral 232 B, and an upper chamber member 221 —the open end of chamber 208 being in communication with the surface intended to be cleaned.
[0025] Resilient skirt 235 is illustrated as extending generally from left and right side portions of deck 216 generally indicated by numerals 216 L and 216 R, and forming left and right air inlets 214 L and 214 R by way of an intended separation between end extremities of skirt 235 and adjacent portion of skirt 232 in proximity to the aforesaid left and right deck sides indicated by numerals 216 L and 216 R of deck 216 .
[0026] Chamber 208 can be characterized as providing a double skirt wall across approximately the rear one-half of chamber 206 , extending from the right air inlet 214 R around the rear portion of chamber 206 and to the left air inlet 216 L (the double skirt wall comprising portions of skirt 232 and skirt 235 ). Side portions of double skirt wall (proximate to air inlets 214 R and 214 L) permit the capture of solution which may otherwise spray out of spraying chamber 206 .
[0027] As further illustrated in the exemplary embodiment of the brushless scrub head 200 illustrated in the drawings, deck 216 is attached to frame members 202 , supported by three caster wheels 204 a - c . Frame members 202 , by way of an example may then be coupled to lifting mechanism (not shown) and appropriate linkage associated with the transport vehicle 100 for lifting and lowering brushless scrub head deck 216 relative to the surface intended to be cleaned. In the preferred embodiment of the present invention, brushless scrub head 200 is intended to be supported by the three caster wheels to provide a consistent scrub head floating just above the surface intended to be cleaned, as illustrated in FIG. 5.
[0028] In the exemplary embodiment of the invention illustrated in the drawings, solution spraying wand system 80 includes three spinner bars 210 a - c each with two nozzles 222 at opposite ends thereof. The attachment of the spinner bars 210 a - c to a solution conduit 30 may be accomplished by way of water swivels 212 a - c . Three independent hydraulic drive motors 224 are attached to an upper surface of deck 216 by way of mounting brackets 226 , and so positioned to facilitate connection to the water swivels 212 a - c , respectively, for rotating spinner bars or wands 210 a - c , respectively.
[0029] Illustrated in FIG. 4 is a top view of the brushless scrub head system 200 in accordance with the present invention and particularly depicting the pair of air inlets 214 L and 214 R in proximity to deck sides 216 L and 216 R respectively provided by the end portions of resilient skirt 235 and skirt 232 . As illustrated in FIG. 4, primary vacuum chamber 208 is generally chevron-shaped, as defined by the inwardly directed shroud 232 faces.
[0030] [0030]FIG. 5 illustrates a cross sectional view of scrubless head system 200 taken along lines 5 - 5 of FIG. 4. A portion of shroud 217 and resilient member 232 B acts as a divider between chamber 206 and chamber 208 . Resilient members 232 and 235 are optimized to control air flow in system 200 . In particular, a distance between a lower edge of resilient members 232 and 235 and the floor surface is generally indicated as distance “D 1 ”. Furthermore a distance between a lower edge of resilient member 232 B and the floor surface is indicated as distance “D 2 ”. In the illustrated exemplary embodiment, distance D 2 is greater than distance D 1 . A gap created by resilient member 232 B facilitates airflow from chamber 206 into chamber 208 . This airflow from chamber 206 into chamber 208 functions to minimize the amount of solution sprayed out of chamber 206 and that is not captured in chamber 208 . Additionally, the airflow from chamber 206 is directed between chamber dividing portion 232 B of skirt 232 and the ground surface to facilitate removal of solution from surface depressions, cracks, etc. In an exemplary embodiment, distance Dl is approximately zero (touching), and distance D 2 is approximately between {fraction (1/16)} to ⅛ inch.
[0031] [0031]FIGS. 6 and 7 illustrate top and bottom perspective views of the scrubless head system 200 being coupled to a surface maintenance vehicle 100 , respectively.
[0032] Brushless scrub head 200 provides a forward spraying chamber 206 and a rearward vacuum chamber 208 . In part, spraying chamber 206 serves as a secondary vacuum chamber provided primarily by skirt 232 and deck 216 . The primary vacuum chamber 208 is coupled to vacuum system pump 114 through a conduit 40 or 220 . Airflow inlets 214 L and 214 R accentuate removal of spent solution which enters through under surfaces of rear portions of skirt 232 which forms, in part vacuum chamber 208 . Airflow from inlets 214 L and 214 R, indicated by arrows in FIG. 4, facilitates spent solution and debris removal by providing a relatively strong airflow to lift and/or transport solution and debris from surface cracks, undulations, pad-eyes, and other surface irregularities.
[0033] Upper chamber member 221 includes a single vacuum duct 220 . In an alternative embodiment, a plurality of vacuum ports may be used to facilitate removal of spent cleaning solution and surface debris from the affected surface area. A single large vacuum duct 220 ( 40 in FIG. 1) may be utilized for transporting the spent cleaning solution and debris to the recovery system or recycling system 112 or any combination thereof.
[0034] In operation, flexible skirt 232 b at the rear of the spraying chamber 206 is specifically designed in such manner to only allow sufficient airflow to be taken from the spraying chamber and enter the primary vacuum chamber 208 to prevent cleaning solution from spraying out of the front portion of the spraying chamber 206 .
[0035] One embodiment of brushless scrub head system 200 of the present invention contains rotating spray wands and accompanying nozzles that are driven by a hydraulic pump and motor. The combination of the hydraulic pump and a variable pressure valve allows for controlling the spray nozzle rotation speed independent of the spray solution pressure, thereby uncoupling the rotation speed from the solution spray pressure. The present invention has solved problems with existing pressurized cleaning systems where the rotation speed of the sprayer arms is created as a reaction to spray solution exiting the fluid nozzles.
[0036] It should be noted that the sprayed cleaning solution used in concert with the inventive brushless cleaning head system, may be an aqueous cleaning solution or a combination aqueous and miscible solvent solution. The aqueous and miscible solvent combination may be combined by one of several methods. One specific embodiment is an injection pump mixing system whereby the two liquids are mechanically mixed. A second embodiment is an aspiration mechanism whereby the two liquids are combined at the spray nozzle.
[0037] The solution recovery system may be any number of combinations of a solution recovery tank, a solution recycling system, a solution tank, a solvent tank, and any number of vacuums and pumps along with the requisite pipes and valves necessary to power and connect the components of the system.
[0038] Resilient skirts 232 and 235 may be constructed by way of a wide array of resilient materials, e.g., rubber, plastics, and the like which function in part as squeegees and develop the requite chambers as described herein.
[0039] In accordance with the present invention, a control system may be employed to regulate the combined solution spray pressure exiting the nozzles and the speed of rotation of the wands in relation the speed of the transport vehicle in order to optimize cleaning performance in the intended application. Of course, the aforementioned control characteristics are dependent upon the selected nozzles and resulting spray patterns and angle of attack relative to the surface intended to be cleaned.
[0040] Although a multiple wand system has been illustrated in the drawings, a single wand system is within the true spirit and scope of the present invention. Furthermore, although a recovery system has been illustrated coupled directly to the spraying chamber, independent control of both exiting solvent pressure and speed of rotation of the wands without a jointly coupled recovery system is within true sprit and scope of the present invention.
[0041] It should be recognized that spraying chamber 206 as well as vacuum chamber 208 may be constructed by wide array of manufacturing techniques and configurations in order to achieve the intended functions.
[0042] Although the invention has been described in connection with particular embodiments thereof other embodiments, applications, and modifications thereof which will be obvious to those skilled in the relevant arts are included within the spirit and scope of the invention.
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A device and method of use for cleaning a ground surface with pressurized cleaning solution is disclosed. The device includes a transportable deck having at least a first chamber and a second chamber, each first and second chamber being in open communication with the surface, said first chamber having a nozzle for directing a pressurized cleaning solution toward the ground surface, and said second chamber having a vacuum outlet for removing cleaning solution and debris from the surface. Additional embodiments of the present invention may include a solution recycling system for reusing recovered solution.
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FIELD OF INVENTION
[0001] The present invention relates to a nutritional or dietary supplement composition that strengthens and promotes immune health through the prevention, stabilization, reversal and/or treatment of cancerous cells. More specifically, the present invention will aid in complementing traditional cancer therapies as it is well tolerated with no toxicity and aids in reduction of cancer cell growth in a synergistic fashion of its inherent comprehensive blend with antioxidant capabilities to aid in cellular longevity, apoptotic properties for cancerous-only cells, and immuno-stimulating properties.
BACKGROUND OF INVENTION
[0002] Cancer is the leading cause of death worldwide. Cancer is a generic term for a large group of diseases that can affect any part of the body. Other terms used are malignant tumors and neoplasms. One defining feature of cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs. This process is referred to as metastasis. Metastases are the major cause of death from cancer. Cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012 (1). The main types of cancer are:
lung (1.59 million deaths) liver (745 000 deaths) stomach (723 000 deaths) colorectal (694 000 deaths) breast (521 000 deaths) oesophageal cancer (400 000 deaths) (1).
[0009] Cancer arises from one single cell. The transformation from a normal cell into a tumor cell is a multistage process, typically a progression from a pre-cancerous lesion to malignant tumors. These changes are the result of the interaction between a person's genetic factors and three categories of external agents, including:
physical carcinogens, such as ultraviolet and ionizing radiation; chemical carcinogens, such as asbestos, components of tobacco smoke, aflatoxin (a food contaminant) and arsenic (a drinking water contaminant); and biological carcinogens, such as infections from certain viruses, bacteria or parasites.
[0013] Recently, attention has been focused on using natural supplements to help prevent and reduce the onset of cancerous cells and maintain and stimulate immune response. Two specific extracts have received particular notice, fucoidan (from seaweed) and beta-glucans (from mushrooms). These two specific extracts, by themselves, have shown clinical evidence of reducing cancerous cells and immune balancing properties. This art is recognizing the combination of these two extracts (including but not limited to seaweed species such as laminaria japonica and undaria pinnatifida and mushroom species ganoderma lucidum and grifola frondosa ) with antioxidant fruits, vegetable or herbs (including but not limited to acai berry ( Euterpe oleracea ), Sumac, and cloves) and a ten essential multivitamins and minerals (vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D3, vitamin E, calcium, thiamin, riboflavin, niacin, folic acid, pantothenic acid) and their synergistic properties to prevent and/or reduce the onset of cancerous cells and maintain and stimulate immune response.
[0014] Vitamins B6, B12, C, E and Folic Acid are well known and documented to aid in heart health, vitamins A, C, and E for immunity and eye health, and finally, Thiamin, Riboflavin and Niacin to aid in converting food to fuel and maintain physical energy.
[0015] Antioxidants; fruit, vegetable or herb (including but not limited to Acai berry [( Euterpe oleracea ), Sumac, and cloves)] have gained increased clinical evidence as being a strong antioxidant for overall cell structure and reducing toxicity from free radicals and oxidizers promoting cell longevity.
[0016] Beta-glucans—These compounds have shown dramatic immunostimulating as well as immune balancing properties.
[0017] Fucoidan—These compounds have been shown to have pro-apototic effects on cancerous cells as well as promoting immune response to foreign bodies.
[0018] Currently, there is no nutritional complement to patients undergoing cancer therapies, moreover, no nutritional complement that may aid them in toleration as well as recovery during that time period. Accordingly, a need exists in the to provide methods and compositions for the complementary treatment of cancer related treatments.
SUMMARY OF INVENTION
[0019] The present invention is a nutritional or dietary supplement composition for administration to humans or other animals that strengthens and promotes cell health through the prevention, stabilization, reversal and/or treatment of cancer in complement to traditional cancer therapies for persons with particular diseases. The present nutritional or dietary supplement composition preferably comprises an effective and efficient amount of specific antioxidants, immune stimulating, immune balancing, antitumor properties with an essential base vitamin and mineral panel to aid in toleration and recovery of cancer therapies. The practice of this invention involves supplementing the diet of humans or animals by oral, intraperitoneal, intravenous, subcutaneous, transcutaneous or intramuscular routes of administration.
[0020] Another object of the present invention is to provide a safe nutritional or dietary supplement composition that strengthens and promotes cell health through the prevention, stabilization, reversal and/or treatment of cancer in complement to traditional cancer therapies for persons with particular diseases.
DETAILED DESCRIPTION
[0021] The following detailed description is provided to enable any person skilled in the art to which the present invention pertains to make and use the same, and sets forth the best mode contemplated by the inventors of carrying out the subject invention.
[0022] The preferred nutritional or dietary supplement composition of the present invention is a formulation of five essential ingredients preferably in quantities not less than those set forth below in Table 1, take as 3 tablets, to be ingested daily.
[0000]
TABLE 1
Composition
Amount
Vitamin A (28% as beta carotene)
5000 International Units (IU)
Vitamin C (as ascorbic acid)
60 mg
Vitamin D3 (as cholecalciferol)
400 International Units (IU)
Vitamin E (as acetate)
30 International Units (IU)
Thiamin (B1)
1.5 mg
Riboflavin (B2)
1.7 mg
Niacin
20 mg
Vitamin B6 (as pyroxidine HCL)
2 mg
Folic Acid
400 mcg
Vitamin B12 (as cyanocobalamin)
6 mcg
Pantothenic Acid (as d-Calcium
10 mg
Pantothanate)
Calcium (as calcium carbonate)
45 mg
(Fucoidan) Laminaria japonica
350 mg
(Fucoidan) Undaria pinnatifida
300 mg
(Beta Glucan) Grifola frondosa
300 mg
(Beta Glucan) Ganoderma lucidum
300 mg
(Antioxidant) Euterpe oleracea
200 mg
[0023] The subject composition is formulated to provide the above-listed essential ingredients at preferably not less than the daily dosage amounts specified above. As stated above, the species of seaweed, mushroom, and antioxidant are specifically used in this formulation due to their research evidence but are not limited to only these species. Any seaweed and/or mushroom and/or antioxidant fruit, vegetable or herb species is considered part of this formulation and thereby synergistic effect within the combination. The subject composition is preferably provided for oral administration in the form of lacquered tablets, unlacquered tablets, caplets or capsules. For purposes of simplicity only, throughout the remainder of this detailed description lacquered tablets, unlacquered tablets, caplets and capsules will each be referred to as simply “tablets” without distinction in form or function there between. Additionally, for purposes of simplicity only, throughout the remainder of the detailed description, all species of seaweed described will be referred to as simply “seaweed” as well as all species mushrooms described will be referred to as simply as “mushroom”. Finally, for purposes of simplicity only, throughout the remainder of the detailed description, the antioxidant set of formulations including but not limited to acai, sumac, and cloves will simply be “antioxidants” for remainder of this detailed description.
[0024] The preferred daily dosage of the subject composition as specified above may be administered in the form of three or more tablets. Most preferably the daily dosage of the subject composition is provided in the form of three tablets taken once daily. The three capsules are preferably taken at the same time to provide improved absorption and better maintenance of blood levels of the essential ingredients as shown from the evidence of their effect. The minimum quantities specified above, per tablet, reflect the minimum amount of each essential ingredient to be provided upon oral administration through to the date of tablet expiration as set forth on the tablet sale label. Typically, the product shelf life for nutritional or dietary supplements is approximately two to three years.
[0025] Variations contemplated in administering the subject composition to humans or other animals include, but are not limited to, providing time-release tablets or tablets manufactured to be administered as a single dose or as other multiple part dosages. Additionally, alternative avenues of administration besides oral administration are contemplated herein such as for example, but not limited to, intraperitoneal, intravenous, subcutaneous, sublingual, transcutaneous, intramuscular or like forms of administration. Each tablet of the subject composition preferably contains the following essential ingredients in the quantities specified below. For purposes of simplicity only, formulations of the subject composition are provided below in accordance with a three-tablet oral daily dosage regime as described above.
Vitamin A
[0026] Beta-carotene, a proform of vitamin A, is a lipid-soluble orange pigment found in many vegetables. Beta-carotene is converted to vitamin A in the body with an efficiency of approximately 50 percent. The US daily recommended allowance (RDA) of vitamin A is 5,000 IU. Beta-carotene has one of the highest antioxidant potentials of the antioxidants. No observed adverse effects are observed for beta-carotene at dosage levels as high as 25 mg per day for healthy, non-smokers. Such a formulation provides a total daily dosage of beta-carotene and Vitamin A. Beta-carotene is preferred in the subject composition due to its ready commercial availability although alternative carotenoid proforms of vitamin A could likewise be used.
Vitamin C
[0027] Vitamin C is a well known water-soluble antioxidant. Humans depend on external sources of vitamin C to meet their vitamin C requirements.
[0028] The U.S. recommended dietary allowance (RDA) for vitamin C in the form of ascorbic acid is 60 mg. Very large daily doses of vitamin C have been taken over many years with no or only minor undesirable effects. Intakes of 1,000 mg or more of vitamin C can be consumed daily without any known adverse effects. The subject composition provides a daily dose of vitamin C.
[0029] Vitamin C is also well known to aid in the bioavailability as well as absorption of large macro molecules and proteins. Specifically, Vitamin C has been shown to aid in absorption of beta-glucans from mushrooms such as Ganoderm lucidum and Grifola frondosa rendering the inherent immunostimulant properties from these mushrooms more available into the bloodstream. In addition, the combination of Vitamin C and Fucoidan from seaweed species such as Laminaria Japonica and Undaria Pinnatifida have shown enhanced antioxidant capabilities and anti-tumor properties via inhibition of tumor invasion of human fibrosarcoma HT-1080 cells. Ascorbic acid is the preferred source of vitamin C in the subject tablets, although other sources such as for example sodium ascorbate could alternatively be used.
Vitamin D3
[0030] Vitamin D is found in many foods, including fish, eggs, fortified milk, and cod liver oil. The sun (UV light) is the catalyst for the body to produce vitamin D. The term “vitamin D” refers to several different forms of this vitamin. Two forms are important in humans: vitamin D2, which is made by plants, and vitamin D3, which is made by human skin when exposed to sunlight. The said formulation is using D3 at the US recommended daily allowance of 400 International Units (IU) but said formulations may also use Vitamin D2. Vitamin D3 is not readily available to all populations and is in said formulation due to this reason.
[0031] The major role of vitamin D is to maintain normal blood levels of calcium and phosphorus. Vitamin D helps the body absorb calcium, which forms and maintains strong bones. It is used alone or together with calcium to improve bone health and decrease fractures.
Vitamin E
[0032] Vitamin E is also a well-known antioxidant. Vitamin E can work synergistically with vitamin C in protecting vital cell function from normal oxidants. Vitamin E is a relatively non-toxic fat-soluble vitamin. Vitamin E is readily oxidized thereby significantly reducing its activity during periods of storage prior to ingestion. Once ingested, vitamin E is stored 45 within the body and can contribute to the total body pool of vitamin E for up to one year.
[0033] The RDA of vitamin E in the form of dl-alpha tocopheryl acetate is 30 IU which is in the said formulation. No adverse effects of dl-alpha tocopheryl acetate have been observed at levels as high as 800 mg, with 1.0 mg of dl-alpha tocopheryl acetate being equal to 1 IU of dl-alpha tocopheryl acetate. Dl-alpha tocopheryl acetate is the preferred source of vitamin E in the subject tablets although other sources of vitamin E, such as for example trimethyl tocopheryl acetate and/or vitamin E succinate, may be used in the alternative.
Thiamin (B1)
[0034] Thiamine is involved in many body functions, including nervous system and muscle function, the flow of electrolytes in and out of nerve and muscle cells, digestion, and carbohydrate metabolism. Very little thiamine is stored in the body and depletion can occur within 14 days. Severe thiamine deficiency may lead to serious complications involving the nervous system, brain, muscles, heart, and stomach and intestines. The RDA for Thiamin is 1.5 mg and is within said formulation.
Riboflavin (B2)
[0035] Riboflavin is a B vitamin. It can be found in certain foods such as milk, meat, eggs, nuts, enriched flour, and green vegetables. Riboflavin is frequently used in combination with other B vitamins in vitamin B complex products. Riboflavin is well known to increase energy levels; boosting immune system function; maintain healthy hair, skin, mucous membranes, nails, while slowing aging; boosting athletic performance and promoting healthy reproductive function. The RDA for Riboflavin is 1.7 mg and is within said formulation.
Niacin (Vitamin B3)
[0036] Niacin is well known as required for the proper function of fats and sugars in the body and to maintain healthy cells. Niacin and nicinamide are forms of Vitamin B3. Vitamin B3 is found in many foods including yeast, meat, fish, milk, eggs, green vegetables, beans, and cereal grains. The RDA for Niacin is 20 mg and is within said formulation.
Vitamin B6
[0037] Vitamin B6 is a vitamin that is naturally present in many foods. The body needs vitamin B6 for more than 100 enzyme reactions involved in metabolism. Vitamin B6 is also involved in as immune function. It is well know that people with low levels of vitamin B6 in the blood may have a higher risk of certain kinds of cancer, such as colorectal cancer.
Folic Acid (Vitamin B9)
[0038] Folic Acid is well known to be necessary for strong blood. Lack of folic acid may lead to anemia (weak blood). Folic acid ability to maintain strong blood is well known to be enhanced when used along with vitamin B12. The RDA for Folic Acid is 400 mcg and is within said formulation.
Vitamin B12
[0039] Vitamin B 12 is a nutrient that helps keep the body's nerve and blood cells healthy and helps make DNA, the genetic material in all cells. Vitamin B12 also helps prevent a type of anemia called megaloblasic anemia that makes people tired and weak. The current RDA for Vitamin B12 is 6 mcg and is within said formulation.
Pantothenic Acid (Vitamin B5)
[0040] Pantothenic Acid, also known as Vitamin B5 essential to all life and is a component of coenzyme A (CoA), a molecule that is necessary for numerous vital chemical reactions to occur in cells. Pantothenic acid is essential to the metabolism of carbohydrates, proteins, and fats, as well as for the synthesis of hormones and cholesterol. The RDA is 10 mg, and is within said formulation.
[0041] This formulation can also be in form as D-pantothenic acid, as well as dexpanthenol and calcium pantothenate, which are chemicals made in the lab from D-pantothenic acid.
Calcium
[0042] Calcium is required for vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling and hormonal secretion, though less than 1% of total body calcium is needed to support these critical metabolic functions. Serum calcium is very tightly regulated and does not fluctuate with changes in dietary intakes; the body uses bone tissue as a reservoir for, and source of calcium, to maintain constant concentrations of calcium in blood, muscle, and intercellular fluids. The RDA for calcium is 900 mg, and this formulation may have anywhere from 1-100% of the calcium needs.
Seaweed
[0043] Seaweed has been a staple food for many Asian countries with no toxicity of note. An extract of seaweed, fucoidan, has been widely shown to have multiple immune stimulating and anti-cancer properties. Seaweed species, including but not limited to, laminaria japonica and undaria pinnatifida , have shown the highest clinical potential for immune stimulation and anti-cancer properties. Alone, they have been shown to help mitigate post chemotherapy and radiation therapy complications for patients with cancers. The formulation has 300 mg of each species listed and is considered the minimal amount needed for a clinical effect. Again, not limited to these two species of seaweed, but have the highest effect from their fucoidans.
Mushroom
[0044] Mushrooms have been a staple medicinal and food product for Asian countries with no toxicity of note. An extract of mushrooms, beta-glucans, has been widely shown to have immune modulating properties as well as anti-cancer properties. Mushroom species, including but not limited to, ganoderma lucidum and grifola frondosa , have shown significant clinical effect for immune modulation and anti-cancer properties. Alone, they have been shown to help mitigate post chemotherapy and radiation therapy complications for patients with cancers. The formulation has 300 mg of each species listed and is considered the minimal amount needed for clinical effect. Again, not limited to these two species of mushroom, but have the highest effect from their beta-glucans.
Antioxidant (fruit, vegetable, and/or herb)
[0045] Antioxidants have been shown to extend the life of cells by reducing telomeric degradation. A unit of measure for antioxidant capacity is the oxygen radical absorbance capacity (ORAC). For purposes of this invention, “antioxidants” use for the formulation are any of the documented ORAC values exceeding 100,000 or more. Fruits, vegetables, and herbs including, but not limited to, such as Euterpe oleracea (Acai berry), sumac, cloves, and cinnamon are considered the highest known antioxidants as measured by the ORAC. The antioxidant in said formulation is 200 mg as this has been determined the minimal amount needed for clinical effect on healthy cells.
REFERENCES
[0000]
1. Attached to patent application
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A nutritional or dietary supplement composition that strengthens and promotes health through the prevention, stabilization, reversal and/or treatment of cancers, chemotherapy, and/or radiation therapy related complications. The nutritional or dietary supplement composition may likewise reduce the risk and/or prevalence of cancerous cells in addition to providing complement to cancer related therapies. The essential ingredients of the nutritional or dietary supplement composition are vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D3, vitamin E, calcium, thiamin, riboflavin, niacin, folic acid, pantothenic acid, fucoidan (extract from seaweed species such as, but not limited to; laminaria japonica and undaria pinnatifida ), beta-glucans (extract from mushroom species such as, but not limited to; ganoderma lucidum and grifola frondosa ), and antioxidants (from vegetable, fruit, or herb such as, but not limited to; acai berry ( Euterpe oleracea ), sumac, cloves, and sorghum). The essential ingredients are preferably provided in a capsule or tablet form suitable for oral ingestion. Preferably the composition is taken in the form of 3 tablets taken once daily.
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This application claims the benefit of U.S. Provisional Application Ser. No. 60/008,370, filed Dec. 8, 1995.
FIELD OF THE INVENTION
This invention relates to airlay fiber handling equipment such as an airlay web former and more particularly to doffing individualized carded fibers into an air stream.
BACKGROUND OF THE INVENTION
Airlays are used for opening fiber and putting the fiber into an air stream. A conventional airlay is disclosed in U.S. Pat. No. 3,797,074 to Zafiroglu issued on Mar. 19, 1974. However, one of the drawbacks or limitations of Zafiroglu is that it has difficulty opening medium and long staple fibers.
By comparison, carding machines are quite good at separating fibers into their individual filaments. However, the individualized fibers on carding machines are typically doffed at slow speeds into a carded web or sliver. To the extent that there are known techniques and arrangements for doffing the fiber from a carding machine into an air stream, such techniques are generally quite unsatisfactory. There are numbers of references, such as U.S. Pat. No. 3,641,628 to Fehrer, U.S. Pat. No. 4,097,965 to Gotchel et al., U.S. Pat. No. 4,130,915 to Gotchel et al., and U.S. Pat. No. 4,475,271 to Lovgren et al. which show air doffing cards. Typical of such arrangements is an air knife or air jets arranged to blow fiber from the doffing roll or main carding roll. With such arrangements, the fiber is carried away by a very turbulent air flow. Such highly turbulent air carries away the fibers in clumps and not individualized.
It has long been understood that carding offers certain advantages and airlays offers others. While it may appear logical to the unskilled person to simply feed a carded web to an airlay, there are significant technical and economic reasons that lead away from such an arrangement.
Carding machines and airlaying equipment are each quite expensive capital items and are generally considered by those skilled in the art to be mutually exclusive and separate technologies. Thus, one selects to use one technology or the other. The potential added value to the customer (the highest price the customer would be willing to pay for such products) would simply not justify the substantial added processing and equipment costs.
In addition to the economic drawbacks of feeding a carded web to an airlay, there are significant technical problems to overcome. Airlays are notorious for pulling clumps of fiber and dispersing the whole clump into the air stream. While the Zafiroglu technique has been used quite satisfactorily, it took significant subsequent development including the development by Contractor et al. in U.S. Pat. No. 3,932,915 on Jan. 20, 1976 to really get the system working satisfactorily. But even now, the fibers that are fed to the airlay are shorter than average staple length fiber.
Longer fibers are much more difficult to control coming through feed rollers or other feed mechanisms to be picked by the disperser roll. Most of the fiber opening done by an airlay is done by the interaction of the disperser roll and the feed rolls. Once the fiber is on the disperser roll, unless it is a chip of fibers, it is dispersed into the air stream in the same basic form in which it is carried to the duct. Pulling or picking a long fiber (as compared to a shorter fiber) from between the feed rolls more typically causes other long fibers to be pulled through the feed rolls with it. With each such long fiber, the disperser picks a clump of fibers. However, if the feed rolls are arranged to press tighter together to control clumping, the fibers may be stretched and broken or the fibers may drag hard through the feed rolls causing the build up of frictional heat. Either result will be deleterious to the commercial operation of the airlay. The problems are particularly exacerbated by the nature of carding machines which tend to provide linearly oriented fibers. As such, the fibers enter the feed rolls in the worst possible orientation for the disperser roll to pick them from the feed rolls. The arrangement for feeding carded fiber to an airlay would be one of the first problems to be overcome to achieve successful operation.
In spite of the apparent difficulties, it is an object of the present invention to provide a system and process for centrifugally dispersing individualized carded fiber which overcomes the above noted drawbacks of the prior art.
It is a more particular object of the present invention to provide a system and process for taking fiber from a carding machine and feeding it to an airlay which overcomes or avoids the problems described above.
SUMMARY OF THE INVENTION
The above and other objects of the invention are accomplished by a process for feeding carded fiber from a carding machine to an airlay wherein the process includes carding fiber with at least one carding roll having a toothed peripheral surface and combing elements engaging fiber on the carding roll into individualized carded fibers. The individualized carded fibers are then transferred from the surface of the carding roll to a rotating disperser roll. The rotating disperser roll then centrifugally doffs the individualized carded fibers therefrom.
The invention may also be summarized as comprising a process for centrifugally doffing fibers from a carding machine wherein fibers are carded by the interaction of toothed carding equipment to individualize and comb the fiber into individualized fibers and the fibers are transferred to a rotating disperser roll. The disperser roll has a toothed peripheral surface and centrifugally doffs the individualized fibers from the disperser roll by being rotated at a rotational speed sufficient to tangentially throw off a substantial portion of individualized fibers.
In addition, the invention generally comprises a system for carding fiber into individualized fibers and centrifugally doffing the individualized carded fibers. The system includes a main carding roll and equipment to comb and individualize the fibers on the main carding roll and a disperser roll having a toothed peripheral surface arranged to receive individualized fibers from the main carding roll. The disperser roll centrifugally doffs fibers from the teeth thereof by rotating at a speed sufficient to tangentially throw fibers therefrom.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be more easily understood by a detailed explanation of the invention including drawings. Accordingly, drawings which are particularly suited for explaining the invention are attached herewith; however, it should be understood that such drawings are for explanation only and are not necessarily to scale. The drawings are briefly described as follows:
FIG. 1 is a generally schematic elevational view of centrifugally doffed carding machine showing the features of the invention;
FIG. 2 is an enlarged fragmentary view of the doffing roll and disperser shroud in FIG. 1; and
FIG. 3 is a view similar to FIG. 1 showing a second embodiment of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings, the invention will be described in greater detail so as to explain the contribution to the art and its application in the industry. Referring specifically to FIG. 1, the fiber handling system of the present invention is generally referred to by the number 10 and may be more easily understood as having an airlay portion generally indicated by the reference number 11 and a carding machine portion generally indicated by the reference number 12 . As the present invention handles the process through the carding machine portion 12 first and then through the airlay portion 11 , the description will begin with the carding machine portion 12 first and then move to the airlay portion 11 so as to follow the path of the fiber through the system 10 of the present invention.
The carding machine portion 12 is arranged to receive fiber in the form of a batt B that is comprised of tufts of fiber to be separated into individualized fibers. The fiber is provided into the system 10 by a suitable feed mechanism such as an opposed pair of feed rollers 15 and 16 . The feed rollers 15 and 16 receive the batt B of fiber from a suitable source by a conveyor and pinch the batt therebetween as the batt B is fed to the lickerin roll 20 . It should be understood that there are numerous potential arrangements for providing fiber on a lickerin roll and that the invention is not limited to any particular illustrated or described fiber delivery technique.
The lickerin roll 20 , as is conventional in the art, comprises a wire or card clothing on its peripheral surface or other suitable toothed surface for picking the fiber from the batt at the feed rolls 15 and 16 . The batt B is effectively dismembered by the teeth on the lickerin roll 20 . The lickerin roll 20 may be provided with one or more workers 22 and associated strippers 23 to pick tufts of fiber from the teeth of the lickerin roll 20 and comb and draft the tufts out to separate the fibers. The lickerin roll 20 passes or transfers the fiber to a communicator roll 30 which may further draft fiber and provide more workers and strippers (not shown) for the carding machine portion 12 of the system 10 .
The communicator roll 30 passes or transfers the fiber onto the main carding roll 40 . The roll communicator roll 30 may be arranged to rotate in either direction but would most likely be rotated in the clockwise direction to move with the lickerin roll 20 and the main carding roll 40 . Arranged along the top surface of the main carding roll 40 are associated worker and stripper rolls 42 and 43 , respectively. In the illustrated configuration, the worker and stripper rollers 42 and 43 are in a garnet configuration such that every other roller is a worker roller 42 with a stripper roller 43 positioned therein between. As is well known in the carded fiber art, the worker and stripper rolls may also be arranged in a conventional arrangement where spaced pairs of stripper and worker rolls are arranged to comb and separate the fibers. It is also similarly known to comb the fiber with combing elements that are not rolls at all, but may be fixed plates, called flats or rotating belts having teeth arranged to comb fiber on the carding roll. The particular arrangement, whether garnet or conventional or other type of arrangement, is really not pertinent to the invention except for the fact that the fiber is carried by a toothed device and is worked by combing elements to separate and individualize the fibers without overworking it into unusable neps or other fiber defects.
On the opposite side of the main carding roll 40 from the lickerin roll 20 and communicator roll 30 is a disperser roll 50 which is part of the airlay portion 11 of the system 10 . The disperser roll 50 doffs the fiber from the main carding roll 40 , but operates considerably different than conventional doffing rolls for carding machines. The disperser roll 50 of the present invention preferably rotates opposite or against the direction of rotation of the main carding roll 40 . In addition, the disperser roll 50 rotates at a relatively high speed to create substantial centrifugal forces to tangentially throw off or centrifugally doff the fiber from the disperser roll 50 . A conventional doffing roll for a carding machine would typically move in the same direction as the main carding roll, but much slower than the main carding roll. As compared to the present invention, all the rolls in a conventional carding machine are operated so as not to allow the fiber to centrifugally separate from the teeth. A carding machine would be “out of control” by conventional standards if fiber were “flying off” any roll.
The disperser roll 50 picks a substantial portion of the fiber carried by the main carding roll 40 therefrom which, as compared to conventional carding arrangements, is contrary to the operation of a standard doffing roll. In a conventional arrangement, a significant portion of the fiber on the main carding roll 40 would be recycled around the bottom portion of its path of rotation to again be subjected to the worker and stripper rolls 42 and 43 . Since the main carding roll 40 has limited capacity, the fiber feed at feed rolls 15 and 16 would have to be controlled so that no more fiber is put into the system than is coming out. The disperser roll 50 increases the productivity and throughput of the carding machine portion 12 of the system 10 by doffing fiber at a higher rate than conventional doffing systems.
The disperser roll 50 picks a high percentage of fiber to transfer from the main carding roll 40 because of its higher surface speed. More teeth on the disperser roll 50 have an opportunity to pick each fiber on the main carding roll 40 when the disperser roll 50 is run faster than the main carding roll 40 . A second reason the disperser roll 50 picks up a high percentage of the fiber from the main carding roll 40 is that the disperser roll 50 is preferably arranged to rotate opposite the direction of rotation of the main carding roll 40 . It should be understood that the teeth on a roll are oriented so as to pick or receive fiber while rotating in a particular direction of rotation. While the invention will still be fully operable with the disperser roll 50 running in the same rotational direction as the main carding roll 40 , it transfers a higher percentage of the fiber from the main carding roll 40 to the disperser roll 50 when rotating opposite the main carding roll 40 . The reason more fiber is transferred is that the teeth on the disperser roll 50 have more opportunities to pick up the fibers from the main carding roll 40 . When one tooth on the disperser roll 50 contacts a fiber but does not pick it up, the fiber is swept back so that the next succeeding tooth may have a chance to pick it off. If the main carding roll 40 rotates in the same direction as the disperser roll 50 , then when a tooth on the disperser roll 50 contacts a fiber but does not pick it off the main carding roll 40 , it is likely that the fiber may well be swept out of reach of the next succeeding tooth on the disperser roll 50 . Thus, it is preferred that the disperser roll 50 rotates at substantial surface speed opposite the direction of rotation of the main carding roll 40 .
It should also be noted that the problems noted above about feeding fiber onto the disperser roll 50 of the airlay portion 11 are avoided by transferring the fibers directly from the main carding roll 40 onto the disperser roll 50 . There are no feed rolls or equipment to pinch a batt of carded fiber being fed to the disperser roll 50 that would lead to the problem of pulling clumps onto the disperser roll 50 .
As previously noted, the disperser roll 50 rotates at a fairly high speed. The disperser roll 50 must be rotated at a speed which, in accordance with its design, will generate sufficient centrifugal force that the fibers will overcome the frictional and other resistive forces to be thrown from the teeth of the disperser roll 50 . The design considerations of the disperser roll 50 include, among other issues, the length, angle and smoothness of the teeth and the diameter of the roll. Teeth projecting from the surface in an orientation close to radially outwardly from the roll will require less rotational speed and centrifugal force to doff fiber than teeth angled more toward a tangential orientation. A smaller diameter roll will generate greater centrifugal forces than a larger roll when the surface speeds are the same. In the preferred arrangement, the roll is approximately twenty inches in diameter and has teeth arranged between one and sixteen degrees from the radius and rotates such that the surface speed is between about 1500 meters per minute up to about 4000 meters per minute. Clearly, there are suitable designs that would be outside one or even all of these parameters, but would still be within the spirit of the invention.
In the preferred arrangement, the disperser roll 50 has three zones at different radial portions of its periphery. The first zone is a fiber receiving zone. The fiber receiving zone is where the fiber is picked up by the disperser roll 50 and, in the embodiment illustrated in FIG. 1 is at the interface with the main carding roll 40 . The second zone immediately follows the fiber loading zone and may be referred to as the fiber handling zone. The third and next zone is the centrifugal doffing zone where the fibers are intended to be doffed from the disperser roll 50 .
The fiber handling zone is characterized by a shroud 60 overlying the surface of the disperser roll 50 . The shroud 60 has a particular design that is best illustrated in FIG. 2 and has a design similar to the disperser plate disclosed in U.S. Pat. No. 3,932,915 on Jan. 20, 1976, to Contractor et al. The shroud 60 is particularly designed to impose drag on the air around the disperser roll 50 , which may also be characterized as aerodynamic drag. In particular, the shroud 60 is provided with a series of grooves 62 which form a rough surface which aerodynamically prevents the boundary layer of air around the disperser roll 50 from building very thick. While air is allowed to be carried between and around the teeth of the disperser roll 50 , the air just beyond the tips of the teeth is not permitted to be carried along therewith at the same surface speed. As such, the slower moving air in close proximity to the teeth causes drag on the fibers carried on the teeth so as to keep them down close to the surface of the disperser roll 50 . When the fibers come out from under the shroud 60 , the boundary layer quickly builds which allows the fibers to separate from the teeth of the disperser roll 50 by the pull of the centrifugal forces. Clearly, there may be other suitable designs for shrouds that will create resistance to the movement of boundary layer air along the disperser roll 50 such as different surface configurations, or air jets, baffles and other suitable devices. The shroud 60 illustrated in FIG. 2 is simply a preferred arrangement for the present invention.
Referring again to FIG. 1, the disperser roll 50 carries the fiber from the main carding roll 40 , under shroud 60 and to an air duct 70 . In the air duct 70 , an air stream is arranged to pass over the surface of the disperser roll 50 in a generally tangential relationship to receive the fiber being doffed from the disperser roll 50 . The fiber is quite likely to doff from the disperser roll 50 without the presence of the air stream creating a cloud of individualized fiber; however, it is preferred to provide the individualized fiber into an air stream where it may be more easily handled. In the present invention, it is preferred that the air stream be generally free of turbulence so as to allow the fiber to be evenly dispersed throughout the air stream. Eddies, vortices and other turbulence tend to disturb the distribution of the fiber in the air duct 70 which causes undesirable consequences depending on the use that will be made with the fiber in the air stream. In the case where a web is produced, as shown in the drawing figures, such webs have splotchiness and non-uniformity's cause by the fiber following the vortices and eddies and not laying down evenly.
Thus, as shown in the drawing figures, an air stream is created in the air duct 70 by a suitable fan (not shown) or other source such that the air stream moves in the same direction as the surface of the disperser roll 50 . The air stream is relative straight and laminar after having been directed through a pre-filter 72 , a honeycomb-type air straightener 73 and secondary filters 74 , 75 , 76 , and 77 . The air stream accelerates as it passes into an area of reduced cross section shortly before it passes over the surface of the disperser roll 50 . It is important that the speed of the air stream be less than or equal to the speed of the disperser roll 50 at its surface. Otherwise, the airstream will tend to blow the fiber off the disperser roll 50 which will undermine the intended effect of centrifugally doffing the fiber. If the fiber were to be blown off the roll, it would tend to come off in clumps and create more turbulence, and larger eddies and vortices. Preferably, the speed of the air stream is less than or equal to about 95 percent of the surface speed of the disperser roll 50 as the air stream passes over the disperser roll 50 . With the straightened air stream passing over the surface of the disperser roll 50 , the fiber tends to transition more gently from one mode of conveyance (the teeth on an roll) to a second mode (the straightened air stream).
An additional element for satisfactorily centrifugally doffing fiber from the disperser roll 50 is a doffing bar 71 . The doffing bar 71 functions similarly to a doctor blade for separating at least a portion of the boundary layer of air around the surface of the disperser roll 50 thereby preventing the fiber from re-entraining with the boundary layer and following the disperser roll 50 back to the main carding roll 40 . In particular, the performance of the doffing bar has been improved by providing a much sharper leading edge as compared to the conventional blunt doffing bars. The sharper doffing bar tends to shear the boundary layer of air where the conventional blunt doffing bar tends to have a buildup of air pressure which causes the boundary layer to divide itself. Also, it apparently collects fewer stray fibers if the air duct side of the doffing bar is co-planar with the remainder of the air duct extending toward the screen consolidation belt 80 and is generally aligned with a plane that is tangential to the surface of the disperser roll 50 at the base of the teeth thereof.
The fiber can be laid into a web on a screen conveyor belt 80 at the base of the air duct 70 . The screen conveyor belt 80 is carried by a series of rollers including roller 82 and 83 . Below the screen conveyor 80 is a vacuum duct 90 arranged to pull air in the air duct 70 down through the screen conveyor belt 80 to pin the fiber thereon and remove it from the system. The air may be discharged from the system 10 or recirculated to be directed again through the air duct 70 as desired.
Turning now to the second embodiment illustrated in FIG. 3, the equipment is essentially the same and the same reference numerals are used to indicate the same equipment or features. However, in this second embodiment, there is a communicator roll 48 between the main carding roll 40 and the disperser roll 50 for transferring fiber from one roll to another. The communicator roll 48 may be arranged to rotate in either direction but would most likely be rotated clockwise to move with the main carding roll 40 and the disperser roll 50 . The reasons for providing one or more communicator rolls 48 are varied. The essential feature of the communicator roll 48 is that it has teeth on the periphery and carries fiber, preferably individualized carded fibers on the teeth from which the disperser roll 50 may pick it off or have it transferred thereto. This second embodiment particularly illustrates the possibility that the disperser roll 50 does not necessarily need to interact directly with the main carding roll 40 to doff individualized carded fiber pursuant to the present invention. For purposes of this invention, the term “main carding roll” is used to mean the only roll or the last roll in an arrangement of several rolls having teeth such as card clothing and which include associated rollers or fixed teeth or the like to draft and comb fibers for the purpose of separating fiber into individual filaments. Thus, roll 48 is not a “main carding roll” as described above. Conversely, the main carding roll 40 is not the only carding roll in the system 10 as the lickerin roll 20 includes worker and stripper rolls 22 and 23 .
Whether the disperser roll 50 picks fiber directly from the main carding roll 40 or from a communicator type roll 48 is really of little significance to the invention. However, it should be understood that the invention is directed to taking fiber which has been carded and individualized by equipment selected from conventional carding technology and almost immediately providing the fiber to the disperser roll 50 without consolidation or doffing to form a sliver, batt, web or other fibrous structure. The disperser roll 50 then centrifugally doffs the fiber as has been described.
The foregoing description and drawings were presented to explain the invention and its operation and should not, in any way, limit the scope of coverage that may be afforded by any patent granted from this application. Clearly, the scope of the exclusivity is defined and should be measured and determined by the claims that follow.
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A process of feeding carded fiber to an airlay and particularly to combining carding technology with airlay technology. A carding machine portion is arranged to card fiber while a disperser-roll in the airlay portion picks the individualized carded fibers from a tool bed roll and centrifugally doffs them into an air stream. As such, airlays will be able to handle longer fiber lengths which conventional airlay equipment is unable to handle or satisfactorily open up. Further, an improved process for doffing fiber from a airlay machine and particularly centrifugally doffing fiber from a carding machine.
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This application is a U.S. national stage filing of PCT International Application No. PCT/FI01/01101, filed on Dec. 14, 2001. This application also claims the benefit of priority under 35 U.S.C. § 119(a) to Finnish patent application no. 20002755, filed on Dec. 15, 2000.
TECHNICAL FIELD
The present invention relates to a method for the treatment of erectile dysfunction by administering levosimendan, or (−)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile (I), or pharmaceutically acceptable salts thereof, to a patient in need of such treatment.
BACKGROUND OF THE INVENTION
Levosimendan, which is the (−)-enantiomer of [[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, and the method for its preparation is described in EP 565546 B1. Levosimendan is potent in the treatment of heart failure and has significant calcium dependent binding to troponin. Levosimendan is represented by the formula:
The hemodynamic effects of levosimendan in man are described in Sundberg, S. et al., Am. J. Cardiol., 1995; 75: 1061–1066 and in Lilleberg, J. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S63–S69, 1995. Pharmacokinetics of levosimendan in man after i.v. and oral dosing is described in Sandell, E.-P. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S57–S62, 1995. The use of levosimendan in the treatment of myocardial ischemia is described in WO 93/21921. The use of levosimendan in the treatment of pulmonary hypertension is described in WO 99/66912. Transdermal delivery of levosimendan is described in WO 98/01111. Transmucosal delivery of levosimendan is described in WO 99/32081. Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients.
Erectile dysfunction is the inability to obtain and sustain sufficient penile erection and is referred to as impotence. It can result from a variety of underlying causes ranging from purely psychogenic to completely physical dysfunctioning. Both surgical and pharmacological therapies have been used in the treatment of impotence.
SUMMARY OF THE INVENTION
It has now been found that levosimendan is capable of restoring or improving the erectile function in patients suffering from erectile dysfunction.
Therefore, the present invention provides the use of levosimendan or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of erectile dysfunction.
The present invention also provides a method for the treatment of erectile dysfunction in a patient, said method comprising administering to a patient in need thereof an effective amount of levosimendan or a pharmaceutically acceptable salt thereof.
DETAILED DESCRIPTION
The method of the invention comprises a step of administering to a subject an amount of levosimendan effective to restore the erectile function of the patient. The drug is preferably administered perorally, transmucosally including transurethrally, intravenously, intramuscularly including intracavernosal injection or transdermally. The administration may be systemic or local.
The effective amount of levosimendan to be administered to a subject depends upon the route of administration. Levosimendan is administered orally to man in daily dose from about 0.1 to 15 mg, preferably from about 0.5 to 10 mg, given once a day or divided into several doses a day. For transmucosal, intravenous, intramuscular or transdermal delivery the daily dose range is from about 0.005 to 0.7 mg/kg, preferably from about 0.01 to 0.5 mg/kg.
Levosimendan is formulated into dosage forms suitable for the treatment of erectile dysfunction using the principles known in the art. It is given to a patient as such or preferably in combination with suitable pharmaceutical excipients in the form of tablets, dragees, capsules, suppositories, emulsions, suspensions or solutions whereby the contents of the active compound in the formulation is from about 0.5 to 100% per weight. Choosing suitable ingredients for the composition is a routine for those of ordinary skill in the art. It is evident that suitable carriers, solvents, gel forming ingredients, dispersion forming ingredients, antioxidants, colours, sweeteners, wetting compounds, release controlling components and other ingredients normally used in this field of technology may be also used.
For oral administration in tablet form, suitable carriers and excipients include e.g. lactose, corn starch, magnesium stearate, calcium phosphate and talc. For oral administration in capsule form, useful carriers and excipients include e.g. lactose, corn starch, magnesium stearate and talc. Disintegrants, such as croscarmellose sodium, may be used to accelerate the dissolution of the formulation.
Tablets can be prepared by mixing the active ingredient with the carriers and excipients and compressing the powdery mixture into tablets. Capsules can be prepared by mixing the active ingredient with the carriers and excipients and placing the powdery mixture in capsules, e.g. hard gelatin capsules. Typically a tablet or a capsule comprises from about 0.1 to 10 mg, more typically 0.2 to 5 mg, of levosimendan. In general, rapidly dissolving peroral tablets or capsules, e.g. having a dissintegration time of 1 to 20 minutes, are preferred.
Formulations suitable for intravenous administration such as injection formulation, comprise sterile isotonic solutions of levosimendan and vehicle, preferably aqueous solutions. Typically an intravenous infusion solution comprises from about 0.01 to 0.1 mg/ml of levosimendan.
Formulations of levosimendan suitable for transmucosal or transdermal administration are disclosed in WO 99/32081 and WO 98/01111, respectively.
Salts of levosimendan may be prepared by known methods. Pharmaceutically acceptable salts are useful as active medicaments, however, preferred salts are the salts with alkali or alkaline earth metals.
EXAMPLES
Pharmaceutical example. Hard gelatin capsule size 3 Levosimendan 2.0 mg Lactose 198 mg
The pharmaceutical preparation in the form of a capsule was prepared by mixing levosimendan with lactose and placing the powdery mixture in hard gelatin capsule.
Clinical Data
Two NYHA III heart failure patients, who had not had erections for several years were treated with levosimendan. Patient I was exposed to 0.05 μg/kg/min continuous infusion of levosimendan for 7 days. The patient reported erections 1 day after starting the infusion and he had erections in the mornings during the whole study. Patient II reported erections after 0.1 μg/kg/min continuous infusion of levosimendan for 2 days.
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Levosimendan, or (−)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, which has been previously suggested for the treatment of congestive heart failure, is useful in the treatment of erectile dysfunction.
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BACKGROUND
1. Field of the Invention
The present invention relates generally to a method of fabricating an aperture plate for a roofshooter type printhead and in particular to a method of forming an aperture plate for a printhead, such as a thermal ink jet (TIJ) printhead, by orientation dependent etching.
2. Description of the Related Art
There are two general configurations for thermal drop-on-demand inkjet printheads. In one configuration, droplets are propelled from nozzles in a direction parallel to the flow of ink in ink channels and parallel to the surface of the bubble generating heating elements of the printhead, such as, for example, the printhead configuration disclosed in U.S. Pat. No. 4,601,777 to Hawkins et al. This configuration is sometimes referred to as "edge or side shooters". The other thermal ink jet configuration propels droplets from nozzles in a direction normal to the surface of the bubble generating heating elements, such as, for example, the printhead disclosed in U.S. Pat. No. 4,568,953 to Aoki et al. and U.S. Pat. No. 4,789,425 to Drake et al. This latter configuration is sometimes referred to as a "roofshooter".
In the "roofshooter" printhead disclosed in U.S. Pat. No. 4,789,425, the disclosure of which is herein incorporated by reference, the printhead comprises a silicon heater plate and a fluid directing structural member. The heater plate has a linear array of heating elements, associated addressing electrodes, and an elongated ink feed slot parallel with the heating element array. The structural member contains at least one recess cavity, a plurality of nozzles, and a plurality of parallel walls within the recess cavity which define individual ink channels for directing ink to the nozzles. The recess cavity and feed slot are in communication with each other and form the ink reservoir within the printhead. The ink the recess cavity. The feed slot is precisely formed and positioned within the heater plate by anisotropic etching. The structural member may be fabricated either from two layers of photoresist, a two stage flat nickel electroform, or a single photoresist layer and a single stage flat nickel electroform.
The roofshooter type of printhead has a number of advantages over the side-shooter geometry. First, the roofshooter type does not have any problem with refill, i.e., it can operate at much higher print rates than a sideshooter geometry printhead. In addition, roofshooters do not suffer from air ingestion problems. A sideshooter geometry printhead can ingest air through the nozzles into the ink channels which can cause printing errors. The roofshooter, on the other hand, can not ingest air through the nozzles into the ink channels due to the geometry of the printhead.
Another basic roofshooter type thermal ink jet printhead is disclosed in U.S. Pat. No. 4,791,440 to Eldridge et al. Eldridge shows a printhead wherein a heater array is located on a substrate. A nozzle plate with apertures is bonded on top of the substrate to form a printhead.
There are many methods and processes for fabricating a thermal ink jet printhead. In particular, there are a number of methods for fabricating a aperture plate for a roofshooter type printhead. For example:
U.S. Pat. No. 4,961,821 to Drake et al., the disclosure of which is incorporated herein by reference and assigned to the same assignee as the present application, i.e., Xerox Corporation, discloses a method of orientation dependent etching (ODE) for forming semiconductor wafers which are used for an aperture plate of a thermal ink jet printer.
U.S. Pat. No. 4,455,192 to Tamai discloses a method for the formation of a multi-nozzle ink jet printhead wherein areas on a single crystal silicon plate are doped with impurities to make those areas more etch resistant than a remainder of the plate. Then, a second silicon plate is grown on top of the first. Both plates are then etched at once by anisotropic etching to form an array of nozzles within the first plate and a trough within the second plate.
The Bassous article from the IBM Technical Disclosure Bulletin, Vol. 19, No. 6, November 1976, pp. 2249-2250, discloses a nozzle array in a mesa structure etched in single crystal silicon wherein the nozzle array is used for an ink jet printhead. A method of fabricating an array of nozzles comprises: 1) defining a pattern on the front side of the wafer and etching mesas in an anisotropic etching solution; 2) defining a nozzle array pattern; 3) performing a p+ diffusion to a required depth; 4) defining a pattern of windows on the back side of the wafer and anisotropically etching the wafer through to the p+ silicon; and 5) stripping the wafer. FIG. 1D shows an anisotropically etched wafer which has troughs on one side of the wafer and a number of apertures formed within the troughs.
The Galicki et al. article from the IBM Technical Disclosure Bulletin, Vol. 22, No. 7, December 1979, pp. 2860-2861, discloses a process for fabricating ink jet nozzles wherein a single crystal silicon substrate is anisotropically etched on one side to form a single opening. The other side of the substrate is then plasma etched to form an aperture as shown in STEP E.
U.S Pat. No. 4,169,008 to Kurth discloses a process for producing uniform nozzle orifices in silicon wafers wherein an aperture plate is formed by a two-stage anisotropic etching process comprising the steps of: 1) etching a front face of a silicon wafer anisotropically to form a pyramidal nozzle; and 2) etching the back face of the silicon wafer anisotropically to form an aperture which is aligned with the nozzle and forms a hole entirely through the wafer.
U.S Pat. No. 4,914,736 to Matsuda discloses a liquid jet recording head having multiple liquid chambers on a single substrate wherein an aperture plate, which may be fabricated from silicon, includes a trough. The trough has a plurality of apertures located within the trough. The trough is placed over the actuating circuitry.
A number of these methods use orientation dependent etching to produce an aperture plate for a thermal ink jet printhead, but these methods do not use a two stage orientation dependent etch.
Orientation dependent etching (ODE) is disclosed in U.S. Pat. No. 4,169,008 to Kurth, the disclosure of which is incorporated herein by reference. First, a silicon wafer is produced which has a major surface lying substantially in the "100" plane. Then, a suitable anisotropic etchant is used to etch a pattern in the silicon wafer. The anisotropic etchant works well normal to the "100" plane as opposed to lateral or parallel to the "100" plane. To control the etch, an etchant masking material is placed on both sides of the silicon wafer. Holes are then made in the masking material in a certain pattern and etching can commence. Thus, any pattern can be made in the masking material and the etched using ODE. The depth that the etchant goes through the silicon wafer depends on the amount of time the etchant continues. Also, the shape that the etchant etches out has a generally inward sloping shape which is caused by the orientation of the silicon in the wafer.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a method of fabricating aperture plates for a roofshooter type TIJ printhead wherein a two-step etch process is used.
It is another object of the present invention to provide method of fabricating a nozzle plate for a TIJ printhead wherein a trough and apertures are etched by orientation dependent etching (ODE).
The present invention uses a two step orientation dependent etching to form an aperture plate for a roofshooter type thermal ink jet printhead. The aperture plate has a trough formed by a first etch step and a plurality of nozzles formed within the trough during the second etch step.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be described with reference to the following drawings in which like reference numerals denote like elements and wherein:
FIG. 1 is a diagram which shows the first stage of the preferred etch process wherein a silicon wafer is orientation dependent etched to form a trough in the wafer;
FIG. 2 is a diagram of the second stage of the preferred etch process wherein the silicon wafer of FIG. 1 is orientation dependent etched a second time from the opposite side of the wafer to form a plurality of apertures within the trough;
FIG. 3 is a diagram of a roofshooter type thermal ink jet printhead which uses the silicon wafer of FIG. 2 as an aperture plate;
FIG. 4 is a diagram of the first stage of another etch process wherein a silicon wafer is orientation dependent etched to form a trough in the wafer;
FIG. 5 is a diagram of the second stage of another etch process wherein the silicon wafer of FIG. 4 is orientation dependent etched a second time from the same side as the trough to form a plurality of apertures within the trough; and
FIG. 6 is a diagram of a roofshooter type thermal ink jet printhead which uses the silicon wafer of FIG. 5 as an aperture plate.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Now, with reference to FIGS. 1-2, a preferred embodiment of the present invention will be described. A silicon wafer is prepared which has a major surface lying substantially in the "100" plane. The wafer 10 preferably has a height, H p , of 20 mils (500 μm). This wafer 10 is then masked on a top side 21 with a masking material and anisotropically etched to form a trough 20 within the wafer 10. The trough 20 has an outer width, W o and an inner width, W i . The trough's sloped ends are formed because ODE etches the wafer 10 according to the orientation of the silicon atoms in the wafer 10. The outer width W o of the trough is preferably 75.5 mils (1.8875×10 3 μm). The inner width W i of the trough is preferably 50 mils (1.25×10 3 μm). The trough 20 is etched down, but not completely through the wafer. A remaining bottom wall of the wafer 25 has a thickness equal to the desired thickness of a roofshooter TIJ printhead aperture plate. This distance, known as H a , is preferably equal to 2 mils (50 μm) for a roofshooter aperture plate.
Now, the wafer 10 is masked on an opposite side 22 of the wafer from the trough 20 with a pattern of apertures 30. These apertures 30 will serve as nozzles for the TIJ printhead when the wafer 10 is bonded to a heater plate as shown in FIG. 3. The masked wafer is then anisotropically etched to form the plurality of apertures 30 with sloped edges due to the ODE. For a thermal ink jet printhead, these apertures preferably have an inner and outer width, N i and N o respectively, of 50 μm and 120 μm. The apertures 30 are etched completely through the bottom wall 25 of the trough 20. The apertures 30 are tapered in such a way, that when a thermal ink jet printhead is fabricated using the aperture plate produced from the silicon wafer 10, the narrower cross-section of the apertures 30 is pointed away from a heater plate 40. This provides the ink which is being ejected from the apertures 30 by the resistors 70 on the heater plate 40 a smooth, high velocity flow. This smooth, high velocity flow permits the thermal ink jet printhead's placement of ink on a piece of paper to be more accurate.
FIG. 3 shows a roofshooter type thermal ink jet printhead which uses an aperture plate 50 which was fabricated by the preferred method of the present invention. The aperture plate 50 includes at least a portion of wafer 10 having the trough 20 and the apertures 30 which were formed by ODE. This aperture plate 50 is bonded to a heater plate 40 which holds the heating elements, associated electronics and appropriate channel geometry formed through polymide processing. Polymide channel walls 60 space the aperature plate 50 from the heater plate 40, thus completing the enclosed channel geometry. The height, G, of the polymide walls 60 is preferably 25 μm. The size of the heater plate 40, H h , is preferably 20 mils (500 μm) which is the same thickness as the silicon wafer 10 used to make the aperture plate 50 of the preferred embodiment.
The heater plate 40 includes a plurality of resistors 70 and an ink supply channel 80. The resistors 70 generate heat which causes ink from the ink supply channel 80 to be ejected through the apertures 30. The layout shown, will allow a resolution of 300 spi (spots per inch) to be achieved. A resolution of 600 spi is also possible using a different layout with smaller dimensions. The aperture plate 50 and heater plate 40 are bonded together and then diced into individual dies.
Walls 27 of the trough 10 on the aperture plate 50 may be retained to provide walls which provide a suitable front face seal for the TIJ printhead when it is not in use. Pieces 29 of the walls 27 can also be diced away to leave a flat aperture plate 50 which makes it compatible with other roofshooter type TIJ printhead aperture plates.
Now, with reference to FIGS. 4 and 5, another embodiment of the present invention will be described. FIG. 4 shows a silicon wafer 10 after it has been orientation dependent etched to form a trough 20 as in FIG. 1. Thus, the method of fabricating the trough 20 will not be described again.
Once the trough 20 is fabricated with the same dimensions as the trough in FIG. 1, the bottom 25 of the trough is masked to define a plurality of apertures. The wafer is then etched by ODE to form a plurality of apertures 35 which are tapered inwardly towards the bottom side 22 of the wafer 10. These apertures 35 have the same dimensions, namely N o =120 μm and N i =50 μm, as the aperture of the preferred embodiment. The apertures 35 are tapered in such a way, that when a thermal ink jet printhead is fabricated using an aperture plate 100 produced from the silicon wafer 10, the narrower cross-section of the apertures 35 is pointed away from a heater plate 40. This provides the ink which is being ejected from the apertures 35 by the resistors 70 on the heater plate 40 with a smooth, high velocity flow. This smooth, high velocity flow permits the thermal ink jet printhead's placement of ink on a piece of paper to be more accurate. These apertures 35 are in the reverse direction of the apertures 30 of the preferred embodiment. Thus, the way the apertures 35 are formed means that a heater plate 40 would necessarily be located within the trough 20 or on top of the trough to make the apertures 35 have their narrowest cross section away from the heater plate 40.
Now, with reference to FIG. 6, a roofshooter TIJ printhead is shown fabricated out of the aperture plate 100 shown in FIG. 5. All of the elements within the heater plate 40 are identical to the previous preferred embodiment. The heater plate 40 will have to be etched from both sides so that the ink feed hole 80 is etched entirely through the heater plate while a pair of side grooves 90 are etched only partially through the heater plate to a depth H d . The width of the grooves 90 is H w . The ink feed hole 80 has an inner width, I a , and an outer width, I b .
The slope angle of the walls of the ink feed hole 80 is α which is preferably equal to 54.7 degrees. The complement slope angle of the groove wall is β, which is preferably equal to 125.3 degrees (i.e., the actual slope of the walls is 54.7 degrees).
The relationships between H w , H d , I a , I b and H h are: ##EQU1## These equations allow one of ordinary skill in the art to fabricated a heater plate 40 which would have the correct dimensions necessary to be use with the aperature plate 100.
The invention has been described with reference to a preferred embodiment thereof, which is intended to be illustrated and not limiting. Many modifications and variations are apparent from the foregoing description of the invention and all such modifications and variations are intended to be within the scope of the present invention. Accordingly, variations of the invention may be made without departing from the spirit and scope of the present invention as defined in the following claims.
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A method of fabricating an aperture plate for a roofshooter thermal ink jet printhead wherein a two step orientation dependent etch is conducted on a silicon wafer. The two step etch forms a trough in one face of the silicon wafer and a plurality of apertures in either the same or opposite face as the trough.
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SUMMARY OF THE INVENTION
The gist of this invention lies in a pressure transducer for monitoring subcutaneous blood pressure, which is applied directly to the body or appendage of a subject, comprising a thin flat diaphragm which is flush-mounted with rigidly mounted edges fixity in the surface of a plate having a contour which conforms to the natural curve of the body or appendage of the subject, and which contoured plate is held against the subject's skin at an adjustable and predetermined bearing pressure by an adjustable-length strap which does not occlude the subject's veins. Subcutaneous blood pressure applied to the contact face of said diaphragm develops mechanical strain in the back face of the same which is sensed by electrical strain gages mounted on the back face thereof. The change in electrical resistance of these strain gages due to this mechanical strain immposed by said pressure operates conventional electrical monitoring and amplification circuitry and recording apparatus.
DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a plan of the dry blood pressure tansducer of this invention having a diaphragm mounted in a substrate for attachment to the finer or thum of the right or left hand.
FIG. 2 shows a side view of the same.
FIG. 3 shwos a blow-up plan view of the contact face of the same.
FIG. 4 shws a cross-sectional view along line 4--4 of FIG. 3.
FIG. 5 shows a block diagram of a system utilizing the subject transducer for monitoring blood pressure.l
FIG. 6 shows the electrical circuit diagram for the transducer.
FIG. 7 shows a cross-sectional side view of one typical placement of the transducer with the dry skin as a sole coupling means.
FIG. 8 shows a cross-sectional side view of another placement thereof.
FIG. 9 shows a cross-sectional side view of still another placement thereof.
FIG. 10 shows end views of FIGS. 7, 8 an 9.
FIG. 11 shows a cros-sectional side view of the transducer with an elastomeric button covering the diaphragm of the transducer as an additional coupling means.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Reference to FIG. 1 shows a blood pressure transducer or monitor element 10 connected to a four-wire multi-conductor cable 12, comprising a rigid metal surstrate 14 of generally rectangular plan-form having a width approximately that of the subject's finger or thumb. Substrate 14 has a contact face which fits to the inner surface of the finger or thumb of subject's right or left hand, as shown in FIGS. 7, 8, 9 and 10. As shown in FIGS. 3 and 4, a folded edge 16 runs the length of one side of substrate 14.
"Velcro" strap 18, as shown in FIG. 1, is secured at one end thereof to the edge of the substrate 14 by forcibly crimping the fold 16 over and on the respective end of strap 18 laid flat on the back face of the substrate, as shown in FIG. 2. From under the crimping edge 16, the strap 18 passes over the back face of the substrate 14. Strap 18 is separately wrapped around the subject's finger or thumb and the substrate 14 and these are secured together in a single assembly, as shown in FIG. 10. A wire clamp 24 mounts to one end of substrate 14 for holding the end of cable 12 and three of the four wires therefrom operationally connect to terminals 34-36 while the fourth wire grounds the substrate 14, as shown in FIGS. 1 and 3.
Reference to FIG. 3 also shows a circular aperture 22 centrally located in and somewhat smaller in area than the contact face of the substrate 14. As shown in FIG. 4, a circumferential shouldered relief 26 centers on the aperture 22 and cuts in the contoured contact face of the substrate 14. A thin, flat, circular diaphragm 27 of slightly smaller diameter than the relief 26 rigidly mounts around itd circumferential edge therein solidly up aginst a shoulder thereon havng the outer edge of its contacting surface bearing a continuous generally flush relation in its central portion with the curved surface of the contoured face of the substrate 14. A diaphragm retention means 28 which in installed at the juncture between the circumference of the back face of diaphragm 27 and the cylindrical wall of the relief 26 retains the diaphragm 27 therein and produces an essentially rigid relationship between the diaphragm 27 and the substrate 14.
Diaphragm 27 mounts in the substrate 14 in flush relation with the contact face therewith so that, in mounting th transducer 10 on the subject's thumb or finger, as shown in FIG. 4, the contact face bears upon the surface of th subject's skin with an average pressure which is approximately the same as that exerted on the subject's skin thereabout by the contoured face of substrate 14. Subject's subcutaneous bloood pressure is then transmitted to the diaphragm 27 in an approximate linear relation therewith, with subject's skin alone acting as the coupling means, and proportional lateral strain from normal deflection due to subcutaneous blood pressure fluctuations threin is developed thereon.
A half-bridge circuit 38, as shown in FIG. 6, has two scaling resisors 39 and 49 each in adjacent arms of said bridge. The bridge 38 also incorporates electrical wire strain gages 29 and 30 in the same adjacent arms which are bonded in proper central location on the back face of the diaphragm 27, as shown in dotted line in FIG. 3 and in solid line in FIG. 4. Half-bridge 38 measures the proportional resistance unbalance due to the change in strain gages 29 and 30 on the back of diaphragm 27, and converts this strain to an electrical signal output therefrom which is proportional to the subject's subcutaneous blood pressure fluctuation applied to the monitor 10.
The monitor 10 has one lead 31 which electrically is in common with and connected at one end to the first end of each of two strain gages 29 and 30 in the adjacent arms of the bridge 38, as shown in FIGS. 3 and 6. The electrical terminal 34 connects to the other end of electrical lead 31. An electrical lead 32 connects at one end to the other end of the strain gage 30 in one arm of the bridge 38. The scaling resistor 49 connects at one end to the other end of electrical lead 32. The electrical terminal 36 connects to the other end of the resistor 49. An electrical lead 33 connects at one end of the other end of the strain gage 29 in the other arm of the bridge 38. The scaling resistor 39 connects at one end to the other end of electrical lead 33. The electrical terminal 35 connects to the other end of the resistor 39. Terminals 34, 35 and 36 are each bonded to the back face of the substrate 14.
The four-wire multi-conductor cable 12 has a first, second and third conductor 45, 46 and 47 each connected at one end to terminals 34, 35 ad 36 respectively. A fourth conductor 48 as one end operationally connected to the fourth wire in cable 12 which grounds the back face of substrate 14.
A four-prong plug-in connector 37 of the quick-disconnect type having flat male terminals 50, 51, 52 and 53 pierced to accomodate solder wiring and spaced for standard plug-in mounting each of which is solder-connected to the other ends of first, second, third and fourth conductors 45, 46, 47 and 48 connects the monitor 10 to standard control and display modules to read-out and record the blood pressure in the subject's finger or thumb.
A standard circuit 40 and automatic recorder 42, as shown in FIG. 5, completes the system.
In another version, as shown in FIG. 11, the diaphragm 27 is mounted in the substrate 14 in flush relation with the contact face therewith so that, in mounting trasducer 10 on the subject's wrist, the contact face theron bears a uniformm contact pressure relation on the surface of the skin thereof for the full area of the substrate 14 and the convex side of an elastomeric button 54 covers said diaphrgm 27. Button 54 has a diameter approximately equal to that of the diaphragm 27 and a thickness of about one-third of its diameter. The flat side of the button 54 also bears this same contact pressure relation on the surface of the diaphragm 27. Likewise, subject's subcutaneous blood pressure is then transmitted to the diaphragm 27 in an essentially linear relation therewith, with the button 54 acting as the coupling means in addition to that of the subject's skin and proportional lateral strain from normal deflection therein is developed therein is developed thereon.
In the installation of monitor 10 on the subjct's finger or thumb either with or without the elastomeric coupling button, proper contact bearing pressure of the diaphragm 27 against the surface of the subject's skin for proportional read-out of subcutaneous blood pressure is insured by use of a contact bearing pressure adjust system 44, as shown in FIG. 10. The pressure adjust system 44 comprise a Velcro strap 18 which is wound around the subject's finger or thumb and transversely over the back face of the substrate 14 placed thereon for the case of using the dry skin as the sole coupling means, as shown in FIGS. 7, 8, 9 and 10, and for the case of using in addition the elastomeric button 54 as a coupling means, as shown in FIG. 11. The strap 18 is wound thereabout subject to a determinable amount of tension according to the degree of tightness desired therein to give the desired contact bearing pressure of the diaphragm 27 against the surface of the subject's skin for essentially linear response of the monitor in recording subject's subcutaneous blood pressure without occlusion of the free flow of blood in his vessels.
One specific use of this invention, although there are others, is in the field of truth verification wherein the stress of emission of a falsehood causes the subcutaneous blood pressure to quickly change and be noted on the monitor.
Although but one specific embodiment of this invention is herein shown and described, it will be understood that details of the construction shown may be altered or omitted without departing from the spirit of the invention as defined by the following claims.
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A non-invasive, non-occluding pressure transducer for monitoring subcutaneous blood pressure, which can be worn for extended periods of time without physical discomfort, for physiological, psychological and psychiatric evaluation, and for clinical procedures and surgical monitoring and truth-verification polygraph applications, having suitable frequency response characteristics for high-fidelity recordation of subcutaneous blood pressure changes.
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This Application is a continuation of 08/883,644 filed Jun. 26, 1997 now U.S. Pat. No. 6,168,880.
BACKGROUND OF THE INVENTION
The present invention relates to electrochemcial devices. Electrochemical devices are typically made of thin electrode and separator layers.
An example of such an electrochemical device is described in Kejha et al U.S. Pat. No. 5,521,023. Kejha et al. describes using a sheet of perforated plastic material along with a liquid ion-conductive polymer. The ion-conductive polymer is cured to form a solid- or semi-solid-state electrolyte composite. The perforated plastic material helps maintain the separation between the electrode layers. The liquid ion-conductive polymer by itself may not sufficiently maintain the separation between the electrode layers.
Another manner of maintaining the separation between the electrode layers is to use a separator using a co-polymer/plasticizer separation layer. The co-polymer/plasticizer layer can be laminated to electrode layers. The co-polymers of the separator will mix with co-ploymers of the electrodes. Later, the plasticizer is removed and an electrolyte solution added. The electrolyte solution provides and ion-conductive path between the electrodes. The co-polymer of the separator provides a relatively constant separation distance for the separator. The co-polymer remains not significantly soluble in the electrolyte solution, so that separation of the electrodes is maintained.
It is desired to have an improved electrochemical device.
SUMMARY OF THE INVENTION
A problem with electrochemical devices is that, under some conditions, a battery runaway can occur. A runaway is a short between the electrode layers which causes the battery to heat up. The head of the thermal runaway can cause additional damage to the battery, further reducing the impedance of the battery. Avoiding such runaway problems is especially important for lithium batteries.
In the present invention, a polymer mesh material made of a material that will melt during battery runaway is used. This material can be placed in a separator layer, electrode layer, or between the battery layers. The mesh is sized so that a solid battery material can be positioned in the mesh holes.
When the mesh material melts, the internal impedance is increased and thermal energy is absorbed to cause the melting. In effect, the holes of the polymer mesh are fused shut. This is useful during thermal runaway, abuse or other elevated temperature conditions. In a preferred embodiment, the melting temperature of the mesh is less than 150° C. but more than 100° C. to allow the battery layers to be laminated under normal lamination pressures and temperatures. Possible plastic materials for the polymer mesh include polyethylene, polypropylene, polyethylene terephthalate, and various co-polymers.
In a preferred embodiment, the mesh is made of ppolypropylene, polyethylene or a polyethylene/polypropylene co-polymer.
When a co-polymer is used in the separator that is substantially non-soluble in an electrolyte material, the separation and uniformity of the electrode layers can be effectively maintained under normal conditions without a polymer mesh. Adding the polymer mesh with the desired melting point has the advantage that thermal runaway can be avoided.
Additionally, placing the polymer mesh in an electrode layer can also help prevent the thermal runaway of an electrochemical device.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other features and aspects of the present invention will become more apparent upon reading the following detailed description in conjunction with the accompanying drawings.
FIG. 1 is a diagram illustrating a die slot producing a mesh material within an active material layer for a battery.
FIGS. 2A and 2B are diagrams illustrating a solvent casting of a battery layer with a mesh material that is embedded therein.
FIG. 3 is a diagram illustrating the forming of a cell from individual die layers by lamination.
FIG. 4 is a diagram illustrating the forming of a bicell from individual battery layers.
FIG. 5 is a diagram illustrating the different battery layers including the non-conductive mesh of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 is a diagram illustrating the die slot production of a battery layer 10 including a battery material 12 with embedded electrically non-conductive mesh 14 . In this embodiment, the battery layer 10 is extruded from the die slot 16 .
In a preferred embodiment, the mesh material 14 is a plastic material. The mesh material 14 forms holes which allow the solid material 12 of the batter layer to be positioned therein. The mesh 14 is preferably expanded mesh formed by perforating and stretching a plastic layer. The mesh can also be produced by screen casting or by molding.
The mesh material is preferably made of material that melts at a temperature below 150° C. to allow for the mesh material to melt during thermal runaway of a battery. The mesh material preferably has a melting temperature above about 100° C. to allow the mesh to be used within battery layers that are laminated together. Plastic materials having a melting point in the desired range are believed to be polypropylene, polyethylene and a polyethylene/polypropylene co-polymer. In a preferred embodiment, the melting point of the mesh material is about 120-140° C.
The battery material 12 can be the separator film material used to form the separator layer, or alternatively be anode or cathode material.
Optionally, the mesh 14 can include an organic or inorganic filler material. Filler material can be used to improve the dielectric strength, change the dielectric constant and/or improve adhesion. Possible particle shape of the solid or hollow filler(s) used in the polymer mesh material include spherical, cubical, block, plate, flake or fiber. Possible filler raw materials include calcium carbonate, silica, glass, mica, alumina trihydrate, calcium metasilicate, aluminum silicate, antimony oxide, carbon or graphite, talc, barium sulfate or kaolin.
FIGS. 2A and 2B illustrate the solvent casting of a mesh 22 within a battery material 20 . In FIG. 2A, the battery material 20 can be a separator layer formed with a co-polymer and an intercellular compound, such as a plasticizer. An example of a co-polymer that is not soluble in the electrolyte is polyvinylidene fluoride/hexafluoropropylene (PVDF-HFT). The plasticizer can be removed by chemical treatment, and after the application of heat or temperature in FIG. 2B, the battery material 20 reduces to a film 24 . FIG. 2A and 2B illustrate the solvent casting of a separator layer, but the solvent casting could be used to produce an anode or cathode layer as well.
FIG. 3 illustrates the lamination of a cell 30 using a separator layer 32 , inner layer 34 , and cathode layer 36 . These layers are pressed together between rollers 38 and 40 to produce the laminated cell 30 . The mesh material can be part of the separator layer 32 , inner layer 34 , or cathode layer 36 . Alternately, the separator layer could be placed between any of these battery layers in the lamination process.
Another way to connect the battery layers to the polymer mesh is to melt or laminate the battery material to the polymer mesh. The co-polymers in the battery material will fuse with the polymer mesh.
FIG. 4 illustrates the production of a bicell 42 by lamination. In the production of a bicell, two cathode layers 44 and 46 are separated by separator layers 48 and 50 from a single anode layer 52 . As discussed above, the mesh material can be placed within any of these layers or between any of these layers. FIG. 5 is a diagram illustrating a battery cell 54 . The battery cell 54 includes an anode layer 56 , separator layer 58 , and cathode layer 60 . The separator layer 58 includes the mesh material 62 . The anode layer 56 is preferably made of a graphite-based carbon material. The anode layer 56 includes a current collector 64 and active material 66 . The cathode layer 60 in a preferred embodiment is lithiated manganese oxide or lithiated cobalt oxide. The cathode 60 includes a current collector 68 and active material 70 .
In a preferred embodiment, a liquid electrode material is added to the battery. The co-polymer of the separator is substantially insoluble in the electrolyte so that the co-polymer can maintain the separation between the electrodes. The polymer mesh material with the desired melting point has the advantage that the mesh will melt during thermal runaway.
Various details of the implementation and method are merely illustrative of the invention. It will be understood that various changes in such details may be within the scope of the invention, which is to be limited only by the appended claims.
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The use of a polymer mesh made of material that melts under thermal runaway helps improve the safety of an electrochemical device. The mesh material can increase the impedance of the battery during the thermal runaway and absorb some of the heat produced.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] Not Applicable.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable.
BACKGROUND OF THE INVENTION
[0003] 1. Field of the Invention
[0004] The present invention relates to an apparatus for receiving a fluid and, more particularly, to such an apparatus which has particular utility in capturing a fluid for subsequent disposal, processing, or other such usage during the performance of a procedure wherein such fluid is present.
[0005] 2. Description of the Prior Art
[0006] A variety of environments exist in which a procedure must be performed without the benefit of adequately controlling all of the conditions involved in performing that procedure. These circumstances arise, for example, in the servicing, maintenance and repair of mechanical devices such as machinery, automotive vehicles, aircraft, boats, and virtually all types of equipment composed of a plurality of systems and subsystems. This is particularly true where such systems and subsystems contain fluids of various types which must, from time to time, be replaced or processed.
[0007] Thus, in the case of, for example, internal combustion engines, lubricating systems have oil filters which must, from time to time, be replaced as well as the lubricating oil from the systems. The positioning of the oil filter is dependent upon the particular design of the engine and may be in virtually any attitude between, for example, an attitude in which the oil filter is removable downwardly along an axis which is substantially vertical, to an oil filter which is removable along an axis varying therefrom to one which must be removed along a substantially horizontal axis.
[0008] In all of these instances, the oil would first be drained from the subsystem before removal of the oil filter. However, even after intentional removal of oil from the subsystem, residual oil remains in the subsystem as well as the oil filter itself. Accordingly, in the typical arrangement for the subsystem, the oil filter must be removed from the engine along an axis varying from substantially downwardly along a vertical axis through a range of possible positions to and including a path of movement along a substantially horizontal axis. Irrespective of the attitude along which the oil filter must be removed, residual degraded oil within the subsystem drains gravitationally from the subsystem of the engine so as typically to create a spill of the residual degraded oil. This may only constitute a nuisance. However, it may also contaminate the area involved creating environmental concerns. At very least, it may create an unsightly condition while spilling upon the person and tools of the person performing the operation.
[0009] Therefore, it has long been known that it would be desirable to have an apparatus for receiving a fluid which was operable to contain fluids released during service, maintenance and other modification or adjustment of mechanical devices; which is particularly well suited for use in the servicing, maintenance and other attention to mechanical devices, particularly where such mechanical devices employ systems and subsystems containing fluids to be replaced, processed, or initially charged in the system or subsystem; which is unusually well suited to use in such processes relative to the removal and installation of filters, such as oil filters, on internal combustion engines wherein residual fluids within the internal combustion engine and filter may interfere with the operation to be performed; which operates to avoid the nuisance and possibly hazardous or damaging consequences of such residual fluids in the maintenance of the mechanical device involved; which is entirely compatible with the existing systems and subsystems involved as well as the procedures normally performed without in any way detracting from the procedures normally involved; and which is otherwise entirely successful in achieving its operational objectives.
BRIEF SUMMARY OF THE INVENTION
[0010] Therefore, it is an object of the present invention to provide an improved apparatus for receiving a fluid which operates to control the flow of fluids during a wide variety of work operations.
[0011] Another object is to provide such an apparatus which has application to a wide variety of operative environments wherein it is desirable to control the release and containment as well as discharge of fluids associated with the operation involved.
[0012] Another object is to provide such an apparatus which has particular utility in the manufacture, servicing, maintenance and other handling of mechanical devices without detracting from the primary intentions of the operations involved.
[0013] Another object is to provide such an apparatus which operates selectively to retain residual fluid in a reservoir for subsequent disposal, processing or reuse while permitting the operation to be performed to continue unabated by such discharge.
[0014] Another object is to provide such an apparatus which is unusually well suited to the manufacture, servicing, maintenance or other handling of mechanical devices, such as internal combustion engines, by affording the opportunity for such operations to continue without interference from substances such as fluids involved in such operations.
[0015] Another object is to provide such an apparatus which is unusually well suited in the servicing of internal combustion engines, and the like, wherein an oil filter or other fluid system filter, is to be removed and replaced in conjunction with the replacement of the fluid of the subsystem involved, and, under such conditions, wherein the attitude of the oil filter involved is such that drainage of residual fluid from the subsystem may interfere with the operation and otherwise creates conditions which constitute a nuisance, a hazardous condition, or simply a resulting condition requiring cleanup, abatement of a hazard, or any number of further work operations which exacerbate the consequences of the primary work operation involved.
[0016] Another object is to provide such an apparatus which can be employed to remove the oil filter, or the like, from the internal combustion engine, or the system or subsystem being handled, while containing to fluid released therefrom for subsequent handling.
[0017] Further objects and advantages are to provide improved elements and arrangements thereof in an apparatus for the purpose described which is dependable, economical, durable and fully effective in accomplishing its intended purposes.
[0018] These and other objects and advantages are achieved, in the preferred embodiment of the present invention, in an apparatus for receiving a fluid having a housing defining a receptacle adapted to receive said fluid from a source of said fluid; and a member for releasibly attaching the housing to a source of said fluid in receiving relation thereto.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0019] [0019]FIG. 1 is a perspective view of the apparatus for receiving a fluid of the first embodiment of the present invention.
[0020] [0020]FIG. 2 is a perspective view of the apparatus for receiving a fluid of the second embodiment of the present invention.
[0021] [0021]FIG. 3 is a fragmentary perspective view of the apparatus for receiving a fluid of the first embodiment of the present invention shown in a typical operative environment.
[0022] [0022]FIG. 4 is a fragmentary perspective view of the apparatus for receiving a fluid of the second embodiment of the present invention shown in a typical operative environment.
[0023] [0023]FIG. 5 is a longitudinal vertical section taken on line 5 - 5 in FIG. 1.
DETAILED DESCRIPTION OF THE INVENTION
[0024] The apparatus for receiving a fluid of the first embodiment of the present invention is shown in FIGS. 1, 3 and 5 of the drawings and is generally identified by the numeral 10 in those views.
[0025] The apparatus for receiving a fluid of the second embodiment of the present invention is generally indicated by the numeral 20 in FIGS. 2 and 4.
[0026] For illustrative convenience, the apparatus for receiving a fluid of the first embodiment 10 and second embodiment 20 are shown in FIGS. 3 and 4 in environments in which an oil filter is to be removed from an internal combustion engine. Within the illustrative environment, as shown in FIG. 3 relative to the apparatus 10 of the present invention, and in FIG. 4 relative to the apparatus 20 , the apparatuses of the two embodiments hereof are shown in typical operative conditions.
[0027] With respect to FIG. 3 and the apparatus 10 of the first embodiment of the present invention, an internal combustion engine is fragmentarily shown and generally indicated by the numeral 30 therein. The internal combustion engine has an engine housing 31 having an outer surface 32 and a lower surface 33 . An oil filter mount 34 is formed in the lower surface 33 of the engine housing 31 and, it will be understood as shown therein, the oil filter mount 34 is adapted to receive an oil filter of a conventional type, screw threadably received therein along an axis which is substantially vertical and substantially right angularly related relative to the lower surface 33 of the engine housing.
[0028] As shown in FIG. 4, relative to the apparatus for receiving a fluid 20 of the second embodiment of the present invention, an internal combustion engine has been fragmentarily shown and generally indicated by the numeral 40 . The internal combustion engine has an engine housing 41 having an outer surface 42 with a substantially downwardly facing surface 43 . An oil filter mount 44 is mounted in the downwardly facing surface 43 of the engine housing 41 , as shown in FIG. 4. The oil filter mount is disposed to receive an oil filter for installation and removal substantially along a vertical axis, as shown therein.
[0029] For illustrative convenience in FIG. 3 in relation to the apparatus 10 of the first embodiment of the present invention, the apparatus is shown with an oil filter generally indicated by the numeral 50 , as viewed therein. The oil filter 50 has a body 51 and will be understood to be a conventional oil filter for purposes of the illustrative environment. The oil filter 50 shown in FIG. 3 is of conventional construction having a body 51 bearing a lower end portion 52 and an opposite upper end portion 53 . The oil filter 50 has an outer surface 54 which is of a generally cylindrical configuration. The oil filter 50 has a substantially concavo-convex lower surface 55 and an opposite upper surface 56 .
[0030] The lower end portion 52 of the oil filter 50 has a gripping surface 60 extending about the outer surface 54 thereof. The upper surface 56 of the oil filter has seals 61 mounted thereon for fluid sealing engagement with the engine housing 31 . The seals 21 define a sealing surface 62 .
[0031] In the case of the second embodiment of the apparatus of the present invention 20 , the lower end portion 52 of the oil filter 50 of the oil filter of the second embodiment 20 of the present invention has different gripping surface than in the case of apparatus 10 . The gripping surface of apparatus 20 is not conventional and is novel, as hereinafter described. The gripping surface preferably has a plurality of arcuate slots 63 formed therein, as shown in FIGS. 2 and 4. In the representative example, there are five (5) such arcuate slots spaced substantially equidistantly about the outer surface 54 of the lower end portion 52 of the body 51 of the oil filter 50 . Each of the arcuate slots 63 constitutes a slot or groove which does not extend through the outer wall of the oil filter, but rather is a recess so configured and positioned as to permit the operation hereinafter to become more clearly apparent. For purposes of illustrative convenience, it will be understood that each arcuate slot 63 has an entrance end portion 64 , a sloped first segment 65 and an arcuately downwardly curved portion 66 ending in a terminal end 67 . Each entrance end portion 64 of each arcuate slot 63 extends through the lower surface 55 so as thereby to form an entrance to its respective arcuate slot.
[0032] As previously noted, the first embodiment 10 of the present invention is shown in FIGS. 1, 3 and 5 of the drawings. The apparatus 10 has a housing or container 70 having, generally, a lower end portion 71 , and an opposite upper end portion 72 . The container has a cylindrical wall 73 having an outer cylindrical surface 74 , an upper peripheral edge 75 and an interior cylindrical surface 76 . The container 70 has a solid lower end wall 80 , having a substantially flat interior surface 81 and a parallel, substantially flat exterior surface 82 . In the case of container 70 of the first embodiment, preferably three (3) magnets are mounted on the interior cylindrical surface 76 adjacent to the upper peripheral edge 75 and in equally spaced relation thereto. The magnets are mounted in spaced relation to each other about the interior cylindrical surface 76 . The magnets are preferably disposed in equally spaced relation. Each magnet has an interiorly facing, substantially flat surface 84 and a sloped upper surface 85 . The spacing of the interior surfaces 84 of the magnets 83 is such that an oil filter 50 can slidably be received within the container 70 in slidable engagement with the interior surfaces of the magnets. The relationship is such that the magnets thereby engage and are magnetically attracted to the outer surface 54 of the oil filter. The container 70 is thereby magnetically mounted on the oil filter while being freely releasable therefrom when desired by overcoming the magnetic attraction thereof. The interior cylindrical surface 76 of the container 70 extends to an upper interior edge 91 , as shown in FIG. 5. The interior cylindrical surface defines a chamber 92 extending to a mouth 93 at the upper end portion 72 of the container, for purposes hereinafter to be described. The container 70 is shown in a work position 101 in FIG. 3.
[0033] The second embodiment of the apparatus 20 of the present invention is shown in FIGS. 2 and 4. The apparatus 20 has a housing or container 170 having, generally, a lower end portion 171 , and an opposite end portion 172 . The container has a cylindrical wall 173 having an outer cylindrical surface 174 , an upper peripheral edge 175 and an interior cylindrical surface 176 .
[0034] The container 170 has a lower end wall 180 having an interior surface 181 and an opposite exterior surface 182 . Five (5) interlocking members or pins are mounted on the interior cylindrical surface 176 of the container 170 . The pins are mounted in positions individually corresponding to the entrance end portions 64 of the arcuate slots 63 of the oil filter 50 , as shown in FIG. 2. The pins are dimensioned slidably individually to be received in the entrance end portions 64 of the arcuate slots and, by pushing the container 170 toward the oil filter, to follow their respective arcuate slots to their respective terminal end portions as the container 170 and oil filter are adjusted about their respective longitudinal axes to accommodate the travel of the pins in their respective arcuate slots. Once the pins travel through the curved portions 66 of their respective arcuate slots and reach the terminal ends 67 of the arcuate slots, the container 170 and oil filter are interlocked. They can be disengaged by reversing this process.
[0035] The interior cylindrical surface 176 of the container 170 extends to an upper interior edge 191 . The interior cylindrical surface defines a chamber 192 extending to a mouth 193 . The container 170 is shown in a work position 201 in FIG. 2.
Operation
[0036] The operation of the described embodiments of the subject invention is believed to be clearly apparent and is briefly summarized at this point. For illustrative convenience, the apparatus 10 and the apparatus 20 of the two embodiments of the present invention are described substantially simultaneously herein.
[0037] In the illustrative environment, the work operation to be performed is the removal of the oil filter 50 from the oil filter mount 34 and 44 of the internal combustion engines 30 and 40 shown respectively in FIGS. 3 and 4. After draining the used or degraded oil from the engine through a drain opening by means not shown, the apparatus 10 and the apparatus 20 are moved to their respective work positions 101 and 201 shown respectively in FIGS. 3 and 4.
[0038] Thus, in the case of the apparatus 10 , the container 70 is moved to the position illustrated in FIG. 3, but with the oil filter in the attached position in the oil filter mount 34 . In this work position 101 , the container 70 is slidably fitted about the oil filter, either in engagement with, or near engagement with, the lower surface 33 of the engine housing 31 so as to expose the mouth 93 of the chamber 92 to residual oil received during removal of the oil filter.
[0039] Similarly, in the case of apparatus 20 of the present invention, the container 170 is moved to the work position 201 shown in FIG. 4 in which the chamber 205 is disposed on, and extending beneath, the oil filter 50 in position to receive residual oil released during removal of the oil filter.
[0040] Thereafter, in the case of both of the apparatuses 10 and 20 , the oil filter 50 is removed from the oil filter mount 34 in the case of apparatus 10 , and 44 in the case of apparatus 20 . Residual oil flowing gravitationally from the oil filter itself or from the oil filter mount 34 or 44 is gravitationally received in the chamber 92 of apparatus 10 or the chamber 192 of the apparatus 20 so that no residual oil is released to the environment, or spilled on the operator.
[0041] In the case of apparatus 10 , the residual oil is captured within the chamber 92 . Subsequently, the operator can discharge the residual oil both from the oil filter and from the chamber 92 through the mouth 93 of the apparatus 10 simply by tipping the container so as to pour the residual oil therefrom into a suitable receptacle for disposal, reuse or the like.
[0042] In the case of apparatus 20 , the residual oil is similarly deposited in a suitable container for subsequent disposal, reuse, processing or the like.
[0043] In the case of the apparatus 10 , magnetic engagement of the magnets 83 with the outer surface 54 of the oil filter 50 permits the container 70 to be employed, in effect, as a wrench screw-threadably to remove the oil filter 50 from the oil filter mount 34 . In the case of apparatus 20 , the interlock of the pins 183 of the container 170 in the arcuate slots 63 of the oil filter 50 permits the container 170 similarly to be used, in effect, as a wrench screw-threadably to remove the oil filter 50 from the oil filter mount 44 .
[0044] Therefore, the apparatus of the present invention is particularly well suited to contain fluids released during service, maintenance and other modification or adjustment of mechanical devices; is well adapted to the servicing, maintenance and other attention to mechanical devices, particularly where such mechanical devices employ systems and subsystems containing fluids to be replaced, processed, or initially charged in the system or subsystem; is unusually well suited to use in such processes relative to the removal and installation of filters, such as oil filters, on internal combustion engines wherein residual fluids within the internal combustion engine and filter may interfere with the operation to be performed; operates to avoid the nuisance and possibly hazardous or damaging consequences of such residual fluids in the maintenance of the mechanical device involved; is entirely compatible with the existing systems and subsystems involved as well as the procedures normally performed without in any way detracting from the procedures normally involved; and is otherwise entirely successful in achieving its operational objectives.
[0045] Although the invention has been herein shown and described in what is conceived to be the most practical and preferred embodiments, it is recognized that departures may be made therefrom within the scope of the invention which is not to be limited to the illustrative details disclosed.
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An apparatus for receiving a fluid, such as degraded oil, from an oil filter to be replaced, removably mounted on an engine, during removal of the oil filter, the apparatus including a housing defining a receptacle adapted to receive the fluid; and a securing member mounted on the housing for releasibly attaching the housing to the oil filter in receiving relation to the fluid during removal of the oil filter.
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RELATED APPLICATIONS
This application is a continuation-in-part application of U.S. Ser. No. 236,999 filed Feb. 23, 1981, now abandoned.
BACKGROUND OF THE DISCLOSURE
In drilling an oil well, especially at an offshore location, it is necessary to install flanges of various sizes of large diameter pipe. Consider, as an example, the instance where several sizes of casing are installed in a well. The well might include, as an example, a 36 inch drive pipe. There may also be a 20 inch casing, 133/8ths inch casing and 95/8ths inch casing. It is necessary to install a termination flange or casing head at every change of size. The flange is typically installed by first cutting the casing, preheating the casing and then welding the flange in place. The flange is necessary to mount other equipment or to otherwise install the next casing string.
Often, this requires cutting a very thick wall casing, even in the range of 11/2inch thick and thereafter making a multi-pass welded bead to attach the flange. This requires a tremendous amount of preheating to obtain a quality weld.
For drilling rigs located at sea, the preheating is something of a problem. In inclement weather, wind shields must be installed and a number of welders will position their torches on the casing and flange to preheat it for perhaps 4 to 6 inches below the casing head in length to perhaps 500° F. This is difficult and time consuming. Moreover, cooling begins on the instant that preheating is stopped. It is difficult to preheat the casing and simultaneously weld a flange to it.
Certain devices have been provided heretofore to serve as preheaters. While these devices have various and sundry advantages, it is believed that the device of this disclosure is much more attractive for the intended purpose, namely to provide a preheater which can be selectively installed within a casing, whereby preheating occurs from the interior. This enables the welder to install the flange or casing head and quickly begin the multi-pass bead required to fasten the flange in place.
The various preheater devices are typified by the patent of Jaeger, U.S. Pat. No. 3,082,760. However, this device and others like it are believed to be limited. There is a real risk that the preheater device will be lost down the casing. If this occurs, it may then be lost in the wellbore. In the wellbore, it poses a serious problem. It is necessary to remove it because it is very difficult to drill through the steel Jaeger device. In either case it is not very desirable.
The preheater device of this disclosure utilizes a cement receptacle which is non-corrosive to saltwater, relatively inexpensive, and able to be broken into small pieces should it fall into the wellbore. It is relatively easy to drill through the cement device. This does not impede the drilling process that occurs subsequently to the use of the preheater device.
The present disclosure is therefore directed to a preheater device which is formed of a cement body of frangible material. This includes a bottom cylindrical receptacle. It terminates at the center in an upstanding stalk with light weight chain pre-cast through the length of the body. The cement body is self-centralizing and supports an elongate cast cylindrical exothermic compound. One suitable material is molded thermite. A deflector plate made of the same cement is positioned on the top. It is sized relative to the casing to direct the flow of hot gases outwardly and against the wall of the casing to be heated. The device is held in place by a chain attached to one of the utility hoist cables common to all drilling rigs.
BRIEF DESCRIPTION OF THE DRAWINGS
So that the manner in which the above recited features, advantages and objects of the invention, as well as others, which will become apparent, are attained and can be understood in detail, a more particular description of the invention, briefly summarized above, may be had by reference to the embodiments thereof illustrated in the appended drawings, which drawings form a part of this specification. It is to be noted, however, that the appended drawings illustrate only typical embodiments of the invention and are not to be considered limiting of its scope, for the invention may admit to other equally effective embodiments.
FIG. 1 is a partial sectional view through the preheater device of the present disclosure positioned in a casing to heat the casing and flange for welding; and
FIG. 2 is a sectional view of an alternate embodiment of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Attention is first directed to the single view which discloses the apparatus of the present disclosure. It is identified generally by the numeral 10. It is shown in a pipe 12. Assume, for purposes of illustration, that the pipe 12 is a large casing having a wall thickness conforming with industry standards. The pipe 12 can range from 1/2 inch thick to about 11/2 inches or greater. Moreover, a flange 14 is to be attached to the pipe 12. The flange 14 is constructed with an internal shoulder 16 to abut the end of the pipe 12. It has a cylindrical portion 18 which telescopes over the pipe. A multi-pass bead is formed at 20, and an inside or finish bead is formed at 22. The bead 20 must be formed first to fully and completely anchor the flange to the pipe 12. The weld 20 is a high quality weld, subject to 100% inspection, and must be formed in many passes.
It is very important to preheat the pipe to a specified temperature. Failure to evenly preheat the pipe may damage the weld 20. It is for this purpose that the present preheater is installed in the pipe 12. Moreover, it is spaced so that the rising hot gases in the pipe are deflected against the pipe in the near vicinity of the weld 20 to preheat that area to the required temperature. Since it requires a substantial period of time to weld the flange in place, the preheater of this disclosure must burn for a significant interval. This is a scale factor which can be varied dependent on the size of the pipe, the temperature required in preheating, the number of passes required in the weld 20 and other factors such as these. Suffice it to say, the present disclosure provides a preheater which can be sized to preheat the pipe to the required temperature for the required interval. To this end, the device 10 is shown in the pipe 12, being located in the position that it maintains during use.
The preheater device 10 includes cement bottom support member 24. This is constructed in the form of a cylinder with centralizing projections. The member 24 is fabricated of heat resistant calcium aluminate cement with expanded vermiculite as grog, and should be capable of supporting the combustible element during its combustion, as for instance, at temperatures upwards of 5,000° F. The support member 24 is of sufficient thickness to retain the white hot slag from the exothermic reaction. Ideally, it is quite frangible and can be easily fractured on drilling through it later in the process should it all fall into the wellbore. There is an air gap 26 at the top of the cylinder to direct hot gases at the casing wall 12.
A smaller diameter cellulose tube 27 fits over the neck 28 of the device and is filled with moulded thermite. This is to support the neck during shipment and to facilitate ignition by means of touch holes in the upper deflector plate. Ideally, the neck 20 is cast as a single piece with the bottom support member 24.
The preheater 10 is centralized within the pipe 12 by several integrally cast protrusions 30. A light weight chain 32 is cast into the device as a means of suspension in the wellbore. It will be recalled that the preheater is partly combusted and, therefore, looses weight during combustion. It is preferable that the chain 32 be sufficiently strong even when heated that it retains its strength to suspend the illustrated shape.
The numeral 44 identifies a top deflector plate. The deflector plate is supported on an inclined circumferential shoulder 46 formed on the neck 28 of the device 10. The angle of the shoulder 46 need not be extreme, and is typically in the range of 45 to 60 degrees. The deflector plate 44 is provided with a matching counter-sunk shoulder for cooperative engagement with the shoulder 46. The deflector 44 terminates at an outer edge which is sized to fit within the casing 12 with perhaps 1/4 to 1/2 inch of clearance. During combustion, rising hot gases flow upwardly through the gap 26, and flow past the edge of the deflector 44. This deflects the hot gases towards the wall and thereby heats the pipe 12 in the most desirable manner. This particularly assists in directing the heat against the casing 12 in the near vicinity of the welded bead 20 on the exterior. The device is positioned so that the edge of the deflector is close to the bead 20 so that the hot gases are deflected against it.
The fuel 42 is a sacrificial, poured mixture made of non-toxic materials. One example is exothermic thermite which is defined, for purposes of this diclosure, as a granulated and cast mixture of aluminum particles with iron oxide. A bonding agent is added and suitable bonding agents include various and sundry binders such as starch. The fuel 42 is sacrificial in that it must be a combustible material which sustains a slow burn for the requisite interval. For instance, the fuel may be poured with suitable ihibitors and binding agents so that it burns at 5,000° F. for sufficient time to heat the casing by convection and subsequently the wellhead by conduction. It will be appreciated that it shrinks during combustion. As is shrinks, it nevertheless gives off great clouds of heated gases which rise towards the deflector 44 and pass through the gap 26 adjacent to the preheater. This preheats the pipe to the required temperature for the required interval. Various and sundry inhibitors can be added to slow down the rate of burning. For added strength, chopped nylon fibers can be mixed in random fashion within the slurry which forms the fuel 42.
For ease of starting the fire, the top portions of the fuel compound 42 may be poured with some oxygen liberating compound. It should be a compound which liberates substantial quantities of oxygen and ideally is a metal salt which does not create toxic fumes. One example is potassium perchlorate. This can be mixed into the fuel compound in portions ranging from 0% to a fairly heavy concentration. The oxygen liberating compound can be evenly mixed or biased at the top to start the fire readily. This makes the device start burning much easier.
Various and sundry starters are known and can be adhesively joined to the top of the fuel compound 42. Alternatively, it can be started in combustion by simply playing an acetylene torch on the top portions of the fuel in the touch-holes in the deflector plate. Once combustion has begun the device is lowered on an overhead suspension apparatus (not shown) into the casing 12 and combustion is permitted to continue until the fuel is entirely consumed.
As an example of one fuel compound, a suitable starch, serving as a binder, is mixed with approximately equal parts by volume of aluminum and iron oxide. They are preferably ground relatively fine, having particles in the range of about 20 mesh or smaller. Other sizes can be used, it being kept in mind that larger particles burn slower and at a lower temperature. The top one-third of the compound is formed with a suitable perchlorate mixed in the slurry before pouring, the concentration ranging up to about 10% by weight.
The device of the present invention is particuarly easy to use. It is positioned in the casing 12 and suspended so that the deflecting plate 44 is exposed. A welder ignites fuel in the touch-holes with his torch and the preheater is then lowered into the casing until it is positioned as shown. Various and sundry temperature sensitive devices are used on the exterior to determine that the casing has been adequately preheated. When this occurs, the welder can then begin welding the flange in position by forming the multi-pass bead 20. On large casing, the bead 20 is formed by many passes. After the several passes are made, the bead can thereafter be inspected on permitting the casing to cool. It is also optionally necessary to form the bead 22 on the interior of the casing. This bead is formed typically after the preheater 10 has been removed from the casing. This bead is less critical in terms of preheating.
The present apparatus can be sized by varying the amount of exothermic compound placed into the cement casting. For a given combustible mixture such as thermite, the dimensions can be varied to control the duration of burning.
The integrally cast projections which extend from the bottom and upper third of the casing 24 radiate outwardly to position the preheater 10 in the casing. They do not have to be precise in length or location. Precise alignment of the bottom end of the equipment is less important than positioning concentrically in the casing of the deflector 44. As a general proposition, the spacing of the deflector plate should be relatively concentric with respect to the pipe 12. As will be understood, a chimney effect may occur which sweeps the heated gases upwardly against the casing. This carries excess heat out through the top and away from the welder so that his field of vision is not obscured.
Referring now to FIG. 2, an alternate embodiment of the invention is shown. It will be observed that the apparatus 40 differs from the apparatus of FIG. 1 in that it is not constructed in the form of a cylinder open at the top and closed at the bottom. The apparatus 40 includes a base member 54 extending radially outwardly from the lower end of the neck 28. Preferably, the neck 28 and the base member 54 are cast as a single piece. Integrally cast projections 50 are equally spaced about the periphery of the base member 54 for centralizing the apparatus 40 within the pipe 12.
The fuel mixture 52, in the alternate embodiment, is molted thermite, a slow burning, non-toxic material previously described herein. The fuel mixture 52 is a cast cylindrical body having an axial opening extending therethrough for receiving the stem 28. It is supported at the lower end thereof by the base 54. The deflector plate 44 caps the fuel mixture 52 as shown in FIG. 2. The cylindrical body of the fuel mixture 52 is sized to fit within the pipe 12 with perhaps one half to one inch of clearance about the periphery thereof. During combustion, hot gases radiate outwardly from the cylindrical body of the fuel mixture 52 to thereby heat the wall of the pipe 12. The hot gases rise upwardly and flow past the edge of the deflector plate 44. The fuel mixture 52 is positioned so that it is opposite the bead 20, as shown in FIG. 2, so that hot gases are deflected against it. As the fuel mixture 52 burns, the white hot slag from the exothermic reaction falls to the bottom of the wellbore and it is drilled through later in the process.
While the foregoing is directed to the preferred embodiment of the present invention, other and further embodiments of the invention may be devised without departing from the basic concept thereof, and the scope thereof is determined by the claims which follow.
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A preheating insert is disclosed. The preferred and illustrated embodiment incorporates an encircling bottom support having a centralized hollow tube. It is made of a frangible material to be easily broken should it fall into the pipe. It supports a hollow, cylindrical, combustible heating element. The heating element is made of thermite as an example. It includes a top located deflector plate to deflect hot gases flowing upwardly from combustion against the wall of a pipe to be heated. The apparatus is concentrically located within the pipe in the vicinity of the pipe section to be heated.
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BACKGROUND OF THE INVENTION
The present invention relates to apparatus for locally expanding ductile tubes of a heat-exchanger into fixed engagement with a supporting metal sheet having openings through which the tubes pass in laterally spaced parallel relation. The invention further relates to means for locating the position of a tube sheet with a probe positioned inside a tube passing through the sheet and for expanding the tube at the precise location where it passes through the sheet as part of the same operation, i.e., without withdrawing the probe from the tube.
In a common form of heat exchange apparatus such as condensers and evaporators in a variety of refrigeration units, a plurality of hollow tubes pass through openings in an essentially planar support sheet. Typically, a plurality of such sheets are provided at spaced intervals along the length of the tubes. Although the tubes are closely surrounded by the openings when axially inserted therethrough, it is necessary to form a tight, mechanical connection between the outer surfaces of the tubes and the portions of the sheet surrounding the openings, in order to eliminate tube vibration and resulting wear.
Since both the tubes and sheets, in order to provide efficient heat conduction, are normally formed of ductile metal, the connection is provided by expanding the tubes with an internal expansion device in the areas where they pass through the openings. It is necessary, of course, to position the expansion device at a predetermined location within the tube to ensure that expansion is effected in the plane of the support sheet. Thus, fabrication of heat exchange apparatus involving controlled expansion of a relatively large number of tubes at several axial locations can be a time-consuming task, requiring a skilled operator, representing a significant portion of the cost of such apparatus.
The principal object of the present invention is to provide apparatus for improving the efficiency, and thus reducing the cost, of fabricating heat exchange devices wherein hollow, elongated tubes are expanded into tight engagement with support sheets.
Another object is to provide novel and improved apparatus for effecting localized, radial expansion of a hollow, elongated tube of ductile metal at a desired axial location.
Other objects will in part be obvious and will in part appear hereinafter.
SUMMARY OF THE INVENTION
A hydraulic pump is connected by a flexible hose to axially adjacent sections of steel tubing forming hydraulic cylinders for a plurality of pistons connected in series by rigid rods. The rod of the forwardmost piston extends past the end of the steel tubing, through an opening in a compressible member and is connected to a rigid member of the same outside diameter as the steel tubing. The compressible member is positioned between the forward end of the steel tubing and the rigid member and is radially expanded as it is compressed by rearward movement of the pistons and the rigid member in response to hydraulic pressure delivered by the pump and multiplied by the number of pistons employed.
An elongated rod is attached to and extends forwardly from the rigid member slidingly through a central opening in a cam support member, to a fixed stop member at its forward end. An eccentric cam element encircles and is rotatably slidable axially through the opening in the cam support member, rotation of the rod is transmitted to the support member. A conventional, metal detecting probe is carried rearwardly of the hydraulic cylinders and connected by electrical leads extending through the hose to an external control box.
In operation, the elongated rod and steel tubing forming the hydraulic cylinders are advanced into a heat exchanger tube which extends through openings in one or more metal support sheets. The cam support member is placed at its rearward most position upon the elongated rod; that is, the front end of the support member is spaced as far as possible from the stop member at the forward end of the rod. As the operator advances the apparatus into the tube, indicating means on the control box provide a visual read-out showing that the probe is at a position where the tube passes through an opening in a support sheet.
With the apparatus in this axial position, the operator rotates the flexible hose, thereby rotating the steel tubing forming the hydraulic cylinders and the elongated rod attached thereto, as well as the cam support member. The outer surface of the cam fits rather closely within and frictionally engages the inside surface of the heat exchanger tube. Thus, the support member rotates within the cam and, due to the eccentric relation of the cam surface to the rotational axis of the support member, is frictionally wedged in its axial position in the tube.
The operator then pulls the apparatus rearwardly in the tube, with the cam and support member remaining stationary as the elongated rod slides through the support member until the latter is contacted by the stop member. Relative dimensions are such that, in this position, the compressible member is positioned within the tube adjacent the opening in the tube support sheet. The pump is then activated to cause the hydraulic cylinders to exert a force squeezing the compressible member between the end of the forward most cylinder and the rigid member on the end of the forwardmost piston rod. The compressible member is thereby expanded with a force sufficient to expand the tube into tight frictional engagement with the portion of the support sheet surrounding the opening through which the tube passes. The operation is repeated for each tube at each tube support sheet.
The foregoing features of construction and operation of the apparatus of the invention will be fore readily understood and fully appreciated from the following detailed disclosure, taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a somewhat diagrammatic illustration of the apparatus of the invention;
FIG. 2 is an end elevational view, in section on the line 2--2 of FIG. 1, showing a portion of the apparatus in an operative position within a heat exchanger tube;
FIG. 3 is a front elevational view, also in section, of other portions of the apparatus, shown in a first position; and
FIG. 4 is a fragment of FIG. 3, showing certain moveable portions in a second position.
DETAILED DESCRIPTION
Referring now to the drawings, in FIG. 1 is shown conventional hydraulic pump 10, connected through relief valve 12 and coupling 14, to flexible hose 16 with gauge 18 providing in the usual manner a visual indication of the fluid pressure delivered by pump 10. Hose 16 is connected at its other end 20 to section 22, constituting the proximal end of that portion of the apparatus which is moved axially into and out of heat exchanger tubes. A portion of one such tube is shown in phantom lines, surrounding the apparatus positioned therein and denoted by reference numeral 24.
In the conventional manner of fabrication of certain types of heat exchange apparatus, or of replacing tubes thereof, a plurality of tubes designed to carry a heat exchange fluid are supported in spaced, parallel relation by metal sheets having openings through which the tubes pass. The support sheets are essentially planar and perpendicular to the parallel axes of the tubes, the latter being locally expanded into tight engagement with the portion of the support sheet surrounding the opening. In FIG. 1, tube 24 extends through opening 26 in support sheet 28, the tube having not yet been expanded into engagement with the sheet.
Section 22 of the hydraulic conduit comprises or incorporates an electronic probe of commercially available form which generates a signal commensurate with the probe's proximity to magnetically permeable metals. The probe is effective when used with the usual copper, or other nonferrous tubes to generate an electrical signal when positioned within a tube adjacent a support sheet. Control box 30, carrying the probe power supply, circuitry and visual readout, is connected by electrical cable 32 to the proximal end of hose 16 and by leads extending through the hose to the probe at section 22. Thus, a visual indication is provided at control box 30 telling the operator when the probe is positioned adjacent a support sheet. Conventional apparatus of this type is capable of locating the probe relative to the support sheet with accuracy to within 0.020" in a direction axially of tube 24.
Cylindrical spacer 34, of teflon or other low-friction material, has a diameter substantially equal to the inside diameter of tube 24 and is positioned forwardly of the probe to support this portion of the apparatus relative to the tube. Spacer 34 ensures that the probe is positioned to one side of the tube, thus providing a consistent output signal regardless of the probe's orientation. Section 36 of the apparatus, extending forwardly from spacer 34, is made up of a plurality of series-connected hydraulic cylinders which will be more fully described later herein. The piston rod of the forwardmost of these cylinders extends through central openings in a plurality of so-called expansion tips which collectively form what is termed compressible member 38 and is attached at its distal end to rigid member 40. Elongated rod 42 is attached to and extends forwardly from rigid member 40, through an opening in cam support member 44, and is attached to stop member 46 at or near the distal end of rod 42.
As will be noted from FIG. 2, rod 42 is square in cross section, as is opening 48 in support member 44. The opening is slightly larger than the cross section of rod 42, allowing the rod to slide freely through support member 44 in an axial direction while being capable of transmitting rotational movement thereto. Cam member 50 has a cylindrical outer surface of substantially the same diameter as the inside diameter of tube 24, the cam member being of a material which exhibits some degree of frictional resistance opposing movement with respect to the tube wall.
Cam member 50 has a circular opening with a central axis laterally offset a small distance from the axis of its outer surface, giving the cam member some degree of eccentricity. The diameter of the opening, i.e., the inside diameter of the cam member, is substantially equal to that of a reduced diameter portion 52 of cylindrical cam support member 44 which is loosely encircled by cam 50. Preferably, cam 50 is of a somewhat flexible material and is split to permit mounting upon support member 44.
In operation, the probe is activated by means of a switch on control box 30. The distal end of the apparatus is inserted into the tube to be expanded and the operator manually advances the apparatus into the tube. When the indicating means on control box 30 shows that the probe is positioned adjacent tube support sheet 28, advancement of the apparatus is stopped and the operator manually rotates the apparatus, grasping the portion thereof or hose 16 outside tube 24. Since all portions of the apparatus except cam support member 44 and cam 50 are rigidly connected, rod 42 is rotated and, due to the square cross sections of the rod and opening 48, the rotation is transmitted to support member 44.
Cam 50 does not rotate, or at least does not rotate to the extent of support member 44, due to the frictional drag of the outer surface of cam 50 on the inner surface of tube 24. Due to the offset of the coaxial axes of rod 42, support member 44 and the opening in cam 50 from the coaxial axes of the outer surface of cam 50 and tube 24, i.e., due to eccentricity of the cam, the aforesaid rotation serves to wedge support member 44 against cam 50. Thus, support member 44 is frictionally restrained from axial movement with respect to tube 24. The amount of rotation required to effect the described frictional restraint of support member 44 is normally not more than about 1/2 turn.
It should be noted that as the apparatus is advanced into tube 24, the rearward or proximal end of support member 44 is engaged against the forward, distal side of rigid member 40 or another portion affixed thereto. This relationship is maintained as the apparatus is advanced due to the frictional drag of cam 50 on the inner surface of tube 24. The axial distance from the probe to compressible member 38 is the same as the distance from the forward, distal end of support member 44 to the rearward, proximal surface of stop member 46. In order to provide precise control of the latter distance, it is preferred that the axial position of stop member 46 on rod 42 be adjustable, e.g., by set screws or other such means.
With support member 44 at a releasably fixed axial position in tube 24, the operator pulls the apparatus-rearwardly, i.e., in a direction withdrawing it from the tube, with rod 42 sliding axially through opening 48 in the stationary support member 44. Such movement is continued until stop member 46 contacts the forward end of support member 44, which thus serves as an abutment surface within tube 24. As a consequence of the aforesaid axial distances, compressible member 38 is now n the position occupied by the probe prior to rearward movement of the apparatus. Thus, forcible expansion of compressible member 38 will produce localized expansion of tube 24 into tight frictional engagement with the portion of tube support sheet 28 surrounding opening 26.
Referring now to FIG. 3, an operative form of apparatus for converting the hydraulic fluid pressure delivered by pump 10 to the force required for expanding tube 24 is illustrated. A plurality of individual cylinders 54 are formed from steel tubing of appropriate inside and outside diameter and length. Cylinders 54 are internally threaded from each end for a portion of their length and the internal surface between the threaded portions is lapped to provide hydraulically sealed contact with rings 56 on moveable pistons 58.
Each of cylinders 54 is firmly connected to axially adjacent cylinders by threaded engagement of opposite, externally threaded ends of connecting members 60 with the internal threads in abutting ends of the cylinders. Connecting rods 64 are each threaded from both ends for a portion of their length and the outer surface between the threaded portions is polished. Each of connecting rods 64 has a through, axial bore 66 and a radial bore 68 communicating at one side of the rod with the axial bore. Each of pistons 58 has an internally threaded, through axial bore 70 and, as previously indicated, carries a pair of piston rings 56 for hydraulically sealing, slidable engagement with the inside walls of cylinders 54.
Connecting rods 64 are threadedly engaged with the internal threads of successive pistons 58, between which they pass through rings 72 carried in internal, annular recesses in connecting members 60. The forwardmost of the connecting rods, indicated by reference numeral 64', extends through central openings in the expansion tips forming compressible member 38 and is affixed at its forward end to rigid member 40.
Compressible member 38, of rubber or rubberlike material of appropriate hardness and other characteristics, is positioned between the forward, distal end of forwardmost cylinder 54' and rigid member 40. Prior to actuation of pump 10, i.e., without application of hydraulic pressure, the elements are positioned as shown in FIG. 3, with each of radial openings 68 positioned between one of pistons 58 and connecting members 60. Hydraulic fluid passes through axial and radial openings 66 and 68, respectively, in each of connecting rods 64 into the spaces between each pair of adjacent pistons 58 and connecting members 60. Since the connecting members are stationary, fluid pressure acts upon the forward sides of pistons 58, urging them in a rearward direction, i.e., toward the right seen in FIG. 3.
The hydraulic pressure delivered by pump 10 is applied simultaneously to all of pistons 58 and, due to the rigid, series connections of the pistons, the rearward force applied by forwardmost connecting rod 64' to rigid member 40 is the hydraulic pressure delivered by pump 10 multiplied by the total of the areas of pistons 58 to which such pressure is applied. This force is sufficient to axially compress or squeeze compressible member 38 between the forward end of the forwardmost of cylinders 54 and the rear side of rigid member 40 to extent causing radial expansion of tube 24 into tight engagement with the surrounding portion of support sheet 28, as shown in FIG. 4.
After localized expansion of tube 24 is completed, pump 10 is deactivated, removing hydraulic pressure, permitting compressible member 38 to expand to its normal configuration and the other elements returning to their positions of FIG. 3. Although cam support member 44 is frictionally wedged in position within tube 24, only a very small portion of the force delivered by the forwardmost piston rod is required to overcome this frictional engagement and move member 44 a short distance within the tube as the latter is expanded. After hydraulic pressure is released, the operator rotates hose 16 and the elements connected thereto by a small amount, sufficient to release the wedging of support member 44 against cam 50 and permit free axial movement of the apparatus within the tube. The apparatus is then advanced to bring the probe to a position adjacent the next support sheet or withdrawn from tube 24 and advanced into a different heat exchanger tube.
From the foregoing it may be seen that the objects and advantages of the invention are realized by the disclosed apparatus and the method of its employment. The relatively high force, concentrated in a small diameter necessary to effect the desired tube expansion is achieved through the use of a plurality of series-connected hydraulic cylinders and pistons, the number of which is selected to fit the needs of the intended application. Other variations in size, type, relative arrangement, etc., of the various disclosed elements of apparatus and methods of employment are possible within the scope of the invention, as defined by the following claims.
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Apparatus for localized radial expansion of a ductile metal tube into tight engagement with a tube support sheet, e.g., for deformable member which is axially compressed by hydraulic pressure to effect radial expansion of the deformable member and the tube. The hydraulic pressure is multiplied to provide a relatively high force in a small diameter by connecting a plurality of pistons in series by rigid connecting rods having axial and radial bores for flow of pressurized fluid. The apparatus carries a probe for locating the position of the tube support sheet and a support member carrying an eccentric cam. Rotation by an operator of the support member, by rotation of a rod passing therethrough, causes the cam to frictionally engage the tube wall and wedge the support member in position to provide an abutment surface for contact by a stop member on the rod, thereby positioning the deformable member at the desired axial location to effect radial expansion of the tube.
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation of U.S. patent application Ser. No. 14/190,264, filed on Feb. 26, 2014, which is a continuation of International Application No. PCT/CN2012/086670, filed on Dec. 14, 2012. The International Application claims priority to Chinese Patent Application No. 201110460211.X, filed on Dec. 31, 2011. The afore-mentioned patent applications are hereby incorporated by reference in their entireties.
TECHNICAL FIELD
The present invention relates to storage technologies, and in particular, to a method for a storage device processing data and a storage device.
BACKGROUND
Tiered storage refers to setting an existing storage device as disk tiers and setting different types of disks onto different tiers so that data can be migrated between different tiers according to data access requirements. For example, a solid state disk (SSD) set comprises a plurality of SSDs. Each of the SSDs is a high-tier disk characterized by a high access speed, and a hard disk drive (HDD) set comprises a plurality of HDDs. Each of the HDDS is a low-tier disk characterized by a low access speed. In the practice of tiered storage, infrequently accessed data is stored into a disk tier characterized by a low access speed such as a HDD set, and frequently accessed data is stored into a disk tier characterized by a high access speed such as a SSD set, and therefore, in accessing frequently used data, the data access speed and the storage device access efficiency are enhanced.
A disk generally stores data in the form of data blocks. Multiple storage units of the same size are set in the disk, and each storage unit is configured to store one data block. When data is migrated between different tiers, the data block as a whole is migrated. Even if only a part of data (called “hot data”) in the data block has an access frequency rising to a set threshold and needs to be migrated to a high-tier disk set, the data block as a whole is actually migrated. That is, the “cold data” (data whose access frequency is still low) in the data block moves together with “hot data”. The data block is generally called a “migration unit”, indicating that the data block is a unit of migration. In addition, the storage device further includes metadata storage resources used to store metadata, where the metadata is information corresponding to a migration unit, for example, a storage address of the migration unit, and each migration unit has corresponding metadata, and therefore, the consumption amount of the metadata storage resources is proportional to the number of migration units.
Currently, the size of the “migration unit” is generally fixed, such as 256 megabytes (MB). However, the setting of the migration units of a fixed size brings the following problems: if the set size of the migration unit is large, few metadata storage resources are consumed, but the phenomenon that cold data moves together with the hot data will lead to waste of the storage space of the expensive high-tier storage medium and low usage of space; and, if the set size of the migration unit is small, the waste of the high-tier storage medium is reduced naturally, but more metadata storage resources are consumed.
SUMMARY
One aspect of the present invention provides a method for a storage device processing data to improve usage of storage media and control reasonableness of metadata storage resource consumption.
Another aspect of the present invention provides a data storage device to improve usage of storage media and control reasonableness of metadata storage resource consumption.
The method for a storage device processing data provided in the present invention includes obtaining an access frequency of a block of the second storage set; determining that the access frequency of the block achieves a first access threshold value; based upon the determination, moving the block to the first storage disk set; obtaining an access frequency of each of sub-blocks into which the block is divided; determining that an access frequency of at least one of the sub-blocks is less than a second access threshold value; and based upon the determination, moving the determined sub-block back to the second storage disk set.
The storage device provided in the present invention comprises a processor, a communication interface, and a communication bus, wherein the processor communicates with the communication interface through the communication bus and the processor is configured to obtain an access frequency of a block of a second storage set, wherein the second storage set includes a plurality of storage disks with low performance; determine that the access frequency of the block achieves a first access threshold value; based upon the determination, move the block to a first storage disk set, wherein the first storage disk set includes a plurality of storage disks with high performance; obtain an access frequency of each of sub-blocks into which the block is divided; determine that an access frequency of at least one of the sub-blocks is less than a second access threshold value; and based upon the determination, move the determined sub-block back to the second storage disk set.
Technical effects of the method for a storage device processing data in the present invention are, when a migration unit is migrated to a high-tier disk set, a data access frequency of each migration subunit is detected respectively so that hot data can be identified more easily; and when cold data is identified, the migration subunit corresponding to the cold data can be migrated to a low-tier disk set, thereby reducing waste of the storage space of the high-tier disk, so that the high-tier disk stores only hot data, and improving the usage of storage media; in addition, when all migration subunits are migrated to the low-tier disk set, integration can be performed by combining all the migration subunits into a migration unit, thereby reducing the number of migration units in time and controlling metadata storage resource consumption effectively.
Technical effects of the storage device in the present invention are, when a migration unit is migrated to a high-tier disk set, a data access frequency of each migration subunit is detected respectively so that hot data can be identified more easily; and when cold data is identified, the migration subunit corresponding to the cold data can be migrated to a low-tier disk set, thereby reducing waste of the storage space of the high-tier disk, so that the high-tier disk stores only hot data, and improving the usage of storage media; in addition, when all migration subunits are migrated to the low-tier disk set, integration can be performed by combining all the migration subunits into a migration unit, thereby reducing the number of migration units in time and controlling metadata storage resource consumption effectively.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a schematic flowchart of an embodiment of a method for a storage device processing data according to the present invention;
FIG. 2 is a schematic principle diagram of another embodiment of a method for a storage device processing data according to the present invention; and
FIG. 3 is a schematic structural diagram of an embodiment of an apparatus for tiered storage processing of data according to the present invention.
DESCRIPTION OF EMBODIMENTS
Embodiment 1
FIG. 1 is a schematic flowchart of an embodiment of a method for a storage device processing data according to the present invention. As shown in FIG. 1 , the method in this embodiment may include the following steps.
101 . When a migration unit of a low-tier disk set is migrated to a high-tier disk, the storage device splits the migration unit into multiple migration subunits, and detects a data access frequency of each migration subunit respectively.
The low-tier disk set comprises a plurality of low-tier disks. Each of the low-tier disks is characterized by a low access speed, such as an HDD; and the high-tier disk set comprises a plurality of high-tier disks. Each of the high-tier disks is characterized by a high access speed, such as an SSD, that is, the high-tier disk provides a better performance and a higher speed than the low-tier disk.
The migration unit and the migration subunit refer to data blocks stored in the disk and migrated as an integral unit. The migration unit of a low-tier disk generally refers to a migration unit of a large size such as 256 MB; and, when the migration unit becomes hot and is migrated to a high-tier disk, the migration unit is split into multiple migration subunits of a smaller size such as 32 MB. In this embodiment, the number of migration subunits obtained after the splitting is not limited. For example, a migration unit may be split into four migration subunits or eight migration subunits. In addition, the size of the migration subunits obtained after the splitting is user-definable.
Optionally, after the migration unit is split into multiple migration subunits, storage address information of the multiple migration subunits is recorded respectively to ensure correct data access subsequently. For example, assuming that the migration unit is split into four migration subunits, the specific physical storage addresses of the four migration subunits in the high-tier disk need to be recorded respectively.
102 . The storage device migrates the migration subunit to the low-tier disk when detecting that the data access frequency of the migration subunit is lower than a set threshold.
If the data access frequency of the migration subunit is lower than a set threshold, it indicates that the access frequency of the migration subunit is low. That means the migration subunit is infrequently accessed. It is also called “cold data.” Therefore, the migration subunit is migrated to the low-tier disk in this embodiment.
In this embodiment, in order to improve usage of storage space of the high-tier disks, a large-sized migration unit is split into small-sized migration subunits. Therefore, hot data in the migration unit can be identified more precisely, and the cold data can be migrated back to the low-tier disk set. Therefore, it prevents the cold data from wastefully occupying the expensive storage space in the high-tier disk set, and the disk usage is improved.
103 . The storage device combines the multiple migration subunits into the migration unit when detecting that the multiple migration subunits are all migrated to the low-tier disk.
When detecting that all migration subunits obtained after the split migration unit migrated to the high-tier disk in 101 are migrated back to the low-tier disk, the migration subunits are re-integrated into a large-sized migration unit in this embodiment, because that means all of the migration subunits become cold again.
The low-tier disk integrates migration subunits into a migration unit in time, thereby reducing the number of migration units and controlling the metadata storage resource consumption effectively.
In the method for a storage device processing data in this embodiment, when a migration unit is migrated to a high-tier disk set, a data access frequency of each migration subunit is detected respectively so that hot data can be identified more easily. When cold data is identified, the migration subunit corresponding to the cold data can be migrated to a low-tier disk, thereby reducing waste of the storage space of the high-tier disks. Accordingly, the high-tier disks store only hot data, and the usage of storage media is improved. In addition, when all migration subunits are migrated to the low-tier disk set, integration can be performed by combining all the migration subunits into a migration unit, thereby reducing the number of migration units in time and controlling metadata storage resource consumption effectively.
Embodiment 2
FIG. 2 is a schematic principle diagram of another embodiment of a method for a storage device processing data according to the present invention. In this embodiment, assuming that the low-tier disk is an HDD and the high-tier disk is an SSD, the method for a storage device processing data in the present invention is described in detail. The HDD and the SSD may be disks that are set on two different tiers in a storage device, where the storage device further includes a relevant controlling unit that is configured to control migration of data between the two tiers of disks, for example, a hotness identifying unit configured to detect the data access frequency, or a migration controlling unit configured to control data migration, or the like.
As shown in FIG. 2 , the storage space in the HDDs and the SSDs is divided into multiple storage units at a large size granularity first. For example, the storage unit may be configured to store a migration unit 11 of a 256 MB size. The migration unit 11 is a data block that is stored and migrated as a whole.
After the storage space is divided into multiple storage units, a mapping relationship is created between each storage unit in the HDDs and the SSDs and a logical block address (LBA) of the storage device respectively. For example, the storage device includes HDDs and SSDs that are tiered, and logical block address information is maintained in the storage device. Data is stored in a physical storage address in the HDDs and the SSDs. However, when a read or write operation is performed for the data, the operation information carries LBA information. Then, according to the mapping relationship between the LBA in the storage device and the physical storage address, the physical storage address of the data is searched out, and the data is found. Therefore, a mapping relationship between each storage unit and the LBA is created in the storage device. Further, each storage unit has a corresponding storage identifier, that is, a physical storage address, where the migration unit also has a data block identifier. The mapping relationship records the data block identifier, the LBA of the data block, and mapping relationship information between the physical storage addresses, so as to identify the storage location of the data block in the disk and ensure the correctness of data reading and writing.
The hotness identifying unit in the storage device may detect the data access frequency of the migration unit 11 in each storage unit, for example, detect Input/Output (IO) statistic information of the migration unit. In addition, an access frequency threshold may be set. If the data access frequency of the migration unit is greater than the threshold, it indicates that the migration unit is frequently accessed and has become “hot data”; if the data access frequency of the migration unit is less than the threshold, it indicates that the migration unit is infrequently accessed and is “cold data”.
After the migration unit becomes hot, the migration controlling unit in the storage device may control the migration unit to migrate to the SSDs; and, after the migration to the SSDs, the hotness identifying unit in the storage device in this embodiment may detect the data access frequency of each migration subunit in the migration unit respectively.
The storage device may preset a size such as 32 MB for the migration subunit. Assuming that the size of the migration unit is 256 MB, the migration unit actually includes 8 migration subunits. After the migration unit is migrated to the SSDs, the hotness identifying unit may detect the data access frequency of the 8 migration subunits respectively rather than detect the data access frequency of the entire migration unit as a whole just like the beginning, and therefore, hot data can be identified more easily. For example, only 64 MB data in the 256 MB migration unit becomes hot and the remaining is still cold data, but because the migration unit as a whole is a unit in the statistics of IO information, the migration unit is still regarded as hot and migrated to an upper tier; and then the IO information of each migration subunit in the migration unit is detected respectively to identify precisely 2 migration subunits that become hot and the remaining 6 migration subunits that are still cold data. In this way, the identification of hot data is more precise.
Optionally, the IO statistics for each migration subunit may be performed before the splitting of the migration unit, that is, when the migration unit is still a whole without being split, and the hot data of each internal migration subunit is identified beforehand; if all the migration subunits are detected as hot data, the migration unit may remain as a whole without being split, and is stored in the large-sized storage unit of the SSDs; and, if some are detected as cold data, the migration unit is controlled to split according to the preset size of migration subunits.
Alternatively, optionally, if no idle large storage unit corresponding to the size of the migration unit exists in the SSDs, the migration unit may be split into multiple migration subunits first, and the migration subunits are migrated to the small storage unit of a corresponding size in the SSDs, and then the IO statistics are detected respectively. That is, before the migration unit is split, the storage unit configured to store the migration unit is a storage space of a large size granularity; and, after the migration unit is split, the storage space is also split into multiple storage spaces of a small size granularity to store the multiple migration subunits after the splitting. Therefore, the order between the hotness identification and the migration unit splitting is not limited strictly, and any order is appropriate as long as the IO statistic information of each migration subunit of the migration unit in the SSDs can be detected and the hot data can be identified.
Assuming that it is already identified that the migration unit includes migration subunits corresponding to cold data, the migration unit 11 is split into multiple migration subunits 12 such as 32 MB; and the migration controlling unit controls the migration subunits corresponding to the cold data to migrate back to the HDDs so that the cold data no longer occupies the expensive storage space in the SSDs, which improves usage of the SSDs' storage space. In addition, the hot data identification is performed in the SSDs all along, that is, the IO statistic information of each migration subunit is detected respectively, and, once it is found that hot data changes to cold data, the cold data is migrated back to the HDDs.
In this embodiment, after the migration unit 11 is split into multiple migration subunits 12 , to ensure data access correctness, the mapping relationship information needs to be updated. That is, in this case, the physical storage address of the migration unit 11 on the disk has changed, and the migration unit has been split into multiple migration subunits 12 , where the multiple migration subunits 12 may be stored in various addresses in a distributed manner. Therefore, the mapping relationship between the migration unit and the multiple migration subunits needs to be recorded, and the current physical storage addresses of the multiple migration subunits need to be recorded. For example, the mapping relationship between the data block identifier of the migration unit 11 and the LBA of the data block remains unchanged. In searching for the migration unit 11 according to the LBA, the multiple migration subunits 12 obtained after the split migration unit 11 can be found. Some of the migration subunits 12 are stored in the physical storage addresses a 1 , a 2 , . . . , in the SSDs, and other migration subunits 12 are stored in the physical storage addresses b 1 , b 2 , . . . , in the HDDs. In specific implementation, addressing may be performed by means of arrays, and an array member points to a migration subunit in the HDDs and the SSDs respectively.
Optionally, when the migration unit in the HDDs is migrated to the SSDs, the idle large-sized storage unit corresponding to the size of the migration unit in the SSDs is preferred. When a cold migration subunit in the SSDs is migrated to the HDDs, the idle small-sized storage unit corresponding to the size of the migration unit in the HDDs is preferred. When the cold migration subunit in the HDDs becomes hot again, the migration subunit is preferably migrated to the idle small-sized storage unit corresponding to the size of the migration subunit in the SSDs.
In this embodiment, the migration subunit migrated back to the HDDs undergoes IO statistics using the migration subunit as a unit. The storage device maintains a count value for each migration unit which is used to obtain the number (which may be referred to as a first number) of migration subunits in the SSDs, or obtain the number (which may be referred to as a second number) of migration subunits in the HDDs. If the first number is zero or the second number is equal to the number of migration subunits after the splitting, it is determined that all the multiple migration subunits are migrated to the HDDs. For example, if the migration unit is split into four migration subunits, the number of migration subunits obtained after the split migration unit and currently located in the SSDs may be recorded. If the number is 4 at the beginning, when the data becomes cold, one of the migration subunits is migrated back to the HDDs, the number decreases by 1. When the number becomes zero, it indicates that all the four migration subunits obtained after the split migration unit have become cold and migrated down to the HDDs.
When all the migration subunits are migrated down to the HDDs, an integration process is triggered so that the multiple migration subunits are re-integrated into a migration unit. It is assumed that, when the migration unit is split into migration subunits and migrated down to the HDDs, the initial large-sized storage unit of the HDDs is split into small-sized storage subunits for storing the migration subunits. For example, a storage unit is split into four storage subunits, and one migration subunit migrated down is stored in one of the storage subunits; and the subsequent three migration subunits migrated down may be stored in other storage subunits obtained after the split storage unit of the HDDs, each migration subunit occupies a part of metadata storage resources, and the IO statistics are performed using the migration subunit as a unit. When it is detected that all the four migration subunits are migrated down, the migration subunits will be re-integrated into a migration unit. That is, the four storage subunits are also re-integrated into a large-sized storage unit. In this case, due to decrease of the number of migration units, the consumption of metadata storage resources decreases, and the consumption of the metadata storage resources is controlled, and the IO statistics begin to be performed using the integrated migration unit as a unit. In addition, the storage address information of each migration subunit, which is recorded when the migration unit is in a split state, changes back to the storage address information of the migration unit, and the resources occupied by the maintained count value of the migration subunits obtained after the split migration unit are released and the count value is not maintained any longer.
In the method for a storage device processing data in this embodiment, when a migration unit is migrated to a high-tier disk set, a data access frequency of each migration subunit is detected respectively so that hot data can be identified more easily. When cold data is identified, the migration subunit corresponding to the cold data can be migrated to a low-tier disk, thereby reducing waste of the storage space of the high-tier disks. Accordingly, the high-tier disks store only hot data, and the usage of storage media is improved. In addition, when all migration subunits are migrated to the low-tier disk set, integration can be performed by combining all the migration subunits into a migration unit, thereby reducing the number of migration units in time and controlling metadata storage resource consumption effectively.
Embodiment 3
FIG. 3 is a schematic structural diagram of an embodiment of an apparatus for tiered storage processing of data according to the present invention. The apparatus can perform the method for a storage device processing data according to any embodiment of the present invention. This embodiment only gives a brief description about the structure of the apparatus. For detailed working principles of the apparatus, reference may be made to the description in the method embodiment.
As shown in FIG. 3 , the apparatus may include a resource adjusting unit 31 , a hotness identifying unit 32 , a migration controlling unit 33 , and an address recording unit 34 .
The resource adjusting unit 31 is configured to split a migration unit into multiple migration subunits, and combine the multiple migration subunits into the migration unit.
The hotness identifying unit 32 is configured to detect a data access frequency of each migration subunit respectively.
The migration controlling unit 33 is configured to migrate a migration unit in low-tier disks to high-tier disks; migrate the migration subunit to the low-tier disks when the hotness identifying unit detects that the data access frequency of the migration subunit is lower than a set threshold; and, detect whether the multiple migration subunits are all migrated to the low-tier disks.
The apparatus may further include an address recording unit 34 , which is configured to, after the migration unit is split into multiple migration subunits and before the multiple migration subunits are combined into the migration unit, record storage address information of the multiple migration subunits respectively, for example, record a mapping relationship between the migration unit and the multiple migration subunits; and record current physical storage addresses of the multiple migration subunits.
The migration controlling unit 33 is further configured to detect whether a storage unit corresponding to a size of the migration unit exists in the high-tier disks and, if a result of the detection is yes, migrate the migration unit to the storage unit; and the resource adjusting unit 31 is further configured to split the migration unit into multiple migration subunits if a migration subunit exists whose data access frequency is lower than a set threshold.
Further, the migration controlling unit 33 is configured to detect whether a storage unit corresponding to a size of the migration unit exists in the high-tier disks, and the resource adjusting unit 31 is configured to split the migration unit into multiple migration subunits if a result of the detection of the migration controlling unit is no.
Further, the migration controlling unit 33 includes a counting subunit 331 and a state detecting subunit 332 . The counting subunit 331 is configured to obtain a first number of the migration subunits in the high-tier disks, or obtain a second number of the migration subunits in the low-tier disks, and the state detecting subunit 332 is configured to determine that the multiple migration subunits are all migrated to the low-tier disks if the first number is zero or the second number is equal to the number of migration subunits obtained after the split migration unit.
With the apparatus for tiered storage processing of data in this embodiment, when a migration unit is migrated to high-tier disks, a data access frequency of each migration subunit is detected respectively so that hot data can be identified more easily, and when cold data is identified, the migration subunit corresponding to the cold data can be migrated to low-tier disks, thereby reducing waste of the storage space of the high-tier disks, so that the high-tier disks store only hot data, and improving the usage of storage media; in addition, when all migration subunits are migrated to the low-tier disks, integration can be performed by combining all the migration subunits into a migration unit, thereby reducing the number of migration units in time and controlling metadata storage resource consumption effectively.
Embodiment 4
The present invention provides a storage device, where the device includes low-tier disks and high-tier disks, and further includes an apparatus for tiered storage processing of data provided in any embodiment of the present invention, where the apparatus for tiered storage processing of data is connected to the low-tier disks and the high-tier disks respectively.
With the apparatus for tiered storage processing of data in the storage device, when a migration unit is migrated to high-tier disks, a data access frequency of each migration subunit is detected respectively, and when cold data is identified, the migration subunit corresponding to the cold data can be migrated to low-tier disks, thereby reducing waste of the storage space of the high-tier disks, so that the high-tier disks stores only hot data, and improving the usage of storage media; in addition, when all migration subunits are migrated to the low-tier disks, integration can be performed by combining all the migration subunits into a migration unit, thereby reducing the number of migration units in time and controlling metadata storage resource consumption effectively.
Persons of ordinary skill in the art may understand that, all or a part of the steps of the foregoing method embodiments may be implemented by a program instructing relevant hardware. The foregoing programs may be stored in a computer readable storage medium. When the program runs, the steps of the forgoing method embodiments are performed. The foregoing storage medium includes various mediums capable of storing program codes, such as a read only memory (ROM), a random access memory (RAM), a magnetic disk, or an optical disk.
Finally, it should be noted that the foregoing embodiments are merely intended for describing the technical solutions of the present invention, rather than limiting the present invention. Although the present invention is described in detail with reference to the foregoing embodiments, persons of ordinary skill in the art should understand that they may still make modifications to the technical solutions described in the foregoing embodiments, or make equivalent replacements to some or all the technical features thereof, as long as the modifications and replacements do not cause the essence of corresponding technical solutions to depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
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A method for managing data in a hierarchical storage device which includes primary storage disks and secondary storage disks. The primary storage disks have higher performance than the secondary storage disks. The storage device detects an access frequency of a data block stored in the secondary storage disks. Based on the access frequency of a data block, the storage device determines that the access frequency of the data block reaches an access threshold value. And then, based upon the determination, the storage device moves the data block to the primary storage disks. After that, the storage device divides the data block into a plurality of sub-blocks and detects an access frequency of each of the sub-blocks. Finally, the storage device moves one or more of the sub-blocks of which access frequencies are less than the access threshold value back to the secondary storage disks.
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CROSS REFERENCE TO PRIOR APPLICATIONS
This application is a 371 of PCT/EP2010/059459, filed Jul. 2, 2010.
This application is a U.S. National Phase application under 35 U.S.C. §371 of International Application No. PCT/EP2010/059459, filed on Jul. 2, 2010 and which claims benefit to German Patent Application No. 10 2009 033 158.1, filed on Jul. 13, 2009. The International Application was published in German on Jan. 20, 2011 as WO 2011/006777 A1 under PCT Article 21(2).
FIELD
The present invention provides a concentrate for producing a cooling and release agent for reusable casting dies, or a cooling and lubricating agent, for example, for machining with an active substance dissolved in water. The present invention also provides cooling and release agent for reusable casting dies and a cooling and lubricating agent, for example, for machining purposes.
BACKGROUND
While the use as a cooling and release agent in reusable casting dies is of particular interest in the context of steel casting dies for die casting purposes or forming tools for hot forming purposes, the use as a cooling and lubricating agent is found in the field of machining, for example, in drilling, milling, grinding, cutting, lathing, sawing or thread cutting of cast iron alloys, steel alloys, nickel base alloys, cobalt base alloys, non-ferrous metals and plastic materials, as well as in the field of cold forming.
Such cooling and release agents or cooling and lubricating agents are known from prior art. They serve to cool used casting dies and machined parts. When used as a release agent, a layer is applied at the same time to improve the demolding of the cast product from the die, whereas when used as a lubricating agent, an additional lubrication of the parts and tools is affected that increases their durability.
For example, when casting work pieces on the basis of aluminum, magnesium and zinc or alloys of these metals in a die cast or a squeeze cast method, water-emulsified polymers, such as waxes, silicones or modified polysiloxanes, are used as cooling/release agent. Prior to their use at the die casting tool, the emulsions delivered as a concentrate are diluted to the working concentration required for obtaining a sufficient effect. Typically, dilutions are used that contain 0.12% by weight to 2.5% by weight of dry substance in the cooling and release agent.
The casting die is supplied, for example, under pressure with an alloy melt of 560-740° C. After the solidification of the melt, the cast part is removed from the casting die that is about 450-580° C. hot, and the die is cooled down to about 120-350° C. by spraying a cooling and release agent thereon, it is cleaned if necessary and is again supplied with a melt. The water contained in the cooling and release agent serves to cool the die as well as to free the die from possible residues which, after demolding, remain on the die due to the cooling and release agent used. The release agent is effective in that, depending on the temperature conditions, the polymers themselves form a release layer by being pyrolytically decomposed as the die is filled with the metal to be cast and by subsequent densification.
The use of the known cooling and release agents yields satisfactory results; however, it has some drawbacks.
For example, the cooling and release agent often settles on portions of the die, such as at the die frame and die parting lines, that are not contacted with the metal to be cast and on contours that are less subjected to high temperatures, since the temperature at these portions is insufficient to pyrolytically decompose the cooling/release agent. Instead, the cooling and release agent dries because of the heat still present and can no longer be completely emulsified in water. With repeated spraying operations, this leads to the build-up of a layer resulting in problems of dimensional accuracy of the cast piece and in sealing problems at the die so that casting quality decreases. Insufficient pyrolytic decomposition of the release agent may also cause accretions in the cavity area, which also compromise the casting quality. Residues may be deposited in the surface of the cast piece, for example, in turbulence zones.
The stability and the disposal of these emulsions are also problematic. Longer times of rest after emulsification often result in an inhomogeneous distribution of the active substance in the emulsion, whereby a wetting of surfaces with these cooling and release agents is non-uniform.
The washed-off residues of the known cooling and release agents must also be supplied to a separate waste water treatment since they are not easily biodegradable. Their gaseous residues, which are formed as a result of pyrolytic decomposition during their application, are also hazardous to humans and the environment.
Residues containing wax or silicon often remain on the surface of the cast piece. These are hard to remove so that an increased cleaning effort is required. The removal of these water repellent residues therefore requires the use of strong acids, bases or other solvents.
With known cooling/lubricating agents for machining purposes, the pressure during the chip removal sometimes leads to the forming of built-up edges at the cutting tool and oftentimes causes a bluish discoloration in the machined region of the work piece. The built-up edges reduce the service life of the cutting tool. When the built-up edges become welded on, they can also deteriorate the work piece quality if, for example, parts of the built-up edge come loose and are pressed into the work piece surface. Cooling/lubricating agents moreover sometimes contain mordants as additives that can damage alloy elements in the work piece alloy. The chips produced in machining often have to be freed from cooling/lubricating agents clinging thereto, using multi-stage complex processes, such as filtering and washing, so that the cooling/lubricating agent can be reused in the cycle. The chips themselves often must be disposed of as hazardous waste, since a recycling thereof is not feasible because of the cooling/lubricating agent clinging thereto.
SUMMARY
An aspect of the present invention is to provide a concentrate of a cooling and release agent, as well as a cooling and lubricating agent, or a cooling and release agent and a cooling and lubricating agent, respectively, which avoid the above-mentioned problems. It is intended, for example, that the provided concentrate be biodegradable, the cycle times in a casting process and in a forming process are reduced and, when used as a cooling and release agent, that residues on the die and on the cast piece are avoided as far as possible. When used as a cooling and lubricating agent, the force required for a forming by machining should be reduced and the cooling performance enhanced. The tendency to form built-up edges should be clearly reduced and the alloy elements of the work piece alloy should not be damaged by possible mordant additives. It is desirable to reduce the percentage of dry substance in the cooling and release agent or the cooling and lubricating agent. It is also desirable to allow the chips produced in machining to be reused simply by melting them, and to pyrolytically decompose the cooling/lubricating agent during the melting of the chips, while giving off an oxygen reducing atmosphere.
In an embodiment, the present invention provides a concentrate for producing a cooling and release agent for reusable casting dies, such as a steel casting die, or a cooling and lubricating agent for machining with an active substance dissolved in water. The concentrate comprises 10 to 50 wt.-% of a protein based on the weight of the concentrate.
DETAILED DESCRIPTION
It has surprisingly been found that a cooling and release agent with proteins, for example, proteins such as gelatin, hydrolysate, casein or the proteins of soy and milk, provides a uniform wetting of the casting die surface when sprayed thereon and, during the spraying, forms a uniform and well adhering release film. With a view to the repeated spraying operations after each respective casting operation, a balanced state is achieved between the newly applied agent and the removal of excess release agent. Compared to known release agents, the decomposition behavior is better, whereby the forming of deposits due to dried excess release agent is significantly reduced both in the cavity area and in the area of the die frame. In the casting process and under the temperature conditions prevailing, the release film is decomposed by pyrolytic decomposition in such a manner that a carbon-rich layer is formed during the casting process, which layer is responsible for the releasing effect. At the same time, a diffusion of aluminum towards the casting die is prevented. The pyrolytic decomposition moreover leads to the creation of a reducing atmosphere, which has positive effects on the quality of the cast pieces because of the reduced formation of oxide. Residues of these release agents can be washed off before and after casting more easily than is possible with conventional wax- or siloxane-based release agents. A continuous build-up of release agent residues in the cooler die areas is thereby prevented in a series of casting operations, which results in an improved dimensional accuracy during casting and provides a reliable opening and closing function of the tool. After having been washed with water and dried thereafter, the cast piece thus manufactured can be painted without any further surface treatment so that time-consuming cleaning steps are avoided. The cycle time is reduced by a significantly improved cooling effect. The agent is suited for the usual application methods such as pressure atomizing or pneumatic atomizing using internal or external mixing nozzles. Due to the increased water content in the cooling and release agent, the surfaces of the tools are wetted better and are cooled more efficiently. In contrast with the known silicon oil- or wax-based agents, the so-called Leidenfrost phenomenon is reduced by the hydrophilic properties of the protein, which translates as a clearly discernible reduction in the vapor volume rising up during the cooling proves.
It has been found for such a cooling and lubricating agent that it is a shearing and pressure resistant system and that uniform and long chips are formed during machining. The tendency to ship breaking has been reduced significantly. Slight canting of the tool at small burrs of the part worked on is largely avoided so that the required cutting force and the heat generation are reduced and the risk of built-up edges forming is lessened. At the same time, the cooling effect is improved and the required effort is reduced by the existing lubrication of the surfaces. The chips produced during the machining are free of disturbing deposits and can be supplied to raw material recycling by simply melting them. The cooling/lubricating agent also acts as a corrosion protection.
In an embodiment of the present invention, the protein used can, for example, have a molecular weight between 1000 and 600000 Dalton and a nitrogen content of 16-19%, the hydroxyproline content being, for example, 10 to 15%. With these proteins, good results have been achieved with respect to surface quality.
In an embodiment of the present invention, the concentrate can, for example, contain a hydrocolloid at a proportion of 0.1 to 10% by weight. The hydrocolloid can, for example, be selected from one of the substances agar agar, locust bean gum flour, pectin, gum arabic or starch or corn flour. These serve as release additives for an additional improvement of the lubricating effect, the releasing effect, the film forming and the wetting behavior. Likewise, polymers, such as polyethylene glycol or polyvinyl alcohol, can be mixed thereto for this purpose at a proportion of 0.1 to 10% by weight.
In an embodiment of the present invention, the concentrate can, for example, contain a preserving agent at a proportion of 0.1 to 5% by weight. This preserving agent can, for example, be potassium sorbate or ascorbic acid for the enhancement of the durability of the concentrate.
In an embodiment of the present invention, the concentrate can, for example, contain an ionic surfactant at a proportion of 0.1 to 5% by weight. Examples include sodium dodecyl sulfate or sodium lauryl sulfate. As an alternative or in addition, an organic or inorganic acid can be added to the concentrate at a proportion of 0.1 to 5% by weight. These are, for example, selected from the group including citric acid, lactic acid, formic acid, oxalic acid, phosphoric acid or para-toluene sulphonic acid. Theses additives enhance the wetting and washing behavior of the cooling and release agent or the lubricating agent and improve the cleaning properties of the agent.
In an embodiment of the present invention, the concentrate can, for example, contain anionic surfactants at a proportion of 0.1 to 5%. Examples of surfactants include anionic surfactants based on long-chain fatty acids, such as palm oil, linseed oil or bone fats, or also based on terpenes, such as limonene. These substances enhance the lubricating and releasing properties of the agent applied.
In an embodiment of the present invention, the concentrate can, for example, contain a softener at a proportion of 1 to 10% by weight, which softener can be a polyol, such as glycerin or sorbitol. These have a positive influence on the film formation and the washability of the cooling and release agent or the lubricating agent.
In an embodiment of the present invention, a fluxant at a proportion of 0.1 to 1% by weight can, for example, be mixed to the concentrate. An additional corrosion protection can thereby be achieved for the application. This fluxant can, for example, be a sodium borate or a lithium fluoride, lithium chloride or lithium carbonate.
In an embodiment of the present invention, the concentrate can, for example, contain a catalyst at a proportion of 100 to 500 ppm which can, for example, be an iron oxide or a ferric pyrophosphate or vanadium or its oxides or chrome or its oxides. This additive accelerates pyrolisis at lower temperatures.
In an embodiment of the present invention, a bactericide and a fungicide can, for example, be added at a proportion of, for example, 0.01 ppm to 1 ppm. Examples include silver salts, zinc salts or copper salts, for example, silver acetate, silver nitrate or silver chloride as bactericide.
In an embodiment of the present invention, solid lubricants, such as molybdenum disulphide or boron nitride, can, for example, be added at a proportion of 0.1 to 1% by weight.
A concentrate or a cooling and release agent or a lubricating agent is thus produced which, compared to the known agents, shows an enhanced cooling behavior while at the same time providing an improved releasing effect with a reproducible heat transfer behavior or an improved lubricating effect, respectively. Errors during the casting operation can thus be avoided and the dimensional accuracy of the cast parts can be maintained even for numerous cycles. When used as a lubricating agent in machining processes, the necessary cutting force is reduced.
The advantageous effects of this cooling and release agent were proven in tests which will hereinafter be described.
EXAMPLES
Example 1
In a first test, the concentrations for a cooling and release agent according to the present invention were determined at which a pyrolytic decomposition shows no adhesion of residues on the simulated cast part. The concentrate used was a solution with 50% by weight of gelatin having a molecular weight of 1000 to 7000 Dalton and with 16 to 19% by weight of nitrogen as a protein, 1% by weight of citric acid, 0.1 ppm of silver acetate as a bactericide, 0.1% by weight of potassium sorbate as a preserving agent and water for the rest.
A steel plate made from the material 1.2343 was first coated with a passivation layer having as its major components manganese phosphate and molybdenum sulphide. At a temperature of about 250° C., this steel plate was subsequently immersed for 10 seconds into a solution with a dry substance content of 0.25% which corresponds to a dilution ratio of the concentrate of about 1:200. A piece of aluminum made from the material AlSi 9 Cu 3 was placed on the steel plate. After the film had dried, adhesion of the aluminum piece was found. The steel plate provided with the aluminum piece was thereafter placed for 1 minute into an oven heated to 750° C. in order to simulate the temperature stress during casting. After the sheet was removed, the aluminum piece could be moved very easily. Ash residues were found. It was shown that no tendency of release agent residues to adhere to the simulated cast part exists when a biodegradable release agent is used.
Example 2
In further tests on die casting tools, the concentration was further adapted to real conditions. For dry substance contents of 0.125%, which corresponds to a dilution ratio of the concentrate of about 1:400, a satisfactory demolding was obtained and no significant build-up of the cooling and release agent in the edge zones of the die or in the cavities could be found. Depending on the casting temperature, a complete pyrolytic decomposition was not always achieved one hundred percent.
Example 3
With dry substance contents of 0.0625%, which corresponds to a dilution ratio of the concentrate of 1:800, optimal cooling and release effects were obtained on the die casting tools. Compared to the use of the cooling and release agents known from prior art, an at least equal cooling effect was achieved while the proportions of the dry substance were reduced by up to 50%. The release effect observed was excellent. The optical quality of the surface was clearly enhanced when compared to the known cooling and release agents. The main reason for this property is the uniform wetting of the surface, since the cooling and release agent is a perfect solution and not merely an emulsion.
Example 4
In subsequent tests, the cooling/release agent with a dry substance content of 0.0625% was compared to a cooling and release agent according to the prior art. The reference cooling and release agent was an emulsion of polysiloxanes and synthetic polymers with a dry substance content of 0.15%.
Both products were used on a steel plate of the material 1.2343. The spray pressure during the wetting of the plate by means of a pressure atomizing spray head was about 1.5 bar.
The washing behavior of both cooling and release agents was first examined. Both products were sprayed as described above onto a steel plate heated to 200° C. A volume of 50 ml was applied, respectively. After cooling the respective films formed were wiped off with a cloth moistened with the corresponding cooling/release agent. The degree of cleaning was determined by dripping water thereon and by evaluating the wetting behavior. Here, the two plates treated with the cooling and release agents were compared.
The plate treated with the cooling and release agent showed a good wetting quality almost without flaws compared to the only mediocre wetting of the plate treated with the known cooling and release agent.
At the same time, a washing behavior was achieved that was enhanced to about the same extent, which thus is directly related to the wetting behavior.
When the steel surface was treated with the known agent, the surface was wetted only moderately, which is an indication of the presence of coatings with low surface tension, such as waxes or silicones, which have not been washed off. When the cooling and release agent of the invention was used, a good wetting of the surface was achieved which is due to the complete water solubility of the product of the invention.
The decomposition behavior of both cooling and release agents was checked on a steel plate made from the material 1.2343, wherein the steel plates were first heated for 5 minutes in an oven at a temperature of 500° C., and one of the products was applied to a respective plate in the manner described above. This process was repeated three times. 150 ml of the cooling and release agents were used per process.
For a determination of the remaining residues, the steel plate was wiped off with a white cloth after the final cooling. Compared to the plate sprayed with the known agent, the plate sprayed with the agent of the invention showed a clear reduction of the residues determined.
The tests performed proved that the use of the cooling and release agent of the present invention achieves both an improved wetting and an improved washability. As a result, better casting qualities can be obtained due to an enhanced decomposition behavior and to the resulting prevention of undesired layer build-up.
Example 5
In another test, the concentrate was mixed with water at a proportion of 1:50 for use as a cooling and lubricating agent. The cooling and lubricating agent was used to cool an HSS drill bit of 7.5 mm in diameter. The drill bit was used to drill a hole into hot-working steel 1.2343 at 850 rpm. Compared to the conventional lubricating agents, it was found that the effort, i.e. the current consumption of the drill drive, decreased. Due to the improved cooling effect, a strong smoke production that had previously occurred, could be completely avoided as well as a bluish discoloring of the steel part and of the chips produced. The chips formed were long and uniform. No built-up edges could be found.
Depending on the temperature, the cooling and lubricating agent described is thus a shear resistant system. For increased drill powers, the cooling performance could be improved with respect to other agents, since the pressure resistant cooling and lubricating agent has an improved releasing effect.
The present invention is not restricted to the particular embodiments described herein, reference should also be made to the claims. Various modifications can also be made by an expert in the field without leaving the scope of protection of the claims.
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A concentrate for producing a cooling and release agent for reusable casting dies such as a steel casting die, or a cooling and lubricating agent for machining with an active substance dissolved in water. The concentrate comprises 10 to 50 wt.-% of a protein based on the weight of the concentrate.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of Invention
[0002] This invention pertains to a method and an apparatus that forms ablated features in substrates such as by laser ablation of polymer substrates for inkjet print head applications.
[0003] 2. Description of the Related Art
[0004] The laser ablation of features on polymer materials using a mask and imaging lens system is well known. In this process, features on the mask are illuminated with laser light. The laser light that passes through the transparent features of the mask is then imaged onto the substrate such as a polymeric film where the ablation process occurs.
[0005] [0005]FIG. 1 illustrates a basic layout of a conventional excimer laser machining system 10 . Typically, the system 10 is controlled by a computer 12 with an interface to the operator of the system. The computer 12 controls the firing of the pulsed laser system 24 and a low speed, low resolution servo system 14 . The function of the servo system 14 is to position the mask 16 and substrate chuck 18 for proper registration of the laser milled pattern with respect to other features on the substrate 19 prior to ablation of substrate 19 . For this purpose, a vision system (not shown) is often interfaced to the computer system. The servo system 14 or computer 12 may control an attenuator module 20 , to vary the amount of UV radiation entering the system. Alternatively, the laser pulse energy may be varied by adjusting the laser high voltage or a control set point for energy, maintained by the laser's internal pulse energy control loop.
[0006] The UV beam path is indicated in this figure with arrows 22 (not intended to be actual ray paths, which are not typically parallel) which show the flow of UV energy within the system. The UV power originates at the pulsed excimer laser 24 . The laser 24 typically fires at 100-300 Hz for economical machining with pulses that have a duration of about 20-40 nanoseconds each. The typical industrial excimer laser is 100-150 watts of time average power, but peak powers may reach megawatts due to the short duration of the pulse. These high peak powers are important in machining many materials.
[0007] From the output end of the laser, the UV energy typically traverses attenuator 20 ; however, this is an optional component not present in all laser machining systems. The attenuator 20 performs either or both of two possible functions. In the first function, the attenuator 20 compensates for the degradation of the optical train. The attenuator 20 thus used, allows the laser to run in a narrow band of pulse energies (and hence a restricted range of high voltage levels), allowing for more stable operation over the long term. With new optics in the system, the attenuator 20 is set to dissipate some of the power of the laser. As the optics degrade and begin to absorb energy themselves, the attenuator 20 is adjusted to provide additional light energy. For this function, a simple manual attenuator plate or plates can be used. The attenuator plates are typically quartz or fused silica plates with special dielectric coatings on them to redirect some of the laser energy toward an absorbing beam dump within the attenuator housing.
[0008] The other possible function of the attenuator 20 is for short term control of laser power. In this case, the attenuator 20 is motorized with either stepper motors or servo system, and the attenuator is adjusted to provide the correct fluence (energy per unit area) at the substrate for proper process control.
[0009] From the attenuator 20 , the UV energy propagates to a beam expansion telescope 26 (optional). The beam expansion telescope 26 serves the function of adjusting the cross sectional area of the beam to properly fill the entrance to the beam homogenizer 28 . This has an important effect on the overall system resolution by creating the correct numerical aperture of illumination upon exit from the homogenizer. Typical excimer laser beams are not symmetric in horizontal vs. vertical directions. Typically, the excimer beam is described as “top hat-gaussian,” meaning that between the laser discharge direction (usually vertical), the beam profile is “top hat” (initially relatively flat and dropping off sharply at the edges). In the transverse direction, the beam has a typical intensity profile that looks qualitatively gaussian, like a normal probability curve.
[0010] The expansion telescope 26 allows some level of relative adjustment in the distribution of power in these directions, which reduces (but does not completely eliminate) distortion of the pattern being imaged onto the substrate 19 due to the resolution differences in these two axes.
[0011] Between the expansion telescope 26 and homogenizer 28 is shown a flat beam folding mirror 30 . Most systems, due to space limitations, will contain a few such mirrors 30 to fold the system into the available space. Generally, the mirrors may be placed between components, but in some areas, the energy density or fluence can be quite high. Therefore, mirror locations are carefully chosen to avoid such areas of high energy density. In general, the designer of such a system will try to limit the number of folding mirrors 30 in order to minimize optics replacement cost and alignment difficulty.
[0012] The UV light next enters the beam homogenizer 28 . The purpose of the homogenizer 28 is to create a uniformly intense illumination field at the mask plane. It also determines the numerical aperture of the illumination field (the sine of the half angle of the cone of light impinging on the mask), which as stated above, has an impact on overall system resolution. Since certain parts of the excimer beam are hotter than others, uniform illumination requires that the beam be parsed into smaller segments which are stretched and overlaid at the mask plane. Several methods for this are known in the art, with some methods being based on traditional refractive optics, e.g., as disclosed in U.S. Pat. Nos. 4,733,944 and 5,414,559, both of which are incorporated herein by reference. The method may also be based on diffractive or holographic optics, as in U.S. Pat. No. 5,610,733, both of which patents are incorporated by reference, or on continuous relief microlens arrays (described in “Diffractive microlenses replicated in fused silica for excimer laser-beam homogenizing”, Nikoladjeff, et. al, Applied Optics, Vol 36, No. 32, pp. 8481-8489, 1997).
[0013] From the beam homogenizer 28 the light propagates to a field lens 32 , which serves to collect the light from the homogenizer 28 and properly couple it into the imaging lens 34 . The field lenses 32 may be simple spherical lenses, cylindrical lenses, anamorphic or a combination thereof, depending on the application. Careful design and placement of field lenses 32 are important in achieving telecentric imaging on the substrate side of the lens 32 .
[0014] The mask 16 is typically placed in close proximity to the field lens 32 . The mask 16 carries a pattern that is to be replicated on the substrate 19 . The pattern is typically larger (2 to 5 times) than the size of the pattern desired on the substrate 19 . The imaging lens 34 is designed to de-magnify the mask 16 in the course of imaging it onto the substrate 19 . This has the desired property of keeping the UV energy density low at the mask plane and high at the substrate plane. High de-magnification usually imposes a limit on the field size available at the substrate plane.
[0015] The mask 16 may be formed from chromium or aluminum coated on a quartz or fused silica substrate with the pattern being etched into the metallic layer by photolithography or other known means. Alternatively, the reflecting and/or absorbing layer on the fused silica mask substrate 16 may comprise a sequence of dielectrics layers, such as those disclosed in U.S. Pat. Nos. 4,923,772 and 5,298,351, both of which are incorporated herein by reference.
[0016] The purpose of the imaging lens 34 is to de-magnify and relay the mask pattern onto the substrate 19 . If the pattern is reduced by a factor of M in each dimension, then the energy density is raised by M 2 multiplied by the transmission factor of the imaging lens 34 (typically 80% or so). In its simplest form, the imaging lens 34 is a single element lens. Typically, the imaging lens 34 is a complex multi-element lens designed to reduce various aberration and distortions in the image. The imaging lens 34 is preferably designed with the fewest elements necessary to accomplish the desired image quality in order to increase the optical throughput and to decrease the cost of the imaging lens 34 . Typically, the imaging lens 34 is one of the most expensive parts of the beam train.
[0017] As noted above, the imaging lens 34 creates a de-magnified image of the pattern of the mask 16 on the substrate 19 . Each time the laser fires, an intense patterned area is illuminated on the substrate 19 . As a result, etching of the substrate material results at the illuminated areas. Many substrate materials may be so imaged, especially polymeric materials. Polyimides available under various trade names such as Kapton™ and Upilex™ are the most common for microelectronic applications and inkjet applications.
[0018] The system 10 described in FIG. 1 is a “typical” system. For non-demanding applications, the system can be further simplified and still produce ablated parts, but with some sacrifice in feature tolerances, repeatability, or both. It is not unusual for systems to make some departure from this typical architecture, driven by the particular needs of the application.
[0019] There are many applications for laser ablation of polymeric materials. Some applications or portions thereof are not demanding in terms of tolerances, e.g., electrical vias, and the emphasis is on small size, high density features and low cost. Other applications require very demanding tolerances and repeatability. Examples of the latter applications are fluid flow applications such as inkjet print head nozzle manufacture and manufacture of drug dispensing nozzles. In these demanding applications, the requirements for exact size, shape, and repeatability of manufacture are much more stringent than the simpler conductive path features provided by a microelectronic via. The detailed architecture of the system is critical to obtaining tight tolerances and product repeatability. In addition, process parameters and the optical components all play important roles in obtaining the tightest possible tolerances, down to the sub-micron level.
[0020] As mentioned above, the invention relates to the formation of nozzles for inkjet print head applications and other fluid flow applications. During the firing of a thermal inkjet print head, a small volume of ink is vaporized. The vaporized ink causes a droplet of ink to shoot through an orifice (i.e., the nozzle) which is directed at the print media. The quality of thermal inkjet printing is dependent upon the characteristics of the orifice. Critical attributes of the orifice include the shape and surface condition of the bore.
[0021] One important aspect for fluid flow applications is the slope of the via walls. Vias made in the conventional manner have very steep wall slopes, with the slope dependent upon the incident radiation fluence (energy per unit area), and to a lesser extent, the number of laser pulses used to create the feature. Using conventional methods, very little can effectively be done to control or shape the via wall slope. One method is controlling the energy distribution of the radiation hitting the substrate. In a projection imaging system, this can be accomplished by placing ring shaped apertures on the masks such as described in U.S. Pat. No. 5,378,137. However, the mask features used to create the hole profiles must be very small (sub-resolution for the imaging system), or they may be imaged into the ablated hole or via. The disadvantage of this method is that the small mask features can easily be damaged and also add difficulty and expense to the mask making process.
[0022] In a typical inkjet print head made currently in the industry, small ablated orifices or vias are made in the polymer film substrate at a concentration of about 300 or more ablated orifices per inch. The size of the orifices may vary depending upon the particular application, but generally have an exit diameter less than about 35 microns. The entrance orifice diameter is typically less than 100 microns, with an average entrance diameter of about 50 microns to about 60 microns being more typical. The objective of the invention described herein is to provide additional control over the shape of the orifice in addition to the traditional process controls of mask features, fluence, laser shots, and so forth in controlling the detailed shape of the orifice.
[0023] In addition to the ring-mask method described above, another method of shaping the orifice wall angle is to displace the beam using an optical method. This can be accomplished, for example, by spinning a flat or wedge-shaped optical element between the mask and projection lens. Such a method is described in U.S. Pat. No. 4,940,881. Placing a spinning element between the mask and the projection lens has the effect of moving the image in a circular orbit. This motion changes the ablated feature profile by moving the incident light at the surface of the substrate. The disadvantage of the method of U.S. Pat. No. 4,940,881 is that the radius of the orbit cannot be easily changed during the machining cycle. If the optical elements are wedge-shaped, as described in U.S. Pat. No. 4,118,109, the method also has the disadvantage that the angle of the beam is altered during the orbit, which limits the smallest possible beam displacement and complicates process control. An additional limitation is that hole wall slope profiles are limited to concave geometry (see FIG. 6), when used in conjunction with a conventional laser mask (e.g. one with simple apertures in the reflecting or absorbing coating for each ablated feature), except at very low fluences.
[0024] An apparatus and method for controlling an ablated orifice shape using two rotating optical elements is described in co-pending U.S. patent application Ser. No. 09/197,127,entitled “LASER ABLATED FEATURE FORMATION DEVICE” filed on like date herewith, and incorporated by reference herein. The invention of copending U.S. patent application Ser. No. 09/127,127 has the advantage over U.S. Pat. No. 4,940,881 in that the profile of the hole wall can be altered by controlling the relative rotational velocities and phase angle between the two rotating optical elements. In this manner, any desired hole profile (i.e., concave, convex or straight) can be obtained without requiring a complicated mask structure.
[0025] Yet another method for moving the image on the substrate utilizes a movable mirror between the mask and the projection lens. The mirror can be tilted in such a manner that the image moves in a prescribed orbit, thereby moving the incident light at the substrate. A major disadvantage of this method is the limited sensitivity of control, since a small tilt of the mirror can be a rather large displacement of the apparent mask position. Further, such mirrors must be of a minimum thickness to insure sufficient mechanical stability and flatness of the reflecting surface. This in turn, makes for a rather large inertia, and limits the bandwidth or highest speed of the device. When the system bandwidth is limited, it places limits on the scan patterns that can be effectively used to shape the holes.
[0026] An alternative to optically or mechanically moving the mask image is to actually move the substrate. This has a disadvantage, however, that the motion of the substrate must be very precise. The requirement for high precision is due to the fact that the projection lens of the ablation system shrinks the projection mask image down to the substrate to concentrate the laser energy. Consequently, the tolerances on the motion profile also shrink proportionately. This approach usually has the same inertial problems as the tilting mirror approach discussed above, except that the problem is further aggravated by additional mass of the substrate holders and motion stages used in typical automated systems.
[0027] As can be seen, there are multiple ways by which the profile of a laser ablated feature may be controlled to some degree. However, it can also be seen that the currently available methods have limitations which restrict their usefulness. What is needed, therefore, and what is provided by the present invention, is an apparatus and method for controlling the profile of laser ablated features which is very flexible in allowing the creation of multiple types of orifice profiles, while at the same time providing accurate and repeatable results. In the present invention, the mask itself is continually moved according to a prescribed set of coordinates for each and every laser pulse. The detailed trajectory of this motion has a strong influence on the final ablated hole shape. The ability to change the hole geometry without any additional optical element is a powerful yet flexible process parameter. Moving the mask itself within a certain prescribed trajectory can change the geometry of the ablated feature in a desirable fashion, including convex, concave and straight-walled features.
SUMMARY OF THE INVENTION
[0028] The present invention provides a method of improving the geometry of laser ablated features. In the method of the invention, the mask is moved at high speed and high resolution during the ablation process in a plane perpendicular to the optical axis of the system, thereby causing the image to move in a like way and change the geometry of the ablated feature on the substrate. The mask can be moved in any desired pattern, such as a circular pattern, spiral pattern, or more general scan pattern to create the desired shape of the wall slope of the ablated feature. The ablated feature can be made oval by moving the mask in an elliptical orbit during the machining cycle.
[0029] In one broad respect, this invention provides a process useful for ablating features in a substrate, comprising: irradiating the substrate with radiation that has passed through a mask to form an ablated feature in the substrate, wherein the mask is orbited perpendicular to the optical axis during formation of the feature thereby forming a selected wall shape.
[0030] The process of this invention may be employed to ablate a variety of materials. For instance, the process may be used to etch or expose patterns in organic or inorganic photoresist during semiconductor fabrication using a variety of radiation sources such as X-rays and ultraviolet light including deep ultraviolet light. The process of this invention can be employed to ablate features in substrates that either completely traverse the substrate, i.e., holes or vias, or features with a given depth which is less than the total depth of the substrate, often described as a “blind” feature.
[0031] In yet another broad respect, this invention provides an apparatus useful for making holes in a substrate, comprising: a radiation source; a mask positioned between the radiation source and a substrate to be irradiated with radiation from the radiation source, wherein the mask is capable of moving perpendicular to the system optical axis when the substrate is being irradiated such that a different feature shape is formed than would have been formed if the mask were not orbited.
[0032] As used herein, the term “laser feature” includes holes, bores, vias, nozzles, orifices and the like, and may be fully ablated through the substrate or only partially through the substrate (“blind” features).
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] [0033]FIG. 1 illustrates a typical laser machining system employing a mask for irradiating a substrate.
[0034] [0034]FIG. 2 illustrates a laser machining system using a compound mask motion device during the ablation process.
[0035] [0035]FIG. 3 illustrates one possible system hardware architecture for controlling motion of the mask.
[0036] [0036]FIG. 4 illustrates trigger feedback to the servo control system.
[0037] [0037]FIG. 5 illustrates the time difference between a laser pulse and when the mask is in position.
[0038] [0038]FIG. 6 illustrates different bore profiles which may be created with the present invention.
[0039] [0039]FIG. 7 illustrates a laser shot pattern which may be created using the present invention for creating a nozzle having an axis which is non-orthogonal to the substrate surface.
[0040] [0040]FIG. 8 illustrates nozzle arrays in which the longitudinal axes of arrays of nozzles are inclined in predetermined directions, for the purpose of directing fluids exiting the nozzle arrays and controlling the relative direction of the exiting fluids.
DETAILED DESCRIPTION OF THE INVENTION
[0041] As discussed above, FIG. 1 illustrates the basic layout of a conventional excimer laser machining system 10 , including servo system 14 control of mask 16 , substrate chuck 18 and attenuator 20 . As noted above, in the typical system 10 of FIG. 1 servo system 14 is a low speed, low resolution system which functions to properly register mask 16 and substrate 19 prior to ablation of substrate 19 . Servo system 14 does not move during the ablation process and only provides gross movement of mask 16 and substrate 19 (movements on the order of several millimeters) to align mask 16 and substrate 19 .
[0042] In contrast to the machining system of FIG. 1, the mask 16 used in the practice of the present invention is capable of moving at high speeds and high resolution in a plane perpendicular to the optic axis of the system during irradiation of the substrate. FIG. 2 schematically represents this concept of a laser system including a high speed active mask scanning subsystem 48 integrated with laser control which is “piggybacked” onto the low speed servo system 14 . The light from the beam conditioning optics (which may consist of the components described in FIG. 1 of attenuator, beam expansion, homogenization, and field lenses, as appropriate for the application) sufficiently overfills the features on the mask 16 so that mask motions on the order of approximately +/−100 microns or less (caused by high speed scanning subsystem 48 ) can be achieved within the homogeneous region of the illumination field. The light passing through the mask is then imaged by imaging lens 24 , onto the fixed substrate 19 . It will be appreciated by those skilled in the art that the schematic illustration of FIG. 2 is non-limiting, and other control systems may also be suitable.
[0043] A mask used in the practice of laser ablation is well known. One representative example of a type of mask which can be used in the practice of this invention is described in U.S. Pat. No. 5,378,137, incorporated herein by reference. Typically, a mask comprises a clear, fused quartz substrate having a thin opaque or reflective layer. The opaque material may be a layer of chrome that has been sputtered onto the substrate, an ultraviolet enhanced coating, or any other suitable reflective or otherwise opaque coating, such as multi-layer dielectric coatings. The reflective or opaque coating on the mask is patterned such that it comprises a series of apertures or other structures through which the light passes, ultimately illuminating the substrate. Each aperture of the mask corresponds to a resulting feature in the substrate.
[0044] The type of laser employed will be a function of the substrate to be ablated. For instance, the polymer film used to make inkjet print heads and electronic packaging applications is typically a polyimide, such as Kapton™ and Upilex™, having a thickness of approximately 2 mils. For these applications an excimer laser is commonly employed, such as KrF excimer (248 nanometers), or XeCl excimer (308 nanometers). Alternatively, for features larger than about 35 microns, a TEA CO 2 laser may be used to ablate polyimides. In general, the excimer laser commonly produces a pulse width of about 30 nanoseconds, which is very fast on the time scale of laser repetition rate and mask motion. The power of the laser may be selected depending on number and type of optical components in the system to deliver a fluence at the substrate in the range from about 400 to about 1000 or more millijoule/cm 2 .
[0045] In the practice of this invention, when the substrate is a polymer such as a polyimide film, the polymer may be provided from a reel and positioned on the substrate stage in the laser system. The laser is then repeatedly pulsed for a predetermined amount of time to ablate the polymer to form a pattern of ablated features. A variety of factors affect the geometry of the feature, including use of structures in the mask, laser power, fluence, number of laser pulses, and so forth, in addition to the mask trajectory of this invention. The finished polymer is then removed, with fresh polymer being positioned on the stage.
[0046] The mask 16 movement can be achieved in variety of ways. As described above, the mask 16 can be mechanically moved through the use of an electromechanical servo motor or its equivalent which is connected, directly or indirectly, to the mask. Such a servo system is adequate for low speed, low resolution motion, such as initial alignment of the mask 16 and substrate 19 . However, such a servo system is not useful for providing the high speed, high resolution movements necessary in the laser machining operation due to the typically high system inertia and other factors, which are discussed in greater detail below.
[0047] For high speed, high resolution movement, the mask 16 is connected to a piezoelectric material or apparatus, such as a linear or rotary piezoelectric micropositioner, which is “piggybacked” onto low speed servo system 14 . Representative, non-limiting examples of such micropositioners are available from Physik Instrumente. Such micropositioners may have typical resolutions of 0.1 μm, having varying travel ranges, rotary angle speeds, and velocity ranges. The aforementioned mechanisms can be readily connected to the mask using conventional techniques.
[0048] The mask scanning system hardware architecture is illustrated in FIG. 3. This is one representative and non-limiting architecture. Referring to FIG. 3, the laser machining system is usually controlled by a computer or microcontroller 12 , which includes an ablation system controller 50 and a laser controller 52 which controls the laser light source 24 . Both ablation system controller 50 and laser controller 52 communicate with a real time servo controller 54 that manages the x,y motion of the laser mask 16 , through x-axis and y-axis micropositioning motion stages 62 , 64 , respectively. A position feedback system 60 sends real time position information back to the real time servo controller 54 (referred to as “closed loop” control). Possible feedback devices include, but are not limited to LVDT sensors, strain gauge sensors, capacitive sensors, and inductive sensors.
[0049] When the laser source is a high pressure gas discharge laser, such as an excimer or TEA CO 2 laser, then the output characteristics of the laser are highly dependent upon a steady firing or repetition rate. A typical repetition rate may be 200-300 Hz. If the laser is fired at an unsteady repetition rate, the refreshing of the gas between the electrodes may be incomplete or vary from laser shot to laser shot, charging of the high voltage capacitors may vary, and perhaps other undesirable effects. Further, the laser manufacturer typically optimizes the laser for the case of steady firing of the laser. Thus, the need for optimal laser performance in turn places rigorous timing demands on the motion control of the mask micropositioning motion stages 62 , 64 . This is further compounded by the high firing rates of the laser, thereby demanding a relatively high bandwidth for the overall positioning system (consisting of mask 16 , the mask holder, micropositioners 62 , 64 , servo amplifiers 58 , position feedback device 60 , and real time servo controller 54 . The high firing rates of the laser preclude the use of a conventional servo system, as such a system is too slow to provide accurate movement at rates of 200-300 Hz.
[0050] The overall system bandwidth is a function of several system components. In particular, the mechanical system may have some inherent time constant. For example, the position feedback device 60 can affect system bandwidth, and the actuator providing the motion can have some delay. For example, moving a piezo device is similar to charging a capacitor through a resistor, and therefore has some inherent RC time constant. In addition, the power supply for the servo or piezo system usually has some impedance or time constant. Therefore, the overall system performance must be considered as a whole when designing the system, and the components must be selected and tested to provide a motion bandwidth appropriate for the desired repetition rate of the radiation source.
[0051] For a given hardware set, several different control schemes are possible. The least complex way to implement this invention would be to trigger the laser after the motion control system is in position (within some prescribed following error). However, as discussed above, for best laser performance the laser must fire at a steady repetition rate, which would be difficult with this type of control scheme. In addition this type of control scheme would likely not achieve the highest material throughputs, which is an important economic consideration. Any practical control scheme must therefore accommodate the steady firing of the laser in the range of 200-300 Hz, and, at the same time, place the mask within some small tolerance of the desired position when the laser fires to achieve a repeatable laser machining process.
[0052] [0052]FIG. 4 schematically illustrates the concepts associated with the timing of the laser firing and motion control systems. First, the real time servo controller 54 for the mask motion may or may not be connected to the laser trigger source 56 . Laser trigger source 56 determines the laser firing rate with its steady clock output by its connection to the laser controller, 52 . When real time controller 54 is not connected to trigger source 56 , the internal time base of the real time controller 54 generates the sequence of times at which the mask is to be in a desired position. In this case, an external signal (such as from the ablation system controller 50 ) is required to synchronize the start of the laser burst and mask motion. In a preferred embodiment, the real time servo controller 54 is connected to the trigger source 56 , allowing data capture of the actual mask position at time of laser firing (within hardware speed limitations). There are several possible choices of trigger sources, including the internal clock of the real time servo controller 54 , the internal clock of the laser controller 52 , or an external clock.
[0053] [0053]FIG. 5 shows a time sequence of a “burst” of several laser shots, represented by the regularly spaced solid bars. In general, due to propagation delays, servo following errors, system inertia, and other inherent system factors, the time when the mask is in the desired (x,y) position will vary somewhat from the regularly occurring laser pulses. In FIG. 5, the time at which the mask is in position (within a sufficiently small tolerance) is represented by the dashed bars. The time difference between these two is represented by τ. The error in the position of the mask is approximated by the product of τ and the instantaneous velocity of the mask.
[0054] The effect of the mask position error on the final ablated results is reduced by an amount proportional to the demagnification of the imaging lens, which is typically in the range of 2×-5×. For high precision applications, placement errors of the light pattern on the substrate of less than 0.2 microns are desired. Thus, for a 5×demagnification system, this translates to a mask position error of 1 micron or less. With trigger source verification, the actual position of the mask can be calculated within a time period determined by the system propagation delays, the speed of the position feedback device and the speed of data capture. Within these inherent limitations, the mask position can be quantified at the time of laser firing. A laser firing at 250 Hz corresponds to 4 ms between laser shots, while the error in capturing the mask position is typically less than 30 microseconds.
[0055] Different control schemes are possible for use in conjunction with the system architecture described above. However, in the preferred embodiment, a set of position, velocity, and time (“PVT”) vectors are pre-calculated. These vectors include the x,y positions of desired mask locations corresponding to the laser triggering. However, they also contain PVT information for a number of points between the actual laser trigger points. By precalculating these intermediate points in the motion profile, the system performance can be optimized by selecting a trajectory to minimize the resonant frequency of the overall system and its harmonics. The PVT vectors are loaded into the real time servo controller 54 in advance of laser processing. The servo controller 54 continuously adjusts the mask velocity to reach the specified positions at the specified times.
[0056] It will be recognized that such a control system may be operated in either a synchronous manner (where laser firing and high speed movement of the mask are controlled from the same clock source), or in an asynchronous manner (where laser firing and high speed movement of the mask are controlled from independent clock sources). Synchronous operation is preferred for greater accuracy. Also, control systems may use a “closed loop” control, where feedback is provided about the position of mask 16 during the ablation process, or an “open loop” control where no feedback about the position of mask 16 is provided during the ablation process. The preferred “PVT” control system described above uses closed loop control, although open loop systems could also be used.
[0057] The system software is parametric in nature and the preferred embodiment is a multi-threaded software architecture. PVT vectors for the motion trajectory and time interval are read from the ablation controller 50 . Intermediate trajectory points and velocities are calculated in such a way as to make the most efficient mask movement given the system bandwidth. Multiple threads are used to manage the flow of information to the real time servo controller 54 , which is synchronized with the ablation controller 50 . Position feedback system 60 provides data back to the ablation controller 50 .
[0058] [0058]FIG. 6 illustrates how the ablated feature in the substrate can have a straight, concave, or convex wall shape, as measured from the bore axis. The wall shape may be adjusted by selectively controlling the motion of the mask 16 as describe above, which allows material to be ablated at different rates from inside the hole and thereby create different wall shapes. The ability to modify the pattern of laser shots (and thereby shape the wall of the bore) by simply changing the motion of the mask 16 is a powerful and flexible process parameter which has been unavailable heretofore.
[0059] A particularly useful ability of the present invention allows the ablated features to have an axial orientation which is not perpendicular to the surface of the substrate. That is, the axis of the orifice may be tilted with respect to the substrate surface. Such a variable axial orientation of the orifice is achieved by creating a spiraling laser shot pattern (as depicted in FIG. 7), while allowing the center of each circular “orbit” to slowly drift in a prescribed direction during the ablation process. Such a laser shot pattern is not possible with, for example, a single rotating optical element as shown in U.S. Pat. No. 4,940,881 which can only move the light in a circular pattern.
[0060] The ability to create an ablated orifice with a non-orthogonal axis is a significant advance and advantage in fluid flow applications. For example, as shown in FIG. 8, a group of two or more nozzles may be positioned such that the axis of each nozzle is directed toward a common predetermined point. In FIG. 8, individual nozzles 82 are arranged in arrays 84 , 85 , 86 , 87 , with four nozzles 82 per array 84 , 85 , 86 , 87 . In each array 84 , 85 , 86 , 87 , the nozzles 82 are angled toward a common point 88 , 89 , 90 , 91 , respectively, in the center of each array 84 , 85 , 86 , 87 . Such an orientation of the nozzles 82 within each array 84 , 85 , 86 , 87 significantly improves, for example, the ability to control the direction in which a fluid drop is projected through each nozzle 82 . This control thereby allows or prevents, for example, the coalescence of drops after exiting the nozzles 82 . Alternatively, it can control the relative placement of drops of fluid on a target material, such as placement of ink from an inkjet print head on paper, thereby effecting the quality of print. It will be recognized by those skilled in the art that any number of nozzles and arrays may be ablated to achieve the necessary result for a particular application.
[0061] It can be seen from examining FIG. 8 that the axis of at least one nozzle 82 ′ in each of arrays 84 , 85 , 86 , 87 , is aligned with a first common axis 92 , while a second nozzle 82 ″ of each array 84 , 85 , 86 , 87 is aligned with a second common axis 94 . Similarly, each nozzle 82 of each array 84 , 85 , 86 , 87 is aligned with a predetermined common axis. When forming arrays 84 , 85 , 86 , 87 , the nozzles 82 ′ are ablated in one step, nozzles 82 ″ are ablated in a separate step, and so on. The different directional axes of the nozzles 82 are created by simply changing the ablation pattern by altering the motion of the mask in a predetermined manner.
[0062] As noted above, the nozzle arrangement illustrated in FIG. 8 is useful in applications where control of the individual drops exiting the nozzles is desired, for example, to allow or prevent the coalescence of drops after exiting the nozzles 82 . The tendency for individual drops to coalesce or not can be controlled by altering the orientation of the longitudinal axes of the nozzles in each array. Particular uses include print heads for ink jet printers (having nozzles with exit diameters in the range of 8 to 35 microns, and preferably between 10 and 25 microns) and aerosol nozzles plates for applications such as medicinal inhalers (having nozzles with exit diameters of less than about 5 microns diameter and preferably in the range of 0.5 to 3.0 microns).
[0063] The inventive mask orbiting apparatus described herein provides significant advantages over other methods of controlling the wall shape of an ablated feature. In particular the invention allows precise, repeatable placement of individual laser shots in any of a variety of manners. The individual laser shots may be placed in widely varying yet easily controllable patterns to achieve the desired wall shape and axial orientation of the ablated feature.
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This invention concerns a process useful for ablating features from a substrate, including the steps of illuminating the substrate with laser light that has passed through a mask to form an ablated feature in the substrate, wherein the mask is orbited perpendicular to the angle of the laser light during formation of the feature thereby forming a selected wall shape. This invention also concerns an apparatus useful for making holes in a substrate having a radiation source; a mask positioned between the radiation source and a substrate to be irradiated with radiation from the radiation source, wherein the mask is capable of following a trajectory perpendicular to the angle of the radiation.
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FIELD OF THE INVENTION
[0001] The present invention relates to the modification of fructan biosynthesis in plants and, more particularly, to methods of manipulating fructan biosynthesis in photosynthetic cells, and to related nucleic acids and constructs.
[0002] The present invention also relates to increasing plant biomass and, more particularly, to methods of enhancing biomass yield and/or yield stability, including shoot and/or root growth in a plant, and to related nucleic acids and constructs.
BACKGROUND OF THE INVENTION
[0003] Fructans are a type of water-soluble carbohydrate whose primary function is to provide a readily accessible energy reserve for plant growth. Fructans are associated with various advantageous characters in grasses, such as cold and drought tolerance, increased tiller survival, enhanced persistence, good regrowth after cutting or grazing, improved recovery from stress, early spring growth and increased nutritional quality.
[0004] Fructan synthesis and metabolism in grasses and cereals is complex. Fructans consist of linear or branched fructose chains attached to sucrose. The chain length of plant fructans ranges from three up to a few hundred fructose units. Different types of fructans can be distinguished based on the linkage types present. In perennial ryegrass three types of fructans have been identified: inulins, inulin neoseries and levan neoseries, with four fructosyltransferse (FT) enzymes involved in this fructan profile.
[0005] The enzyme 1-SST (sucrose: sucrose 1-fructosyltransferase) catalyses the first step in fructan biosynthesis while the remaining enzymes elongate the growing fructose chain (1-FFT: fructan: fructan 1-fructosyltransferase, 6G-FFT: 6-glucose fructosyltransferase, and 6-SFT: sucrose: fructose 6-fructosyltransferase). The enzymes 1-FEH or 6-FEH (fructoexohydrolase) reduce fructan chain length by releasing fructose molecules.
[0006] Bacteria use only one FT enzyme which contains both 1-SST and 1-FFT activities to synthesize high molecular weight fructan polymers. Most bacterial fructosyltransferases produce levan type fructan (levansucrases), which is characterized by β-2,6 linkages of fructose molecules, although inulosucrases that produce fructans of the inulin type (β-2,1 linkage) have been isolated from a few bacteria.
[0007] At least 3 bacterial levansucrases have been expressed in transgenic plants including, the SacB gene from Bacillus subtilis , the SacB gene from Bacillus amyloliquefaciens , and the FTF gene from Streptococcus mutans . Expression of these bacterial levansucrases in plants leads to the synthesis of very high molecular weight fructans of a DP of several thousands (for review see Cairns, 2003).
[0008] Fructans represent the major non-structural carbohydrate in 15% of plant species and play a key role in forage quality. Ruminant livestock grazing on high fructan diets show improved animal performance.
[0009] In grasses the level and composition of fructans has been increased in stems and leaf sheaths through the engineered expression of FT genes.
[0010] However, manipulating biochemical pathways by manipulating the activity of enzymes in the pathways may be difficult because of the ways in which the various enzymes and their substrates may interact.
[0011] Thus, it would be desirable to have improved methods of manipulating biochemical pathways, particularly in plants. For example, it would be desirable to have methods of manipulating fructan biosynthesis in plants, including forage grass species such as Lolium, Festuca , and Brachiaria ; sugarcane and other grasses; and sorghum and other cereals such as wheat and maize; thereby facilitating the production of, for example:
forage grasses with improved herbage quality and/or yield, leading to improved pasture production, improved animal production and/or reduced environmental pollution; bioenergy grasses and crops such as switchgrass, Miscanthus , sorghum (grain, forage and energy sorghum), sugarcane and energy cane with enhanced biomass yield, such as for bioethanol production; and cereals such as wheat, rice, maize, barley with increased grain and/or biomass yield.
Nucleic acid sequences encoding some of the enzymes involved in the fructan biosynthetic pathway have been isolated for certain species of plants. For example, PCT/AU01/00705 to the present applicants, describes fructosyltransferase homologues from Lolium and Festuca . However, there remains a need for materials useful in the modification of fructan biosynthesis in plants, and also to engineer fructan accumulation in different parts of the plant.
[0015] International patent application PCT/AU2009/001211 describes constructs useful for modifying fructan biosynthesis in plants. However, those constructs preferably include a fusion gene encoding a translational fusion of two or more fructan biosynthetic enzymes, the genes making up the fusion preferably corresponding to plant fructan biosynthetic genes.
[0016] It is an object of the present invention to overcome, or at least alleviate, one or more of the difficulties or deficiencies associated with the prior art.
SUMMARY OF THE INVENTION
[0017] Applicants have found that it is possible to nutritionally enhance plants eg. forage grasses and/or to increase plant biomass by spatial reprogramming of the fructan-biosynthesis pathway in photosynthetic cells using a construct including a promoter or a functionally active fragment or variant thereof, operatively linked to a gene encoding a bacterial FT enzyme, or a functionally active fragment or variant thereof. Using this process it is possible to drive fructan accumulation in leaf blades, the plant organs that are primarily grazed by livestock, and which may not normally accumulate fructans. Thus, accumulation of fructans, especially those exhibiting a high degree of polymerization (high DP fructans'), provides more accessible nutrition for grazing animals. Fructans accumulate in the stems and leaf sheaths, with leaf fructans only forming during periods where CO 2 assimilation outperforms growth. Forage grasses may be nutritionally enhanced by expressing fructan genes in photosynthetic cells where sucrose is synthesised, thus driving fructan accumulation preferentially in leaf blades and providing more energy to grazing livestock.
[0018] Fructans in forage grasses contribute significantly to the readily available energy in the feed for grazing ruminant animals. The fermentation processes in the rumen require considerable readily available energy. The improvement of the readily available energy in the rumen can increase the efficiency of rumen digestion. An increased efficiency in rumen digestion leads to an improved conversion of the forage protein fed to the ruminant animal into milk or meat, and to a reduction in nitrogenous waste.
[0019] Applicants have also found that the methods of the present invention may be facilitated by reprogramming photosynthetic cells for extended life, for example by delaying leaf senescence, to help increase plant biomass.
[0020] Applicants have found that a construct including a gene encoding a bacterial FT gene or functionally active fragment or variant thereof, may give superior results to a construct including a fusion gene encoding a translational fusion of two or more fructan biosynthetic enzymes. Use of a bacterial FT gene, for example containing both 1-SST and 1-FFT activities, may be technically less difficult than fusing separate genes, and may result in a construct that is more readily introduced into plants and/or performs better than a construct including fused genes.
[0021] For example, by expressing a bacterial FT gene, for example containing both 1-SST and 1-FFT activities, problems associated with differences in the expression patterns of these genes independently integrated into the plant genome may be alleviated, resulting in conversion of the sucrose molecules directly to fructans, those exhibiting a low degree of polymerisation (‘low DP fructans’) and a high degree of polymerization (‘high DP fructans’). Furthermore, the FT protein may form a metabolic channel for the efficient biosynthesis of fructans.
[0022] Expression of FT genes in photosynthetic cells leading to the accumulation of low and high DP fructans in photosynthetic cells may lead to a release from inhibition mechanisms of photosynthesis, facilitating solar energy capture and increased CO 2 fixation.
[0023] Thus, applicants have found that reprogramming photosynthetic cells for extended life and enhanced fructan biosynthesis facilitates solar energy capture and increases plant biomass production including shoot and/or root growth.
[0024] Furthermore, since accumulation of low and high DP fructans has been associated with plant's tolerance to abiotic stress such as cold and drought; and since enhanced root growth and delayed leaf senescence has also been implicated in plant's tolerance of drought stress, reprogramming photosynthetic cells for extended life and enhanced fructan biosynthesis may facilitate yield stability and plants' tolerance of abiotic stresses.
[0025] Accordingly, in one aspect, the present invention provides a method of manipulating fructan biosynthesis in photosynthetic cells of a plant, said method including introducing into said plant an effective amount of a genetic construct including a promoter, or a functionally active fragment or variant thereof, operatively linked to a nucleic acid encoding a bacterial fructosyltransferase (FT) enzyme, or a functionally active fragment or variant thereof.
[0026] By ‘manipulating fructan biosynthesis’ is generally meant increasing fructan biosynthesis in a transformed plant relative to an untransformed control plant. However, for some applications it may be desirable to reduce or otherwise modify fructan biosynthesis in the transformed plant relative to the untransformed control plant. For example, it may be desirable to increase or decrease the activity of certain enzymes in the fructan biosynthetic pathway, in the transformed plant relative to the untransformed control plant.
[0027] By ‘photosynthetic cells’ is meant those cells of a plant in which photosynthesis takes place. Such cells generally contain the pigment chlorophyll and are otherwise known as green cells. Most photosynthetic cells are contained in the leaves of plants. Preferably, the genetic construct of the present invention is expressed in bundle sheath cells, more preferably in mesophyll and/or parenchymatous bundle sheath cells.
[0028] By ‘an effective amount’ is meant an amount sufficient to result in an identifiable phenotypic trait in said plant, or in a plant, plant seed or other plant part derived therefrom. Such amounts can be readily determined by an appropriately skilled person, taking into account the type of plant, the route of administration and other relevant factors. Such a person will readily be able to determine a suitable amount and method of administration. See, for example, Maniatis et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, the entire disclosure of which is incorporated herein by reference.
[0029] By ‘genetic construct’ is meant a recombinant nucleic acid molecule.
[0030] By a ‘promoter’ is meant a nucleic acid sequence sufficient to direct transcription of an operatively linked nucleic acid sequence.
[0031] By ‘operatively linked’ is meant that the nucleic acid(s) and a regulatory sequence, such as a promoter, are linked in such a way as to permit expression of said nucleic acid under appropriate conditions, for example when appropriate molecules such as transcriptional activator proteins are bound to the regulatory sequence. Preferably an operatively linked promoter is upstream of the associated nucleic acid.
[0032] By ‘upstream’ is meant in the 3′->5′ direction along the nucleic acid.
[0033] By ‘nucleic acid’ is meant a chain of nucleotides capable of carrying genetic information. The term generally refers to genes or functionally active fragments or variants thereof and or other sequences in the genome of the organism that influence its phenotype. The term ‘nucleic acid’ includes DNA (such as cDNA or genomic DNA) and RNA (such as mRNA or microRNA) that is single- or double-stranded, optionally containing synthetic, non-natural or altered nucleotide bases, synthetic nucleic acids and combinations thereof.
[0034] By a ‘nucleic acid encoding a bacterial fructosyltransferase (FT) enzyme’ or ‘bacterial fructosyl transferase gene’ is meant a nucleic acid encoding an enzyme normally present in a bacterium which catalyses the synthesis of oligo- and/or polyfructans by transferring fructosyl moieties from sucrose-containing saccharides to acceptor molecules. The bacterial FT enzyme may include levansucrase activity and/or produce levan type fructan. The bacterial FT enzyme may include inulosucrase activity and/or produce inulin type fructan. A preferred bacterial FT includes both sucrose:sucrose 1-fructosyltransferase (1-SST) and fructan:fructan 1-fructosyltransferase (1-FFT) enzymatic activities. A SacB, Lsc or FTF gene may be used. A SacB or Lsc gene is particularly preferred.
[0035] By ‘functionally active fragment or variant’ in relation to a promoter is meant that the fragment or variant (such as an analogue, derivative or mutant) is capable of directing transcription of an operatively linked nucleic acid. Such variants include naturally occurring allelic variants and non-naturally occurring variants. Additions, deletions, substitutions and derivatizations of one or more of the nucleotides are contemplated so long as the modifications do not result in loss of functional activity of the fragment or variant. Preferably the functionally active fragment or variant has at least approximately 80% identity to the relevant part of the above mentioned sequence to which the fragment or variant corresponds, more preferably at least approximately 90% identity, even more preferably at least approximately 95% identity, most preferably at least approximately 98% identity. Preferably the fragment has a size of at least 20 nucleotides, more preferably at least 50 nucleotides, more preferably at least 100 nucleotides, more preferably at least 200 nucleotides, more preferably at least 300 nucleotides.
[0036] By ‘functionally active’ in relation to the nucleic acid encoding a bacterial FT enzyme is meant that the fragment or variant (such as an analogue, derivative or mutant) is capable of manipulating fructan biosynthesis in a plant by the method of the present invention, for example by being translated into an enzyme that is able to participate in the fructan biosynthetic pathway. Such variants include naturally occurring allelic variants and non-naturally occurring variants. Additions, deletions, substitutions and derivatizations of one or more of the nucleotides are contemplated so long as the modifications do not result in loss of functional activity of the fragment or variant. Preferably the functionally active fragment or variant has at least approximately 80% identity to the relevant part of the above mentioned sequence to which the fragment or variant corresponds, more preferably at least approximately 90% identity, even more preferably at least approximately 95% identity, most preferably at least approximately 98% identity. Such functionally active variants and fragments include, for example, those having conservative nucleic acid changes.
[0037] By ‘conservative nucleic acid changes’ is meant nucleic acid substitutions that result in conservation of the amino acid in the encoded protein, due to the degeneracy of the genetic code. Such functionally active variants and fragments also include, for example, those having nucleic acid changes which result in conservative amino acid substitutions of one or more residues in the corresponding amino acid sequence.
[0038] By ‘conservative amino acid substitutions’ is meant the substitution of an amino acid by another one of the same class, the classes being as follows:
Nonpolar: Ala, Val, Leu, Ile, Pro, Met Phe, Trp Uncharged polar: Gly, Ser, Thr, Cys, Tyr, Asn, Gln Acidic: Asp, Glu Basic: Lys, Arg, H is
[0043] Other conservative amino acid substitutions may also be made as follows:
Aromatic: Phe, Tyr, H is Proton Donor: Asn, Gln, Lys, Arg, H is, Trp Proton Acceptor: Glu, Asp, Thr, Ser, Tyr, Asn, Gln
[0047] Particularly preferred fragments and variants include one or more conserved sucrose binding/hydrolysis domains. Examples of such domains are shown in FIG. 1 and include LDVWDSWP, QEWSGSA, LRDPH and DEIER.
[0048] Particularly preferred fragments and variants include a catalytic core. By a “catalytic core” is meant an internal region of the polypeptide excluding signal peptide and N- and C-terminal variable regions, which contains conserved sucrose binding and/or hydrolysis domains. An example of a catalytic core is shown in FIG. 1 and includes amino acid residues 65-468 of the SacB protein from Bacillus subtilis.
[0049] Particularly preferred fragments and variants include those lacking a signal peptide. By a “signal peptide” is meant an N-terminal signal sequence. An example of a signal peptide is shown in FIG. 1 and includes amino acids 1-27 of the SacB protein from Bacillus subtilis.
[0050] Particularly preferred fragments and variants have codon usage adapted for plants, including the start of translation for monocots and dicots.
[0051] Particularly preferred fragments and variants have cryptic splice sites and/or RNA destabilizing sequence elements inactivated or removed.
[0052] Preferably, the nucleic acid encoding a bacterial FT is isolated from or corresponds to a gene or genes from a bacterial species selected from the group consisting of Bacillus, Lactobacillus and Streptococcus , including Bacillus subtilis, Bacillus amyloliquefaciens, Lactobacillus johnsonii and Streptococcus mutans . Even more preferably, the nucleic acid encoding a bacterial FT enzyme is isolated from or corresponds to a SacB gene from Bacillus subtilis or Bacillus amyloliquefaciens , a Lsc gene from Lactobacillus johnsonii or a FTF gene from Streptococcus mutans.
[0053] In a particularly preferred embodiment the SacB gene includes a sequence selected from the group consisting of the sequence shown in FIG. 2 and the nucleotide sequences encoding the polypeptide sequence shown in FIG. 3 ; and functionally active fragments and variants thereof.
[0054] Ina particularly preferred embodiment the Lsc gene includes a sequence selected from the group consisting of the sequence shown in FIG. 4 and the nucleic acid sequences encoding the polypeptide sequence shown in FIG. 5 ; and functionally active fragments and variants thereof.
[0055] Transgenic plants expressing bacterial levansucrases have been reported, in some instances, to display aberrant developmental phenotypes. While applicants do not wish to be restricted by theory, this may arise from inadequate compartmentalization of the levansucrase enzymes and fructan polymers. Cytosolic expression of a bacterial SacB gene in transgenic tobacco and potato plants was shown to be particularly disruptive to plant development (Caimi et al., 1997). However, plants expressing a bacterial fructosyltransferase fused to vacuole-targeting signals accumulate fructans with no discernible effect on plant development (Ebskamp et al., 1994, Ye et al. 2001).
[0056] To reduce the possibility of aberrant developmental phenotypes the bacterial FT gene may be modified to alter its targeting signal sequence to direct the bacterial FT proteins to compartments where high fructan levels exist.
[0057] More particularly, a chimeric sequence may be created, whereby the N-signal peptide of the bacterial FT gene may be removed and replaced by a sub-cellular targeting sequence, preferably a vacuolar targeting sequence.
[0058] In a preferred embodiment, the vacuolar targeting sequence may be from or correspond to a gene encoding a preprosporamin protein, such as SPOR531 of sweet potato.
[0059] In a particularly preferred embodiment, the vacuolar targeting sequence may include a sequence selected from the group consisting of the sequence shown in bold underline in FIG. 6 and the nucleic acid sequences encoding the polypeptide shown in bold underline in FIG. 7 ; and functionally active fragments and variants thereof.
[0060] In a particularly preferred embodiment the nucleic acid encoding the bacterial FT enzyme may be a SPOR:SacB chimeric sequence. Preferably the SPOR:SacB chimeric sequence includes a sequence selected from the group consisting of the sequence shown in FIG. 8 and the nucleic acid sequences encoding the polypeptide sequence shown in FIG. 9 ; and functionally active fragments and variants thereof.
[0061] In a particularly preferred embodiment the nucleic acid encoding the bacterial FT enzyme may be a SPOR:Lsc chimeric sequence. Preferably, the SPOR:Lsc chimeric sequence includes a sequence selected from the group consisting of the sequence shown in FIG. 9 and the nucleic acid sequences encoding the polypeptide sequence shown in FIG. 12 ; and functionally active fragments and variants thereof.
[0062] In a particularly preferred embodiment, the genetic construct includes a sequence selected from the group consisting of the sequences shown in FIGS. 8 and 11 and the nucleic acid sequences encoding the polypeptides shown in FIGS. 9 and 12 ; and functionally active fragments and variants thereof.
[0063] In another preferred embodiment, a chimeric sequence may be is created, whereby the N-signal peptide of the bacterial FT gene may be removed and replaced by a transmembrane domain of a fructosyltransferase enzyme such as 1-SST.
[0064] In a particularly preferred embodiment, the transmembrane domain includes a sequence selected from the group consisting of the sequence shown in bold italics in FIG. 15 and the nucleic acid sequences encoding the polypeptide shown in bold italics in FIG. 16 ; and functionally active fragments and variants thereof.
[0065] In a particularly preferred embodiment, the genetic construct includes a sequence selected from the group consisting of the sequences shown in FIGS. 17 and 20 and the nucleic acid sequences encoding the polypeptides shown in FIGS. 18 and 21 ; and functionally active fragments and variants thereof.
[0066] By a ‘chimeric sequence’ is meant a hybrid produced recombinantly by expressing a fusion gene including two or more linked nucleic acids which originally encoded separate proteins, or functionally active fragments or variants thereof.
[0067] By a ‘fusion gene’ is meant that two or more nucleic acids are linked in such a way as to permit expression of the fusion protein, preferably as a translational fusion. This typically involves removing the stop codon from a nucleic acid sequence coding for a first protein, then appending the nucleic acid sequence of a second protein in frame. The fusion gene is then expressed by a cell as a single protein. The protein may be engineered to include the full sequence of both original proteins, or a functionally active fragment or variant of either or both.
[0068] The genetic construct may also include a nucleic acid sequence encoding a linker between the two linked nucleic acids. A ‘linker’ is any chemical, synthetic, carbohydrate, lipid, polypeptide molecule (or combination thereof) positioned between and joined to two adjacent active fragments in a fusion protein. A preferred linker of the invention is a flexible linker, such as a polypeptide chain consisting of one or more amino acid residues joined by amino acid bonds to the two active fragments. For example, a (Gly 4 Ser) 3 linker may be positioned between the two active fragments in the fusion protein.
[0069] The promoter used in the constructs and methods of the present invention may be a constitutive, tissue specific or inducible promoter. In a preferred embodiment, the promoter may be a light-regulated promoter, more preferably a photosynthetic promoter. By a ‘light regulated promoter’ is meant a promoter capable of mediating gene expression in response to light stimulus. By a ‘photosynthetic promoter’ is meant a promoter capable of mediating expression of a gene encoding a protein involved in a photosynthetic pathway in plants.
[0070] Less fructans accumulate in mature leaf blades than in leaf sheaths and stems. In order to specifically increase the level of fructans in leaf blades, a strategic approach has been devised that co-ordinately expresses fructan biosynthesis genes in photosynthetic cells. While applicants do not wish to be restricted by theory, the use of light-regulated or photosynthetic promoters may provide the following advantages:
Photosynthetic promoters are active in a large group of cells including leaf blades, the upper and outer stem (>55% cells); They are active in sucrose producing cells (mesophyll and parenchymatous bundle sheath cells); Their expression pattern temporally and spatially overlaps with sucrose accumulation; Frutosyltransferase activity will remove sucrose from the source thereby preventing feedback suppression on photosynthesis, and may facilitate increases in CO 2 fixation;
[0075] Particularly preferred light-regulated promoters include a ribulose-1,5-bisphosphate carboxylase/oxygtenase small subunit (RbcS) promoter and a chlorophyll a/b binding protein (CAB) promoter, and functionally active fragments and variants thereof.
[0076] The light-regulated promoter may be from any suitable plant species including monocotyledonous plants [such as maize, rice, wheat, barley, sorghum, sugarcane, energy cane, forage grasses (e.g. Festuca, Lolium, Brachiaria, Paspalum, Pennisetum ), bioenergy grasses (e.g. switchgrass, Miscanthus )], dicotyledonous plants (such as Arabidopsis , soybean, canola, cotton, alfalfa and tobacco) and gymnosperms.
[0077] For transformation of monocots, preferably the light-regulated promoter is isolated from or corresponds to a promoter from a monocot species, more particularly a Triticum or Lolium species, even more particularly Triticum aestivum or Lolium perenne.
[0078] For transformation of dicots, preferably the light-regulated promoter is isolated from or corresponds to a promoter from a dicot species, more particularly an Arabidopsis species, even more particularly Arabidopsis thaliana.
[0079] In a particularly preferred embodiment, the RbcS promoter includes a sequence selected from the group consisting of the sequence shown in lower case italics in any one of FIGS. 23 to 26 , and functionally active fragments and variants thereof.
[0080] In another particularly preferred embodiment, the RbcS promoter includes a sequence selected from the group consisting of the sequence shown in lower case italics in any one of FIGS. 29 to 36 , and functionally active fragments and variants thereof.
[0081] The genetic constructs of the present invention may be introduced into the plants by any suitable technique. Techniques for incorporating the genetic constructs of the present invention into plant cells (for example by transduction, transfection, transformation or gene targeting) are well known to those skilled in the art. Such techniques include Agrobacterium -mediated introduction, Rhizobium -mediated introduction, electroporation to tissues, cells and protoplasts, protoplast fusion, injection into reproductive organs, injection into immature embryos and high velocity projectile introduction to cells, tissues, calli, immature and mature embryos, biolistic transformation, Whiskers transformation, and combinations thereof. The choice of technique will depend largely on the type of plant to be transformed, and may be readily determined by an appropriately skilled person.
[0082] Cells incorporating the genetic constructs of the present invention may be selected, as described below, and then cultured in an appropriate medium to regenerate transformed plants, using techniques well known in the art. The culture conditions, such as temperature, pH and the like, will be apparent to the person skilled in the art. The resulting plants may be reproduced, either sexually or asexually, using methods well known in the art, to produce successive generations of transformed plants.
[0083] The methods of the present invention may be applied to a variety of plants, including monocotyledons [such as grasses (e.g. forage and bioenergy grasses including perennial ryegrass, tall fescue, Italian ryegrass, red fescue, reed canarygrass, big bluestem, cordgrass, napiergrass, wildrye, wild sugarcane, Miscanthus , switchgrass), corn or maize, rice, wheat, barley, sorghum, sugarcane, rye, oat) and energy crops (e.g. energy cane, energy sorghum)], dicotyledons [such as Arabidopsis , tobacco, soybean, canola, alfalfa, potato, cassaya, clovers (e.g. white clover, red clover, subterranean clover), vegetable brassicas, lettuce, spinach] and gymnosperms.
[0084] In a further aspect of the present invention, there is provided a genetic construct capable of manipulating fructan biosynthesis in photosynthetic cells of a plant, said genetic construct including a light-regulated promoter, or functionally active fragment or variant thereof, operatively linked to a nucleic acid encoding a bacterial FT enzyme, or a functionally active fragment or variant thereof.
[0085] In a preferred embodiment, the genetic construct according to the present invention may be a vector.
[0086] By a ‘vector’ is meant a genetic construct used to transfer genetic material to a target cell.
[0087] The vector may be of any suitable type and may be viral or non-viral. The vector may be an expression vector. Such vectors include chromosomal, non-chromosomal and synthetic nucleic acid sequences, eg. derivatives of plant viruses; bacterial plasmids; derivatives of the Ti plasmid from Agrobacterium tumefaciens ; derivatives of the Ri plasmid from Agrobacterium rhizogenes ; phage DNA; yeast artificial chromosomes; bacterial artificial chromosomes; binary bacterial artificial chromosomes; vectors derived from combinations of plasmids and phage DNA. However, any other vector may be used as long as it is replicable or integrative or viable in the plant cell.
[0088] In a preferred embodiment of this aspect of the invention, the genetic construct may further include a terminator; said promoter, gene and terminator being operably linked.
[0089] The promoter, gene and terminator may be of any suitable type and may be endogenous to the target plant cell or may be exogenous, provided that they are functional in the target plant cell.
[0090] A variety of terminators which may be employed in the genetic constructs of the present invention are also well known to those skilled in the art. The terminator may be from the same gene as the promoter sequence or a different gene. Particularly suitable terminators are polyadenylation signals, such as the (CaMV)35S polyA and other terminators from the nopaline synthase (nos) and the octopine synthase (ocs) genes.
[0091] The genetic construct, in addition to the promoter, the gene and the terminator, may include further elements necessary for expression of the nucleic acid, in different combinations, for example vector backbone, origin of replication (ori), multiple cloning sites, spacer sequences, enhancers, introns (such as the maize Ubiquitin Ubi intron), antibiotic resistance genes and other selectable marker genes [such as the neomycin phosphotransferase (nptll) gene, the hygromycin phosphotransferase (hph) gene, the phosphinothricin acetyltransferase (bar or pat) gene], and reporter genes (such as beta-glucuronidase (GUS) gene (gusA)]. The genetic construct may also contain a ribosome binding site for translation initiation. The genetic construct may also include appropriate sequences for amplifying expression.
[0092] In particular, the genetic construct may further include a nucleic acid sequence encoding a linker between the two linked nucleic acids, as hereinbefore described.
[0093] Those skilled in the art will appreciate that the various components of the genetic construct are operably linked, so as to result in expression of said nucleic acid. Techniques for operably linking the components of the genetic construct of the present invention are well known to those skilled in the art. Such techniques include the use of linkers, such as synthetic linkers, for example including one or more restriction enzyme sites.
[0094] Preferably, the genetic construct is substantially purified or isolated. By ‘substantially purified’ is meant that the genetic construct is free of the genes, which, in the naturally-occurring genome of the organism from which the nucleic acid or promoter of the invention is derived, flank the nucleic acid or promoter. The term therefore includes, for example, a genetic construct which is incorporated into a vector; into an autonomously replicating plasmid or virus; or into the genomic DNA of a prokaryote or eukaryote; or which exists as a separate molecule (eg. a cDNA or a genomic or cDNA fragment produced by PCR or restriction endonuclease digestion) independent of other sequences. It also includes a genetic construct which is part of a hybrid gene encoding additional polypeptide sequence. Preferably, the substantially purified genetic construct is at least approximately 90% pure, more preferably at least approximately 95% pure, even more preferably at least approximately 98% pure.
[0095] The term “isolated” means that the material is removed from its original environment (eg. the natural environment if it is naturally occurring). For example, a naturally occurring nucleic acid present in a living plant is not isolated, but the same nucleic acid separated from some or all of the coexisting materials in the natural system, is isolated. Such nucleic acids could be part of a vector and/or such nucleic acids could be part of a composition, and still be isolated in that such a vector or composition is not part of its natural environment.
[0096] As an alternative to use of a selectable marker gene to provide a phenotypic trait for selection of transformed host cells, the presence of the genetic construct in transformed cells may be determined by other techniques well known in the art, such as PCR (polymerase chain reaction), Southern blot hybridisation analysis, histochemical assays (e.g. GUS assays), thin layer chromatography (TLC), northern and western blot hybridisation analyses.
[0097] Applicant has also found that the methods of the present invention may result in enhanced biomass in the transformed plant relative to an untransformed control plant. This enhanced biomass may in turn be used as a selection tool for identifying transformed plants. This has the advantage that in some circumstances there may be no need to include an antibiotic resistance or other marker to select for transformants, where subsequent removal of such markers (and for the creation of marker-free plants) may present difficulties.
[0098] By ‘enhancing biomass’ or ‘enhanced biomass’ is meant enhancement of, increase in, or increased stability of biomass yield, including shoot and/or root growth, in a transformed plant relative to an untransformed control plant. For example, one or more growth characteristics selected from the group consisting of total leaf area, cumulative leaf area, leaf growth dynamics (ie. number of leaves over time), number of shoots, number of tillers, number of roots, root mass or weight, shoot mass or weight, root length, shoot length, stolon length, number of tubers, tuber weight, number of flowers, number of fruits, number of seeds, seed weight, fruit weight, percentage of flowering plants and seed yield per flower or per area sown; may be enhanced, increased or more stable in a transformed plant relative to an untransformed control plant.
[0099] This technique is particularly applicable to plants that are substantially genetically uniform or genetically identical or exhibit small phenotype differences in biomass prior to transformation.
[0100] Accordingly, in a further aspect of the present invention, there is provided a method of enhancing biomass in a plant, said method including introducing into said plant an effective amount of a genetic construct including a promoter, or a functionally active fragment or variant thereof, operatively liked to a nucleic acid encoding a bacterial FT-enzyme, or a functionally active fragment or variant thereof. Preferably, the promoter is a light regulated promoter.
[0101] The methods, nucleic acids and genetic constructs of the present invention may be used in combination with other methods of genetic manipulation, or other transferred nucleic acids or genetic constructs, thereby stacking traits. Thus, transgenic plants, plant cells, plant seeds or other plant parts with stacked genes (or stacked traits) may be produced. For example, the technology of the present invention may be combined with herbicide resistance technology (eg. glufosinate, glyphosate), insect resistance technology (eg. Bacillus thuringiensis ) or delayed senescence technology. The nucleic acids or genetic constructs may be introduced into the plant by any suitable technique, as hereinbefore described, and may be introduced concurrently, sequentially or separately.
[0102] In a still further aspect of the present invention, there is provided a method of enhancing biomass in a plant, said method including introducing into said plant effective amount of
(a) a genetic construct capable of manipulating fructan biosynthesis in photosynthetic cells of the plant, said genetic construct including a promoter, or a functionally active fragment or variant thereof, operatively linked to a nucleic acid encoding a bacterial FT enzyme, or a functionally active fragment or variant thereof; and (b) a genetic construct capable of manipulating senescence in the plant.
[0105] The genetic constructs may be introduced into the plant by any suitable technique, as hereinbefore described, and may be introduced concurrently, sequentially or separately.
[0106] Preferably the genetic construct capable of manipulating fructan biosynthesis is as hereinbefore described.
[0107] Preferably the genetic construct capable of manipulating senescence in the plant is capable of manipulating senescence in photosynthetic cells of the plant.
[0108] Preferably the genetic construct capable of manipulating senescence includes a myb gene promoter or modified myb gene promoter, or a functionally active fragment or variant thereof, operatively linked to a gene encoding an enzyme involved in biosynthesis of a cytokinin, or a functionally active fragment or variant thereof.
[0109] Suitable genetic constructs or vectors are described in International patent application PCT/AU01/01092 and U.S. patent application Ser. No. 11/789,526, the entire disclosures of which are incorporated herein by reference.
[0110] “Manipulating senescence” generally relates to delaying senescence in the transformed plant or cells or organs of the transformed plant, eg photosynthetic cells, relative to an untransformed control plant. However, for some applications it may be desirable to promote or otherwise modify senescence in the plant. Senescence may be promoted or otherwise modified for example, by utilizing an antisense gene.
[0111] The myb gene promoter may be of any suitable type. Preferably the myb gene promoter is a myb32 gene promoter. Preferably the myb gene promoter is from Arabidopsis , more preferably Arabidopsis thaliana . Most preferably the myb gene promoter includes a nucleotide sequence selected from the group consisting of the sequence shown in Sequence ID No: 1 of PCT/AU01/01092 and functionally active fragments and variants thereof.
[0112] A suitable promoter is described in Li et al., Cloning of three MYB-like genes from Arabidopsis (PGR 99-138) Plant Physiology 121:313 (1999), the entire disclosure of which is incorporated herein by reference.
[0113] By a “modified myb gene promoter” is meant a promoter normally associated with a myb gene, which promoter is modified to delete or inactivate one or more root specific motifs and/or pollen specific motifs in said promoter.
[0114] Preferably the modified myb gene promoter is a modified myb32 gene promoter. Preferably the modified myb gene promoter is modified from the myb gene promoter from Arabidopsis , or more preferably Arabidopsis thaliana.
[0115] A suitable promoter which may be modified according to the present invention is described in Li et al., Cloning of three MYB-like genes from Arabidposis (PGR 99-138) Plant Physiology 121:313 (1999), the entire disclosure of which is incorporated herein by reference.
[0116] By a “root specific motif” is meant a sequence of 3-7 nucleotides, preferably 4-6 nucleotides, more preferably 5 nucleotides, which directs expression of any associated gene in the roots of a plant.
[0117] Preferably the root specific motif includes a consensus sequence ATATT or AATAT.
[0118] By a “pollen specific motif” is meant a sequence of 3-7 nucleotides, preferably 4-6 nucleotides, more preferably 4 or 5 nucleotides, which directs expression of an associated gene in the pollen of a plant.
[0119] Preferably the pollen specific motif includes a consensus sequence selected from the group consisting of TTTCT, AGAAA, TTCT and AGAA.
[0120] A root or pollen specific motif may be inactivated by adding, deleting, substituting or derivatizing one or more nucleotides within the motif, so that it no longer has the preferred consensus sequence.
[0121] Preferably the modified myb gene promoter includes a nucleotide sequence selected from the group consisting of the sequences show in Sequence ID Nos: 2, 3 and 4 of U.S. Ser. No. 11/789,526 and functionally active fragments and variants thereof.
[0122] By a “gene encoding an enzyme involved in biosynthesis of a cytokinin” is meant a gene encoding an enzyme involved in the synthesis of cytokinins such kinetin, zeatin and benzyl adenine, for example a gene encoding isopentyl transferase (ipt), or ipt-like gene such as the sho gene (eg. from petunia). Preferably the gene is an isopentenyl transferase (ipt) gene or sho gene. In a preferred embodiment, the gene is from a species selected from the group consisting of Agrobacterium , more preferably Agrobacterium tumefaciens; Lotus , more preferably Lotus japonicus ; and Petunia , more preferably Petunia hybrida.
[0123] Most preferably the gene includes a nucleotide sequence selected from the group consisting of the sequences shown in Sequence ID Nos: 5, 7 and 9 of U.S. Ser. No. 11/789,526, sequences encoding the polypeptides shown in Sequence ID Nos: 6, 8 and 10 of U.S. Ser. No. 11/789,526, and functionally active fragments and variants thereof.
[0124] The present invention also provides a method of selecting for transformed plants, said method including introducing into said plants an effective amount of a genetic construct including a promoter, or a functionally active fragment or variant thereof, operatively liked to a nucleic acid encoding a bacterial FT enzyme, or a functionally active fragment or variant thereof and selecting plants with enhanced biomass. Preferably the promoter is a light regulated promoter.
[0125] In a further aspect of the present invention there is provided a transgenic plant cell, plant, plant seed or other plant part with modified fructan biosynthetic characteristics or enhanced biomass relative to an untransformed control plant; said plant cell, plant, plant seed or other plant part including a genetic construct or vector according to the present invention.
[0126] By “modified fructan biosynthetic characteristics” is meant that the transformed plant exhibits increased fructan biosynthesis and/or contains increased levels of soluble carbohydrate relative to an untransformed control plant.
[0127] In a preferred embodiment the a transgenic plant cell, plant, plant seed or other plant part with enhanced biomass has an increase in biomass of at least approximately 15%, more preferably at least approximately 25%, more preferably at least approximately 35%, more preferably at least approximately 50% relative to an untransformed control plant.
[0128] For example, biomass may be increased by between approximately 15% and 500%, more preferably between approximately 25% and 300%, more preferably between approximately 35% and 200%, more preferably between approximately 50% and 100% relative to an untransformed control plant.
[0129] In a preferred embodiment, the transgenic plant cell, plant, plant seed or other plant part with modified fructan biosynthetic characteristics has an increase in soluble carbohydrate of least approximately 15%, more preferably at least approximately 25%, more preferably at least approximately 35%, more preferably at least approximately 50% relative to an untransformed control plant.
[0130] For example, soluble carbohydrates may be increased by between approximately 15% and 500%, more preferably between approximately 25% and 300%, more preferably between approximately 35% and 200%, more preferably between approximately 50% and 100% relative to an untransformed control plant.
[0131] Preferably the transgenic plant cell, plant, plant seed or other plant part is produced by a method according to the present invention.
[0132] The present invention also provides a transgenic plant, plant seed or other plant part derived from a plant cell of the present invention and including a genetic construct or vector of the present invention.
[0133] The present invention also provides a transgenic plant, plant seed or other plant part derived from a plant of the present invention and including a genetic construct or vector of the present invention.
[0134] Preferably, the transgenic plant cell, plant, plant seed or other plant part is a Lolium species, more preferably Lolium perenne or Lolium arundinaceum.
[0135] Preferably, the transgenic plant cell, plant, plant seed or other plant part is a cereal grain, more preferably a Triticum species, more preferably wheat ( Triticum aestivum ).
[0136] For example, the present invention enables the production of transgenic perennial ryegrass plants with increased fructans in leaf blades, vigorous growth and greater tolerance to abiotic stress, for improved nutrition for grazing animals.
[0137] The present invention also enables the production of transgenic wheat plants with increased fructans, vigorous growth, and tolerance to abiotic stress, for increased mass of usable carbohydrates, eg. for bio-fuel production or animal feed.
[0138] By ‘plant cell’ is meant any self-propagating cell bounded by a semi-permeable membrane and containing a plastid. Such a cell also requires a cell wall if further propagation is desired. Plant cell, as used herein includes, without limitation, algae, cyanobacteria, seeds suspension cultures, embryos, meristematic regions, callus tissue, leaves, roots, shoots, gametophytes, sporophytes, pollen and microspores.
[0139] By ‘transgenic’ is meant any cell which includes a DNA sequence which is inserted by artifice into a cell and becomes part of the genome of the organism which develops from that cell. As used herein, the transgenic organisms are generally transgenic plants and the DNA (transgene) is inserted by artifice into either the nuclear or plastidic genome.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0140] The present invention will now be more fully described with reference to the accompanying examples and drawings. It should be understood, however, that the description following is illustrative only and should not be taken in any way as a restriction on the generality of the invention described above.
[0141] In the figures:
[0142] FIG. 1 : Schematic representation of SacB protein from Bacillus subtilis , member of GH68 family. The four different regions shown are: N-terminal signal sequence; N-terminal variable region; catalytic core; and C-terminal variable region. Amino acid residues, including the catalytic triad (D86, D247 and E342) and sucrose binding (W85, W163 and R246).
[0143] FIG. 2 . Nucleotide sequence of SacB gene from Bacillus subtilis (Levansucrase). Nucleotide sequence coding for the N-terminal signal peptide is in bold.
[0144] FIG. 3 . Amino acid sequence SacB protein from Bacillus subtilis (Levansucrase). The N-terminal signal peptide is in bold.
[0145] FIG. 4 . Nucleotide sequence of Lsc gene from Lactobacillus johnsonii NCC 533 (Inulosucrase). Nucleotide sequence coding for the N-terminal signal peptide is in bold.
[0146] FIG. 5 . Amino acid sequence of Lsc protein from Lactobacillus johnsonii NCC 533 (lnulosucrase). The N-terminal signal peptide is in bold.
[0147] FIG. 6 . Nucleotide sequence of SPOR531, Preprosporamin protein from I. batatas . Vacuolar targeting signal sequence is shown in bold underlined.
[0148] FIG. 7 . Amino acid sequence of SPOR531, Preprosporamin protein from I. batatas . Vacuolar targeting signal sequence is shown in bold underlined.
[0149] FIG. 8 . SPOR:SacB chimeric nucleotide sequence. The N-terminal signal sequence of SacB has been replaced by the vacuolar targeting signal of SPOR (indicated by bold underlined).
[0150] FIG. 9 . SPOR:SacB chimeric protein sequence. The N-terminal signal sequence of SacB has been replaced by the vacuolar targeting signal of SPOR (indicated by bold underlined).
[0151] FIG. 10 . Secondary Structure Prediction of SPOR-SacB fusion protein using Secondary Structure Prediction of Membrane Proteins software SOSUI http://bp.nuap.nagoya-u.ac.jp/sosui/
[0152] FIG. 11 . SPOR:Lsc chimeric nucleotide sequence. The N-terminal signal sequence of Lsc has been replaced by the vacuolar targeting signal of SPOR (indicated by bold underlined).
[0153] FIG. 12 . SPOR:Lsc chimeric protein sequence. The N-terminal signal sequence of Lsc has been replaced by the vacuolar targeting signal of SPOR (indicated by bold underlined).
[0154] FIG. 13 . Secondary Structure Prediction of SPOR-Lsc fusion protein using Secondary Structure Prediction of Membrane Proteins software SOSUI http://bp.nuap.nagoya-u.ac.jp/sosui/
[0155] FIG. 14 . Secondary Structure Prediction of Lp1-SST using Secondary Structure Prediction of Membrane Proteins software SOSUI http://bp.nuap.naqoya-u.ac.ip/sosui/
[0156] FIG. 15 . Lp1-SST nucleotide sequence from L. perenne . The Lp1-SST transmembrane domain coding sequence is shown in bold italics.
[0157] FIG. 16 . Lp1-SST protein sequence from L. perenne . The Lp1-SST transmembrane domain is shown in bold italics.
[0158] FIG. 17 . Lp1-SST-SacB chimeric nucleotide sequence. The N-terminal signal coding sequence of SacB has been replaced by the Lp1-SST transmembrane domain coding sequence (indicated by bold italics).
[0159] FIG. 18 . Lp1-SST-SacB chimeric protein sequence. The N-terminal signal sequence of SacB has been replaced by the Lp1-SST transmembrane domain (indicated by bold italics).
[0160] FIG. 19 . Secondary Structure Prediction of Lp1-SST-SacB fusion protein using Secondary Structure Prediction of Membrane Proteins software SOSUI http://bp.nuap.nagoya-u.ac.jp/sosui/
[0161] FIG. 20 . Lp1-SST-Lsc chimeric nucleotide sequence. The N-terminal signal coding sequence of Lsc has been replaced by the Lp1-SST transmembrane domain coding sequence (indicated by bold italics).
[0162] FIG. 21 . Lp1-SST-Lsc chimeric protein sequence. The N-terminal signal sequence of Lsc has been replaced by the Lp1-SST transmembrane domain (indicated by bold italics).
[0163] FIG. 22 . Secondary Structure Prediction of Lp1-SST-Lsc fusion protein using Secondary Structure Prediction of Membrane Proteins software SOSUI http://bp.nuap.naqoya-u.ac.jp/sosui/
[0164] FIG. 23 . Nucleotide sequences of the AtRbcS::SPOR-SacB::NOS expression cassette
[0165] FIG. 24 . Nucleotide sequences of the AtRbcS::SPOR-Lsc::NOS expression cassette
[0166] FIG. 25 . Nucleotide sequences of the AtRbcS::Lp1-SST-SacB::NOS expression cassette
[0167] FIG. 26 . Nucleotide sequences of the AtRbcS::Lp1-SST-Lsc::NOS expression cassette
[0168] FIG. 27 . Gateway pDestination vector
[0169] FIG. 28 . Gateway pDestination vectors for transformation of dicots:
[0170] A. AtRbcS::SPOR-SacB::NOS; B. AtRbcS::SPOR-Lsc::NOS C. AtRbcS::Lp1-SST-SacB::NOS and D. AtRbcS::Lp1-SST-Lsc::NOS.
[0171] FIG. 29 . Nucleotide sequences of the TaRbcSp::SPOR-SacB::TaRbcst expression cassette
[0172] FIG. 30 . Nucleotide sequences of the TaRbcSp::SPOR-SacB::TaRbcst TaRbcst+AtMYB32::IPT::35S expression cassette
[0173] FIG. 31 . Nucleotide sequences of the TaRbcSp::SPOR-Lsc::TaRbcst expression cassette
[0174] FIG. 32 . Nucleotide sequences of the TaRbcSp::SPOR-Lsc::TaRbcst+AtMYB32::IPT::35S expression cassette
[0175] FIG. 33 . Nucleotide sequences of the TaRbcSp::Lp1-SST-SacB::TaRbcst expression cassette
[0176] FIG. 34 . Nucleotide sequences of the TaRbcSp::Lp1-SST-SacB::TaRbcst TaRbcst+AtMYB32::IPT::35S expression cassette
[0177] FIG. 35 . Nucleotide sequences of the TaRbcSp::Lp1-SST-Lsc::TaRbcst expression cassette
[0178] FIG. 36 . Nucleotide sequences of the TaRbcSp::SPOR-Lsc::TaRbcst+AtMYB32::IPT::35S expression cassette
[0179] FIG. 37 . Gateway pDestination vector pBS:ubi::bar::NOS
[0180] FIG. 38 . Gateway pDestination vectors for transformation of monocots:
[0181] A. TaRbcS::SPOR-SacB::TaRbcS and B. TaRbcS::SPOR-SacB::TaRbcS+AtMYB32::IPT::35S
[0182] FIG. 39 . Gateway pDestination vectors for transformation of monocots:
[0183] A. TaRbcS::SPOR-Lsc::TaRbcS and B. TaRbcS::SPOR-Lsc::TaRbcS+AtMYB32::IPT::35S
[0184] FIG. 40 . Gateway pDestination vectors for transformation of monocots:
[0185] A. TaRbcS::Lp1-SST-SacB::TaRbcS and B. TaRbcS::Lp1-SST-SacB::TaRbcS+AtMYB32::IPT::35S
[0186] FIG. 41 . Gateway pDestination vectors for transformation of monocots:
[0187] A. TaRbcS::Lp1-SST-Lsc::TaRbcS and B. TaRbcS::Lp1-SST-Lsc::TaRbcS+AtMYB32::IPT::35S
[0188] FIG. 42 . Isolation of mesophyll-derived protoplasts of Nicotiana tabacum . A)-B) Dissection of 4-6 week-old in vitro leaf material; pre-enzymatic digestion; C) Digestion of 4-6 week-old in vitro leaf material; 16 hours incubation; D) Harvesting of protoplast suspension; E) Separation of protoplast-rich interphase; F)-G) Intact, chloroplast-rich protoplasts.
[0189] FIG. 43 . Isolation of mesophyll-derived protoplasts of Nicotiana tabacum for transient expression analysis. A)-B) Intact, chloroplast-rich protoplasts; C) Culturing of protoplasts in liquid enrichment medium; D) Viable protoplast; 48 hours post isolation.
[0190] FIG. 44 . Isolation of mesophyll-derived protoplasts of Nicotiana tabacum for stable transformations. A)-B) Intact, chloroplast-rich protoplasts; C) Protoplast-embedded sea plaque agarose plug, day 0; D) Viable protoplasts; 6 days post isolation and embedding; E)-F) Embedded and liberated protoplast-derived micro-calli; 4 weeks post isolation and embedding.
[0191] FIG. 45 . Regeneration of shoots from mesophyllprotoplast-derived micro-calli of Nicotiana tabacum . A) Liberated micro-calli in liquid growth medium A, 6-7 weeks post isolation and embedding; B-C) Proliferation of calli on solidified growth medium; D)-E) Shoot induction and regeneration from mesophyllprotoplast-derived calli; F) Root development from regenerated shoots; G)-H) Growth and development of plants under glasshouse containment.
[0192] FIG. 46 . Evaluation of untransformed protoplast viability; 48 hours post isolation.
[0193] FIG. 47 . Evaluation of PEG-transformed protoplast viability; 48 hours post isolation and transfection.
[0194] FIG. 48 . Agrobacterium -mediated transformation of tobacco leaf discs. A) Co-cultivation of transformed leaf discs, day 0; B) Stage 1 initiation of shoots; 3 days post co-cultivation.
[0195] FIG. 49 . Detection of gfp expression in transformed leaf discs of Tobacco. A) Untransformed leaf disc, white light; B) Untransformed leaf disc, gfp2 filter; C) Untransformed leaf disc, gfp3 filter; D)&G) Turbo gfp-transformed leaf discs, white light; E)&H) Turbo gfp-transformed leaf discs, gfp2 filter; F)&I) Turbo gfp-transformed leaf discs, gfp3 filter.
[0196] FIG. 50 . Electrophoresis of RT-PCR samples and controls.
[0197] Lane 1 and 13: 1 kb+DNA Ladder
[0198] Lane 2: Amplification of sacB transcript from 2 μL cDNA generated by reverse transcription of mRNA from transfected protoplast 1 (sample 9A) with gene specific primer
[0199] Lane 3: Amplification of sacB transcript from 1 μL cDNA (sample 9A)
[0200] Lane 4: Control reaction performed without reverse transcriptase (sample 9A)
[0201] Lane 5: Control reaction performed without template (sacB primers)
[0202] Lane 6: Amplification of sacB transcript from 2 μL cDNA generated by reverse transcription of mRNA from transfected protoplast 1 (sample 12A) with gene specific primer
[0203] Lane 7: Amplification of sacB transcript from 1 uL cDNA (sample 12A)
[0204] Lane 8: Control reaction performed without reverse transcriptase (sample 12A)
[0205] Lane 9: Amplification of 18S transcript from 2 μL cDNA generated by reverse transcription of mRNA from untransfected protoplast with gene specific primer
[0206] Lane 10: Amplification of 18S transcript from 1 μL cDNA generated by reverse transcription of mRNA from untransfected protoplast with gene specific primer
[0207] Lane 11: Control reaction performed without reverse transcriptase (untransfected protoplast)
[0208] Lane 12: Control reaction performed without template (18S primers)
EXAMPLES
Example 1
Isolation of Bacterial Fructan Biosynthesis Genes
[0209] FIG. 1 presents a schematic representation of SacB protein from Bacillus subtilis . The four different regions shown are: N-terminal signal sequence; N-terminal variable region; catalytic core; and C-terminal variable region. Structurally, most of the bacterial inulosucrases and levansucrases share the N-terminal signal peptide, a catalytic triad. This sequence is removed during the sequence modification. The residues involved in sucrose binding are located inside the catalytic core sequences and remain untouched during the modification.
[0210] The bacterial levansucrase (SacB) and inulosucrase (Lsc) nucleotide and protein sequences are provided in FIGS. 2-5 , respectively. However, for transformation into plants the bacterial levansucrase and inulosucrase sequences are also modified in the following manner:
Removal of the bacterial N-signal peptide; Adaptation of codon usage, including the start of translation for monocots and dicots; Removal of cryptic splice sites and RNA destabilizing sequence elements; The coding sequence is further modified with putative sub-cellular targeting sequences including vacuolar targeting sequences for monocots and dicots as well as including plant 1-SST-specific transmembrane domains.
[0215] Outlines of these changes are indicated in the following example.
Example 2
Modification of Bacterial Fructan Biosynthesis Genes
Targeting of Bacterial FT Genes to Specific Cellular Compartments
[0216] To direct the bacterial FT genes away from the cytosol and to compartment where both sucrose and fructan accumulate the coding sequences of SacB and Lsc are modified with a putative vacuolar targeting sequence from the preprosporamin protein (SPOR531) of sweet potato ( Ipomoea batatas ). The propeptide of a precursor to sporamin is required for targeting of sporamin to the vacuole (Hattori et al., 1985). The vacuolar targeting information of sporamin is encoded in an amino-terminal propeptide and is indicated in FIGS. 5 and 6 .
[0217] Sequence modification involves the removal of the N-signal peptide from both the SacB and Lsc bacterial fuctan biosynthesis genes and the addition of SPOR531 vacuolar targeting signal ( FIGS. 7-8 and 10 - 11 , respectively).
[0218] Prediction of subcellular localisation and topology of the modified proteins using the Secondary Structure Prediction of Membrane Proteins software SOSUI http://bp.nuap.nagoya-u.ac.ip/sosui/ indicates a transmembrane localization triggered by the vacuolar targeting signal ( FIGS. 9 and 12 ).
[0000] Addition of Transmembrane Domains from Lp1-SST Protein to Bacterial FT Genes
[0219] The SOSUI software was also used to predict the secondary structure of the Lolium perenne 1-SST gene. This structure, indicating a transmembrane domain at the N terminus is indicated in FIG. 13 . The transmembrane domain coding and protein sequences are indicated in FIGS. 14 and 15 , respectively.
[0220] Sequence modification involves the removal of the N-signal peptide from both the SacB and Lsc bacterial fuctan biosynthesis genes and the addition of the Lp1-SST transmembrane domain ( FIGS. 16-17 and 19 - 20 , respectively). The modified sequences of SacB and Lsc were assessed using the Secondary Structure Prediction of Membrane Proteins software SOSUI for subsellular localization and protein topology and their predicted secondary structures are presented in FIGS. 18 and 21 , respectively.
Example 3
Generating Vectors for Stable Transformation in Dicots
Synthesis of Expression Constructs
[0221] Expression constructs utlising photosyntheic promoters, the modified bacterial fructan biosynthesis genes indicated in Example 2 and the NOS terminator sequence for transformation into dicot plants is artificially synthesised.
[0222] The use of a photosynthetic promoter expresses the genes in tissues that accumulate fructans, while the modified sequences target the protein to specific plant cell compartments.
[0223] The Ribulose-1,5-bisphosphate carboxylase/oxygenase Small subunit (RbcS) is a well-characterised light-regulated gene in higher plants. A 1700 bp fragment of the Arabidopsis thaliana Ribulose-1,5-bisphosphate carboxylase/oxygenase Small subunit (AtRbcS) promoter sequence has previously been cloned. Primers are designed to amplify a smaller fragment containing the TATA signal from the AtRbcS promoter for use in expression vectors.
[0224] The newly predicted sequences for the modified bacterial fructan biosynthetic genes are be artificially synthesised altering codon usage for expression in plants, as well as removing cryptic splice sites and RNA destabilizing sequence elements, to optimise their performance in the plant cell.
[0225] FIGS. 23-26 represent the expression cassettes AtRbcS::SPOR-SacB::NOS,
[0226] AtRbcS::SPOR-Lsc::NOS, AtRbcS::Lp1-SST-SacB::NOS and AtRbcS::Lp1-SST-Lsc::NOS, respectively, and have not yet had codon optimisation or removal of destabilising elements.
Generation of Constructs Containing Modified Bacterial FT Genes Driven by an Arabidopsis Photosynthetic Promoter for Transformation of Dicots
[0227] Each synthesised expression cassette is placed in a Gateway enabled pDONOR vector for recombination into the final destination vector for transformation into plants.
[0228] A Gateway enabled destination vector, containing the 35Sp:hph:35St selectable marker cassette has been generated, pPZP200 — 35Sp_hph — 35St_R4/R3 ( FIG. 27 ).
[0229] Gateway LR recombination reactions produce the following destination vectors for transformation into dicots:
AtRbcS::SPOR-SacB::NOS (FIG. 28A);
AtRbcS::SPOR-Lsc::NOS (FIG. 28B);
[0230] AtRbcS::Lp1-SST-SacB::NOS ( FIG. 28 c ) and
AtRbcS:Ip1-SST-Lsc::NOS ( FIG. 28 d ).
Example 4
Generating Vectors for Stable Transformation in Monocots
Synthesis of Expression Constructs
[0231] Expression constructs utilising the bread wheat photosyntheic promoter (TaRbcsp), the modified bacterial fructan biosynthesis genes, indicated in Example 2, and the TaRbcS terminator sequence for transformation into monocot plants are artificially synthesised. The use of a photosynthetic promoter expresses the genes in tissues that accumulate fructans, while the modified sequences target the protein to specific plant cell compartments.
[0232] The bread wheat ( Triticum aestivum ), TaRbcS regulatory sequences (promoter and terminator) have previously been cloned (Zeng, et al., 1995; Sasanuma, 2001). A 695 bp promoter fragment from sequence previously published containing the TATA signal from the TaRbcS gene (NCBI accession number AB042069) is amplified for use in expression vectors.
[0233] The newly predicted sequences for the modified bacterial fructan biosynthetic genes are artificially synthesised altering codon usage for expression in plants, as well as removing cryptic splice sites and RNA destabilizing sequence elements, to optimise their performance in the plant cell.
[0234] Using the methods outlined above expression cassettes are synthesised to generate transgenic plants that contain both fructan biosynthetic genes and the LXR™ technology. LXR™ technology is based on an expression cassette containing one candidate gene (IPT) for delayed leaf senescence under the control of the AtMYB32 gene promoter. The expression cassette AtMYB3p::IPT::35St is described in International patent application PCT/AU01/01092. The phenotype of transgenic LXR™ plants includes a decrease in leaf yellowing and chlorophyll loss associated with plant age leading to an increased photosynthetic ability resulting in improved tillering and vegetative biomass.
[0235] Integration of the two technologies leads to an increased expression of fructans via an extension of activation of the photosynthetic promoters and may have significant impact on the efficacy of a variety of applications by increasing the range of productivity in plants.
[0236] FIGS. 29-36 represent the expression cassettes, TaRbcS::SPOR-SacB::TaRbcS, TaRbcS::SPOR-SacB::TaRbcS+AtMYB32::IPT::35S, TaRbcS::SPOR-Lsc::TaRbcS, TaRbcS::SPOR-Lsc::TaRbcS+AtMYB32::IPT::35S, TaRbcS::Lp1-SST-SacB::TaRbcS, TaRbcS::Lp1-SST-SacB::TaRbcS+AtMYB32::IPT::35S, TaRbcS::Lp1-SST-Lsc::TaRbcS and TaRbcS:: Lp1-SST-Lsc::TaRbcS+AtMYB32::IPT::35S, respectively, and have not yet had codon optimisation or removal of destabilising elements.
Generation of Constructs Containing Modified Bacterial FT Genes Driven by a Trificum Photosynthetic Promoter for Transformation of Monocots
[0237] Each synthesised expression cassette is placed in a Gateway enabled pDONOR vector for recombination into the final destination vector for transformation into plants.
[0238] A Gateway enabled destination vector, containing the Ubi::bar::NOS selectable marker cassette has been generated, pBS::Ubi::bar::NOS_R4/R3 ( FIG. 37 ). Gateway LR recombination reactions produce the following destination vectors for transformation in to monocots:
TaRbcS::SPOR-SacB::TaRbcS (FIG. 38A);
TaRbcS::SPOR-SacB::TaRbcS+AtMYB32::IPT::35S (FigureB);
TaRbcS::SPOR-Lsc::TaRbcS (FIG. 39A);
TaRbcS::SPOR-Lsc::TaRbcS+AtMYB32::IPT::35S (FIG. 39B);
TaRbcS::Lp1-SST-SacB::TaRbcS (FIG. 40A);
TaRbcS::Lp1-SST-SacB::TaRbcS+AtMYB32::IPT::35S (FigureB);
TaRbcS::Lp1-SST-Lsc::TaRbcS (FIG. 41A) and
TaRbcS:: Lp1-SST-Lsc::TaRbcS+AtMYB32::IPT::35S (FIG. 41B)
Example 5
[0239] Constructs for Dicotolydons— N. tabacum Protoplasts and A. thaliana
[0240] The following constructs were made in versions for direct delivery (transient expression in protoplasts) and versions in binary transformation vectors for stable delivery to Arabidopsis ( A. thaliana ) and tobacco ( N. tabacum )
1. AtRbcS::1-SST-SacB*
2. AtRbcS::SPOR-SacB*
3. AtRbcS::1-SST-Lsc*
4. AtRbcS::SPOR-Lsc*
[0000]
* The bacterial levansucrase and inulosucrase sequences are modified in the following manner:
Removal of the bacterial N-signal peptide; Adaptation of codon usage, including the start of translation for monocots and dicots Removal of cryptic splice sites and RNA destabilizing sequence elements The coding sequence is further modified with putative sub-cellular targeting sequences including vacuolar targeting sequences for monocots and dicots as well as including plant 1-SST- and FFT-specific trans-membrane domains.
Example 6
Polyethylene Glycol-Mediated Transformation of Mesophyll-Derived Protoplasts of Tobacco
[0246] This example describes delivery of the expression cassettes hereinbefore described to tobacco protoplasts (see FIGS. 42-45 ).
I. Isolation of Mesophyll-Derived Protoplasts for Direct Gene Transfer
A. Digestion of In Vitro Shoot Cultures to Yield Mesophyll-Derived Protoplasts Enzyme Solution
[0247] 1.0% (w/v) cellulase “Onozuka” R10 and 1.0% (w/v) Macerozyme® R10 dissolved in K4 medium [medium K3 with 0.4 M sucrose instead of 0.3 M]. Spin down (Sorvall centrifuge, SS 34 rotor; at 7,000 rpm for 10 min.) in order to pellet contaminating starch of the enzyme preparations. Adjust pH 5.6 with KOH and filtersterilize (0.2 μm pore size). Store at 4° C. for no longer than 3-4 weeks.
Materials
[0000]
400 ml culture vessels containing solidified MS medium with shoot cultures of Nicotiana tabacum
90×20 mm sterile Petri dishes
Forceps
Scalpel
Sterile scalpel blades; #11 or #22
Solutions
[0000]
Enzyme solution; 1% Cellulase and 1% Macerozyme dissolved in K4 medium
Sterile water
Procedure
[0000]
1. Into sterile 90×20 mm Petri dishes, decant a volume of enzyme solution sufficient to generously cover plate base; 15 ml should suffice.
2. Transfer 2-4 healthy, fully expanded leaves of a 4-6 week-old shoot culture to an empty 90×20 mm Petri dish.
3. With the abaxial-side up, carefully remove the mid-rib of one leaf, ensuring a sharp, sterile blade is used to minimise tearing of surrounding leaf tissue. Repeat for remaining 3 leaves.
Handle small quantities of leaf material (maximum 4) at any one time to minimise desiccating effect of laminar flow.
4. Gently stack leaf halves and, with a sharp, sterile blade, slice into 1-2 mm strips.
5. Carefully transfer leaf segments into a Petri dish containing enzyme solution (abaxial-side down). Seal dish with Parafilm® and incubate overnight for 16-18 hours at 25° C. in the dark without shaking.
B. Isolation of Mesophyll-Derived Protoplasts
Materials
[0000]
Sterile 5 ml pipettes
Sterile 10 ml pipettes
Pipette boy
Sterilised protoplast filtration unit: 100 μm stainless steel mesh sieve resting on a 100 ml glass beaker
Sterile 14 ml plastic round-bottomed centrifuge tubes
Clements Orbital 500 bench centrifuge
Waterbath
Media
[0000]
90×20 mm sterile Petri dish/es containing digesting leaves of Nicotiana tabacum
Solidified 1:1 mix of K3:H medium containing 0.6% Sea Plaque™ agarose
Solutions
[0000]
Autoclaved W5 Solution
Autoclaved K3 Solution
Procedure
[0000]
6. Gently agitate the overnight digest to release protoplasts into the enzyme solution.
Agitation should be gentle, yet thorough, and performed in a side-to-side (horizontal) motion.
7. Angle plate slightly to aid transfer of digesting suspension (enzyme solution and plant debris). Using a 10 ml sterile pipette, transfer digesting suspension to a sterilised protoplast filtration unit to separate protoplast suspension from plant debris.
8. Tap filtration unit gently to release excess liquid caught in sieve.
9. Mix the protoplast suspension gently and distribute into 14 ml sterile plastic round-bottomed centrifuge tubes, filling to approximately 8 ml (maximum 9 ml).
10. Re-distribute suspension to obtain a uniform distribution of volumes (max. 9 ml).
11. Carefully overlay each suspension with 1.5 ml W5 solution.
To aid dispensing W5 solution, place suspension-filled tube on an angle and allow pipette tip to touch wall surface near tube opening before slowly lowering to just above the suspension surface. Slowly dispense W5 solution, adding drop-by-drop, ensuring to keep pipette tip as close to the suspension surface as possible. Minimal agitation of protoplast suspension and, thus, mixing with W5 solution will result if correctly performed.
12. Carefully replace lids and centrifuge tubes for 5 minutes at 70 g (Clements Orbital 500 bench centrifuge, swing-out rotor, 400 rpm). Protoplasts will float at the interphase.
13. Keeping protoplast-filled tube upright, carefully lower a sterile 5 ml pipette to a point just above the layer of protoplasts and collect the protoplasts at the interphase, taking as little as possible of the lower phase.
W5 solution will be collected simultaneously.
14. Collect and transfer protoplasts to one new 14 ml centrifuge tube. Upon completing protoplast collection, gently mix protoplast suspension by gently pipetting up and down.
15. Determine protoplast yield by removing a 100 μl aliquot of the protoplast suspension and transferring to a tube containing 900 μl W5 solution. Count the protoplasts in a haemocytometer and determine the number of protoplasts per ml.
16. Calculate the total volume required to obtain approximately 1×10 6 (maximum 1.5×10 5 ) protoplasts per ml. Distribute protoplast suspension in new 14 ml round-bottomed centrifuge tubes, ensuring equal volumes are obtained.
17. Using a 10 ml pipette, fill each protoplast-containing tube with W5 solution up to a total volume of 10 ml. To minimise disruption to the protoplasts, spray W5 solution along the tube wall when filling.
18. Replace lids and resuspend the protoplasts by gently inverting the capped tube once.
19. Pellet the protoplasts [spin 70 g (Clements Orbital 500 bench centrifuge, 400 rpm) for 5 min.] before removing all W5 solution, leaving pure protoplast suspension.
20. Resuspend protoplast suspensions by gently shaking.
21. Fill each protoplast-containing tube to a total volume of 5 ml with W5 solution and incubate at room temperature for a minimum of 1 hour and a maximum of 4.
22. During 1-4 hour incubation time, organise the following components in preparation for direct gene transfer into isolated protoplasts:
Remove 40% PEG solution from −20° C. storage and store at room temperature. 30 minutes prior to proceeding with the direct gene transfer, incubate PEG solution in a beaker of hot water. Melt solidified K3:H medium in microwave. Once completely melted, place in a 40° C. water-bath until ready to use.
II. Direct Gene Transfer to Protoplasts Using Polyethylene Glycol
Transforming DNA
[0294] Plasmid DNA is sterilized by precipitation and washing in 100% (v/v) ethanol and dried in a laminar flow hood [precipitation of plasmid DNA in 70% ethanol is also possible, but DNA pellet will take longer to dry]. DNA pellet is resuspended in 30 μl sterile double distilled water at a final concentration of 0.7 μg/μl for transient transformations. The physical structure of the DNA should be supercoiled for transient and linearized—outside of the gene of interest—for stable transformations. Addition of carrier DNA (e.g. fish-sperm DNA) to the transforming plasmid DNA usually gives better stable transformation frequencies. For stable transformations 10 μg of linearized plasmid DNA and 40 μg of sheared fish-sperm DNA are co-precipitated as indicated above, dried and dissolved in 30 μl of sterile double-distilled water.
Transformation Buffer
[0295] 15 mM MgCl 2 , 0.1% (w/v) morpholinoethanesulphonic acid (MES) and 0.5 M mannitol. After dissolving in distilled water, adjust pH 5.8 with KOH and autoclave. Store at 4° C.
PEG Solution
[0296] 40% (w/v) PEG 4000 in 0.4 M mannitol and 0.1 M Ca(NO 3 ) 2 . Dissolve PEG in 0.4 M mannitol and 0.1 M Ca(NO 3 ) 2 (the final concentration of these two components will be lower due to the volume of PEG). Adjust pH 8-9 and autoclave (the pH will take several hours, e.g. overnight, to stabilize in this solution and will drop to pH 6-7 after autoclaving).
Materials
[0000]
Sterile 1 ml pipettes
Sterile 5 ml pipettes
Sterile 10 ml pipettes
Pipette boy
Sterile 14 ml plastic round-bottomed centrifuge tubes
Clements Orbital 500 bench centrifuge
Waterbath
50×10 mm Petri dishes
Media
[0000]
14 ml round-bottomed centrifuge tubes containing isolated protoplast suspension, pelleted
Solidified 1:1 mix of K3:H medium containing 0.6% Sea Plaque™ agarose
Solutions
[0000]
Autoclaved W5 Solution
Autoclaved K3 Solution
Autoclaved H Solution
40% PEG Solution
Transformation Buffer
10 μg Transforming DNA dissolved in 30 μl sterile double-distilled water.
Procedure
[0000]
1. Pellet the protoplasts [spin 70 g (Clements Orbital 500 bench centrifuge, 400 rpm) for 5 min.] before removing all W5 solution, leaving pure protoplast suspension.
2. Using a 1 ml pipette, add (drop-wise) 300 μl (approximately 7 drops) of transformation buffer to each 14 ml round-bottomed centrifuge tube containing isolated protoplasts.
3. Carefully resuspend pellet by gently tapping base of tube.
4. To each protoplast suspension, add 10 μg (30 μl) of transforming DNA before adding 300 μl (approximately 7 drops when using a 1 ml pipette for dispensing) of pre-warmed PEG solution. Mix protoplast suspension by gently tapping tube base.
Time interval between resuspending protoplasts in transformation buffer and the addition of transforming DNA and PEG should be kept at a minimum.
5. Incubate transformation mix for 15 minutes at room temperature with no agitation.
6. Using a 10 ml pipette, gradually add 10 ml W5 solution to each tube in intervals of:
1 ml (approximately 12 drops) drop-wise to each tube. Gently invert all tubes to mix. 1 ml (approximately 12 drops) drop-wise to each tube. Gently invert all tubes to mix. 1 ml (approximately 12 drops) drop-wise to each tube. Gently invert all tubes to mix. 2 ml as a gentle stream to each tube. Gently invert all tubes to mix. 2 ml as a gentle stream to each tube. Gently invert all tubes to mix. 3 ml as a gentle stream to each tube. Gently invert all tubes to mix. To aid dispensing, in a 10 ml pipette collect the total volume required at each interval to fill each tube with the required volume of W5 solution, prior to dispensing. Repeat at each interval.
7. Pellet the protoplasts [spin 70 g (Clements Orbital 500 bench centrifuge, 400 rpm) for 10 min.] before removing all W5 solution, leaving pure protoplast suspension. Tap all tube bases once before proceeding.
For Transient Transformations
[0000]
8. Resuspend protoplast pellet in equal volumes of K3 medium and H medium up to a total volume of 5 ml (2.5 ml of each solution).
9. Slowly transfer the liquid K3:H+protoplast-suspension-mix to the centre of a 50×10 mm Petri dish.
10. Seal all dishes with Parafilm® and culture protoplasts for 24-72 hours under dim light at 24° C., before proceeding with transient expression analysis.
For Stable Transformations
[0000]
11. Continue with “Part III. Culture of Mesophyll-derived Protoplasts and Regeneration of Plants”, below.
III. Culture of Mesophyll-Derived Protoplasts and Regeneration of Plants
[0332] For Steps 1 & 2, each protoplast-containing tube must be handled one tube at a time.
Materials
[0000]
Sterile 1 ml pipettes
Sterile 5 ml pipettes
Sterile 10 ml pipettes
Pipette boy
Clements Orbital 500 bench centrifuge
Waterbath
50×10 mm Petri dishes
Autoclaved stainless steel spatula
Media
[0000]
14 ml round-bottomed centrifuge tubes containing isolated protoplast suspension, pelleted
Solidified 1:1 mix of K3:H medium containing 0.6% Sea Plaque™ agarose; 40° C.
Autoclaved K3 Solution
250 ml culture vessel containing 20 ml A medium
12-well Costar® plates containing solidified MS Morpho medium
250 ml culture vessels containing solidified MS Morpho medium
250 ml culture vessels containing solidified MS medium
Procedure
[0000]
1. Add 0.5 ml K3 medium close to the protoplast pellet to resuspend the protoplasts.
2. Slowly transfer the K3+protoplast-suspension-mix to the centre of a 50×10 mm Petri dish.
3. Repeat Steps 1 and 2 for all protoplast-containing tubes before proceeding.
4. Add 5 ml pre-warmed 1:1 mix of K3:H medium containing 0.6% Sea Plaque™ agarose one plate at a time. In a gentle swirling motion, shake plate once only to evenly distribute protoplast suspension in medium. Repeat for all plates.
5. Leave plates to stand, untouched, until medium has solidified (10-30 minutes depending on ambient temperature).
6. Seal all dishes with Parafilm® and culture protoplasts for 24 h in complete darkness at 24° C., followed by 6 days under continuous dim light (5 μmol m −2 s 1 , Osram L36 W/21 Lumilux white tubes), where first and multiple cell divisions occur.
7. Using a sterile spatula, divide the protoplast-containing sea plaque agarose plugs into quadrants and place into 250 ml plastic culture vessels containing 20 ml of A medium supplemented with appropriate antibiotic (1 quadrant per 250 ml vessel). Incubate on a rotary shaker at 80 rpm and 1.25 cm throw at 24° C. in continuous dim light.
8. Replace liquid A medium+appropriate antibiotic every 2 weeks, monitoring growth of protoplast-derived colonies.
9. When protoplast-derived colonies are approximately 2-3 mm in diameter (5-6 weeks incubation in liquid A medium), transfer colonies into individual wells of a 24-well Costar® plate containing solidified MS Morpho medium.
10. Incubate plate/s for 1-2 weeks at 24° C. under continuous dim light (5 μmol m −2 s −1 , Osram L36 W/21 Lumilux white tubes), where calli proliferate and reach a size of 8-10 mm in diameter.
11. When protoplast-derived calli are approximately 1-2 cm in diameter, transfer calli to individual 250 ml culture vessels containing solidified MS Morpho medium. Incubate vessels at 24° C. under 16 hour light/8 hour dark conditions (20 μmol m −2 s −1 , Osram L36 W/21 Lumilux white tubes). Within 1-2 weeks, multiple shoots should be visible.
12. Transfer shoots of 3-4 cm lengths to 250 ml culture vessels containing solidified MS medium to encourage root formation. Incubate vessels at 24° C. under 16 hour light/8 hour dark conditions (20 μmol m −2 s −1 , Osram L36 W/21 Lumilux white tubes). Within 3 weeks, signs of root formation should be visible.
13. Plantlets with an established root system should be maintained as in vitro plant cultures as sources for mesophyllprotoplasts of Tobacco.
Example 7
Evaluation of Tobacco Protoplast Viability Using Evans Blue Stain
[0361] See FIGS. 46 and 47 .
BACKGROUND INFORMATION
[0000]
Evans blue stain (EVB; 6,6′-[(3,3′-dimethyl1[1,1′-biphenyl]-4,4′-diyl)bis(azo)bis[4-amino-5-hydroxy-1,3-naphthalenedisulfonic acid] tetrasodium salt).
Non-fluorescent dye.
Method of action: Living cells retain the ability to exclude Evans blue at the plasma membrane and remain their natural colour. Cells damaged by salt or osmotic stress are unable to exclude Evans blue, are stained deep blue, and are readily distinguished upon microscopic examination.
Method of preparation: 400 mg/l stock solution (solvent: 0.65 M Mannitol)
Method of staining: Evans blue stock solution was added to an equal volume of protoplast suspension, gently mixed and incubated at room temperature for 10 minutes prior to microscopic visualisation.
Method of detection: Leica MZFL III Light Dissecting Microscope.
Example 8
Gene Expression Analysis in Nicotiana Tabacum Protoplasts
[0368] Aim of the experiment: The expression of the cloned genes AtRbcS::1-SST-SacB and AtRbcS::SPOR-SacB in transfected tobacco protoplasts was tested using RT-PCR
[0369] Materials and methods: 3 plates of protoplasts named
[0000] i) Transfected protoplasts (sample 9A): AtRbcS::1-SST-SacB
ii) Transfected protoplasts (sample 12A): AtRbcS::SPOR-SacB
iii) Untransfected protoplasts
[0370] Steps involved in the expression analysis:
1. Primer design and optimisation of PCR 2. Total RNA isolation 3. RT reaction 4. qRT-PCR assay
[0375] Primer design and PCR product identity: Primer pairs were designed to amplify the gene of interest using beacon design software (Premier Biosoft International) and the gene sequences available in gene bank. The gene specific primers were chosen so that the resulting PCR product size ranged from 200 to 250 bp. The PCR products were identified by melt curve analysis and size based on gel electrophoresis.
[0376] Total RNA isolation: Total RNA was isolated by SV Total RNA isolation system by PROMEGA from 1×10 6 protoplasts per treatment. http://www.promega.com/tbs/tm048/tm048.pdf
Yield of Total RNA:
[0377]
[0000]
Sample
Quantity
9A
3.4 ng/μl
12A
4.2 ng/μl
Control (untransfected protoplasts)
10.2 ng/ul
Reverse Transcriptase Reaction
[0378] RT reaction was performed by using QIAGEN RT kit. Four RT reactions were performed (9, 12, control and WT tobacco RNA) by using primer mix (QIAGEN).
[0379] http://www1.qiagen.com/products/pcr/QuantiTectPcrSystems/QuantiTectRevTranscriptionKit.aspx#Tabs=t2
[0380] A replicate of each of the above samples was subjected to RT reaction using gene-specific primers. Specifically, samples 9A and 12A were transcribed using the reverse sacB primer, and the control (untransfected) sample with the reverse 18S primer.
PCR
[0381] Reactions were set up as follows:
[0000]
2x GoTaq ® Green MasterMix (Promega)
10 μL
cDNA template
2.0 μL
Forward primer (10 μM)
0.5 μL
Reverse primer (10 μM)
0.5 μL
Nuclease free water
7.0 μL
[0382] Reactions were cycled:
[0000]
Step 1:
95° C.
2 min
Step 2:
95° C.
30 sec
Step 3:
55° C.
30 sec
Step 4:
72° C.
60 sec
25 cycles from Step 2 (18S) or 35 cycles from Step 2 (sacB)
Step 5:
4° C.
hold
[0383] Reaction products were visualised under UV light after electrophoresis through 1% (w/v) agarose in 1×TBE buffer, staining with SYBR (50 μL/L).
[0384] Detection of the sacB transcript was shown in both transfected protoplast cDNA samples (9 and 12), while the method used was validated by amplification of 18S from the untransfected protoplast cDNA sample ( FIG. 50 ).
[0385] Expression of chimeric sacB genes under control of light regulated promoters was observed in transfected protoplasts. No products were observed for no-RT controls and no Template controls. sacB gene expression could be detected in protoplasts transfected with vectors used in samples 9A and 12A.
Example 9
[0386] Agrobacterium tumefaciens -Mediated Leaf Disc Transformation of Tobacco
[0387] This example describes stable transformation of tobacco leaf discs using Agrobacterium carrying binary vectors engineered with the expression cassettes hereinbefore described (see FIGS. 48 and 49 ).
Introduction
[0388] Utilising Agrobacterium tumefaciens -mediated leaf disc transformation is an efficient method of producing transgenic plants. A. tumefaciens is a natural dicot pathogen that contains the genetic machinery to infect the plant and incorporate the bacterial DNA into the plant genome. As a result of this capability, A. tumefaciens can be adopted as a cloning vehicle to incorporate DNA of specific interest into tobacco, for example.
[0389] The method can be used to generate a model system in tobacco, to assess the function of cDNA heterologous clones for the gene of interest.
Materials and Chemicals
Equipment and Instruments
[0390] Laminar flow hood with horizontal flow (series HWS180, CLYDE-APAC, a division of Evans Deakin Pty. Ltd., Woodville North, South Australia 5012, Australia), rotary shaker (Infors type RC-406, Infors AG, CH-4103 Bottmingen, Switzerland), bench centrifuge with swing-out rotor (Clements Orbital 500), forceps (bend, cat no. 2108/160, Crown Scientific, Rowville, Victoria 3178, Australia), scalpel handles (No 3, cat no. SHN3, Crown Scientific, Rowville Victoria 3178, Australia) with sterile surgical scalpel blades (size 11, cat no. 1838, Laboratory Supply Pty. Ltd., Milperra DC, New South Wales 1891, Australia) were used.
Stock Solutions
[0391] The macro-elements, micro-elements and vitamins required for all culture media must be prepared as concentrated stocks (macro-elements stock: 10-fold concentrated; micro-elements and vitamins stocks: 100-fold concentrated) to aid in their addition. All stocks, except that containing the micro-elements are prepared at room temperature. Preparation of the micro-elements stock requires the heating of components prior to mixing. Na 2 -EDTA and FeS0 4 ×7H 2 0 must each be dissolved in 400 mL distilled water (for a total volume of 1000 mL) prior to mixing. Mix dissolved solutions and heat at ca. 60° C. until solution turns yellow in colour. Allow solution to cool before adding remaining components. Make solution up to 1000 mL with distilled water. Store all stocks at 4° C. Dissolve hormones [2,4-D (2,4-dichlorophenoxyacetic acid) and kinetin] in 1 M KOH and dilute with distilled water to prepare 100 mg/liter concentrated stocks.
Culture Media
[0392] The composition of the media used at the final concentrations of their individual ingredients is given in Appendix 1: MS micro, MS macro, B5 vitamins, Lauria Bertani media, Wash media, PC media, SEL media, RM media and SEM media.
Chemicals
[0393] 2,4-D: 2,4-dichlorophenoxyacetic acid, Activated charcoal, Timentin (can be replaced by Cefotaxime at same concentrations), BAP (6-benzylaminopurine), Zeatin, AgNO 3 , Rifampicin, Agar (Difco, Bacto-Agar, cat. no: 0140-01) is used as the gelling agent. Other chemicals (PEG 4000, Tween 80, KOH, NH 4 0H, NaCl, KCl, Ca(N0 3 ) 2 , MgCl 2 and CaCl 2 ) were purchased from BDH; MES (2-[N-morpholino]ethanesulfuric acid) from Sigma (Cat. No. N-8250), kanamycin sulphate were from Sigma; hygromycin B was purchased from Calbiochem; Ca(OCl) 2 (−65%) and phosphinotricin were from Roth and Riedel de Haen, respectively. Sucrose was purchased from Fluka (cat. no: 84100). Parafilm® “M” (American National Can™, Greenwich, Conn. 06836, USA) was used as sealing tape. Sterile disposable bottle-top filters (0.2 μm vacucap 90; cat. no 4622, Gelman Sciences® Pty. Ltd., Cheltenham, Victoria 3192, Australia) and disposable filter units (0.2 μm; cat. no. 16534, Sartorius AG, 37070 Gottingen, Germany) were used for filter-sterilisation. Sterile disposable pipettes: 1 mL_ (TRP®; cat. no. 94001) 5 mL_ (TRP®; cat. no. 94005) and 10 ml_ (TRP®; cat. no. 94010); all from Life Technologies Pty. Ltd., Mulgrave, 3170 Australia, sterile plastic centrifugal tubes with screw cap (14 mL, TRP®; cat. no. 91016, Life Technologies Pty. Ltd., Mulgrave, 3170 Australia); sterile plastic petri dishes (90×14 mm; cat. no. 82.9923.484, and 60×14 mm, cat. no. 83.1801.011, Sarstedt® Australia Pty. Ltd., Technology Park, South Australia 5095, Australia and 90×20 mm; cat. no. 664160, Greiner Labortechnik GmbH, 72636 Frickenhausen, Germany); and autoclavable culture vessels (250 mL, cat. no. 75.9922.519, Sarstedt Australia Pty. Ltd, Technology Park, South Australia 5095, Australia) were used.
Plant Material
[0394] A) Sterile shoot cultures of N. tabacum cv. Petit Havana SR1 can be utilised. They are established from corresponding seeds surface-sterilised in hypochlorite solution [1.4% (w/v) Ca(OCl) 2 , 0.05% (v/v) Tween 80] for 15 min., and after 3-4 rinses in sterile distilled water, plated for germination on half-strength MS medium (Appendix 1) solidified with 0.8% (w/v) agar. Shoots with 2-3 leaves are cut and grown in 250 mL culture vessels on 0.8% (w/v) agar-solidified MS medium at 25° C. in 16 h/d light (20 μnol m −2 s −1 , Osram L36 W/21 Lumilux white tubes). Rooted shoots are subcultured at 6 weeks intervals as stem cuttings, several times before use.
[0395] B) Glasshouse grown N. tobacum can also be utilised, but requires leaf surface sterilisation as described below [I. B)]. Plant seeds in sterile soil ensuring they are not planted too deeply and that they remain moist. Grow under 16 h/d light (20 umol m″2 s″ 1 , Osram L36 W/21 Lumilux white tubes) conditions 25° C., fertilising with Osmocote slow release fertiliser.
[0396] C) The strain of Agrobacterium tumefaciens utilised for leaf disc transformations is AGL1.
[0000] I. Preparation of Agrobacterium tumefaciens for Transforming Tobacco Leaf Discs with Vector pBinhph200
[0397] Commence pre-culture of transformed Agrobacterium tumefaciens strain AGL1 two days prior to tobacco transformation date ensuring sterile conditions are maintained, (see Appendix 2 for the ID card for pBinhph200)
1. Scratch the surface of −70° C. frozen glycerol bacterial stock with an innoculation loop and inoculate 2 mL of LB (containing 20 mg/mL rifampicin, plus 10 mg/L spectinomycin) in a sterile tube. Incubate for 24 hours at 28° C. at 150 rpm. 2. Inoculate 4 mL of LB plus antibiotics (in a 12 mL sterile tube) with 0.25 mL of the 24 hour pre-culture. Incubate for 6-7 hours at 28° C. 3. Inoculate 25 mL LB with no antibiotics (in a 150 mL sterile flask) with 0.025 ml of 6-7 hour pre-culture and incubate overnight at 28° C. and 150 rpm. 4. Add 25 ml of LB to the 25 ml overnight pre-culture and continue to grow at 28° C. for a further 90 minutes at 150 rpm. 5. Transfer 50 ml pre-culture to centrifuge tubes and spin for 12 minutes at 2,000 rpm at room temperature in a Clements bench centrifuge. 6. Remove supernatant and gently resuspend the pellet in 20 mL of WM. Measure OD 600 . Add further WM to bacterial suspension to provide a final OD 600 of 0.45. This preparation is for use in step III) 1.
II. Preparation of Leaf Discs
A) Preparation of Leaf Discs Using Tobacco Shoot Cultures
[0000]
1. In a laminar flow, harvest 4-6 leaves from tobacco plants grown on MS media. Place the leaves in 1.5×9 cm petri dishes containing WM. Using a scalpel, remove the mid-rib and cut the leaf tissue into squares ˜1 cm 2 . The tissue or leaf discs are now ready for transformation with Agrobacterium tumefaciens (AGL1). The discs should be transformed within an hour.
B) Preparation of Leaf Discs Using Non-Sterile Tobacco Tissue
[0000]
1. Harvest 4 young leaves (˜8 cm long) from a glasshouse grown tobacco plant.
2. Place leaves into a sterile beaker containing 70% ethanol, cover with aluminium foil and swirl gently on an orbital shaker (Bio-Line Orbital Shaker, Edwards Instrument Company) for 1 minute.
3. Remove 70% ethanol and replace with 1% Ca(OCl) 2 . Swirl tissue for 8 minutes. Wash leaves in sterile water at least 3 times.
4. In a laminar flow, remove the mid-rib and cut the remaining leaf tissue into squares ˜1 cm 2 . Place the prepared discs in a 1.5×9 cm petri dish containing WM. The discs are now ready for transformation with Agrobacterium tumefaciens (AGL1).
III. Incubation and Co-Cultivation of Leaf Discs with Agrobacterium tumefaciens
1. Replace WM (from last step in leaf disc preparation) with Agrobacterium culture and incubate for 1-2 minutes.
2. Remove bacterial suspension and rinse explants briefly with WM. Blot explants on sterile napkins before plating onto PC media. Place in the growth room (16 h/d light (20 μmol m −2 s −1 , Osram L36 W/21 Lumilux white tubes) conditions 25° C.) for 3 day co-cultivation.
IV. Pre-Regeneration of Leaf Discs Following Agrobacterium -Mediated Transformation
[0000]
1. Transfer explants (5/plate) to SEL media and return to growth room for a further 7 days.
V. Regeneration
[0000]
1. Transfer explants (5/plate) to RM and return to growth room. Shoot formation should occur within 3-6 weeks. Transfer explants to fresh RM after 4 weeks.
2. If calli becomes too large, and particularly if not all shoots are in contact with the media, divide calli using a scalpel. Expose as many of the shoots to selection as possible.
VI. Shoot Elongation and Root Development
[0000]
1. After eight weeks on selection, or when the untransformed control explants on selection are dead, transfer green shoots (5/plate) to SEM media (include IBA (1 mg/L)) in 9×2 cm petri dishes. Roots should appear in 4-5 weeks.
VII. In Vitro Plantlet Development
[0000]
1. When roots appear, transfer rooted plantlets to SEM media in tissue culture vessels.
REFERENCES
[0000]
Stewart, C. N. Jr., Adang, M. J., All, J. N., Rayner, P. L., Ramachandran, S, and Parrott, W. A. (1996) Insect control and dosage effects in transgenic canola containing a synthetic Bacillus thuringiensis crylAc gene. Plant Physiol 112: 115-120.
APPENDICES
Appendix 1: Stock Solutions and Media
[0417]
[0000]
MS Media
1 Litre
MS powder
4.74
g
3% sucrose
30
g
dH 2 0
Up to 1
L
[0418] Adjust pH to 5.8-6.0 with 1M NaOH
Autoclave
[0419]
[0000]
MS Macro (10 x)
1 Litre
2 Litre
NH 4 NO 3
16.5 g
33.0 g
KNO 3
19.0 g
38.0 g
CaCl 2 × 2H 2 O
4.4 g
8.8 g
MgS0 4 × 7H 2 O
3.7 g
7.4 g
KH 2 PO 4
1.7 g
3.4 g
[0000]
MS Micro (100 x)
1 Litre
2 Litre
KI
0.083 g
0.166 g
H 3 BO 3
0.62 g
1.24 g
MnS0 4 × H 2 O
1.69 g
3.38 g
ZnS0 4 × 7H 2 O
0.86 g
1.72 g
Na 2 Mo0 4 × 2H 2 O
0.025 g
0.05 g
CuS0 4 × 5H 2 0
0.0025 g
0.005 g
C0Cl 2 × 6H 2 O
0.0025 g
0.005 g
Na 2 -EDTA
3.73 g
7.46 g
FeS0 4 × 7H 2 O
2.78 g
5.56 g
[0420] Dissolve Na 2 -EDTA and FeS0 4 ×7H 2 O in 400 ml ddH 2 0, respectively, mix and heat (do not boil). Let cool down and add the other Micro salts in the remaining volume.
[0000]
MS Vitamins (100 x)
1 Litre
2 Litre
Inositol
10 g
20 g
Nicotinic acid
0.05 g
0.1 g
Pyridoxine HCl
0.05 g
0.1 g
Thiamine
0.01 g
0.02 g
Glycine
0.2 g
0.4 g
[0000]
B5 Vitamins (100 x)
1 Litre
2 Litre
Inositol
10 g
20 g
Nicotinic acid
0.1 g
0.2 g
Pyridoxine HCl
0.1 g
0.2 g
Thiamine
1.0 g
2.0 g
[0000]
RM Media: regeneration media
stock
/1 litre
MS Macro
10 x
100
ml
MS Micro
100 x
10
m!
B5 Vitamins
100 x
10
ml
MES
500
mg
Sucrose
30
g
Adjust pH 5.80 with KOH (1M)
Agar
8.0
g
Autoclave
Once cool add:
BAP
2 mg/ml
2
ml
Zeatin
1 mg/ml
2
ml
AgN0 3
5 mg/ml
1
ml
Timentin
250 mg/ml
1
ml
Hygromycin
25 mg/ml
0.4
mi
[0421] To prepare BAP and Zeatin weigh powder into a small vessel and start dissolving with 0.5-1 ml of 1 M KOH. Transfer the solution to ddH 2 0 and fill up to the final volume.
[0000]
SEL media: selection media
stock
/litre
MS Macro
10 x
100
ml
MS Micro
100 x
10
ml
B5 Vitamins
100 x
10
ml
MES
500
mg
Sucrose
30
g
Adjust pH 5.80 with KOH (1M)
Agar
8.0
g
Autoclave
Once cool add:
2,4-D
1 mg/ml
1
ml
Timentin
250 mg/ml
1
ml
Hygromycin
25 mg/ml-
0.4
ml
[0422] To prepare 2,4-D weigh the powder into a small vessel and start dissolving with 0.5-1 ml of 1 M KOH. Transfer the solution to ddH 2 0 and fill up to the final volume.
[0000]
SEM Media
stock
/litre
MS Macro
10 x
50
ml
MS Micro
100 x
5
ml
B5 Vitamins
100 x
5
ml
MES
500
mg
Sucrose
10
g
Adjust pH 5.8 with KOH(1M)
Agar
8.0
g
Activated Charcoal
0.5
g
Autoclave
Once cool add:
Timentin
250 mg/ml
1
ml
[0000]
WM medium: wash media
stock
/litre
MS Macro
10 x
100
ml
MS Micro
100X
10
ml
B5 Vitamins
100 x
10
ml
MES
500
mg
Sucrose
3
0 g
Adjust pH 5.8 with KOH (1M)
Autoclave
Example 10
[0423] Stable Transformation of Arabidposis Using Agrobacterium tumefaciens Carrying Binary Vectors Engineered with the Same Expression Cassettes Via the ‘Floral Dip’ Method.
Preparation of Electrocompetent Agrobacterium tumefaciens Cells
Experimental Procedure
[0000]
1. Streak out Agrobacterium tumefaciens (AGL1 strain) from a frozen −80° C. glycerol stock onto MGL agar containing 20 mg/L rifampicin and 100 mg/L ampicillin, and incubate at 27° C. for two days.
2. Measure 5 ml MGL into a 50 ml Falcon tube and add rifampicin to a final concentration of 20 mg/L and ampicillin 100 mg/L. Inoculate with a single colony of Agrobacterium tumefaciens AGL1.
3. Incubate at 27° C. for 24 h on an orbital shaker at 150 rpm in a tilted rack (ca. 30 degrees).
4. In late afternoon inoculate 100 ml MGL containing 20 mg/L rifampicin and 100 mg/L amplicillin (in a 500 ml flask) with the 500 μl of an overnight culture.
5. Incubate at 27° C. overnight on an orbital shaker at 150 rpm until an OD 600 reading between 0.4-0.6 (max. 0.6) is obtained. See comments below if overgrown.
6. Transfer cells to an autoclaved JA10 centrifuge tube and chill on ice for 10 min.
7. Centrifuge for 10 min, 9000 rpm, at 4° C. using the JA10 rotor.
8. Carefully discard supernatant (pellet is not very stable) by pouring into the 500 ml flask used for culture.
9. Add 20 ml ice cold 10% glycerol to the pellet in the JA10 centrifuge tube and resuspend pellet by vortexing.
10. Pour the suspension into a JA20 centrifuge tube and spin for 10 min, 10000 rpm, at 4° C. using the JA20 rotor.
11. Discard supernatant by pouring into the 500 ml flask.
12. Add 15 ml ice cold 10% glycerol to the pellet and resuspend by pipetting. Centrifuge for 10 min, 10000 rpm, at 4° C. in the JA20 rotor.
13. Repeat steps 11 and 12 twice.
14. Resuspend the pellet in 1 ml ice cold 10% glycerol (pipette or vortex) and transfer to a sterile microfuge tube.
15. Spin for 3 min, 13000 rpm, at 4° C. in microfuge.
16. Finally resuspend pellet in 1 ml 10% ice cold glycerol.
17. Aliquot 50 μl batches into labelled 1.7 ml microtubes, snap freeze in liquid nitrogen.
18. Remove tubes from liquid nitrogen and store competent cells at −80° C.
Comments
[0442] Wear latex gloves while handling A. tumefaciens bacterial cultures. Collect all bacterial waste in 500 ml flask and autoclave. If the A. tumefaciens 100 ml culture overgrows, dilute ⅓-¼ with fresh MGL medium containing 20 mg/L rifampicin, and incubate for further 1-2 h.
[0000] Transformation of Agrobacterium tumefaciens Via Electroporation
Experimental Procedure
[0000]
1. Pre-chill Gene pulser cuvette holder on ice.
2. Remove aliquots of competent Agrobacterium (AGL1) cells from −80° C. and thaw on ice.
3. Turn on main switch at the back of the Gene pulser. Adjust the voltage to 2.5 kV (use the ‘raise’ button until ‘2.5’ registers on the display), capacitance 25 μFD and resistance 600Ω.
4. Add 0.1 μg of DNA in a volume not smaller than 50 μl of thawed cells.
5. Mix by pipetting and transfer the cell/DNA mix to a pre-chilled 0.2 cm gap Gene Pulser cuvette.
6. Carefully tap or shake the cells to the bottom of the cuvette so that the cells touch both electrodes.
7. Dry the outside of the cuvette with a tissue and place it into the cuvette holder. A notch on the cuvette ensures correct orientation. Slide the cuvette holder into the chamber until the cuvette is seated between the contacts at the base of the chamber.
8. Pulse the cells by depressing both red buttons until a beep sounds. The machine will display CHG whilst charging and will beep as it discharges. Place cells back on ice for 1 min to assist recovery.
9. Add 1 ml LB medium to the cells in the cuvette with a glass transfer pipette.
10. Mix the suspension up and down then transfer to a sterile 15 ml tube.
11. Incubate at 27° C. on an orbital shaker at 150 rpm for 1 to 2 hours using a tilted rack (ca. 30 degree).
12. Add 9 ml of LB to the cell suspension mix thoroughly and plate out 100 μl of this culture onto an LB plate containing 20 mg/L rifampicin and the appropriate antibiotic (e.g. 100 mg/L spectinomycin for pPZP series of vectors). Transfer 100 μl of this suspension into a 1.7 ml microtube containing 900 μl of LB broth, mix thoroughly and plate out 100 μl onto another LB plate containing the appropriate antibiotics. Remove 100 μl from the above suspension and place into a fresh 1.7 ml microtube and add 900 μl of LB broth. Mix thoroughly and plate out 100 μl onto another LB plate containing the appropriate antibiotics.
13. Seal plates with Parafilm and incubate at 27° C. for 2-3 days until single large colonies become visible.
Storage of Transformed Agrobacterium
Experimental Procedure
[0000]
1. In a 50 ml sterile tube inoculate a single colony into 5 ml LB broth containing 20 mg/L rifampicin and appropriate selection antibiotic (i.e. 100 mg/L spectinomycin for pZP series and 50 mg/L kanamycin for pBin series). This is best done early morning so that you can closely monitor the degree of growth the following day.
2. Incubate tubes in the dark at 27° C. for 24-36 hours shaking at 250 rpm. Regularly observe culture growth after first 24 hours of incubation. Remove from incubation once cells are actively growing (highly visible). Rapid growth will occur soon after the first signs of turbidity. Growing time depends on individual strains and transformants.
3. Each culture should be checked to verify that AGL1 contains the desired binary vector. This is done using the protocol set out in section 5.2.
4. Aliquot 500 μl of culture into a cuvette. Measure OD 600 reading, blanking with 500 μl of LB broth, containing the appropriate antibiotics, between each reading.
5. Allow cultures to grow until the OD 600 reading ranges between 0.8 to 1.0.
6. In a sterile 15 ml tube add 5.0 ml of culture and 5.0 ml of conservation stock. Mix thoroughly before proceeding to step 7.
7. Aliquot 500 μl into fully labelled sterile cyrotubes. Invert all tubes before snap freezing in liquid nitrogen. Store at −80° C. until required. Discard any stock if shown to be PCR negative.
PCR Analysis of Agrobacterium
[0000]
1. Add 1 μl of Agrobacterium culture to 9 μl of sterile MQ H2O in a sterile PCR tube.
2. Incubate cells at 98° C. for 5 mins. Transfer tubes to ice.
3. Add 10 μl of the prepared 2×PCR master mix. 10 μl of 2×PCR master mix contains the following:
[0000]
10 × Dynazyme Buffer
2 μl
10 mM dNTPs
1.0 μl
10 μM forward primer (10 μM)
1.0 μl
10 μM reverse primer (10 μM)
1.0 μl
Dynazyme II polymerise
1 μl
MQ water
3 μl
4. Include a positive control (50 ng of the original plasmid DNA) and a negative control (no template DNA). Carry out a total of 35 cycles using standard PCR conditions
1. 95′C for 3 mins 2. 94° C. for 30 secs 3. 55° C. for 30 secs 4. 72° C. for 1 mins 5. 72° C. 10 mins Repeat steps 2 to 4 a total of 35 times.
5. Analyse the PCR product on a 1% agarose gel.
Comments
[0474] Wear gloves while handling Agrobacterium . Collect and autoclave all bacterial and DNA waste. Gene pulser cuvettes are reusable: Soak lids in 70% EtOH and autoclave cuvettes in a closed container with water to remove Agrobacterium . Cuvettes can then be stored in 70% EtOH and be reused after drying.
[0000] In Planta Transformation of Arabidopsis thailana
Experimental Procedure
Preparation of Plant Material
[0000]
1. Fill seedling punnets with seed raising mixture to form a mound. Cover with two layers of anti-bird netting and secure with rubber bands at each end. Saturate the soil by sitting punnets in a tray of water. Sow sufficient seed to obtain ˜40 plants per punnet.
2. Vernalise the seed by placing the punnets at 4° C. for 2-3 days. Transfer punnets to a growth chamber at 22° C. under fluorescent light (constant illumination, 55 μmol m −2 s −1 ) and feed with Miracle-Gro or Aquasol once per week.
3. Remove primary bolts when they appear and allow secondary bolts to grow until around 2-10 cm tall (this should take around 4-6 days, the plants should have numerous unopened floral buds and few siliques). Using forceps carefully remove any siliques or open flowers. Water plants well the day before infiltration so that the stomata will be open. Prior to infiltration saturate the soil with water to minimise absorption of bacterial solution into the soil.
4. Enter details into LWS to generate barcodes. Label punnets with LWS barcode details.
Preparation of Agrobacterium tumefaciens
1. In the morning inoculate 200 ml LB media containing the appropriate selection antibiotic (ie 100 mg/ml of spectinomycin for pPZP vector) with a single 500 μl starter culture of Agrobacterium conservation stock (section 5.1). Incubate for 24 hours at 27° C. in an orbital shaker at 250 rpm. A 200 ml culture is sufficient to infiltrate about 2 punnets of plants.
2. Centrifuge overnight cultures in 500 ml centrifuge bottles at 5500 g at room temperature for 15 mins to pellet cells. Discard the supernatant removing as much liquid as possible. Resuspend the pellet in infiltration media (see appendix 1) to an OD 600 reading of approximately 0.7 to 0.9
Agroinfiltration
[0000]
1. Place half of the Agrobacterium solution into a 250 ml vessel.
2. Invert the punnet immersing the entire plant including rosette leaves in the bacterial solution and shake gently to dislodge air bubbles. Co-cultivate the plants for 2 mins.
3. Remove the punnet and briefly drain, however, the thin layer of film surrounding the plants should be retained. Cover the plants with plastic film to maintain humidity and return to the growth room away from direct light. Autoclave waste solution and dispose of in a chemical waste drum for correct disposal.
4. Repeat steps one to three for all punnets of A. thaliana to be transformed.
5. Enter details into LWS to generate barcodes. Label individual punnets with LWS barcode details.
6. The next day, uncover the pots and place back into direct light. Water the plants until plants have fully developed siliques.
Seed Collection
[0000]
1. Once plants have dried out, remove the silique bearing stems and place them into a paper bag and leave to dry for one week at 37° C. Label bags with LWS barcode. Crush the dried siliques in the paper bag. This will shatter the siliques and release the seed.
2. Place a 200 micron sieve onto a fresh piece of A4 paper and tip the seed and crushed siliques into it. Tap the sieve gently allowing the seed to fall onto the paper underneath. Discard the plant material that remains in the sieve. Repeat this process until the majority of the plant material has been removed (note plant material can be a source of contamination in subsequent steps). Place seeds into a 1.7 ml microfuge tube and label with LWS barcode details. Place the tube into a small manila envelope and label with LWS barcode. Note that this barcode will relate back to the original transformation event.
3. Store seeds at −20° C. for 24 hours before transferring the seeds to 4° C. for storage.
Selection of Positive T 1 Transgenic Arabidopsis thaliana Plants
Surface Sterilisation of Seeds
[0000]
1. Working in a laminar flow hood, place seed to be sterilised (40 mg =˜2000 seeds per 150×15 mm plate) into a 2.0 ml microtube.
2. Add 1000 μl 70% ethanol and leave for two mins.
3. Remove the ethanol and add 1000 μl of seed sterilisation solution (4% chlorine:water:5% SDS at a ratio of 8:15:1 respectively) and mix thoroughly by vortexing.
4. Place the tubes on the Ratek ‘ferris wheel’ to ensure mixing of the seeds and solution, leave for ten mins.
5. In the laminar flow, remove the sterilisation solution and replace with sterile water. Vortex the tube(s) and spin for 30 seconds in a bench top centrifuge to sediment the seeds. Remove the water and replace with another 1 ml of sterile water. The seed washing steps should be repeated until no visible bubbles are apparent (at least 4 times). After the final wash, leave approximately 200 μl of water covering the seeds.
Selection of T 1 Transformants
[0000]
1. Prepare 150×15 mm plates with selection germination medium (SGM) containing the appropriate selection antibiotic (eg. Hygromycin at 8 mg/L for PZP200 series). Include Timentin (250 mg/L) to inhibit growth of Agrobacterium . Approximately 125 ml of SGM is required for each plate.
2. Working in a laminar flow hood, run a sterile scalpel across the surface of the SGM agar plate in a parallel fashion (see FIG. 4 ). This will help to spread the seeds.
3. Using a sterile 1 ml tips, with its end removed, pipette the sterilised seeds onto a plate. Distribute the seeds with a sterile disposable spreader.
4. Cold treat the seeds at 4° C. for two days, and then grow under continuous fluorescent light (55 μmol m −2 s −1 ) at 22° C.
5. When putative transformants are at the 6-8 leaf stage they can be transferred to soil. With a pair of forceps carefully remove plants from the tissue culture media ensuring the roots remain intact. Transplant into moist in-vitro mix soil using the ARASYSTEM (see FIG. 5 in appendix 2) Cover with a plastic tube. Create new LWS barcode and label tubes. Cover top of tubes with plastic wrap for a few days to assist recovery.
Verification of Integration of Transgene: Alkali-Treated Leaf Tissue as a Source of Genomic DNA
[0500] Three days after putative transformants have been transferred to soil, individual plants can be molecularly characterised for presence of the transgene using the following protocol.
1. Prepare a 1×PCR buffer mix for every alkali-treated leaf tissue to be tested (see below for details). 2. In a 1.7 ml microtube, add 200 μl of 0.25 M NaOH to a small young leaf (removed from a T 1 plant). 3. Immerse the tube in boiling water for 2 min. Note, to prevent lid popping during boiling, secure the lid with a microtube lid lock or pierce the lid with a fine needle. 4. After boiling, remove the tube from the water and add 200 μl of 0.25 M HCl and 100 μl of 0.25% (v/v) igepal [0.5 M Tris HCl pH 8.0]. Immerse the tube in boiling water for a further 4 mins. 5. Remove a small portion of the alkali-treated leaf (˜2 mm 2 ) and place in the pre-prepared PCR mix:
[0000]
10 × PCR reaction buffer (including Mg(SO4)•7H2O)
5.0
ml
10 mM dNTP's
1.0
μl
10 μM forward primer
1.0
μl
10 μM reverse primer
1.0
μl
PWO DNA polymerase
1.0
μl
MQ H2O
41.5
μl
6. Carry out 35 cycles using standard PCR conditions;
1. 95° C. for 3 mins 2. 94° C. for 30 secs 3. 55° C. for 30 secs 4. 72° C. for 1 mins 5. 72° C. 10 mins Repeat steps 2 to 4 a total of 35 times.
7. Analyse the PCR Product on a 1% Agarose Gel.
[0514] Note if an insert is not amplified using alkali-treated leaf tissue the first time, re-boil the tissue for a further 2 mins and repeat the PCR amplification of the transgene. If this second PCR fails, extract a small quantity of genomic DNA from leaf tissue using Qiagen plant genomic DNA extraction kit. Update LWS.
Seed Collection
[0000]
1. Once plants have dried out, remove the silique bearing stems and place them a paper bag and leave to dry for one week at room temperature. Label bags with LWS barcode. Crush the dried siliques in the paper bag. This will shatter the siliques and release the seed.
2. Place a 200 micron sieve onto a fresh piece of A4 paper and tip the seed and crushed siliques into it. Tap the sieve gently allowing the seed to fall onto the paper underneath. Discard the plant material that remains in the sieve. Repeat this process until the majority of the plant material has been removed (note plant material can be a source of contamination in subsequent steps). Place seeds into a 1.7 ml microfuge tube and label with LWS barcode details. Place the tube into a small manila envelope and label with LWS barcode. Note that this barcode will relate back to the original transformation event.
3. Store the T 2 seed at −20° C. for 24 hours (helps reduce chances of fungal contamination during selection for positive transgenic T 2 plants) before storing the seeds at 4° C.
Comments
[0518] All containers that come into contact with Agrobacterium , including the ARASYSTEM trays, holders, etc should be thoroughly cleaned using commercial bleach and 70% ethanol.
[0519] Depending on the experiment, T 1 plants can be used for phenotypic characterisation, i.e. reporter gene analysis, and it may not be necessary to continue these lines beyond the T 1 stage.
Generation of Homozygous T 3 Seeds
Introduction
[0520] The protocols detailed below describe the methods employed to select for homozygous plants carrying a single copy of a transgene. Integration of the transgene into Arabidopsis thaliana using the infiltration method occurs in the gynoecium prior to fertilisation of the ovary. Therefore any seeds produced by infiltration that carry the transgene are considered to be T 1 . T 1 seeds germinate to produce T 1 plants, which in turn produce T 2 seeds. The aim is to obtain at least five independent transgenic plants per construct that have a single insert and are expressing the transgene. Each LWS barcode generated for T 1 seeds represents a distinct transformation event. As each T 1 plant is harvested for T 2 seeds they are given a new LWS barcode number. This LWS barcode will relate back to the original transformation event.
Selection of T 2 Transformants to Generate T 3 Seeds
[0000]
1. Working in a laminar flow hood surface sterilise approximately 100 T 2 seeds (see section 7.1)
2. Plate out approximately 25 seeds per plate (4 in total) onto selection SGM media containing 250 mg/L timetin and 8 mg/L hygromycin (selection agent for pPZP200-35s-hph-35st).
3. Cold treat the seeds at 4° C. for two days then transfer to growth room with constant illumination (55 μmol·m −2 ·s −1 ) at 22° C.
4. After two weeks, segregation analysis of plants resistant or sensitive to hygromycin is performed.
5. When the putative transformants are at the 6 to 8-leaf stage, transfer at least 10 individual plants into soil using the Arasystem. Generate new LWS barcode (relates back to original transformation) and label each plant individually with the barcode. Cover tubes with plastic film for a few days to aid recovery.
6. To confirm that each individual plant has the transgene integrated, use the alkali treated leaf tissue method (section 7.3). Update LWS.
7. Once plants have dried out, remove the silique bearing stems and place them into a paper bag and leave to dry for one week at 37° C. Label bags with LWS barcode. Crush the dried siliques in the paper bag. This will shatter the siliques and release the seeds.
8. Place a 200 micron sieve onto a fresh piece of A4 paper and tip the seed and crushed siliques into it. Tap the sieve gently allowing the seed to fall onto the paper underneath. Discard the plant material that remains in the sieve. Repeat this process until the majority of the plant material has been removed (note plant material can be a source of contamination in subsequent steps). Place seeds into a 1.7 ml microfuge tube and label with LWS barcode details. Place the tube into a small manila envelope and label with LWS barcode. Note that this barcode will relate back to the original transformation event.
9. Store the seed at −20° C. for 24 hours (helps reduce chances of fungal contamination during selection for positive transgenic T 3 plants) before transferring the seeds to 4° C. for storage.
Segregation Analysis
[0000]
1. Score the total number of T 2 plants from each line that is either resistant or sensitive to hygromycin.
2. If the T-DNA is inserted at one locus, the ratio of resistant to sensitive plants should be 3:1. If the T-DNA locus is inserted at two loci, the ratio of resistant to sensitive plants should be 15:1. If the T-DNA is inserted at more than two loci, the ratio of resistant to sensitive plants should be >15:1.
3. Use the Chi-square (χ2) statistical test to determine how well the segregation data fits a particular hypothesis.
4. Continue growing transgenic lines that Chi-square analysis indicated contained a single copy of the transgene.
5. Update LWS
Verification of Integration of Transgene: Alkali-Treated Leaf Tissue as a Source of Genomic DNA
[0000]
1. Harvest one small leaf for each T 2 plant.
2. Follow alkali-treated leaf protocol (section 7.3) to determine presence of a transgene.
3. Update LWS.
Selection for Homozygous T 3 Lines
[0000]
1. Continue growing T 2 transgenic lines that indicate that they contain a single insertion of the transgene.
2. Collect T 2 seeds (section 8.2), and update LWS and generate new barcodes.
3. Germinate ˜40 T 3 seeds on SGM
4. After 2 weeks score the total number of T 3 plants from each line that is either resistant or sensitive to hygromycin.
5. Homozygous T 3 lines will be indicated by the absence of sensitive plants.
6. When the putative transformants are at the 6 to 8-leaf stage, transfer at least 20 individual plants into soil using the Arasystem. Generate new LWS barcode and label each plant individually with the barcode. Cover tubes with plastic film for a few days to aid recovery.
7. To further validate that a line is homozygous for a single insertion use the alkali treated leaf tissue method (section 7.3) to confirm that all plants contain a transgene. Update LWS.
8. Harvest sufficient material from putative homozygous lines to perform a Southern Hybridisation to confirm transgene integrated number. Update LWS.
9. Harvest seeds from T 3 homozygous lines following the protocol set out in section 8.2.
REFERENCES
[0000]
Caimi P G, McCole L M, Klein T M, Hershey H P. 1997. Cytosolic expression of the Bacillus amyloliquefaciens SacB protein inhibits tissue development in transgenic tobacco and potato. New Phytologist 136, 19-28
Caimi P G, McCole L M, Klein T M, Kerr P S. 1996. Fructan accumulation and sucrose metabolism in transgenic maize endosperm expressing a Bacillus amyloliquefaciens sacB gene. Plant Physiology 110, 355-363
Cairns A J. Fructan biosynthesis in transgenic plants. 2003. J Expt Biol 54: 549-67
Clough, S. J. and Bent, A. F., 1998. Floral dip: a simplified method for Agrobacterium -mediated transformation of Arabidopsis thaliana . The Plant Journal 16: 735-743.
Ebskamp M J M, van der Meer I M, Spronk B A, Weisbeek P J, Smeekens S C M. 1994. Accumulation of fructose polymers in transgenic tobacco. Bio/Technology 12, 272-275
Hattori T, Nakagawa T, Maeshima M, Nakamura K, Asahi T (1985) Molecular cloning and nucleotide sequence of cDNA for sporamin, the major soluble protein of sweet potato tuberous roots. Plant Mol Biol 5: 313-320
Klimyuk, V. I., Carroll, B. J. Thomas, C. M. and Jones, J. D. (1993) The Plant Journal 3(3):493-494
Sasanuma, T. (2001). Characterization of the rbcS multigene family in wheat: subfamily classification, determination of chromosomal location and evolutionary analysis. Mol Genetics Genomics 265(1): 161-171.
Ye X D, Wu X L, Zhao H, Frehner M, Noesberger J, Potrykus I, Spangenberg G. 2001. Altered fructan accumulation in transgenic Lolium multiflorum plants expressing a Bacillus subtilis sacB gene. Plant Cell Reports 20, 205-212
Zeng, W. K., et al. (1995). PCR Amplification and Sequencing of a Wheat rbcS Gene Promoter. Acta Bot Sinica 37, 496-500.
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Genetic constructs capable of manipulating fructan biosynthesis in photosynthetic cells of a plant include a promoter, or functionally active fragment or variant thereof, operatively linked to a nucleic acid encoding a bacterial FT enzyme, or a functionally active fragment or variant thereof. Such constructs can be used in the modification of fructan biosynthesis in plants and, more particularly, to methods of manipulating fructan biosynthesis in photosynthetic cells, for increasing plant biomass and, more particularly, to methods of enhancing biomass yield and/or yield stability, including shoot and/or root growth in a plant, and for enhancing the productivity of biochemical pathways.
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CROSS-REFERENCE TO RELATED APPLICATION
This application claims priority to German Patent Application No. 10 2011 116 450.6, filed Oct. 20, 2011, which is incorporated herein by reference in its entirety.
TECHNICAL FIELD
The present disclosure relates to a safety device, in particular for a motor vehicle, with an elastic membrane which delimits a hollow space, which is provided for the accident-initiated filling subject to elastic expansion of the membrane.
BACKGROUND
From DE 195 46 143 A1 a safety device for a motor vehicle is known, wherein an expandable bladder of rubber or latex is inflated.
Elastomers, in particular rubber, comprise active substances which over the course of time escape from the material, in particular outgas. In particular, such active substances can be aromatic substances, allergens or other harmful substances. For example, rubber emits aromatic substances which are perceived as unpleasant by many persons. Such active substances escaping from an elastic membrane of corresponding material impair its use in safety devices, in particular when these are arranged in spatial proximity to persons, so that these are exposed to the escaping active substances in higher concentration.
Accordingly, it is desirable to make available an improved safety device.
SUMMARY
According to an embodiment, a safety device comprises an elastic membrane, which partially or completely delimits at least one hollow space, which is provided for the accident-initiated filling subject to elastically expand the membrane.
A membrane is a body the wall thickness of which relative to its surface in a state that is not elastically deformed is small, in particular a body wherein the quotient of wall thickness divided by surface area is a maximum of 0.05%, for example a maximum of 0.01%, as is the case for example with a rectangular plate having 10 cm side length and 1 mm wall thickness (1/(100×100)=0.01%). An elastic membrane is a membrane which is highly deformable elastically, in particular a membrane, the elongation at break of which, for example in the tensile test according to DIN53504, is at least 100% and at least 500% and/or the modulus of elasticity of which at room temperature is a maximum of 0.5 GPa, for example a maximum of 0.1 GPa. An elastic membrane in one embodiment comprises one or a plurality of elastomers, and in some embodiments it consists of this elastomer or these elastomers. An elastomer can be in particular natural or synthetic rubber, silicone or a thermoplastic elastomer (TPE).
A hollow space can, at least substantially, be entirely or wholly delimited by the elastic membrane in that it is embodied in a double-walled or hose-like manner. This makes available a lot of expansion material and can thus make possible a greater expansion. Equally, a hollow space can only be partially delimited by the elastic membrane in that it is single-walled and fastened to a carrier, by its edge, in an at least substantially fluid-tight manner, which carrier in turn defines a wall of the hollow space. Relative to a double-walled embodiment, this can reduce the installation space. In particular, the carrier can be fastened to a structural element of a motor vehicle or form such. Equally, a carrier can form a housing of the safety device, in particular of the gas generator, or form part of such a housing.
According to an aspect, the membrane is covered by a separate envelope in a gas-tight manner. Generalizing, gas-tight is to mean that the envelope covers the membrane in such a manner that at least one undesirable active substance, which escapes from the membrane, does not penetrate the envelope, at least not substantially. In particular, the envelope can form a barrier for this active substance, so that it at least substantially does not reach a person, in particular an occupant of a motor vehicle with a safety device according to the present disclosure. Covering is to mean that the envelope hermetically covers the membrane either alone or together with a carrier, to which the envelope is fastened in a gas-tight manner.
The separate envelope is provided for the opening through the expansion of the membrane. Here, the envelope can be at least partially destroyed, in particular disassembled or torn. To this end, it can comprise one or a plurality of predetermined opening points, which can in particular be defined through a material weakening. In addition or alternatively, a detaching of the envelope from a carrier can be provided through the expansion of the membrane.
In one embodiment, the envelope is designed flexibly. This can facilitate in particular the stowage of the membrane and/or improve the haptic impression of the safety device. In particular, the envelope can be a single or multiple-layer foil, wherein at least one layer can be designed as barrier for an active substance escaping from the membrane.
Equally, the envelope can be designed dimensionally stable. In particular, it can thus simultaneously act as a carrier, to which the membrane is fastened, and in some embodiments as a housing or part of a housing, in which the membrane is received.
In one embodiment, the envelope is connected to a carrier through material joining, for example through vulcanizing, gluing and/or welding. Additionally or alternatively, it can also be detachably fastened to the carrier, for example through screwing, or through caulking. As explained above, the carrier can act as housing or part of a housing in which the membrane is received. The envelope can also be designed as a coating, which is gas-tight relative to one or a plurality of the active substances, in particular allergens, aromatic substances and/or pollutants escaping from the membrane.
In a one embodiment, the envelope is additionally or alternatively fastened to the membrane in a materially joined manner, for example through vulcanizing, gluing and/or welding. This can prevent a relative movement and thus a chafing between the membrane and the envelope.
According to a further aspect, which can be combined with the aspect of the gas-tight envelope explained above, the safety device comprises one or a plurality of catalysts for removing one or a plurality of active substances escaping from the membrane.
Active substances escaping from the membrane can in particular be aromatic substances, allergens and/or pollutants. Through a suitable catalyst, these are removed, entirely or at least partially through oxidation or oxidative reactions, in oxygen, water and/or other reaction products.
A catalyst can in particular comprise one or a plurality of metals, in particular at least one precious metal, such as silver, gold, platinum, iron and/or titanium, a salt and/or an oxide thereof, for example titanium oxide TiO2.
In addition or alternatively to one or a plurality of catalysts, the safety device can comprise one or a plurality of overlaying active substances for the active overlaying of one or a plurality of active substances escaping from the membrane. An overlaying active substance comprises at least one fragrant substance, for example a citrus, pine, rose or other fragrance. In particular, an overlaying active substance can comprise or be an ethereal oil. An active overlay here is to mean in particular that the overlaying active substance has the same active mechanism as the active substances escaping from the membrane, for example an olfactory effect. Thus, the overlaying of a smell of the elastic membrane in particular with a fragrant substance it is possible to arrange the safety device in spatial proximity to a person, in particular in an interior of a motor vehicle, on an item of clothing or the like.
One or a plurality of catalysts and/or overlaying active substances can be arranged in particular in the membrane. To this end, the membrane can be suitably produced, doped, impregnated, coated or the like. Additionally or alternatively, one or a plurality of catalysts and/or overlaying active substances can be arranged on a carrier, on which the membrane is fastened and/or on in particular, in a separate envelope, which covers the membrane in a gas-tight manner and is provided for the opening through the expansion of the membrane. Carrier and/or envelope can be produced, doped, impregnated, coated or the like with the catalyst or catalysts and/or overlaying active substances.
In addition or alternatively, it is possible to arrange one or a plurality of catalysts and/or overlaying active substances adjacent to the membrane. By means of this, active substances escaping from the membrane can also be efficiently removed or overlayed. In particular, a catalyst carrier and/or an overlaying active substance storage unit can be arranged on, in particular, in a housing or an envelope in which the membrane is received.
In one embodiment, one or a plurality of catalysts are present in each case in particle form, wherein the particle size amounts to a maximum of 500 nm, in particular to a maximum of 100 nm and to a maximum of 25 nm. Such nano particles can be added during the production of membrane, carrier, in particular housing, and/or envelope, they are equally suitable for subsequent coating.
In a further embodiment, the safety device comprises a filling fluid source. This can comprise a control device which is equipped in order to fill one or a plurality of hollow spaces of the safety device on the basis of an activation signal, which is transmitted to the control device for example from one or a plurality of spacing, deceleration, deformation and/or force sensors. To this end, the control device can comprise a computer unit for processing the activation signal, a valve device in order to fluidly connect the filling fluid source to the hollow space or to the hollow spaces, and/or an ignition device for the pyrotechnical liberation of filling fluid. A filling fluid source is equipped in particular for the accident-initiated filling when it automatically initiates, in particular carries out the filling as soon as an imminent or occurred accident has been detected.
The filling fluid source can comprise one or a plurality of pyrotechnical and/or pressure gas generators. These can be connected to the hollow space or hollow spaces via one or a plurality of filling fluid lines and be spaced from these. In a further embodiment, the filling fluid source comprises one or a plurality of micro gas generators (MGG). In a further embodiment, these can be designed as a structural unit with the membrane and be arranged directly on or even in a hollow space. In one embodiment, the filling fluid source is at least partially fastened to a carrier, to which the membrane is also fastened.
The membrane can be designed in single or multiple layers. In particular, reinforcing elements such as, for example, bands, areal elements or nets, of textile material, can be locally arranged on a membrane, which have a greater modulus of elasticity and therefore expand less during inflating. Reinforcing elements can be connected at certain locations or substantially with a complete side to the inside and/or outside of the membrane in a materially joined manner, for example glued, welded, laminated-in or vulcanized thereon. The elastic membrane then expands during inflating in a substantially tied-up manner through reinforcing elements connected to it in certain locations and acting as catching bands or in addition to the reinforcing elements that are completely connected to it, so that these influence the shape and expansion characteristic of the inflated membrane.
In various embodiments, a safety device is used in a motor vehicle, in particular in a passenger car, wherein the hollow space is provided for catching an occupant. Equally, the safety device can be, for example, on an item of clothing in order to protect its wearer in the event of an accident.
BRIEF DESCRIPTION OF THE DRAWINGS
The present disclosure will hereinafter be described in conjunction with the following drawing figures, wherein like numerals denote like elements, and:
FIG. 1 illustrates a safety device according to an embodiment of the present disclosure in cross section; and
FIG. 2 illustrates a safety device according to a further embodiment of the present disclosure realized corresponding to FIG. 1 .
DETAILED DESCRIPTION
The following detailed description is merely exemplary in nature and is not intended to limit the disclosure or its application and uses. Furthermore, there is no intention to be bound by any theory presented in the preceding background or the following detailed description.
FIG. 1 shows in cross section a safety device according to one embodiment with a carrier 3 of plastic, which has an open, U-shaped cross section. An opening 3 . 3 of the carrier 3 is spanned by an elastic membrane 1 of synthetic or natural rubber, which is fastened on the edges to the carrier 3 in a materially joined manner, for example vulcanized on or glued.
A film-like separate envelope 2 hermetically covers the membrane 1 towards the surroundings. To this end, it engages over the membrane 1 and is fastened to the carrier 3 in a materially joined manner, for example glued. Additionally or alternatively it can also be glued to the membrane 1 (not shown).
The envelope 2 is designed as an olfactory barrier, which is at least substantially tight with respect to aromatic substances, in particular a rubber smell of the membrane 1 . In this manner, the membrane 1 can be used in particular without further treatment in a safety device, which is only or also separated from a passenger interior of a motor vehicle through the envelope 2 .
In the case of an accident, a gas generator 4 fills a hollow space partially defined by the membrane 1 , partially by the carrier 3 , as a result of which the membrane 1 expands elastically and forms an impact cushion for catching a passenger. In the process, the membrane 1 tears the film-like envelope 2 .
In a representation corresponding to FIG. 1 , FIG. 2 shows a safety device according to a further embodiment. Elements corresponding to the embodiment described above are designated through identical reference characters, so that in the following only the differences to the embodiment according to FIG. 1 are discussed.
With the embodiment according to FIG. 2 , the hose-like membrane 1 ′ delimits the hollow space entirely, i.e. without the carrier, and to this end is designed in a double-walled manner and connected to the gas generator 4 . With an outside, the membrane 1 ′ is fastened in a materially-joined manner to a structural element 3 . 2 of the motor vehicle, for example glued on, which forms a carrier for the membrane 1 ′.
Additionally to the envelope 2 , the membrane is covered by a housing lid 3 . 2 of plastic, which is fastened to the structural element 3 . 2 in a gas-tight manner, for example glued on or welded on, and itself is designed in a gas-tight manner. In this case, the envelope 2 can be omitted. Advantageously, the covering function with respect to the active substances, in particular pollutants and/or aromatic substances escaping from the membrane 1 ′ is integrated in the housing lid 3 . 1 , which acts as a dimensionally stable envelope. Equally, the housing lid 3 . 2 itself and/or its fastening on the structural element 3 . 2 can be designed not gas-tight and thus simpler and active substances escaping from the membrane 1 ′ be retained through the flexible, film-like envelope 2 . The gas-tight envelope 2 can also be provided, as in the exemplary embodiment of FIG. 2 , in addition to a gas-tight housing lid 3 . 1 , which is also fastened to the structural element 3 . 2 in a gas-tight manner, in order to form a second barrier and/or retain active substances escaping from the membrane 1 ′ even upon an opening of the housing lid 3 . 1 . Generally, a film-like envelope 2 and an inherently stiff envelope, as in this case in the form of a housing lid 3 . 2 , can also be gas-tight relative to different active substances escaping from the membrane 1 ′, for example through suitable materials, coatings or the like.
In addition or alternatively to the hermetic covering of the membrane through one or a plurality of envelopes 2 , 3 . 1 described above, as shown in FIG. 2 , a catalyst and/or fragrance storage unit 5 can be arranged on the surface of the housing lid 3 . 1 facing the membrane 1 ′. Through a catalyst, active substances, especially when the housing lid 3 . 1 has no barrier function and no envelope 2 is provided, in particular an elastomer smell of the membrane 1 ′ can be removed and thus neutralized. Equally, through a fragrance storage unit, which gives off fragrances, an elastomer smell of the membrane 1 ′ can be overlayed and thus largely be neutralized olfactorily.
Additionally or alternatively, a catalyst and/or fragrance storage unit can also be arranged on the carrier 3 ( FIG. 1 ) or 3 . 2 ( FIG. 2 ), on which the membrane 1 ( FIG. 1 ) or 1 ′ ( FIG. 2 ) is fastened.
While at least one exemplary embodiment has been presented in the foregoing detailed description, it should be appreciated that a vast number of variations exist. It should also be appreciated that the exemplary embodiment or exemplary embodiments are only examples, and are not intended to limit the scope, applicability, or configuration of the invention in any way. Rather, the foregoing detailed description will provide those skilled in the art with a convenient road map for implementing an exemplary embodiment, it being understood that various changes may be made in the function and arrangement of elements described in an exemplary embodiment without departing from the scope of the invention as set forth in the appended claims and their legal equivalents.
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In various embodiments, a safety device for a motor vehicle is provided. The safety device includes an elastic membrane, which partially or completely delimits a hollow space, which is provided for an accident-initiated filling subject to elastically expand the membrane. The elastic membrane is covered by a separate envelope in a gas-tight manner, which provides an opening through the expansion of the membrane.
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a divisional of U.S. patent application Ser. No. 12/869,479 filed on Aug. 26, 2010, which claims the benefit of U.S. Provisional Patent Application No. 61/237,572 entitled “METHODS AND APPARATUS FOR MANIPULATING AND DRIVING CASING,” filed Aug. 27, 2009, the disclosure of which is incorporated herein in its entirety by this reference.
TECHNICAL FIELD
Embodiments of the present invention relate to manipulating casing for subterranean well bores. More particularly, embodiments of the present invention relate to methods and apparatus for gripping and rotating casing by the interior thereof from the earth's surface, which methods and apparatus may be employed to drill or ream with casing.
BACKGROUND
It is known in the art of subterranean drilling to use a so-called “top drive” to connect a section, also known as a “joint,” of well bore casing above a drilling rig floor to the upper end of a casing string substantially disposed in the well bore. Such casing strings, commonly termed “surface casing,” may be set into the well bore as much as 3,000 feet (914.4 meters), and typically about 1,500 feet (457.2 meters), from the surface.
Examples of methods and apparatus for making casing joint connections to a casing string are disclosed in U.S. Pat. Nos. 6,742,584 and 7,137,454, the disclosure of each of which patents is incorporated herein by this reference.
It is known in the art of subterranean drilling to drill and ream with casing, using a drilling or reaming shoe including a cutting structure thereon to drill a well bore, or to ream an existing well bore to a larger diameter, to remove irregularities in the well bore, or both. It would be highly desirable for the subterranean drilling industry to employ a top drive to apply weight on the casing in combination with casing rotation to drill or ream with casing using a drilling or reaming device at the distal end of the casing string.
BRIEF SUMMARY
In one embodiment, the present invention comprises a casing assembly having a longitudinal passage therethrough in communication with a plurality of circumferentially spaced, radially movable pistons and extending to at least one outlet of the lower end of the assembly, a plurality of selectively mechanically actuable, radially movable slips, a plurality of spring-biased friction blocks longitudinally spaced from the slips, a downward-facing packer cup positioned between the slips and the at least one outlet, and a tapered stabilizer guide below the downward-facing packer cup.
In another embodiment, the present invention comprises a method of manipulating casing comprising inserting an assembly into an upper end of a casing joint, gripping the casing joint by an interior thereof with the assembly responsive to longitudinal movement of one portion of the assembly with respect to another portion of the assembly, pumping drilling fluid through the assembly to cause the assembly to grip the interior of the casing joint responsive to hydraulic pressure of the drilling fluid, preventing drilling fluid from exiting the upper end of the casing joint, and rotating the casing joint.
Another embodiment comprises a method of driving casing, including engaging an uppermost casing joint of a casing string having a device with a cutting structure thereon at a lower end thereof substantially only on an interior of the uppermost casing joint, rotating the casing string by application of torque to the interior of the uppermost casing joint and applying weight to the casing string during rotation thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a partial sectional elevation of a casing drive assembly according to an embodiment of the present invention.
FIG. 1B is a detail view of FIG. 1A showing a hydraulic anchor of the casing drive assembly.
FIG. 1C is a detail view FIG. 1A showing a mechanical spacing spear of the casing drive assembly.
FIG. 1D is a detail view of FIG. 1A showing a cup type packer and a tapered stabilizer of the casing drive assembly.
FIG. 2 is a schematic of a casing drive assembly, such as shown in FIG. 1A , disposed within a casing joint of a casing string above another casing joint.
DETAILED DESCRIPTION
The illustrations presented herein are not actual views of any particular drilling system, assembly, or device, but are merely idealized representations which are employed to describe embodiments of the present invention.
While embodiments of the present invention are described herein with respect to manipulation of, and drilling with, casing, it is also contemplated that an appropriately sized drive assembly may be used to engage, rotate, and apply weight for drilling with any suitable tubular goods having sufficient longitudinal compressive and torsional (shear) strength to withstand application of longitudinal force and torque for drilling. Accordingly, as used herein, the term “casing” means and includes not only convention casing joints but also liner joints, drill pipe joints, and drill collar joints. In addition, multiple-joint assemblies, termed “stands,” of any and all of the foregoing tubular goods may be used with, and manipulated by, embodiments of the apparatus of the present invention.
As used herein, the terms “upper,” “lower,” “above,” and “below,” are used for the sake of clarity in a relative sense as an embodiment of the casing drive assembly is oriented during use to manipulate and drive a casing joint or string.
Referring to FIG. 1A of the drawings, an embodiment of a casing drive assembly 10 according to the present invention comprises, from an upper to a lower end thereof, a hydraulic anchor 100 , a mechanical casing spear 200 , a cup type packer 300 , and a tapered stabilizer 400 .
As shown in FIG. 1B , the hydraulic anchor 100 comprises a housing 102 having a circumferential stop collar 106 about the upper end thereof for limiting insertion of the casing drive assembly 10 into a casing joint. The housing 102 includes a longitudinal passage 104 extending therethrough from top to bottom, in communication with lateral passages 108 extending to the interiors of spring-loaded, inwardly biased pistons 110 in two longitudinally separated groups, each group comprising a plurality of pistons 110 (in this instance, four) equally circumferentially spaced in pockets 112 in the housing 102 . Seals (not shown) enable fluid-tight movement of the pistons 110 in the pockets 112 responsive to a drilling fluid pressure within the longitudinal passage 104 . The pistons 110 comprise gripping structures 114 on exterior surfaces 116 thereof, as is conventional in the art. Such gripping structures 114 may comprise, by way of non-limiting example, machined teeth, crushed tungsten carbide, tungsten carbide inserts in the form of bricks, buttons or discs, superabrasive elements such as natural or polycrystalline diamond, or a combination thereof. In one embodiment, gripping structures comprise carbide inserts configured with teeth.
Secured to the lower end of the hydraulic anchor 100 is the casing spear 200 , which may be configured substantially as a Baker Oil Tools (Tri-State) Type “D” Casing Spear. As shown in FIG. 1C , the casing spear 200 comprises a mandrel 202 having a longitudinal passage 204 extending therethrough and in communication with the longitudinal passage 104 of the hydraulic anchor 100 . An outer housing 206 is longitudinally slidably and rotationally disposed over the mandrel 202 , longitudinal movement of the outer housing 206 being constrained by engagement of a lug 208 protruding radially from the mandrel 202 through a J-slot 210 having a longitudinally extending segment L and a laterally extending segment LA, the lug 208 extending through the wall of outer housing 206 . A plurality of slips 212 is disposed in a like plurality of slots 214 extending through the outer housing 206 . The slips 212 include lips 216 at longitudinally upper and lower ends thereof to retain the slips 212 within the slots 214 . The interior of the slips 212 comprise a plurality of stepped wedge elements 218 having concave, partial frustoconical radially inner surfaces 220 . The outer surfaces 222 of the slips 212 comprise gripping structures 224 , as is conventional in the art. Such gripping structures 224 may comprise, by way of non-limiting example, machined teeth, crushed tungsten carbide, tungsten carbide inserts in the form of bricks, buttons or discs, superabrasive elements such as natural or polycrystalline diamond, or a combination thereof. In one embodiment, gripping structures comprise tungsten carbide inserts in the form of buttons having four projecting, pyramidal points. Two longitudinally extending groups of eight to ten buttons per slip 212 may be employed.
Inner surfaces 220 of stepped wedge elements 218 are sized and configured to cooperate with stepped convex, frustoconical wedge surfaces 226 on an exterior surface of the mandrel 202 to move the slips 212 radially outwardly responsive to upward movement of the mandrel 202 within the outer housing 206 . A plurality of circumferentially spaced stabilizer friction blocks 228 are radially outwardly biased by springs 230 and are disposed within slots 232 in outer housing 206 and retained therein against the outward spring biased by lips 234 at upper and lower ends of the stabilizer friction blocks 228 . A lower housing 236 is secured to the lower end of the mandrel 202 .
Secured to the lower housing 236 of the casing spear 200 at the lower end thereof is a packer mandrel 302 of the cup-type packer 300 , as shown in FIG. 1D , the cup-type packer 300 having a longitudinal passage 304 therethrough in communication with the longitudinal passage 204 of casing spear 200 . A downward-facing, elastomeric, wire mesh-reinforced annular packer cup 308 is disposed over the upper mandrel 302 and retained thereon between an annular support wedge 310 abutting a downward-facing annular shoulder 312 and the upper end of a guide sleeve 314 , from which an annular, radially projecting casing guide 316 projects. The casing guide 316 comprises frustoconical upper and lower surfaces 318 , 320 longitudinally separated by a cylindrical guide surface 322 , circumferentially spaced, longitudinally extending slots 324 communicating between the upper and lower surfaces 318 , 320 .
As further shown in FIG. 1D , the tapered stabilizer 400 is secured at its upper end 402 to the lower end of the packer mandrel 302 , and includes a longitudinal passage 404 in communication with the longitudinal passage 304 of the cup-type packer 300 . The longitudinal passage 404 extends to, and communicates with, outlet slots 406 extending through an outer surface of a frustoconical, tapered stabilizer guide 408 terminating at a nose 410 .
In use, and with reference to drawing FIGS. 1A , 1 B, 1 C, 1 D and 2 , wherein a casing joint 500 is shown disposed above another casing joint 502 , a single joint of casing 500 is picked up using the rig elevators, as is conventional, and stabbed up into an existing casing joint 502 (if a casing string has already been started). The casing drive assembly 10 is made up with and suspended from a top drive via a slack joint, and lowered by the top drive into the bore of the casing joint 500 from the top thereof. The elevators stay latched and ride down the casing joint 500 during this operation. Once the casing drive assembly 10 has entered casing joint 500 sufficiently so that stop collar 104 arrests further travel of casing drive assembly 10 into the casing joint 500 , casing joint 500 is rotated to engage casing joint 502 . The casing joint 500 may be run up with the rig tongs or casing drive assembly 10 may be used to transmit rotation to the casing joint 500 once it is fully engaged with casing joint 500 , after engagement with the interior of casing joint 500 , as described below. The tapered stabilizer guide 408 , the casing guide 316 and the spring-biased friction blocks 228 aid insertion and centering of the casing drive assembly 10 into and within the casing joint.
If the casing joint 500 is the first joint in the casing string, a cutting structure, such as a drilling or reaming device, is made up with the lower end thereof prior to insertion of casing drive assembly 10 . Non-limiting examples of such devices are, for drilling, the EZ Case™ casing bit and, for reaming, the EZ Ream™ shoe. Otherwise, such a device 504 is already secured to the distal end of the lowermost casing joint in the casing string. To initially engage the casing drive assembly 10 with the interior of casing joint 500 , the casing spear 200 is manipulated, as by right-hand (clockwise, looking downward) rotation of the casing drive assembly 10 to move the lug 208 within the laterally extending segment LA of the J-slot 210 and align the lug 208 with the longitudinal segment L of the J-slot 210 , followed by application of an upward force to the casing drive assembly 10 . The spring-biased friction blocks 228 provide sufficient, initial frictional drag against the interior of the casing joint 500 to maintain the outer housing 206 of the casing spear 200 stationary within the casing joint 500 until the gripping structures 224 on the outer surfaces 222 of the slips 212 engage the interior of the casing joint 500 as the stepped convex, frustoconical wedges surfaces 226 of the mandrel 202 move upwardly with respect to the stepped wedge elements 218 on the interior surfaces 220 of the slips 212 and force the slips 212 radially outwardly to securely grip the interior of the casing joint.
The engaged casing joint 500 is then lifted using the top drive to permit slips of a holding device at the rig floor, commonly termed a “spider,” which are employed to suspend the existing casing string below the rig floor, as is conventional.
The rig pump may then be engaged and circulation of drilling fluid established through the casing drive assembly 10 through the longitudinal passages 104 , 204 , 304 and 404 and out into the interior of the casing joint 500 through the outlet slots 406 . Upward circulation of drilling fluid within the casing joint 500 is precluded by the packer cup 308 , which expands against and seals with the interior of the casing joint 500 under drilling fluid pressure, a prompt and fluid-tight seal being facilitated by the presence of the slots 324 of the casing guide 316 . Drilling fluid pressure is increased until sufficient pressure is observed to cause the pistons 110 of the hydraulic anchor 100 to grip the interior of the casing joint 500 .
The casing drive assembly 10 , with the casing joint 500 secured thereto by the hydraulic anchor pistons 110 , is then rotated by the top drive to rotate the casing joint 500 and any others therebelow (if any) in the casing string, the top drive also providing weight, and drilling or reaming commences. Notably, both torque and weight are applied to the casing joint 500 via engagement of the casing drive assembly 10 substantially only with the interior of the casing joint 500 .
The rig elevators remain attached as the casing joint 500 descends until a point just above the rig floor, where they can be reached and released for picking up the next casing joint. When the upper end of the casing joint 500 , engaged by the casing drive assembly 10 , approaches the rig floor, the slips of the spider are then employed to grip the casing joint 500 , drilling fluid circulation ceases, releasing the pistons 110 of the hydraulic anchor 100 from the casing joint under their inward spring-loading, the casing drive assembly 10 is lowered sufficiently to release the slips 210 of the casing spear 200 from the casing joint and rotated slightly to the left (counterclockwise, looking downward) to maintain the release of the slips 212 , and the casing drive assembly 10 is withdrawn from the casing joint 500 for subsequent insertion into another casing joint picked up by the rig elevators, the above-described process then being repeated.
A significant advantage of the use of a casing drive assembly according to an embodiment of the present invention is reduced casing thread wear, due to the lack of a threaded connection between the casing drive assembly and the casing joint engaged thereby.
While particular embodiments of the invention have been shown and described, numerous variations and alternate embodiments will occur to those skilled in the art. Accordingly, it is intended that the invention only be limited in terms of the appended claims and their legal equivalents.
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An apparatus and methods for manipulating and driving casing. The apparatus includes mechanically responsive elements for gripping an interior of a casing joint, and hydraulically responsive elements for gripping an interior of the casing joint responsive to pressure of drilling fluid flowing through the apparatus. One method comprises manipulating a casing joint by mechanically gripping an interior thereof, hydraulically gripping the interior of the casing joint responsive to drilling fluid pressure, and rotating the casing joint. Another method comprises driving casing by applying weight and torque thereto through engagement with an interior thereof.
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CROSS REFERENCE TO RELATED APPLICATION
This is a continuation of U.S. application Ser. No. 10/246,470, filed Sep. 19, 2002, now U.S. Pat. No. 6,684,639, the subject matter of which is incorporated by reference herein.
BACKGROUND OF THE INVENTION
1. Filed of the Invention
The present invention relates to a combustion turbine power generating system that can realize high efficient and high reliable operation and method of controlling the same.
2. Description of Related Art
As disclosed in JP-A-09-289776, in a case of a conventional combustion turbine power generating system, a command value for number of revolutions is calculated from a load power to be outputted and the command value for the number of revolutions is inputted to a turbine controller to control the number of revolutions for a combustion turbine, thereby controlling the number of revolutions for a power generator.
In the above technique, the command value for the number of revolutions is calculated from the output power of the turbine on the basis of the knowledge that the output power of the turbine is proportional to its the number of revolutions.
The turbine controller adjusts a quantity of fuel to be fed on the basis of the command value for the number of revolutions calculated as above and controls the number of revolutions. However, since the efficiency of turbine is influenced by a temperature of suction air or the like, the turbine cannot be always operated at the number of revolutions that the highest efficiency and a low Nox (nitrogen oxide) are attained for a certain fuel quantity. Accordingly, it is difficult that the efficiency of the turbine is always kept to be high.
SUMMARY OF THE INVENTION
It is an object of the present invention to make power generation at high efficient state of turbine by controlling the number of revolutions of a power generator.
According to an aspect of the present invention, in a combustion turbine power generating system for supplying an output of turbine to an electric power system through a power generator and a power converter capable of converting the power between AC current and DC current, the speed of power generator is always controlled by means of the power converter connected to the power generator.
Further, an optimum speed command is produced from state quantity of the turbine and the speed of power generator is controlled on the basis of the optimum speed command by means of the power converter connected to the power generator.
Moreover, when a fuel quantity is varied by adjustment of fuel or the like and a current of the power generator is greater than a predetermined value, the speed of power generator is increased temporarily.
Other objects, features and advantages of the invention will become apparent from the following description of the embodiments of the invention taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram schematically illustrating the whole of a main circuit and a control system of a combustion turbine power conversion system according to an embodiment of the present invention;
FIG. 2 is a block diagram schematically illustrating a generator-speed control unit according to an embodiment of the present invention in detail;
FIG. 3 is a block diagram schematically illustrating a DC voltage control unit according to an embodiment of the present invention in detail;
FIG. 4 is a block diagram schematically illustrating a turbine control unit according to an embodiment of the present invention in detail;
FIG. 5 is a diagram explaining an optimum speed calculation unit of a turbine control unit according to a second embodiment of the present invention;
FIG. 6 is a block diagram schematically illustrating a generator-speed control unit according to a second embodiment of the present invention in detail;
FIG. 7 is a block diagram schematically illustrating a speed command calculation unit according to a second embodiment of the present invention in detail; and
FIG. 8 is a block diagram schematically illustrating another speed command calculation unit according to a second embodiment of the present invention in detail.
DETAILED DESCRIPTION OF THE EMBODIMENTS
An embodiment of a combustion turbine power generating system to which the present invention is applied is now described with reference to the accompanying drawings. FIG. 1 is a block diagram schematically illustrating the combustion turbine power generating system.
Referring to FIG. 1, a rotation axis 12 of a turbine 10 is connected to a shaft that supports a rotor 16 of a permanent-magnet generator 14 . The side of a stator 18 of the permanent-magnet generator 14 is connected to an AC side 22 of a converter 20 . The permanent-magnet generator 14 supplies an output power itself to the converter 20 in power generating operation and receives electric power from the converter 20 in motor operation.
DC terminals 24 and 26 of the converter 20 are connected to a DC side 32 of a converter 30 through a capacitor 28 . An AC output side 34 of the converter 30 is connected to a reactor 36 constituting an AC filter for eliminating harmonics. The converters 20 and 30 are constituted by well-known semiconductor switching elements and make conversion between AC current and DC current by turning a gate pulse on and off.
In this embodiment, in power generating operation, the converter 20 converts AC output power of the AC power generator 14 into DC power and the converter 30 converts DC output power from the converter 20 into AC power. Further, the converter 30 converts AC power from an electric power system 44 into DC power and supplies the DC power to the converter 20 . In motor operation, conversely, the converter 30 receives the AC power from the electric power system 44 and converts the AC power into DC power to supply the DC power to the converter 20 . The converter 20 converts the DC power into AC power and operates the AC power generator as an electric motor.
The reactor 36 is connected to a capacitor 38 and a reactor 40 constituting an AC filter. The two series-connected reactors 36 and 40 and the capacitor 38 connected to the junction thereof constitute a T-type AC filter. The reactor 40 is connected through a circuit breaker 42 to the electric power system 44 .
A DC voltage control unit 46 for the converter 30 is supplied with detection values S 1 and S 2 , a voltage detection value S 3 and a DC voltage command value S 4 to supply a gate signal S 5 to the converter 30 .
The detection values S 1 , S 2 and the voltage detection value S 3 are produced from a current detector 48 that detects a current flowing through the reactor 40 , a voltage detector 50 disposed on the side of the electric power system 44 of the reactor 40 , and a voltage detector 52 for the capacitor 28 disposed on the DC side of the converter 30 , respectively.
Further, a generator-speed control unit 54 connected to the converter 20 is supplied with a detection value S 6 and an optimum speed command value S 7 and supplies a gate signal S 8 to the converter 20 . The detection value S 6 and the optimum speed command value S 7 are produced from a current detector 56 for detecting a current produced by the permanent-magnet generator 14 and a turbine control unit 58 , respectively.
The turbine control unit 58 is supplied with a power detection value S 9 , a power command S 10 and state quantity S 11 such as temperature and pressure from the turbine 10 and supplies a fuel adjustment command S 12 to the turbine 10 .
A power detector 60 detects electric power from AC current S 1 and AC voltage S 2 and produces the power detection value S 9 . Further, the turbine control unit 58 supplies the optimum speed command value S 7 to the generator-speed control unit 54 connected to the power converter 20 .
FIG. 2 is a block diagram schematically illustrating the generator-speed control unit 54 connected to the converter 20 in detail. Referring to FIG. 2, the generator-speed control unit 54 is supplied with the optimum speed command value S 7 and the generator current detection value S 6 . The optimum speed command value S 7 is supplied to a subtracter 64 .
A phase detector 62 is supplied with output voltage command values S 13 and S 14 of a 2-phase/3-phase coordinate converter 68 and the generator-current detection value S 6 to calculate a phase signal Thg of an induced voltage from the power generator 14 by means of a sensor-less phase detection system. The phase signal is supplied to a 3-phase-to-2-phase coordinate converter 66 , the 2-phase-to-3-phase coordinate converter 68 and a speed calculation unit 70 .
The speed calculation unit 70 calculates a speed Omeg from the phase signal Thg of the induced voltage in accordance with the expression (1):
Omeg=Δθ/Δ t (1)
Δθ: increment of the phase signal Thg
Δt: variation of time
The subtracter 64 calculates a deviation between the optimum speed command value S 7 and the calculated speed value Omeg to supply the deviation to a speed regulator 72 . The speed regulator 72 can be constituted by, for example, a proportional integral controller. The speed regulator 72 regulates a q-axis current command value (torque current command value) S 15 so that the speed deviation is reduced to zero and supplies the command value to a subtracter 74 .
The 3-phase-to-2-phase coordinate converter 66 calculates a d-axis current (excitation current component) Id and a q-axis current (torque current component) Iq from the inputted generator-current detection value S 6 and the phase signal Thg of the induced voltage in accordance with the expression (2). The d-axis current detection value Id is supplied to a subtracter 76 and the q-axis current detection value Iq is supplied to the subtracter 74 . ( Id Iq ) = ( Iu · cos ( 0 ) + Iv · cos ( 2 π / 3 ) + Iw · cos ( 4 π / 3 ) Iu · sin ( 0 ) + Iv · sin ( 2 π / 3 ) + Iw · sin ( 4 π / 3 ) ) ( cos ( Thg ) sin ( Thg ) sin ( Thg ) - cos ( Thg ) ) ( 2 )
The subtracter 74 calculates a deviation between the q-axis current command value S 15 and the q-axis current detection value Iq and supplies it to a current regulator 78 . The current regulator 78 regulates a q-axis voltage command value S 16 so that the deviation between the command value S 15 and the detection value Iq is reduced to zero and supplies the regulated value to the 2-phase-to-3-phase coordinate converter 68 .
Further, the subtracter 76 calculates a deviation between a d-axis current command value S 17 and the d-axis current detection value Id to thereby supply the deviation to a current regulator 80 . The current regulator 80 regulates a d-axis voltage command value S 18 which is an output thereof so that a deviation between the command value S 17 and the detection value Id is reduced to zero, and supplies the regulated value to the 2-phase-to-3-phase coordinate converter 68 . The current regulators 78 and 80 can be constituted by, for example, a proportional integration controller.
The 2-phase-to-3-phase coordinate converter 68 is supplied with the phase signal Thg, the d-axis voltage command value S 18 and the q-axis voltage command value S 16 to be thereby calculated voltage command values S 13 , S 14 and S 19 produced by the 2-phase-to-3-phase coordinate converter 68 in accordance with the expressions (3) and (4) to be supplied to a PWM calculation unit (pulse-width-modulation calculation unit) 82 . ( Vagr Vbgr ) = ( cos ( Thg ) sin ( Thg ) sin ( Thg ) - cos ( Thg ) ) ( Vdgr Vqgr ) ( Vugr Vvgr Vwgr ) = ( cos ( 0 ) sin ( 0 ) cos ( 2 π / 3 ) sin ( 2 π / 3 ) cos ( 4 π / 3 ) sin ( 4 π / 3 ) ) ( Vagr Vbgr )
The PWM calculation unit 82 calculates a gate signal S 8 on the basis of the inputted voltage commands S 13 , S 14 and S 19 . The signal S 8 is supplied to the converter 20 constituted by the pulse-width-modulation system to turn on and off semiconductor elements thereof.
An example of operation of FIG. 2 is now described. In the generator-speed control unit 54 of FIG. 2, it is defined that a torque current in motor operation of the generator 14 is positive and a torque current in power generating operation is negative.
When the optimum speed command value S 7 of the turbine control unit 58 is now increased, the input of the speed regulator 72 is increased. Accordingly, the output (a torque current command value S 15 ) of the speed regulator 72 is increased in the positive direction.
Since the torque current in power generating operation is defined to be negative, the fact that the torque current command value S 15 is increased in the positive direction means that the torque current is reduced. When the torque current command value S 15 is increased in the positive direction, the input of the current regulator 78 is increased.
In order to reduce the torque current, the current regulator 78 changes the q-axis voltage command value S 16 to delay the phase of the voltage produced by the converter 20 . Consequently, the phase difference between the voltage and the induced voltage of the generator 14 is made small and the torque current is reduced.
The reduction of the torque current corresponds to reduction of electric energy taken out from the generator 14 . The generator 14 increases rotational energy by the reduction of the taken-out energy, so that the rotational speed thereof is increased.
This can be explained from the equation of motion of the generator given by the expression (5). In the expression (5), when energy of the generator 14 received from the turbine 10 is T and energy taken out by the converter 20 from the generator 14 is Ti, T>Ti represents acceleration, T=Ti fixed speed and T<Ti deceleration.
T−Ti=j·dω/dt (5)
Conversely, when the speed command value S 7 is reduced in power generating operation, the positive-direction input of the speed regulator 72 is reduced. Accordingly, the output (torque current command value S 15 ) of the speed regulator 72 is increased in the negative direction.
Since the torque current in power generating operation is defined to be negative, change of the torque current command value S 15 in the negative direction means that the torque current is increased. In order to increase the torque current, the current regulator 78 reduces the q-axis voltage command value S 16 and advances the phase of the voltage produced by the converter 20 . Thus, a phase difference between the voltage and the induced voltage of the generator 1 is increased.
The increase of the torque current corresponds to increase of electric energy taken out from the generator 14 . The generator 14 reduces the rotational energy by the increase of the taken-out energy, so that the rotational speed thereof is reduced.
In this case, the relation of the energy T inputted to the generator 14 from the turbine 10 and the energy Ti taken out from the generator 14 by the converter 20 is T<Ti, so that the generator is decelerated.
FIG. 3 is a block diagram schematically illustrating the DC voltage control unit 46 for the converter 30 in detail. In FIG. 3, the DC voltage control unit 46 is supplied with the current detection value S 1 , the voltage detection value S 2 , the DC voltage detection value S 3 and the DC voltage command value S 4 .
The AC voltage detection value S 2 is supplied to a phase detector 84 and a 3-phase-to-2-phase coordinate converter 86 . The phase detector 84 calculates a phase signal Thn following the voltage of the electric power system 44 by means of the phase-locked loop (PLL) system, for example, and supplies the phase signal Thn to 3-phase-to-2-phase coordinate converters 88 and 86 and a 2-phase-to-3-phase coordinate converter 90 .
The DC voltage command value S 4 and the DC voltage detection value S 3 are inputted to a subtracter 92 , which supplies a deviation between the DC voltage command value S 4 and the DC voltage detection value S 3 to a voltage regulator 94 .
The voltage regulator 94 can be constituted by, for example, a proportional integration controller. The DC voltage regulator 94 regulates a d-axis current command value (effective current command value) S 22 produced therefrom so that the inputted deviation is reduced to zero and supplies the command value to a subtracter 96 .
The 3-phase-to-2-phase coordinate converter 88 calculates a d-axis current detection value Idn (effective current) and a q-axis current detection value Iqn (reactive current) from the inputted current S 1 in accordance with the conversion equation given by the expression (2) and supplies the d-axis current detection value Idn and the q-axis current detection value Iqn to the subtracter 96 and a subtracter 98 , respectively.
The subtracter 96 calculates a deviation between the d-axis current command value S 22 and the d-axis current detection value Idn and supplies the deviation to a current regulator 100 . The current regulator 100 regulates a d-axis voltage command value S 23 so that the deviation between the command value S 22 and the detection value Idn is reduced to zero and supplies the command value to an adder 103 .
Similarly, the subtracter 98 calculates a deviation between a q-axis current command value S 24 and the q-axis current detection value Iqn and supplies the deviation to a current regulator 102 . The current regulator 102 regulates a q-axis voltage command value S 25 so that a deviation between the inputted command value and the detection value is reduced to zero and supplies the command value to an adder 104 . The current regulators 100 and 102 can be constituted by, for example, a proportional integration controller.
The 3-phase-to-2-phase coordinate converter 86 calculates a d-axis voltage detection value (phase component coincident with system voltage 44 ) and-a q-axis voltage detection value (component orthogonal to the d-axis voltage detection value) Vqn from the inputted voltage S 2 in accordance with the conversion equation given by the equation (2) and supplies the values Vdn and Vqn to the adders 103 and 104 , respectively.
The adder 103 adds the d-axis voltage command value S 23 and the d-axis voltage detection value Vdn and supplies its sum to the 2-phase-to-3-phase coordinate converter 90 . Similarly, the adder 104 adds the q-axis voltage command value S 25 and the q-axis voltage detection value Vqn and supplies its sum to the 2-phase-to-3-phase coordinate converter 90 .
The 2-phase-to-3-phase coordinate converter 90 is supplied with the phase signal Thn and the results of the adders 104 and 103 and calculates voltage command values S 26 , S 27 and S 28 produced therefrom in accordance with the conversion expressions (3) and (4) to supplies them to the PWM calculation unit 106 .
The PWM calculation unit 106 calculates the gate signal S 5 from the inputted voltage commands S 26 , S 27 and S 28 . In order to control to turn on and off the semiconductor elements of the converter 30 constituted by the pulse width modulation system, the gate signal S 5 is supplied to the converter 30 .
FIG. 4 is a block diagram schematically illustrating the turbine control unit 58 in detail. In FIG. 4, the turbine control unit 58 is supplied to the power command value S 10 , the power detection value S 9 and the state quantity S 11 .
A subtracter 108 calculates a deviation between the power command value S 10 and the power detection value S 9 and supplies the deviation to an AC power regulator 110 . The AC power regulator 110 can be constituted by, for example, a proportional integration controller. The AC power regulator 110 produces a power command value S 30 which is the power command value S 10 corrected so that the deviation between the command value and the detection value is reduced to zero.
The corrected power command value S 30 is supplied to a fuel conversion unit 112 . The fuel conversion unit 112 calculates the fuel adjustment command value S 12 from the power and outputs the command value.
Further, the corrected power command value 30 is also supplied to an optimum speed calculation unit 114 . The optimum speed calculation unit 114 is supplied with the corrected power command value S 30 and the state quantity S 11 and refers to optimum operation conditions in previously set states to produce the optimum speed command value S 7 for satisfactory turbine efficiency.
Referring now to FIG. 5, operation of the optimum speed calculation unit 114 is described. The graph shown in (a) of FIG. 5 shows a relation of the number of revolutions of the generator 14 and a temperature at an outlet of the turbine 10 . Further, the graph shown in (b) of FIG. 5 shows a relation of the power generation efficiency and the temperature at the outlet of the turbine 10 .
When the temperature at the outlet of the turbine, for example, is used as the state quantity S 11 of the turbine 10 , the optimum speed command S 7 is decided from the optimum number of revolutions (shown in the graph of (a) in FIG. 5) for operation at the highest power generation efficiency.
When the optimum number of revolutions is tabulated for each output power, for example, which is a certain power output condition from the graphs shown in FIG. 5, the optimum speed calculation unit 114 can always produce the optimum speed command value S 7 .
Further, in addition to the tabulation, the optimum speed command value S 7 can be obtained even by reducing the speed when the outlet temperature of the turbine is low and by increasing the speed when the outlet temperature of the turbine is high so that the temperature of the turbine is equal to the permissible maximum temperature Tmax.
In the above description, the outlet temperature of the turbine is used, while even the state quantity corresponding to the outlet temperature of the turbine is used to attain the same function. Further, the efficiency of the general combustion turbine as described above is varied depending on the number of revolutions and even the combustion turbine utilizing high-humidity air can attain the same effects.
According to the embodiment, since the speed of the generator can be always controlled by the converter 20 connected to the generator 14 even in power generating operation, its control is simplified as compared with the case where control is once stopped and rectification by diodes is made.
Further, the optimum speed command S 7 is prepared from the state quantity S 11 of the turbine 10 and the speed of the generator is controlled by the converter 20 connected to the generator 14 on the basis of the optimum speed command S 7 , so that the generator 14 can be operated at the speed of the satisfactory turbine efficiency.
In the embodiment, sensor-less control is used for control of the converter of the generator 14 , while even in the case where a position detector connected to the rotation axis 12 of the generator 14 is used to detect a phase, the same effects can be attained.
Another embodiment of the present invention is now described. Like constituent elements are designated by like reference numerals throughout the drawings and detailed description thereof is omitted.
[Embodiment 2]
FIGS. 6 to 8 schematically illustrate another embodiment for realizing a combustion turbine power converting apparatus and a control method of the present invention. The generator-speed control unit 118 of FIG. 6 is different in partial configuration from the generator-speed control unit 54 of the embodiment 1.
The optimum speed command value S 7 inputted from the turbine control unit 58 is supplied to a speed command calculation unit 116 and an output of the speed command calculation unit 116 is used as the speed command value. The generator-speed control unit 54 of FIG. 1 can be replaced by the generator-speed control unit 118 . Other configuration shown in FIG. 6 is the same as FIG. 2 and accordingly detailed description thereof is omitted.
FIG. 7 is a block diagram schematically illustrating the speed command calculation unit 116 shown in FIG. 6 . The speed command calculation unit 116 is supplied with the d-axis current detection value Id (exciting current component), the q-axis current detection value Iq (torque current component) and the optimum speed command value S 7 .
The d-axis current detection value Id and the q-axis current detection value Iq are inputted to an amplitude calculation unit 119 , which calculates an amplitude Is of the current in accordance with the expression (6) and supplies it to a dead-band limiter 120 .
Is=√{square root over (Id 2 +Iq 2 )} (6)
The dead-band limiter 120 outputs the input value Is when the input value Is exceeds a set value. The output value of the dead-band limiter 120 is supplied to a gain multiplier 122 , which multiplies the output value by a predetermined gain and supplies its result to an adder 124 .
The adder 124 is supplied with the multiplication result and the optimum speed command value S 7 and supplies its addition result to a limiter 126 for preventing over-speed exceeding the command value. The limiter 126 produces a limit value when the input value exceeds the limit value and produces the input value when the input value is smaller than or equal to the limit value.
According to the embodiment, in addition to the advantages of the embodiment 1, the speed of the generator is temporarily increased to absorb or discharge energy produced by inertial energy upon transient variation that fuel is varied by adjustment of fuel fed to the turbine and the current of the converter 20 is larger than a predetermined value.
More particularly, since variation of mechanical input can be absorbed by mechanical energy of the rotating body to suppress electrical variation, there can be realized the reliable system that can prevent the over-current of the converter 20 .
Further, in the embodiment, the system using the amplitude of the current has been described, while even a speed command calculation unit 128 using the q-axis current (torque current) detection value as shown in FIG. 8 can attain the same effects.
As described above, in the embodiment, since the speed is always controlled by the converter connected to the generator even in power generating operation, the control is simplified as compared with the case where control is once stopped and rectification by diodes is made.
Further, the optimum speed command is prepared from the state quantity of the turbine and the speed of the generator is controlled by the converter connected to the generator on the basis of the optimum speed command, so that the generator can be operated at speed of the satisfactory turbine efficiency.
Moreover, since the speed of the generator is increased temporarily to absorb or discharge energy produced by inertial energy upon transient variation that fuel is varied by adjustment of fuel and the current of the converter is larger than a predetermined value, there can be realized the reliable system that can prevent the over-current of the converter.
When the current of the converter is increased, the speed is controlled to be increased temporarily and accordingly there can be realized the reliable system that can prevent the over-current of the converter.
According to the present invention, since the speed is always controlled by the converter connected to the generator even in power generating operation, the control is simplified as compared with the case where control is once stopped and rectification by diodes is made.
It should be further understood by those skilled in the art that although the foregoing description has been made on embodiments of the invention, the invention is not limited thereto and various changes and modifications may be made without departing from the spirit of the invention and the scope of the appended claims.
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A combustion turbine power generating system and method in which the system includes a permanent magnet type AC power generator, a combustion turbine that drives the AC power generator, a first converter enabling conversion between AC current and DC current and having an AC side connected to the AC power generator, a second converter enabling conversion between AC current and DC current and having a DC side connected to a DC output side of the first converter, a capacitor connected between the first and second converters, a generator-speed control unit that controls the first converter and a DC voltage control unit that controls a DC-side voltage of the second converter. The generator-speed control unit controls the first converter on the basis of a number of revolution command value.
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[0001] This application claims priority to U.S. provisional application No. 61/495,024 filed on Jun. 9, 2011 and to European application No. 11176634.1 filed on Aug. 4, 2011, the whole content of each of these applications being incorporated herein by reference for all purposes.
[0002] The present invention relates to polyamide compositions featuring improved thermal stability. These new compositions are very well suited for the manufacture of articles exposed to high temperature environments such as articles used in automotive applications.
BACKGROUND
[0003] Semi-aromatic polyamides are a class of high-performance polyamides featuring outstanding properties such an excellent resistance to creep and fatigue, good mechanical properties, low moisture absorption, improved dimensional stability, very high strength and stiffness at elevated temperatures, as well as a great resistance to a broad range of chemicals.
[0004] Some demanding applications require a high resistance to very high temperatures. Semi-aromatic polyamides are candidates of choice for those applications, typically because of their intrinsic high melt temperatures. However, the thermal stability of those materials still needs to be improved, especially over the long term. When molded compositions are subjected to relatively high temperatures for a prolonged period, such as is the case with objects that serve in automotive under-the-hood applications and in several electric or electronic applications, the compositions generally tend to show a decrease in mechanical properties (such as tensile properties) due to thermal degradation of the polymer. This effect is called heat ageing.
[0005] Thermal stabilizers are typically added to polymer compositions to better retain the properties of the polymers upon exposure to elevated temperature. When using a thermal stabilizer, the useful lifetime of the molded material can be extended significantly, depending on the type of material, use conditions and type and amount of heat stabilizer. Examples of heat stabilizers typically used in polyamides are organic stabilizers, like phenolic antioxidants and aromatic amines, and combination of potassium iodide or copper iodide. Unfortunately, semi-aromatic polyamide compositions comprising those stabilizers do not achieve acceptable heat ageing performances that are required in some demanding applications.
[0006] It is therefore an object of the present invention to provide semi-aromatic polyamide compositions featuring a very good heat ageing performance while maintaining all the other properties of semi-aromatic polyamides at a good level.
[0007] WO 2005/007727 discloses a process for preparing heat stabilized molding compositions comprising melt-mixing of a thermoplastic polymer, a non-metallic inorganic filler and elemental iron having a weight average particle size of at most 450 μm to form a composition wherein the thermoplastic polymer forms a continuous phase and the use of those compositions in applications wherein they are exposed to elevated temperature. WO 2005/007727 claims a remarkable improvement in heat ageing properties, exhibited by a much better retention of the mechanical properties at elevated temperature, in respect of the prior art copper salt/potassium iodide or elemental copper containing compositions. WO 2005/007727 discloses aliphatic polyamides (such as PA 6, PA 6,6, and PA 4,6) compositions comprising an elemental iron thermal stabilizer. It also discloses in its example IV a composition comprising PA 6,6/6T and elemental iron.
[0008] WO 2011/051123 relates to thermoplastic molding compounds comprising a polyamide and powdered iron having a particle size of no greater than 10 μm that can be obtained by thermally disintegrating iron pentacarbonyl.
[0009] However, the use and handling of powders having very fine particle size should preferably be avoided for health and safety considerations. The risk of inhalation of fine particles raises major health concerns since it has been shown to cause lung cancer, whereas the presence of fine particles in the air presents a number of safety issues, the most dangerous one being an explosion hazard.
[0010] The Applicant has surprisingly found out that the addition of PA 6 and/or PA 6,6 to compositions comprising semi-aromatic polyamides and elemental iron having a weight average particle size of at least 10 μm leads to outstanding results regarding the heat ageing performance while maintaining all the other properties of semi-aromatic polyamides at a very good level and without the health and safety risk associated with the prior art.
BRIEF DESCRIPTION OF THE FIGURE
[0011] FIG. 1 is a graph showing the tensile strength in MPa of example E1 (according to the invention) and comparative examples CE1 and CE2 as a function of the thermal oxidative treatment time they were subjected to in hours.
DETAILED DESCRIPTION
[0012] It is a first object of the present invention to provide a polymer composition comprising at least one semi-aromatic polyamide, at least one aliphatic polyamide selected from PA 6 and PA 6,6, and elemental iron having a weight average particle size of at least 10 μm.
[0013] It is another object of the present invention to provide a process for preparing the polymer composition as above described wherein it comprises melt-mixing of at least one semi-aromatic polyamide, at least one aliphatic polyamide selected from PA 6 and PA 6,6, and elemental iron having a weight average particle size of at least 10 μm.
[0014] Still another object of the present invention relates to the use of the above mentioned composition for the preparation of a molded part and to the molded part itself.
[0015] Finally, a last object of the present invention relates to the use of such molded part in a machine, an engine, an electric or electronic installation and in particular to an automotive vehicle, general transport means, domestic appliance, or general industry installation, comprising said molded part.
the Semi-Aromatic Polyamide
[0016] The term “polyamide” is generally understood to indicate a polymer comprising units deriving from at least one diamine and at least one dicarboxylic acid and/or from at least one amino carboxylic acid or lactam.
[0017] The semi-aromatic polyamide of the composition according to the present invention is intended to denote any polyamide comprising more than 35 mol. % of aromatic recurring units. It comprises advantageously more than 55 mol. %, preferably more than 65 mol % of aromatic recurring units, more preferably more than 70 mol %, still more preferably more than 80 mol %, even more preferably more than 85 mol % and most preferably more than 90 mol %. In a specific embodiment, the semi-aromatic polyamide of the composition according to the present invention comprises 100 mol % of aromatic recurring units. For the purpose of the present invention, the term “aromatic recurring unit” is intended to denote any recurring unit that comprises at least one aromatic group. The aromatic recurring units may be formed by the polycondensation of at least one aromatic dicarboxylic acid and at least one diamine or by the polycondensation of at least one dicarboxylic acid and at least one aromatic diamine.
[0018] Non limitative examples of aromatic dicarboxylic acids are notably phthalic acids, including isophthalic acid, terephthalic acid and orthophthalic acid, naphtalenedicarboxylic acids (including 2,6-naphthalene dicarboxylic acid, 2,7-naphthalene dicarboxylic acid, 1,4-naphthalene dicarboxylic acid, 2,3-naphthalene dicarboxylic acid, 1,8-naphthalene dicarboxylic acid and 1,2-naphthalene dicarboxylic acid), 2,5-pyridinedicarboxylic acid, 2,4-pyridinedicarboxylic acid, 3,5-pyridinedicarboxylic acid, 2,2-bis(4-carboxyphenyl)propane, bis(4-carboxyphenyl)methane, 2,2-bis(4-carboxyphenyl)hexafluoropropane, 2,2-bis(4-carboxyphenyl)ketone, 4,4′-bis(4-carboxyphenyl)sulfone, 2,2-bis(3-carboxyphenyl)propane, bis(3-carboxyphenyl)methane, 2,2-bis(3-carboxyphenyl)hexafluoropropane, 2,2-bis(3-carboxyphenyl)ketone, bis(3-carboxyphenoxy)benzene. Phthalic acids, including isophthalic acid, terephthalic acid and orthophthalic acid, are the preferred aromatic dicarboxylic acids. Terephthalic acid and isophthalic acid are even more preferred.
[0019] Non limitative examples of aromatic diamines are notably meta-phenylene diamine, meta-xylylene diamine and para-xylylene diamine. Para-xylylene diamine is the most preferred.
[0020] The semi-aromatic polyamide of the composition according to the present invention may comprise in addition to the at least one aromatic dicarboxylic acid and/or at least one aromatic diamine described above, recurring units deriving from at least one aliphatic dicarboxylic acid and/or at least one aliphatic diamine and/or at least one lactam.
[0021] Non limitative examples of aliphatic dicarboxylic acids are notably oxalic acid (HOOC—COOH), malonic acid (HOOC—CH 2 —COOH), succinic acid [HOOC—(CH 2 ) 2 —COOH], glutaric acid [HOOC—(CH 2 ) 3 —COOH], 2,2-dimethyl-glutaric acid [HOOC—C(CH 3 ) 2 —(CH 2 ) 2 —COOH], adipic acid [HOOC—(CH 2 ) 4 —COOH], 2,4,4-trimethyl-adipic acid [HOOC—CH(CH 3 )—CH 2 —C(CH 3 ) 2 —CH 2 —COOH], pimelic acid [HOOC—(CH 2 ) 5- COOH], suberic acid [HOOC—(CH 2 ) 6 —COOH], azelaic acid [HOOC—(CH 2 ) 7 —COOH], sebacic acid [HOOC—(CH 2 ) 8 —COOH], undecanedioic acid [HOOC—(CH 2 ) 9 —COOH], dodecanedioic acid [HOOC—(CH 2 ) 10 —COOH], tetradecanedioic acid [HOOC—(CH 2 ) 11 —COOH] and 1,4-cyclohexane dicarboxylic acid, are non limitative examples of aliphatic dicarboxylic acids. Sebacic acid, adipic acid and 1,4-cyclohexane dicarboxylic acid are preferred.
[0022] Non limiting example of aliphatic diamines are notably 1,2-diaminoethane, 1,2-diaminopropane, propylene-1,3-diamine, 1,3-diaminobutane, 1,4-diaminobutane, 1,5-diaminopentane, 2-methyl-1,5-diaminopentane, 1,6-hexamethylenediamine, 2,4,4-trimethyl-1,6-hexamethylenediamine, 1,8-diaminooctane, 2-methyl-1,8-diaminooctane, 1,9 nonanediamine, 5-methyl-1,9-nonanediamine, 1,10-diaminodecane, 1,11-diaminoundecane, 1,12-diaminododecane, 1,13-diaminotridecane, 1,14-diaminotetradecane, 1,16-diaminohexadecane, 1,18-diaminooctadecane and 1-amino-3-N-methyl-N-(3-aminopropyl)-aminopropane. Among those, 1,6-hexamethylenediamine, 2-methyl-1,8-diaminooctane, 1,9 nonanediamine, 5-methyl-1,9-nonanediamine, 1,10-diaminodecane, 1,11-diaminoundecane and 1,12-diaminododecane are preferred, and 1,6-hexamethylenediamine, 1,9 nonanediamine, 1,10-diaminodecane, are even more preferred.
[0023] In a first embodiment, the semi-aromatic polyamide of the composition according to the present invention is preferably a polyphthalamide (PPA). For the purpose of the present description, the term “polyphthalamides” should be understood as defining any polymer of which more than 70 mol. %, preferably more than 80 mol. %, more preferably more than 90 mol. % of the recurring units are formed by the polycondensation reaction between at least one phthalic acid and at least one diamine. The phthalic acid can be notably o-phthalic acid, isophthalic acid or terephthalic acid. The diamine can be notably 1,6-hexamethylenediamine, 1,9-nonanediamine, 1,10-diaminodecane 2-methyl-octanediamine, 2-methyl-1,5-pentanediamine or 1,4-diaminobutane; a C 6 and/or a C 10 diamine, especially 1,6-hexamethylenediamine and 1,10-diaminodecane are preferred. Suitable polyphthalamides are notably available as AMODEL® polyphthalamides from Solvay Advanced Polymers, L.L.C.
[0024] The polyphthalamide (PPA) of the invented composition is more preferably a polyterephthalamide. For the purpose of the present description, the term “polyterephthalamide” should be understood as defining any polymer of which more than 70 mol. %, preferably more than 80 mol. %, more preferably more than 90 mol. % of the recurring units are formed by the polycondensation reaction between at least terephthalic acid with at least one diamine. The diamine may be aliphatic or aromatic. It is preferably an aliphatic diamine selected from the group consisting of 1,6-hexamethylenediamine, 1,9-nonanediamine, 1,10-diaminodecane, 2-methyl-octanediamine, 2-methyl-1,5-pentanediamine or 1,4-diaminobutane.
[0025] Of course, more than one semi-aromatic polyamide may be used in the composition in accordance with the invention.
[0026] In a second embodiment, the semi-aromatic polyamide of the composition according to the present invention is preferably a class of polyamides consisting of PXDAs, i.e. aromatic polyamides comprising more than 50 mole % of recurring units formed by the polycondensation reaction between at least one aliphatic diacid and paraxylylenediamine. The aliphatic diacid can be chosen notably from oxalic acid (HOOC—COOH), malonic acid (HOOC—CH 2 —COOH), succinic acid [HOOC—(CH 2 ) 2 —COOH], glutaric acid [HOOC—(CH 2 ) 3 —COOH], 2,2-dimethyl-glutaric acid [HOOC—C(CH 3 ) 2 —(CH 2 ) 2 —COOH], adipic acid [HOOC—(CH 2 ) 4 —COOH], 2,4,4-trimethyl-adipic acid [HOOC—CH(CH 3 )—CH 2 —C(CH 3 ) 2 —CH 2 —COOH], pimelic acid [HOOC—(CH 2 ) 5- COOH], suberic acid [HOOC—(CH 2 ) 6 —COOH], azelaic acid [HOOC—(CH 2 ) 7 —COOH], sebacic acid [HOOC—(CH 2 ) 8 —COOH], undecanedioic acid [HOOC—(CH 2 ) 9 —COOH], dodecanedioic acid [HOOC—(CH 2 ) 10 —COOH], tetradecanedioic acid [HOOC—(CH 2 ) 11 —COOH] and 1,4-cyclohexane dicarboxylic acid. Sebacic acid, adipic acid and 1,4-cyclohexane dicarboxylic acid are preferred. Adipic acid or sebacic acid are even more preferred, and PXDAs derived from adipic acid or sebacic acid with paraxylylenediamine are usually referred to as PXD6 and PXD10 respectively.
[0027] Excellent results were obtained when the polyphthalamide is selected from the group consisting of PA 6T, PA9T, PA10T, PA11T, PA12T, PA6T/6I, PA6T/6I/10T/10I, PA6T/10T/6,10/10,10, PA6T/11 and PA10T/11.
[0028] The semi-aromatic polyamide may be semi-crystalline or amorphous.
[0029] When the semi-aromatic polyamide is semi-crystalline, it has a melting point advantageously greater than 220° C., preferably greater than 270° C., more preferably greater than 280° C., and still more preferably greater than 320° C. In addition, the semi-aromatic polyamide has a melting point advantageously of below 350° C., preferably below 340° C. and more preferably below 330° C.
[0030] The melting point of the semi-aromatic polyamide was measured by Differential Scanning calorimetry using ASTM D3418 with the following heating/cooling cycle: 1 st heating from room temperature up to 350° C. at a rate of 10° C./min, followed by cooling from 350° C. down to room temperature at a rate of 20° C./min, followed by 2 nd heating from room temperature up to 350° C. at a rate of 10° C./min. The melting point was measured during 2 nd heating.
[0031] The semi-aromatic polyamide is generally present in the polymer composition in an amount of at least 30 wt. %, preferably of at least 35 wt. %, more preferably of at least 40 wt. %, still more preferably of at least 45 wt. % and most preferably of at least 50 wt. %, based on the total weight of the composition. Besides, the semi-aromatic polyamide is generally present in the polymer composition in an amount of at most 85 wt. %, preferably of at most 80 wt. %, more preferably of at most 75 wt. %, still more preferably of at most 70 wt. % and most preferably of at most 65 wt. %, based on the total weight of the composition.
The Elemental Iron
[0032] The inventive composition further comprises elemental iron. Elemental iron is preferably in the form of particles, the majority of which having a small particle size, such as a powder. In general, the elemental iron has a weight average particle size of at most 450 μm, preferably at most 200 μm. It is further preferred that the elemental iron having a small particle size has a weight average particle size of at most 200 μm, more preferably at most 100 μm, and still more preferably at most 50 μm. On the other side, the elemental iron has a weight average particle size of at least 10 μm, preferably at least 13 μm. It is further preferred that the elemental iron having a small particle size has a weight average particle size of at least 15 μm, more preferably at least 18 μm, and still more preferably at least 20 μm.
[0033] The elemental iron of the present invention has preferably a weight average particle size of 10 to 50 μm, more preferably 15 to 45 μm, still more preferably 20 to 40 μm and most preferably 25 to 35 μm.
[0034] The weight average particle size is determined as D m according to ASTM standard D1921-89, method A. Preferably the size, to be understood as the largest dimension, of at least 99 wt. % of the elemental iron particles is at most 450 μm and preferably at most 200 μm, more preferably at most 100 μm, even more preferably at most 90 μm, still more preferably at most 80 μm and most preferably at most 70 μm.
[0035] Preferably the size, to be understood as the smallest dimension, of at least 99 wt. % of the elemental iron particles is at least 10 μm and preferably at least 15 μm, more preferably at least 20 μm and most preferably at least 25 μm.
[0036] The elemental iron in the polymer composition according to the present invention may be used in any amount, which can be varied over a wide range. The elemental iron has shown to be a very effective stabilizer, showing an effect already at very low amounts.
[0037] The elemental iron is generally present in the polymer composition in an amount of at least 0.1 wt. %, preferably of at least 0.2 wt. %, more preferably of at least 0.5 wt. %, still more preferably of at least 0.9 wt. % and most preferably of at least 1.0 wt. %, based on the total weight of the composition. Besides, the elemental iron is generally present in the polymer composition in an amount of at most 10 wt. %, based on the total weight of the composition. Higher amounts of elemental iron may be used, however without any additional effect on the heat ageing properties of the composition. More preferably, the elemental iron is generally present in the polymer composition in an amount of at most 5 wt. %, more preferably of at most 4 wt. %, still more preferably of at most 3 wt. % and most preferably of at most 2.5 wt. %, based on the total weight of the composition.
[0038] Excellent results were obtained when the elemental iron was used in an amount ranging from 0.1 to 5 wt. %, preferably from 0.5 to 3 wt. % and most preferably from 0.9 to 2.5 wt. %, based on the total weight of the polymer composition.
The Aliphatic Polyamide
[0039] The Applicant has surprisingly found that the presence of an aliphatic polyamide selected from PA 6 and PA 6,6 in combination with elemental iron improves the heat ageing performance of semi-aromatic polyamides.
[0040] The aliphatic polyamide of the composition according to the present invention is selected from PA 6 and PA 6,6. Excellent results were obtained with PA 6.
[0041] PA 6 is a polyamide synthesized by ring opening polymerization of caprolactam.
[0042] PA 6,6 is a polyamide synthesized by the polycondensation of 1,6-hexamethylene diamine and adipic acid.
[0000]
[0043] The at least one aliphatic polyamide is generally present in the polymer composition in an amount of at least 1 wt. %, preferably of at least 2 wt. %, more preferably of at least 2.5 wt. %, still more preferably of at least 3 wt. % and most preferably of at least 4 wt. %, based on the total weight of the composition. Besides, the at least one aliphatic polyamide is generally present in the polymer composition in an amount of at most 20 wt. %, preferably of at most 18 wt. %, more preferably of at most 16 wt. %, still more preferably of at most 14 wt. % and most preferably of at most 12 wt. %, based on the total weight of the composition.
Other Optional Additives
[0044] The composition in accordance with the invention can optionally comprise additional additives/components such as fillers, pigments, dyes, lubricants, thermal stabilizers, light stabilizers, flame retardants and antioxidants etc.
Fillers
[0045] A large selection of reinforcing fillers may be added to the composition according to the present invention. They are preferably selected from fibrous and particulate fillers. A fibrous reinforcing filler is considered herein to be a material having length, width and thickness, wherein the average length is significantly larger than both the width and thickness. Generally, such a material has an aspect ratio, defined as the average ratio between the length and the largest of the width and thickness of at least 5. Preferably, the aspect ratio of the reinforcing fibers is at least 10, more preferably at least 20, still more preferably at least 50.
[0046] Preferably, the reinforcing filler is selected from mineral fillers (such as talc, mica, kaolin, calcium carbonate, calcium silicate, magnesium carbonate), glass fiber, carbon fibers, synthetic polymeric fiber, aramid fiber, aluminum fiber, titanium fiber, magnesium fiber, boron carbide fibers, rock wool fiber, steel fiber, wollastonite etc. Still more preferably, it is selected from mica, kaolin, calcium silicate, magnesium carbonate and glass fiber etc.
[0047] Among fibrous fillers, glass fibers are preferred; they include chopped strand A-, E-, C-, D-, S- and R-glass fibers, as described in chapter 5.2.3, p. 43-48 of Additives for Plastics Handbook, 2nd edition, John Murphy. Preferably, the filler is chosen from fibrous fillers. It is more preferably a reinforcing fiber that is able to withstand the high temperature applications.
[0048] In a preferred embodiment of the present invention the reinforcing filler is chosen from wollastonite and glass fiber. Excellent results were obtained when glass fibers were used. Glass fibers may have a round cross-section or a non-circular cross-section.
[0049] Excellent results were obtained when the reinforcing filler was used in an amount of 20-60 wt. %, preferably of 30-50 wt. %, based on the total weight of the composition.
[0050] The fillers are contained in the polymer composition in a total amount of advantageously more than 15% by weight, preferably more than 20% by weight, still more preferably more than 25% by weight, and most preferably more than 30% by weight, based on the total weight of the polymer composition. On the other hand, reinforcing fibers are contained in the polymer composition in a total amount of advantageously less than 65% by weight, preferably less than 60% by weight, still more preferably less than 55% by weight, and most preferably less than 50% by weight, based on the total weight of the polymer composition.
Pigments and Dyes
[0051] The composition according to the present invention may further comprise pigments and dyes. It may notably comprise black pigments such as carbon black and nigrosine.
Lubricants
[0052] The composition according to the present invention may further comprise lubricants such as linear low density polyethylene, calcium or magnesium stearate, sodium montanate etc.
Further Stabilizers
[0053] The composition according to the present invention further comprises in another preferred embodiment, in addition to the elemental iron thermal stabilizer, at least a well known thermal stabilizer different from the elemental iron that further promote the heat ageing properties. They can typically be one or more selected from phenolic thermal stabilizers (such as Irganox 1098 or Irganox 1010, available from Ciba Specialty Chemicals), organic phosphites (such as Irgafos 168, available from Ciba Specialty Chemicals), aromatic amines, metals salts of elements from group IB, IIB, III and IV of the periodic Table and metal halides of alkaline and alkaline earth metals.
[0054] Preferably, the composition according to the present invention further comprises a combination of a copper salt and an alkaline metal halide. More preferably, it comprises a copper halide and an alkaline metal halide, such as CuI and KI. Most preferably, CuI and KI are used in a ratio varying from 1/6 to 1/10, preferably 1/7 to 1/9.
[0055] This further thermal stabilizer may be present in an amount of from 0.1 to 5 wt. %, preferably of from 0.2 to 2.5 wt. %.
[0056] Light stabilizers such as hindered amine light stabilizers (HALS) may also be present in the composition.
Flame Retardants
[0057] The composition according to the present invention may further comprise flame retardants such as halogen and halogen free flame retardants.
[0058] Another aspect of the present invention is related to a process for preparing the polymer composition as above described, wherein it comprises melt-mixing at least one semi-aromatic polyamide, at least one aliphatic polyamide selected from PA 6 and/or PA 6,6, and elemental iron.
[0059] The process according to the invention can be carried out by any known melt-mixing process that is suitable for preparing thermoplastic moulding compositions. Such a process is typically carried out by heating the thermoplastic polymer above the melting temperature or in case the thermoplastic polymer is an amorphous polymer above the glass transition temperature, of the thermoplastic polymer thereby forming a melt of the thermoplastic polymer. The process according to the invention can be carried out in a melt-mixing apparatus, for which any melt-mixing apparatus known to the man skilled in the art of preparing polymer compositions by melt mixing can be used. Suitable melt-mixing apparatus are, for example, kneaders, Banbury mixers, single-screw extruders and twin-screw extruders. Preferably, use is made of an extruder fitted with means for dosing all the desired components to the extruder, either to the extruder's throat or to the melt. In the process according to the invention the constituting components for forming the composition are fed to the melt-mixing apparatus and melt-mixed in that apparatus. The constituting components may be fed simultaneously as a powder mixture or granule mixer, also known-as dry-blend, or may be fed separately. The process according to the invention is not limited in the way the elemental iron is added. It may be added, for example, as a powder, a dry-blend or premix comprising the thermoplastic polymer in granulate form and the elemental iron in powder form, or as a masterbatch of finely dispersed elemental iron in a carrier polymer. Advantageously, the elemental iron is added in the form of a masterbatch, since this allows a better control of the dosing accuracy of the elemental iron when the elemental iron is added in small quantities relative to the thermoplastic polymer. The carrier polymer that can be used in the masterbatch may be the same as the thermoplastic polymer, as well as another polymer, such a lower melting thermoplastic polymer, an elastomer or a rubber. Non-limiting examples of such carriers include SBS rubber, EPDM rubber, polyethylene, polypropylene and ethylene/propylene copolymers.
[0060] The advantage of the inventive composition is that it shows a remarkable improvement in heat ageing properties, exhibited by a much better retention of the mechanical properties at elevated temperature, in respect of the known copper salt/potassium iodide containing compositions. Another advantage is that the composition could be prepared with a lower mass percent of heat stabilizer, relative to the total mass of the composition, to achieve the same or even higher level of heat ageing properties.
[0061] Preferred embodiments of the composition according to the invention directly relate to preferred embodiments of the process according to the invention and specific components used therein, as described above, and the reported advantages thereof.
[0062] The invention also relates to the use of a polymer composition according to the invention for the preparation of a molded part, as well as to a molded part comprising a composition according to the invention.
[0063] A further object of the present invention relates to the use of a molded part comprising the above mentioned polymer composition in a machine, an engine, an electric or electronic installation, such as automotive vehicles, general transport means, domestic appliances, oil and gas exploration equipments or general industry installations.
[0000] The advantage of the molded part according to the invention is that it has very good heat ageing properties. The molded part can have a primarily 2-dimensional shape, such as for engine covers. The molded may also have a more complex 3-dimensional shape, as is the case for many parts used in high temperature applications. Generally, the part has a thickness of at least 0.5 mm, though the parts may have a lower thickness as well. Preferably, the part has a thickness of at least 1 mm, more preferably at least 2 mm, and still more preferably at least 4 mm. The advantage of the part having a higher thickness is that the mechanical properties are better retained under heat ageing conditions at elevated temperature. More particular, the molded part is a molded part for use in machines and engines, which can be applied, for example, in automotive vehicles, such as personal cars, motor bikes, trucks and vans, general transport means, including trains, aviation and ships, domestic appliances, such as lawn mowers and small engines, and general industry installations, such as in pumps, compressors, conveyor belts, or a molded part for use in electric and electronic installations, such as in domestic power tools and portable power equipment. The part may be, for example, a bearing, a gear box, an engine cover, an air duct, an intake manifold, an intercooler end-cap, a castor, or a trolley part.
[0064] The invention furthermore relates to products, including automotive vehicles, general transport means, domestic appliances, and general industry installations, electric and electronic installations, comprising a molded part according to the invention. The advantage is that the service lifetime of the said products in respect to the necessary replacement of the said molded part due to deterioration of the molded part by exposure to elevated temperature is longer, and/or that the product can be operated at higher temperature, compared with a corresponding product comprising a molded part made of the known composition comprising a copper iodide/potassium iodide stabilizing system.
[0065] The invention is further illustrated with the following examples and comparative examples.
Examples
Components and Ingredients Used
[0000]
(1) PA 1: Vicnyl 600, PA10,T/10,6 (92/8) available from Kingfa;
(2) PA 2: PA 6 Ultramid® 8202 HS from BASF;
(3) PA 3: Amodel A-4002, PA 6,T/6,6 (65/35) available from Solvay Specialty Polymers;
(3) Stabilizer: mixture of copper iodide and potassium iodide in a 1/9 ratio with a stearate binder;
(4) Compatibilizer: Fusabond® MB226 from Dupont™ (anhydride modified LLDPE);
(5) Elemental iron: SHELFPLUS™ O 2 2400 from ALBIS Plastic Corporation, masterbatch containing 20 wt. % of elemental iron particles in polyethylene having a D99 particle size of 63 μm;
(6) Fiberglass 1: OCV 983 chopped strand 10 micron diameter commercialized by Owens Corning®;
(7) Fiberglass 2: HP3540 chopped strand 10 micron diameter commercialized by PPG Industries;
(8) Lubricant: Linear low density polyethylene (LLDPE) GRSN-9820 commercialized by Dow® Chemical.
Preparation of the Polymer Compositions
[0075] Examples E1, E2, E3 and comparative examples CE1, CE2 and CE3 were prepared by melt blending the ingredients listed in Table 1 in a 26 mm twin screw extruder (ZSK 26 by Coperion) operating at about 290° C. barrel setting using a screw speed of about 200 rpm, a throughput of 13.6 kg/hour and a melt temperature of about 310-325° C. The fiberglass 1 or 2 were added to the melt through a screw side feeder. Ingredient quantities shown in Table 1 are given in weight % on the basis of the total weight of the polymer composition.
[0076] The compounded mixture was extruded in the form of strands cooled in a water bath, chopped into granules and placed into sealed aluminum lined bags in order to prevent moisture pickup. The cooling and cutting conditions were adjusted to ensure that the materials were kept below 0.15 wt. % of moisture level.
[0000]
TABLE 1
Nature and quantities of the ingredients
of the prepared compositions
CE1
CE2
CE3
E1
E2
E3
PA1
64.1
57.54
52.54
PA2
5
5
10
PA 3
57.54
52.54
47.54
Stabilizer
0.4
0.81
0.81
0.81
0.81
0.81
Compatibilizer
1.65
1.65
1.65
1.65
1.65
Iron masterbatch
5
5
5
5
5
Lubricant
0.5
Fiberglass 1
35
Fiberglass 2
35
35
35
35
35
Initial Properties of the Polymer Compositions
[0077] Initial mechanical tensile properties, i.e. stress at break (tensile strength) and strain at break (elongation at break) were measured according to ISO 527-2/1A and are reported in Tables 2 and 3 at aging time of 0 hour. Measurements were made on injection molded ISO tensile bars. Mold temperature for the test specimen ranged from 115-120° C. and melt temperature ranged from 315-330° C.
[0078] The thickness of the test bars was 4 mm and their width was of 10 mm. According to ISO 527-2/1A, the tensile strength and elongation were determined at a testing speed of 5 mm/min.
Thermal Oxidation Ageing
[0079] The test bars were heat aged in a re-circulating air oven (Blue M) at a temperature set at 230° C., according to the procedure detailed in ISO 2578. At various heat aging times, the test bars were removed from the oven, allowed to cool down to room temperature and sealed into aluminum lined bags until ready for testing. The tensile mechanical properties were then measured according to ISO 527 as described above. All values reported in Tables 2 and 3 are average values obtained from 5 specimens.
[0080] Tensile strength results of examples E1, CE1 and CE2 are also presented in FIG. 1 .
[0000]
TABLE 2
Tensile strength results in MPa
Heat aging
time in hours
CE1
CE2
CE3
E1
E2
E3
0
220.82
181.87
185
183.28
192
193
48
157.28
152.55
148
156.02
148
156
96
126.4
151.25
128
144.04
131
145
500
109.55
97.04
143
168.76
136
140
1000
28.6
83.26
144
167.69
138
146
2000
CE
45.2
146
180.3
146
158
3000
CE
0
155
185.75
152
172
4000
CE
CE
159
186.82
169
180
5000
CE
CE
128
—
158
175
*CE: complete embrittlement
[0000]
TABLE 3
Tensile elongation results in %
Heat aging
time in hours
CE1
CE2
CE3
E1
E2
E3
0
2.72
2.73
1.79
2.57
1.91
1.97
48
1.52
1.57
1.29
1.6
1.28
1.35
96
1.13
1.55
1.14
1.43
1.11
1.23
500
0.98
0.94
1.26
1.81
1.15
1.18
1000
0.44
0.84
1.26
1.84
1.15
1.24
2000
CE
0.64
1.3
2.03
1.26
1.4
3000
CE
CE
1.41
2.17
1.33
1.57
4000
CE
CE
1.43
2.2
1.5
1.66
5000
CE
CE
1.13
—
1.43
1.67
* CE: complete embrittlement
[0081] CE1 and CE2 do not appear to resist the long term or even the short term high heat treatment. On the other side, the example E1 according to the invention shows a very surprising response to the extreme heat treatment applied to it. Its tensile strength is somewhat reduced in the short term but comes back to the initial level after 2000 hours of heat treatment at 230° C. Even more surprisingly, the tensile strength is even improving to reach higher levels after 4000 hours of heat treatment.
[0082] The comparison of the results obtained with examples CE3, E2 and E3 demonstrate that the presence of the aliphatic polyamide in the composition improves also the heat ageing performance of semi-aromatic polyamide comprising lower amounts of aromatic recurring units. In this case, the benefit of the presence of the aliphatic polyamide is observed on the long term, i.e. by comparing tensile properties at 5000 hours.
[0083] These examples demonstrate the benefit of the presence of an aliphatic polyamide selected from PA 6 and PA 6,6 in semi-aromatic polyamides that are heat stabilized with elemental iron. This effect is even greater when the semi-aromatic polyamide has a high aromatic content (compare the wholly aromatic E1 example with E2 and E3 which have a lower aromatic content).
[0084] The advantage of the polymer composition having the good retention of tensile strength and/or elongation at break, tested after heat ageing, is that it can be used for molded parts and applications of molded parts made thereof, wherein the molded part has an extended lifetime or can be used at higher temperature, than a molded part not having such good retention of mechanical properties after heat ageing. A further advantage is that the polymer composition having the good retention of tensile strength and/or elongation at break can be used at a higher continuous use temperature, and/or that it can be used for a longer time at the same continuous use temperature.
[0085] Should the disclosure of any patents, patent applications, and publications which are incorporated herein by reference conflict with the description of the present application to the extent that it may render a term unclear, the present description shall take precedence.
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The present invention relates to polyamide compositions featuring improved thermal stability comprising at least one semi-aromatic polyamide, PA 6 and/or PA 6,6, and elemental iron. These new compositions are very well suited for the manufacture of articles exposed to high temperature environments such as articles used in automotive applications.
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BACKGROUND OF THE INVENTION
(1) Field of the Invention
This invention relates to chemical finishing processes for textiles. More particularly it relates to catalysts for treatment of cellulose-containing textile materials with crosslinking agents to produce easy-care properties.
(2) Description of the Prior Art
It is well known that smooth drying appearance and wrinkle resistance of cellulose-containing textiles can be enhanced by suitable treatment of such materials with certain chemical agents. The chemical agents employed in such treatments generally require catalysts to affect reaction with the cellulosic components to achieve improvement of the desirable properties in the finished products. Consideration of strength losses and formaldehyde release have limited the scope of catalysts acceptable in finishing operations. Those catalysts widely employed in the processing of textiles for durable-press, for instance, are not normally useful in other processes.
Sulfur acids such as hydroxymethanesulfonic, methanesulfonic, and para-toluenesulfonic have been cited for their use as catalysts in durable press finishing. These are strong acids capable of promoting crosslinking in cotton with a high degree of efficiency. However, because they are strong acids, careful control in finishing must be maintained so as to avoid severe damage to the physical properties of the treated fabrics. Even with this careful control and use of these acids, treated fabrics have tearing and breaking strength retention values much lower than desired. It is also known from work by Andrews, Harper, and Vail (Textile Research Journal, Vol. 50, pages 315-322, May 1980) that Bronsted acids, such as the sulfonic acids mentioned above, catalyze the crosslinking reaction and, if not completely washed out after finishing, catalyze the reverse reaction (hydrolysis of crosslinks) to release odiferous formaldehyde. Also taught by Andrews, Harper, and Vail (op. cit.) is the knowledge that Lewis acids also are capable of catalyzing the crosslinking reaction but are not as hydrolytically active as the Bronsted acids. Mixtures of these two types of catalysts are known to those skilled in the art as mixed catalysts. One of the more widely used of these mixed catalysts is the mixture of magnesium chloride and citric acid. A synergistic effect from this combination is such that higher durable-press ratings result than can be produced from either component by itself from a given set of finishing conditions. However, this synergistic effect of catalyzing the crosslinking reaction also applies itself to the hydrolysis or reverse reaction in which decrosslinking or promotion of formaldehyde release occurs.
An ideal catalyst would be one which is acidic enough to promote the crosslinking reaction but is not so acidic as to severely weaken the fabric during finishing. Also, this same catalyst must not after finishing be capable of reversing these crosslinks and promote formaldehyde release. Thus, the theory that any acid will do in catalysis of durable press finishing must be flawed. Researchers in catalysis have tried to show why certain catalysts are better than others, and if not better overall, than at least better for a specific application.
Salts of strong acids, and in particular, ammonium salts, such as ammonium chloride have been used as catalysts because they are the combination of a strong acid and a weak base. Hydrolysis of such salts produces an acidic solution.
There are also organic compounds which contain both acid and basic moieties. Dependent upon the strength of these acidic and basic moieties, these compounds are capable of attracting or releasing protons. Such compounds are known as zwitterions. In much the same manner as the inorganic ammonium salts hydrolyze to produce an acidic solution, the solubilization of zwitterions which contain an amine group and a strongly acidic group such as sulfonic, sulfinic, phosphinic, phosphonic, and multiples thereof also produce an acidic solution. Acidic amino acids, that is compounds which contain fewer amino groups than carboxyl groups are also included in this class of compounds, zwitterions.
SUMMARY OF THE INVENTION
This invention provides an improved process for the finishing of cellulosic fabrics to produce easy-care textiles characterized by an unusual combination of smooth-drying appearance, wrinkle resistance, serviceable strength, and inoffensive formaldehyde release properties. Said process comprises treatment of the fabrics by impregnating with a solution containing a cellulose-crosslinking agent and as catalyst a zwitterion, alone or in combination with a magnesium salt, drying the fabric, and curing the fabric.
It is thus an object of this invention to produce cellulose-containing fabrics with excellent durable-press appearance, serviceable strength, and inoffensive formaldehyde release.
It is a further object to provide improved catalyst systems that are efficient and practical for use in treatments of cellulose-containing textiles with suitable agents.
A still further object is to furnish catalyst systems that will provide effective and efficient catalysis on flash curing as well as in conventional pad-dry-cure finishing.
The objects of this invention are achieved by use of the catalyst systems based on appropriate zwitterions or appropriate zwitterions and magnesium chloride in treatments for cellulose-containing textiles with aldehyde or formaldehyde-amide finishing agents. The specific combination of aminomethanesulfonic acid or 2-aminoethanesulfonic acid and magnesium chloride provides efficient, rapid catalysis and produces a fabric with excellent smooth drying appearance, serviceable strength and low formaldehyde release.
Because of their zwitterion structures, aminomethanesulfonic acid and 2-aminoethanesulfonic acid, differ dramatically in their performance as catalysts when compared to aromatic alkane, and substituted alkanesulfonic acids. The latter are so strongly acidic that they must be used under milder curing conditions and/or in much more dilute concentrations lest the strength of the finished fabrics be severly diminished.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
We have found catalyst systems consisting of zwitterions such as aminomethanesulfonic or aminoethanesulfonic acid and magnesium chloride to be highly efficient in treatments for producing durable-press fabric with serviceable strength and low formaldehyde release. This is particularly noteworthy as anyone skilled in the art would avoid use of a sulfonic acid on the fabric at elevated temperatures because of the well known deleterious effect of the hydrolytic action of strong acids on textile properties. Also, particularly noteworthy is the use of a mixture of aminomethanesulfonic acid and magnesium chloride as a mixed catalyst to produce a durable-press fabric with low formaldehyde release. The catalyst systems consisting of aminomethanesulfonic acid or aminomethanesulfonic acid and magnesium chloride are effective at conventional curing temperatures up to about 200° C. A rapid, high temperature cure, hereinafter referred to as flash curing can be accomplished at 200° C. in 20 seconds.
The textile material treated according to the teachings of this invention may be in the form of fibers, yarns, or fabrics. The preferred form is fabric which may be woven, knitted, or nonwoven. The textile may be composed entirely of cellulosic fibers, either natural or regenerated, or may be composed of said cellulosics as components of the textile structure with other cellulosic, noncellulosic natural, or synthetic fibers. Textiles composed of cotton and of cotton and polyester fibers are well suited to use in the processes of this invention.
The chemical agents that may be employed as finishing agents in treatment of textiles with the zwitterion catalysts of this invention include aldehydes such as formaldehyde, glyoxal, glutaraldehyde, and the like, and methylolamide compounds such as dimethylol derivatives of ureas, ethyleneurea, dihydroxyethyleneurea, urons, triazones, pyrimidones, melamines, carbamates, and the like. Among specific agents that have been found to be particularly useful in the process of this invention are formaldehyde, glyoxal, dimethylol dihydroxyethyleneurea (DMDHEU), dimethylol ethyleneurea (DMEU), and dimethylol methoxyethyl carbamate (DMMEC). Alkoxylated methylolamides also should be applicable as finishing agents with the zwitterion catalysts. The amount of finishing agent used in the treatment may vary from about 2% to about 15%, by weight of the treatment bath. About 8% to 10% is the most usual concentration employed.
Additives, softeners, modifiers, and other components customarily used in textile finishing pad baths can be used with the catalyst systems of this invention. The composition of the treatment bath is limited only by the compability of the ingredients with the catalyst.
The catalyst systems of this invention are composed of suitable zwitterions alone or in combination with a magnesium salt. Among the suitable zwitterions are taurine, aminomethanesulfonic acid, aminomethanephosphonic acid, aminoethanephosphonic acid, aminomethanephosphinic acid, aminomethanesulfinic acid, aspartic acid, and glutamic acid and the like.
A particularly attractive zwitterion for use by the teachings of this invention is aminomethanesulfonic acid. This potentially inexpensive compound is readily prepared as a stable crystalline compound, m.p. 185°-186° C., from formaldehyde, sodium bisulfite, and ammonium hydroxide, followed by acidification. The reaction scheme is depicted in the following equations.
CH.sub.2 O+NaHSO.sub.3 →HOCH.sub.2 SO.sub.3 Na
HOCH.sub.2 SO.sub.3 Na+NH.sub.4 OH→H.sub.2 NCH.sub.2 SO.sub.3 Na
H.sub.2 NCH.sub.2 SO.sub.3 Na+H.sup.+ →H.sub.2 NCH.sub.2 SO.sub.3 H
It is sufficiently water soluble for use as a catalyst in textile treatment baths. It is less acidic than hydroxymethanesulfonic acid; acidity of aqueous solutions of aminomethane-sulfonic acid ranged from pH 3.81 for a 0.3% solution to pH 3.45 for a 5% solution (by weight).
Concentrations of zwitterion that may be used are from about 0.2% to about 1.5% by weight of the finishing bath. These concentrations of zwitterion may be used alone or in combination with suitable Lewis acids such as magnesium chloride, magnesium bromide, magnesium sulfate, magnesium nitrate, and the like. Concentration of magnesium chloride (as the hexahydrate) of from about 0.5% to about 2.0% may be employed with zwitterion. The ratios, by weight, of zwitterion to magnesium chloride hexahydrate, may be in the range from about 1.2:1 to about 1:7.5. From economic considerations, the total catalyst concentration of zwitterion plus magnesium chloride hexahydrate did not exceed 2.4% by weight of the finishing bath. Preferred catalyst compositions are demonstrated in the examples below.
Finishing treatments in which the zwitterion catalyst systems of this invention can be employed include conventional methods such as pad-dry-cure finishing, flash-cure finishing, post-cure finishing and the like as well as specialized finishing treatments such as one-step dry-cure finishing, super-heated steam cure finishing and the like.
Treatments were carried out by impregnating fabric by immersing it in the treatment solution (finishing pad bath), squeezing free of excess solution by passing through pad rolls, drying at a moderately elevated temperature (usually so that the temperature of the fabric does not exceed about 100° C.) and curing at a higher temperature. Curing temperatures from about 120° to about 160° C. are satisfactory at times ranging from about 1 minute to about 3 minutes, the longer times being preferred for the lower temperatures. Temperatures to achieve flash curing range from about 175° C. to about 215° C. with the preferred temperature being about 200° C. Times for flash curing may be from about 10 seconds to about 45 seconds. The preferred flash curing conditions are 20 seconds at 200° C. While the fabric can be utilized after finishing, it is good finishing practice to afterwash the fabric to remove residual chemicals and by-products.
The following examples further describe the invention and are given as illustrations but should not be considered as limiting the scope of the invention.
Properties of the fabrics were determined by known test methods: durable-press (DP) ratings after machine washing and tumble drying by AATCC Test Method 124-1969; wrinkle recovery angles by AATCC Test Method 66-1968; formaldehyde release by AATCC Test Method 112-1978 (sealed jar method); breaking strength by ASTM D1682-64; tearing strength by ASTM 1424-63; and nitrogen by the Kjeldahl method. Testing for formaldehyde release was performed on unwashed specimens; all other testing was done on washed fabrics. In the tables, breaking strengths and tearing strengths of the finished fabric are expressed as percentage of the original value of the untreated fabric.
EXAMPLE 1
Aqueous solutions were prepared to contain (by weight) 9% dimethylol dihydroxyethyleneurea (hereinafter referred to as DMDHEU) and 0.33-1.5% aminomethanesulfonic acid (hereinafter referred to as AMSA). A 3.2 oz/sq yd cotton printcloth fabric was used for treatments. Samples of the fabric were impregnated with these solutions and squeezed through pad rolls to achieve approximately 90% (by weight) wet pick-up of the treatment solution. The wet, impregnated samples were pinned on frames, then dried for 7 minutes at 65° C. and cured for 3 minutes at 160° C. Samples were washed and tested. This example illustrates that the zwitterion AMSA can serve as an efficient catalyst for durable-press finishing. Results are given in Table I.
TABLE I______________________________________ BREAKING TEARINGAMSA DP STRENGTH STRENGTH NITROGEN% RATING % % %______________________________________0.33 2.3 79 79 0.940.66 3.6 67 68 1.291.00 4.1 66 66 1.401.50 4.3 64 59 1.36______________________________________
EXAMPLE 2
Finishing baths contained 9% DMDHEU and catalyst concentrations as tested in Table II. Cotton printcloth was treated under the same drying and curing conditions as specified in Example 1. This example describes the treatments in which catalysis is provided by a combination of zwitterion and magnesium salt as well as the control experiments with AMSA and magnesium chloride alone as catalyst. Results are given in Table II.
TABLE II__________________________________________________________________________CATALYST BREAKING TEARING FORMALDEHYDEAMSA % MgCl.sub.2.6H.sub.2 O % DP RATING STRENGTH % STRENGTH % RELEASE PPM.__________________________________________________________________________1.0 -- 4.2 62 62 19470.75 0.63 4.7 56 63 12460.50 1.25 4.8 52 57 10060.25 1.88 4.7 50 50 918-- 2.5 4.3 55 55 1635__________________________________________________________________________
EXAMPLE 3
Cotton printcloth was impregnated with solutions containing 9% DMDHEU and the indicated concentrations of AMSA and magnesium chloride, dried at 65° C. for 7 minutes and cured at 160° C. for 3 minutes or 200° C. for 20 seconds. This example illustrates the use of a constant ratio (by weight) of AMSA to MgCl 2 but with various levels of the catalyst. It also demonstrates use of the zwitterion catalyst in flash cure treatment as well as at more conventional treatment curing temperatures. Results are given in Table III.
TABLE III__________________________________________________________________________CURE CATALYSTTEMP AMSA MgCl.sub.2 DP BREAKING TEARING FORMALDEHYDE° C. % .6H.sub.2 O % RATING STRENGTH % STRENGTH % RELEASE PPM__________________________________________________________________________160 0.2 0.5 3.4 66 68 2193160 0.3 0.75 4.4 59 65 1354160 0.4 1.00 4.6 59 64 967160 0.5 1.25 4.8 52 57 1006200 0.2 0.5 3.6 74 64 2164200 0.3 0.75 4.0 65 58 1459200 0.4 1.00 4.7 59 53 1090200 0.5 1.25 4.6 62 55 1001__________________________________________________________________________
EXAMPLE 4
Cotton printcloth was impregnated with solutions containing 9% DMDHEU and the indicated concentration of AMSA and magnesium chloride, dried at 65° C. for 7 minutes and cured at the listed temperatures for 3 minutes. This example illustrates the utility of different curing temperatures in the finishing reaction. Results are given in Table IV.
TABLE IV__________________________________________________________________________CURE BREAKING TEARINGTEMP AMSA MgCl.sub.2 STRENGTH STRENGTH FORMALDEHYDE° C. % .6H.sub.2 O % DP RATING % % RELEASE PPM__________________________________________________________________________120 0.5 1.25 2.8 83 77 1859130 0.5 1.25 3.9 78 70 1726140 0.5 1.25 4.4 65 63 1569120 1.0 -- 3.0 86 81 1659130 1.0 -- 3.5 75 73 1758140 1.0 -- 4.2 77 69 1839__________________________________________________________________________
EXAMPLE 5
Cotton printcloth was impregnated with solutions containing 9% DMDHEU, 0.5% AMSA, and 1.25% MgCl 2 .6H 2 O, dried at 65° C. for 7 minutes and cured at 160° C. for the listed times. This example indicates the latitude of times operative with this catalyst system. Results are given in Table V.
TABLE V__________________________________________________________________________CURE TIME BREAKING TEARING(at 160° C.) STRENGTH STRENGTH WRA (COND) FORMALDEHYDEMINUTES DP RATING % % DEG. RELEASE PPM__________________________________________________________________________1.0 4.6 63 53 280 10591.5 4.5 61 53 280 10422.0 4.7 60 52 280 10122.5 4.5 59 53 280 979__________________________________________________________________________
EXAMPLE 6
Cotton printcloth was impregnated with solutions containing 0.5% AMSA and 1.25% MgCl 2 .6H 2 O or 1% AMSA and the listed agents and their concentrations. Fabrics were dried at 65° C. for 7 minutes and cured at 160° C. for 3 minutes or at 200° C. for 20 seconds. This example illustrates the use of the zwitterion catalysts with aldehyde and methylol-amide finishing agents. Results are shown in Table VI.
TABLE VI______________________________________ DP RATING OF FINISHED FABRIC AMSAFINISHING AGENT AMSA MgCl.sub.2.6H.sub.2 OAND 160° 200° 160° 200°CONCENTRATION CURE CURE CURE CURE______________________________________10% FORMALDEHYDE 3.3 2.6 4.4 4.310% GLYOXAL 1.3 2.1 3.1 3.38% DIMETHYLOL- 3.5 3.7 4.3 4.4ETHYLENEUREA10% DIMETHYLOL 2.7 2.7 3.7 3.6METHOXYETHYLCARBAMATE______________________________________
EXAMPLE 7
Cotton printcloth was impregnated with solutions containing 9% DMDHEU and another zwitterion, 2-aminoethanesulfonic acid (taurine) alone or in combination with MgCl 2 .6H 2 O at the concentrations listed in the following table. The fabrics were dried at 65° C. for 7 minutes and cured at either 160° C. for 3 minutes or 200° C. for 20 seconds. This example illustrates that a zwitterion with a different chain length may be employed in the durable-press finishing of fabrics by the process of this invention. The results are shown in Table VII.
TABLE VII__________________________________________________________________________CATALYST CURING COND. FABRIC PROPERTIES2-aminoethane- BREAKINGsulfonic acid, MgCl.sub.2.6H.sub.2 O, TIME TEMP DP STRENGTH FORMALDEHYDE% % MIN. °C. RATING % RELEASE PPM__________________________________________________________________________1 -- 3 160 2.7 77 10331 -- .33 200 3.0 75 9650.5 1.25 3 160 4.2 60 9800.5 1.25 .33 200 4.4 60 1019__________________________________________________________________________
EXAMPLE 8
Cotton/polyester (50/50) sheeting was impregnated with solutions containing 9% DMDHEU and 1% AMSA or 0.5% AMSA and 1.25% MgCL 2 .6H 2 O, dried at 65° C. for 7 minutes and cure at 160° C. for 3 minutes or 200° C. for 20 seconds. This example illustrates the finishing of cotton/polyester fabrics by the process of this invention. The results are shown in Table VIII.
TABLE VIII__________________________________________________________________________CATALYST CURE FABRIC PROPERTIESAMSA MgCl.sub.2 TEMP TIME NITROGEN FORMALDEHYDE% .6H.sub.2 O % °C. MIN. DP RATING % RELEASE PPM__________________________________________________________________________1.0 -- 160 3 4.1 0.94 13451.0 -- 200 0.33 4.0 0.90 12740.5 1.25 160 3 4.3 1.01 7250.5 1.25 200 0.33 4.2 0.97 657__________________________________________________________________________
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Zwitterions are employed as catalysts in a chemical finishing process to treat cellulosic textiles with crosslinking agents and produce easy-care properties in the finished materials. The process comprises treatment of the textile material, such as cotton fabric, by impregnating it with a solution containing a cellulose-crosslinking agent and, as catalyst a zwitterion, alone or in combination with a magnesium salt, drying and curing the fabric. Said finished fabrics are characterized by an unusual combination of useful, desirable properties--smooth-drying appearance, wrinkle resistance, serviceable strength, and inoffensive formaldehyde release.
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CROSS-REFERENCE TO RELATED APPLICATION
This application claims the benefit of U.S. Provisional Application No. 60/725,662 filed Oct. 13, 2005. The disclosure of U.S. Provisional Application No. 60/725,662 is incorporated herein by reference in its entirety.
BACKGROUND
This invention relates to lithography apparatus and methods of performing lithographic exposure, commonly used to transfer a pattern onto a substrate in order to manufacture devices such as, for example, semiconductor devices, liquid crystal displays, etc.
Many current lithography apparatus have a large body structure that holds the projection lens, the metrology system and that supports the reticle stage and components of the illumination unit. FIGS. 1 and 2 show such an apparatus. In particular, body 20 , which can be mounted on a base 100 , includes one or more platforms and a plurality of columns, and supports a projection optical system 60 and a reticle stage 80 . The metrology system also is mounted to the body 20 . The metrology system includes laser interferometers 30 for measuring the position of the wafer stage 70 , laser interferometers 40 for measuring the position of the reticle stage 80 , and other sensors such as auto-focus sensors for measuring the vertical position of the wafer and/or reticle and alignment microscopes, etc. (generally represented by 50 ).
The body 20 is designed to hold all of the metrology elements in a fixed position relative to the projection optical system 60 . Of course, some vibrations and distortions occur and cause degradation of the lithography apparatus performance.
One problem with existing lithography apparatus is that the body 20 is a relatively large structure, and therefore has undesirably low vibration frequencies. One contributing factor to the large size of the body is that the stage interferometers 30 and 40 are located relatively far from the projection optical system. Accordingly, when the interferometers are mounted to the same body that supports the projection optical system and other components of the lithography apparatus, that body becomes large.
SUMMARY
According to aspects of the invention, the reticle and/or wafer stage interferometers are mounted to a supporting body to define an interferometer unit that is separate from the body that supports the projection system. This enables the size of the body supporting the projection system to be reduced so that it has more favorable dynamic characteristics.
According to preferred embodiments, the interferometer unit is suspended. This is beneficial in that the interferometer unit can be isolated from background vibrations.
According to one aspect of the invention, a lithography apparatus includes a projection system, a stage for holding an object and an interferometer unit. The interferometer unit mounts an interferometer that emits a first measurement beam to the projection system and that emits a second measurement beam to the stage. A position of the stage relative to the projection system is determined from the first and second measurement beams. The interferometer unit is suspended from a support member and is movable relative to the projection system.
At least one suspension member is disposed between the interferometer unit and the support member so as to flexibly suspend the interferometer unit from the support member. The suspension member preferably is stiff in an axial direction and is flexible in directions orthogonal to the axial direction. However, according to some embodiments, the suspension member can be flexible in its axial direction.
According to some embodiments, the suspension member is a wire or a rod. The wire or rod preferably is rotatably attached to the interferometer unit. The point of attachment to the interferometer unit preferably is vertically above the center of gravity of the interferometer unit. In embodiments having three or more suspension members, the suspension members can be attached to the interferometer unit at a location that is in or below a horizontal plane containing the center of gravity of the interferometer unit.
The suspension member can be directly attached to the support member or it can be attached to the support member through a mounting device. The mounting device, which is disposed between the support member and the suspension member, has a stiffness in the axial direction that is less stiff than a stiffness of the suspension member in the axial direction. According to some embodiments, the mounting device includes a piston supported by gas or a vacuum so as to absorb vibrations in the axial direction.
The stage can be a reticle stage or a substrate stage, and thus the interferometer can measure the position of the reticle or the substrate stages. In some embodiments, the interferometer unit includes interferometers for the reticle stage and for the substrate stage.
In some embodiments, a plurality of interferometer units are separately suspended from a support member and measure the position of the stage relative to the projection system in different directions (for example, different orthogonal directions). Alternatively, the plurality of interferometer units can be attached to each other so that their positions are fixed relative to each other.
The support member can be a frame from which the interferometer unit(s) is/are suspended. The frame can also suspend the projection system and support the reticle stage. Alternatively, the frame supporting the interferometer unit(s) can be separate from the frame that supports the reticle stage and/or projection system. The frame can be mounted on vibration isolation mounts.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be described in conjunction with the following drawings of exemplary embodiments in which like reference numerals designate like elements, and in which:
FIG. 1 is a simplified elevational view illustrating a conventional lithography apparatus;
FIG. 2 is a simplified perspective view of part of the body of the lithography apparatus in FIG. 1 ;
FIG. 3 is an elevational view of a lithography apparatus to which aspects of the invention are applied;
FIG. 4 schematically illustrates an interferometer unit according to one embodiment of the invention;
FIG. 5 illustrates an interferometer unit according to a second embodiment of the invention; and
FIG. 6 illustrates an arrangement in which separate X and Y interferometer units are provided.
DETAILED DESCRIPTION OF EMBODIMENTS
In accordance with aspects of the invention, the interferometer system is supported separately from the projection system, and preferably separately from the other components of the lithography apparatus such as the wafer and the reticle stages. In the illustrated embodiments, one or more interferometer units holding components of the reticle and wafer interferometer systems are suspended from a support member (or frame) that also suspends the projection system. However, the invention also can be implemented by providing a separate support frame from which only the interferometer unit(s) is/are suspended. That is, a first support member or frame can be provided to support the projection system and/or reticle stage while a second support member or frame can be provided to support (by suspension) the interferometer unit(s). In addition, the invention can be applied to systems that support the projection system by means other than suspension. For example, the invention can be applied to systems in which the projection system is rigidly held to a support frame, as is well known, rather than being suspended. In such an arrangement, the interferometer unit(s), however, would be suspended from either the support member (or frame) that rigidly supports the projection system or from a separate support member (or frame).
FIG. 3 illustrates a lithography apparatus according to one embodiment of the invention. A support member or frame 25 is mounted to a base unit 100 , either directly or by vibration isolation mounts 104 . Vibration isolation mounts 104 can be passive or active devices. Passive vibration isolation mounts typically include resilient components made from rubber and/or including gas or other damping devices. Active vibration isolation mounts include a precisely controlled and actively driven member such as a voice-coil motor and/or gas-driven piston unit whose movement is controlled by controlling the supply of gas to opposite sides of a piston.
A wafer stage base 72 is mounted to the base unit 100 , for example, by active or passive vibration isolation mounts 74 . A wafer stage 70 that holds a wafer W is supported by the wafer stage base 72 . As is well known, the wafer stage 70 moves in the X and Y directions to expose multiple shot areas on the wafer to a pattern projected through projection system 60 .
Projection system 60 is suspended from the support member 25 by three suspension members 65 (only two are shown in FIG. 3 ). The suspension members 65 can be wires or rods that are stiff in the Z direction but flexible in the X and Y directions. The projection system 60 can be supported, for example, in the manner described and shown in WO 2006/038952 published on Apr. 13, 2006. The disclosure of WO 2006/038952 is incorporated herein by reference in its entirety. Active or passive vibration isolation units can be provided between the support member 25 and each suspension member 65 to prevent Z-direction vibrations from transmitting to the suspension members 65 from the support member 25 .
A reticle stage base 85 is mounted on the support member 25 , for example, by passive or active vibration isolation mounts 84 . A movable reticle stage 80 holding a reticle R is controlled to move in the X and Y directions on the reticle stage base 85 . An illumination optical system (not shown) also is provided and can be entirely mounted on, or have components mounted on, the support member 25 .
An interferometer unit 200 , shown in FIGS. 3 and 4 , is suspended from the support member 25 by a suspension member 250 . Member 250 is stiff in the Z direction but flexible in the X and Y directions. Member 250 can be a wire, rod, or beam, for example. A first end 252 of the flexible suspension member 250 is attached to the interferometer unit 200 at a position located above the center of gravity 275 of the interferometer unit 200 . The first end 252 of member 250 should be attached to the interferometer unit 200 in a manner that allows it to rotate freely relative to the interferometer unit 200 . This rotatable attachment of the flexible suspension member 250 to the interferometer unit 200 above the center of gravity 275 enables the interferometer unit 200 to hang freely with the desired orientation. For example, if the suspension member 250 is a flexible wire, the end of the wire can be rigidly attached to the interferometer unit 200 because the wire itself can bend or twist to act like a flexible joint. If the suspension member 250 is a beam or a rod that is relatively stiff in bending, then flexible joints should be provided, preferably at both ends of the suspension member 250 . Each flexible joint can be, for example, a universal joint, a ball joint, a ball-in-socket, etc.
In the embodiment of FIG. 4 , the second, upper end of the flexible suspension member 250 is attached to an isolation member 300 that is supported by the support member 25 . In particular, the second end of flexible suspension member 250 is attached to a piston 310 of isolation member 300 . The isolation member 300 is filled with gas (or a vacuum) such that it has a low stiffness in the Z-direction. Therefore, isolation member 300 reduces or prevents Z-direction vibrations from being transmitted to the suspension member 250 (and thus to the interferometer unit 200 ) from the support member 25 . Isolation member 300 also provides the lifting force to support the weight of the interferometer unit 200 . Other examples of structures that can be used as isolation member 300 include: rubber or elastomer members, attractive or repulsive magnets (permanent magnets, electromagnets or a combination), mechanical springs (coil, leaf, etc.), or any combination of passive and active isolation devices. Isolation member 300 also can be provided at the other (lower) end of suspension member 250 .
In the FIG. 4 embodiment, a reticle stage interferometer 220 and a wafer stage interferometer 210 are mounted to the interferometer unit 200 . The invention also could be implemented by attaching only one of the reticle stage or wafer stage interferometers to the interferometer unit 200 .
The reticle stage interferometer 220 emits a measurement beam 261 to the reticle stage 80 and a measurement beam 262 to the projection system 60 so that the position of the reticle stage 80 relative to the projection system 60 can be determined. This information then is used to control the movement of the reticle stage 80 . The wafer stage interferometer 210 emits a measurement beam 264 to the wafer stage 70 and a measurement beam 263 to the projection system 60 . Based on measurement beams 263 and 264 , the position of the wafer stage 70 relative to the projection system 60 can be determined similar to the way in which the position of the reticle stage 80 relative to the projection optical system 60 is determined. For simplicity of explanation, each measurement beam 261 - 264 is referred to in the singular; however, as is known, each beam 261 - 264 can be one or more beams depending on the number of axes measured. For example, each beam can include four or more beams, and measurements can be obtained in the X, Y, Z, θX, θY and θZ axes.
FIG. 4 illustrates beams 261 - 264 extending in a single direction. However, as is known, the position of the stages 70 / 80 relative to the projection system 60 usually is determined in both the X and Y directions. Thus, FIG. 4 is merely a simplified diagram. The stage position preferably is measured in six degrees of freedom (X, Y, Z, θX, θY and θZ). The interferometer unit 200 could be L-shaped so as to hold reticle stage and wafer stage interferometers that emit beams in the X and Y directions. Alternatively, as shown in FIG. 6 , separate interferometer units 200 X and 200 Y can be provided to obtain information in the X and Y directions. FIG. 6 also shows (in phantom) an L-shaped bracket that can be provided to rigidly fix the interferometer units 200 X and 200 Y to each other.
FIG. 5 shows a second embodiment in which the flexible suspension member 250 is directly attached to the support member 25 without any vertical isolation piston or other structure between the members 25 and 250 . In this implementation, there is no vertical isolation between the support member 25 and the interferometer unit 200 . This implementation may be more appropriate for architectures in which the interferometer unit is supported by a member (or frame) separate from the member (or frame) that supports the reticle stage (and possibly the projection system), which tends to receive vibrations due to movement of the reticle stage. That separate support member (or frame) for the interferometer unit 200 preferably is vibrationally isolated from the ground by providing active or passive vibration isolation mounts between the support member (or frame) and the ground or base unit on which the support member (or frame) is mounted.
An alternative embodiment would be to incorporate the vertical compliance in the suspension member 250 itself. This could be done by using an axially flexible member such as a spring or elastic strap/band as the suspension member.
FIG. 6 illustrates an embodiment in which an X-direction interferometer unit 200 X and a Y-direction interferometer unit 200 Y are provided. Each interferometer unit is suspended in the manner that was described in conjunction with FIG. 4 . The X-direction interferometer unit 200 X supports a reticle interferometer that emits a reticle stage beam 261 X and a projection system beam 262 X, whereas the Y-direction interferometer unit 200 Y supports a reticle stage interferometer that emits a Y-direction reticle stage beam 261 Y and a Y-direction projection system beam 262 Y. Using these beams, the position of the reticle stage 80 relative to the projection system 60 is determined in both the X and Y directions. Each of the beams 261 X, 261 Y, 262 X and 262 Y consists of one or more beams so as to measure position in one or more axes, preferably in X, Y, Z, θX, θY and θZ directions. The X-direction interferometer unit 200 X and the Y-direction interferometer unit 200 Y respectively emit wafer stage and projection system beams 263 X, 264 X, 263 Y and 264 Y (each consisting of one or more beams) so that the position of the wafer stage 70 relative to the projection system 60 can be determined in at least the X and Y directions, and preferably in X, Y, Z, θX, θY and θZ directions, similar to the manner in which determination is made for the reticle stage 80 .
A single suspension member can be provided for the, or each, interferometer unit, or each interferometer unit can be supported by more than one suspension member. For example, according to one embodiment, each interferometer unit is supported by three suspension members. If there are three or more suspension members for an interferometer unit, the point of attachment of the suspension members to the interferometer unit need not be above the interferometer unit center-of-gravity, but can be in or below the horizontal plane containing the interferometer unit center-of-gravity.
Attaching the X and Y interferometer units 200 X and 200 Y to each other, for example, with one or more L-shaped brackets (one is shown with phantom lines in FIG. 6 ), keeps the units properly oriented relative to each other. In addition, suspending the assembly formed by the joined units with a third suspension member (also shown with phantom lines in FIG. 6 ) reduces rotation of the interferometer unit assembly relative to the projection system 60 . When additional stabilization of the interferometer units is desired, actuators, preferably non-contact electromagnetic actuators such as voice-coil motors, for example, can be provided to prevent the interferometer unit(s) from moving excessively in the θX, θY and θZ directions. It is noted that the tendency of the interferometer unit(s) to move increases as the number of suspension members decreases (a single suspension member permitting more movement than arrangements using three or more suspension members) and as the flexibility of the suspension member(s) increases. Thus, if three or more suspension members are used, particularly if the suspension members are rods or beams, no actuators may be needed to further stabilize the interferometer unit(s).
The lithography apparatus can be a step-and-repeat apparatus that exposes the pattern onto the substrate while the substrate is stationary or it can be a scanning lithography apparatus that exposes the pattern onto the substrate while the substrate is moving. The lithography apparatus can use immersion technology in which an immersion liquid is disposed between the projection system and the substrate.
The lithography apparatus of the above-mentioned embodiments can be manufactured by incorporating and optically adjusting an illumination optical system composed of a plurality of lenses and a projection system into the main body of the lithography apparatus, and installing the reticle stage and the wafer stage composed of a plurality of mechanical parts to the main body of the lithography apparatus, connecting wires and pipes, and performing overall adjustment (electrical adjustment, operation check, etc.). Furthermore, it is preferable that manufacturing of the lithography apparatus is performed in a clean room with controlled temperature and cleanliness.
Furthermore, when a semiconductor device is manufactured by using the lithography apparatus of the above-described embodiments, the semiconductor device is manufactured by a step of designing a performance capability and function of the device, a step of manufacturing a reticle based on the designing step, a step of forming a wafer from a silicon material, a step of performing alignment by the lithography apparatus of the above-mentioned embodiment and exposing a pattern of the reticle onto a wafer, a step of forming a circuit pattern such as etching or the like, a step of assembling a device (including a dicing process, a bonding process, a packaging process), a step of testing, and the like.
This invention can be applied to a liquid crystal panel manufacturing exposure apparatus disclosed in, for example, International Publication No. WO 99/49504. Furthermore, this invention can be applied to a lithography apparatus using extreme ultraviolet light (EUV light) having a wavelength of several nm-100 nm as an exposure beam.
Furthermore, this invention is not limited to the application for the lithography apparatus for manufacturing a semiconductor device. For example, this invention can be applied to a lithography apparatus for manufacturing various devices such as a liquid crystal display element formed on a square-shaped glass plate, or a display device such as a plasma display or the like, or an imaging element (CCD), a micro-machine, a thin-film magnetic head, a DNA chip, or the like. Furthermore, this invention can be applied to a lithography process (lithography apparatus) in which a mask (photomask, reticle, or the like) having a mask pattern of various devices is formed by using a photolithographic process.
While the invention has been described with reference to preferred embodiments thereof, which are exemplary, it is to be understood that the invention is not limited to the preferred embodiments or constructions. The invention is intended to cover various modifications and arrangements. In addition, while the various elements of the preferred embodiments are shown in various combinations and configurations, that are exemplary, other combinations and configurations, including more, less or only a single element, are also within the spirit and scope of the invention.
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Reticle and/or wafer stage interferometers are mounted to a supporting body that is separate from the body that supports the projection optical system of a lithography apparatus. This enables the size of the body supporting the projection optical system to be reduced so that it has more favorable dynamic characteristics.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of The Invention
[0002] The present invention relates to a heating apparatus in a color test machine, and, more particularly, to an improvement on a heating apparatus in a color test machine, with which the test tumbler can be heated up and preserve the heat quickly to shorten the time duration needed for performing the color dyeing in the color test machine.
[0003] 2. Description of Related Art
[0004] Usually, a color test is a required lead operation of a dye work for a yarn or a cloth. It is necessary for a small amount of cloths or yarns to be tested the color dyed prior to a mass production of dyeing being performed in spite of cloths or yarns in order to make sure a correct color being dyed. Thus, it is preferable that the color test for a small amount of cloths or yarns is performed under a condition identical with that for the mass production of dyeing.
[0005] A mass production of dyeing is processed in a closed system so that the temperature in the closed system is in a state of steadiness and the color dyed for all the cloths or the yarns is identical in the same lot. However, it is a challenge for a color test machine to simulate the treatment condition in the mass production of dyeing. Especially, the color test machine has to treat a variety of materials with different colors at the same time so that it is a difficult problem to maintain a preset temperature.
[0006] The heating apparatus provided in the conventional color test machine usually adopts the oil as the medium for transferring the heat, that is, the oil is filled in the color test machine at lower part thereof and the oil is heated up by way of a heater to maintain a constant temperature. A rotary shaft is mounted at the upper part of the color test machine and in conjunction with the test tumbler containing dyeing stuff and dyed samples such as cloths or yarns. As soon as the rotary shaft rotates, the test tumbler below the rotary shaft may immerge in the heated oil and the heat may transmit to the test tumbler. The procedure is kept circulated sequentially to perform the color test job.
[0007] However, There are deficiencies existing in the conventional heating apparatus applied in the color test machine. Usually, it is slow for the oil to be heated up and the oil being heated to a preset temperature requires a period of time. A bad smell may generate as soon as the oil is heated up and the bad smell may affect the air of the work site. It is serious that the cooling speed is slow so that it takes a long waiting time for the operator before the test tumbler can be taken out. Besides, the tumbler contacts with the oil directly so that the outer side of the test tumbler has to be cleaned up after completing the color test.
SUMMARY OF THE INVENTION
[0008] An object of the present invention is to provide a heating apparatus in a color test machine, in which the heat transfer medium is made of sand material so that heating and the heat preservation can be reached quickly to shorten the time duration needed by the process of dyeing.
[0009] Another object of the present invention is to provide a heating apparatus in a color test machine, which further offers a temperature measure device and an automatically controlled cooling system such that the test tumbler can be cooled down quickly and the temperature in the test machine can be measured precisely.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The present invention can be more fully understood by referencing to the following description and accompanying drawings, in which:
[0011] [0011]FIG. 1 is a perspective view of a heating apparatus in a color test machine according to the present invention;
[0012] [0012]FIG. 2 is sectional view illustrating the heating apparatus in a color test machine according to the present invention in use;
[0013] [0013]FIG. 3 is a sectional view illustrating the heating apparatus shown in FIG. 2 with an added temperature reduction device and a temperature measure device;
[0014] [0014]FIG. 4 is an exploded sectional view of the temperature measure device shown in FIG. 3; and
[0015] [0015]FIG. 5 is a sectional view illustrating the temperature measure device in a normal state of connecting.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0016] Referring to FIG. 1, a color test machine according to the present invention basically provides a closed tank and comprises a rotating shaft 1 , at least a heater 2 driven by the rotating shaft 1 , and a rotary tumbler seat 3 . In addition, a temperature reduction device 4 and a temperature measure device 5 may be added while the color test machine is in practice.
[0017] Wherein, the rotating shaft 1 is moved by way of a motor 11 via a belt 12 so that the rotating shaft 1 can turn with a constant speed. Because the rotating speed may affect the timing for a test tumbler contacting the heat transmitting medium, a speed limit device can be added to adjust the speed from the rotating shaft 1 such as the speed can be lowered down to 1 revolution per minute. Alternatively, the rotating shaft can be driven by a servomotor to provide an intermittent rotation so that the test tumbler can pause from time to time. However, this is a prior art and no detail will be described further.
[0018] The heater 2 may be a conventional electric heater, an electric light, or any other heating device. The heater 2 also belongs to the prior art and no detail will be described further too.
[0019] The rotary tumbler seat 3 basically is a disk viewed from the front side thereof and provides a plurality of tumbler recesses 31 around the periphery thereof for locating test tumblers A so that the inner diameter of each tumbler recess 31 is corresponding to the outer diameter of each test tumbler for the test tumbler tightly fitting with the tumbler recess. A recess clearance 33 is formed between each tumbler recess 31 and an outer wall 32 so that the tumbler recess 31 can communicate with the outer wall. A heat transfer medium 34 is received in the recess clearance 31 to guide the heat and it is preferably that the heat transfer medium 34 does not occupy the entire recess clearance 31 .
[0020] Referring to FIG. 2, a greatest change of the heat guide medium 34 used in the present invention is that solid particles such as the sand material instead of the oil traditionally used. The sand material applied in the present invention is the natural sand such as the sand from the river, chemical micro particles, aluminum oxide, ceramic powder, magnesium oxide, or other micro particle materials such that an excellent effect with regard to the heat transfer and the heat preservation can be reached by the heat transfer medium 34 . In the meantime, an excellent effect of the heat reduction and dissipation can be obtained substantially.
[0021] Referring to FIG. 2 again, as soon as the respective test tumbler A is inserted into the respective tumbler recess 31 and is closed in the color test machine, the rotating shaft 1 starts to rotate the color test machine and the respective heat transfer medium 34 in the respective recess clearance 33 may rotate along with the rotary tumbler seat 3 . The test tumbler A may fall down during the rotation so as to be heated up and keep worm continuously by way of the heat transfer medium 34 . In this way, the test tumbler A can obtain a uniform heat and maintain at a constant temperature due to the sand material, and the sample in the test tumbler can be dyed steadily.
[0022] As it has been mentioned above, the sand medium 34 is solid so that it is possible for the heat therein to be dissipated quickly with a reduction of temperature. Hence, the test tumbler A can be taken out shortly and the sample in the test tumbler A can be treated further with an check after the process of dying being complete with a stop heating due to a shorter cooling time.
[0023] Referring to FIG. 3, the temperature reduction device 4 is disposed in the color test machine and further comprises a water inlet pipe 41 , at least a nozzle head 42 , an automatic switch 43 , an inlet valve 44 /or a filter 45 .
[0024] Wherein, the water inlet pipe 41 is mounted in the test machine with an outward inlet end 411 for connecting the water source, and the other end of the inlet pipe 41 is disposed next to the rotary tumbler seat 3 with the nozzle head 42 . The water passing through the nozzle head 42 can spray in a radial shape toward the rotary tumbler seat 3 to perform the cooling job after the process of dying.
[0025] The automatic switch 43 is connected to a programmable automatic device and the automatic switch 43 is in a state of being off during the process of dying and is tuned on automatically at the time of the temperature being reduced after the process of dying such that the water spraying can be started. Because the automatic switch 43 is a prior art, no detail will be described further.
[0026] The inlet valve 44 is disposed in the test machine too for controlling the admittance of the water, that is, the inlet valve 44 can be closed in case of no water being needed to avoid an excess of water supply. Besides, the filter 45 is placed before the automatic switch 43 to remove the foreign substance from the water for keeping the cleanness of the supply water.
[0027] Moreover, a water discharge hole 45 is provided at the bottom of the test machine to drain off the sprayed water after cooling and a pipeline can be connected to the water discharge hole 46 for the drained water flowing outward properly or being recycled. This part also belongs to the prior art and no further detail will be described.
[0028] Referring to FIG. 3 again, after the color test machine of the present invention having completed the process of dying, the rotary tumbler seat 3 still keeps in a state of rotating without heating and the automatic switch 43 is started so that the nozzle head 42 sprays the water to cool down the rotary tumbler seat 3 so as to shorten the time duration before the test tumbler A being possible to be taken out. The sprayed water then can be discharged through the water discharge hole 46 .
[0029] Referring to FIG. 3 again, the rotary tumbler seat 3 is exposed in a closed space with high temperature and it is hard to measure the temperature thereof. Thus, the temperature measure device 5 is mounted for being feasible for the measurement of temperature.
[0030] Referring to FIGS. 4 and 5 with accompanying FIG. 3 again, the temperature measure device 5 basically comprises a feeler rod 51 , a drive part 52 , and a follower part 53 . The feeler rod 51 electrically connects with the drive part 52 via wires, and the drive part 52 contacts with the follower part 53 .
[0031] Wherein, the feeler rod 51 is disposed in and fixedly attached to the rotary tumbler seat 3 to sense the temperature in the rotary tumbler seat 3 with two sensing polar lines 511 passing through the rotating shaft 1 .
[0032] The drive part 52 provides a shape of sleeve and is disposed in the rotating shaft 1 driven by the belt 12 . The drive part 52 comprises an active polar cylinder 521 made of conductive material and an active polar shaft 522 and the two sensing polar lines 511 connect with the active polar cylinder 521 and the active polar shaft 522 respectively. An inner insulating cylinder 523 is disposed between the active polar cylinder 521 and the active polar shaft 522 to insulate the active polar cylinder 521 from the active polar shaft 522 . An outer insulating cylinder 524 is disposed to surround the drive cylinder 521 to insulate from the inner wall of the rotating shaft 1 . The active polar shaft 522 at the front end thereof is a sharp active polar end 5221 and the active polar cylinder 521 at the front end thereof is a flat surface with an inward recess 5211 .
[0033] The follower part 53 is disposed corresponding to the drive part 52 and comprises a passive polar cylinder 531 and a passive polar shaft 532 . An inner insulating cylinder 533 is provided between the passive polar cylinder 531 and the passive polar shaft 532 to constitute insulation in between. The passive cylinder 531 is surrounded with an outer insulating cylinder 534 to insulate from the rotating shaft 1 . Besides, the passive polar cylinder 531 at the front end thereof provides an tilt passive polar slope 5311 corresponding to the drive polar recess 5211 obliquely. The passive polar shaft 532 at the front end thereof provides a passive polar recess 5321 corresponding to the drive polar end 5321 corresponding to drive polar end 5221 . Furthermore, the passive polar cylinder 531 and the passive polar shaft 532 connect with a lead wire respectively.
[0034] In order to keep the drive part 52 contacting with the follower part 53 constantly, a spring is arranged at outside the follower part 53 to urge the follower part 53 against the drive part 52 .
[0035] Referring to FIG. 5 again, the spring 54 urges the follower part 53 to move outward such that it results in the passive polar cylinder 531 and the passive polar recess 5321 keep a constant contact with the active polar cylinder 321 and the active polar end 5221 , respectively. Hence, the two sensing polar lines 511 may be extended outward the test machine so that the feeler rod 51 may be in a close circuit.
[0036] It is appreciated from the preceding description that the advantages of the present invention can be summarized in the following:.
[0037] (1) The present invention can enhance the safety. Due to the solid particles of sand material being applied to act as heat transfer medium, the undesirable effect with regard to the careless hurt resulting from heating oil and the explosion resulting from a great pressure as the conventional heater does can be avoided completely.
[0038] (2) The foul smell derived from the oil can be avoided. Because the sand material is used as the heat transfer medium, no odor would be spread out during heating so that it is not possible to produce the foul smell as the oil does. Hence, the working environment becomes better for the operators and the willingness for work and the efficiency during work can be enhanced greatly.
[0039] (3) It is not necessary to consider the problem of metamorphism in case of the medium being used repeatedly. The medium of sand material does not occur the chemical reaction during heating so that it can be reused again without the need for replacement. The oil used in the conventional heater easily becomes bad after heating and the old oil has to be replaced. Comparing to the oil, the medium of sand material can lower down the cost for processing the color test.
[0040] (4) It is possible to shorten the time during processing the operation of color test. Because the medium of sand material provides a better capability to perform the heat transfer, the functions such as heating, heat preservation, and heat reduction can be performed more quickly than the oil does. Hence, the speed and the efficiency for executing the color test can be promoted and the derived cost for carrying out the color test can be reduced.
[0041] (5) The sensed temperature is highly precise. Because the temperature sensing is conducted in the test machine and the temperature is read outside the test machine. Due to the temperature being measured in an airtight space, the accuracy of temperature sensing is enhanced greatly.
[0042] While the invention has been described with reference to a preferred embodiment thereof, it is to be understood that modifications or variations may be easily made without departing from the spirit of this invention, which is defined in the appended claims.
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A heating apparatus in a color test machine comprises a rotary tumbler seat, a rotating shaft for turning the rotary tumbler seat, a heater for heating the rotary tumbler seat, and tumbler recesses provided in the rotary tumbler. It is characterized in that solid micro particles are used as heat transfer media for heating and preserving the heat.
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BACKGROUND OF THE INVENTION
α-L-aspartyl-L-phenylalanine methyl ester is a sweetening agent which is about 200 times sweeter than sucrose. The compound and its uses are extensively taught in U.S. Pat. Nos. 3,492,131; 3,642,491; and 3,780,189. A variety of methods for the economical synthesis of α-L-aspartyl-L-phenylalanine are known, for example, U.S. Pat. Nos. 3,933,781 and 4,173,562 describe the use of N-protected-L-aspartic anhydride in preparing α-L-aspartyl-L-phenylalanine methyl ester.
Chem Abstracts 64 19754C (1966) describes acetoacetyl derivatives of glycine, alanine, leucine, threonine, methionine and tryptophan made from the reaction of the corresponding amino acid with diketene. The acetoacetyl derivative of leucylglycine methyl ester is described in Tetrahedron Letters 10, 605-608 (1965). J. Chem Soc (C), 350, (1969) describes the preparation of N-acetoacetylvaline and N-acetoacetylvalyvaline from valine and valylvaline respectively and diketene.
BRIEF DESCRIPTION OF THE INVENTION
The present invention involves a high yield large scale synthesis of α-L-aspartyl-L-phenylalanine methyl ester.
The preferred embodiment of the invention is illustrated in Scheme I. ##STR1##
It has been discovered that diketene selectively reacts with the amino group of aspartic acid in high yield even though two carboxylic acid groups are present in aspartic acid. This reaction is conducted in basic solution, preferably basic methanol. The acetoacetyl group is stable during dehydrating procedures which form the anhydride and it is surprising that N-acetoacetyl L-aspartic anhydride is formed instead of the predicted oxazolidinone 4 in Scheme I. Acid anhydrides such as acetic anhydride and propionic acid anhydride and phosphorous trichloride are preferred dehydrating agents for converting N-acetoacetyl L-aspartic acid to N-acetoacetyl L-aspartic anhydride. The acetoacetyl group is removed with hydroxylamine salt such as the hydrochloride or sulfate under mild conditions in 99% yield without disturbing the ester and/or the free carboxyl group--a problem associated with removal of the formyl and acetyl group. For example, the formyl is removed by strong acids in aqueous methanol which causes esterification and hydrolysis.
Thus, the invention encompasses a method for preparing L-aspartyl-L-phenylalanine methyl ester comprising:
(a) reacting L-aspartic acid with diketene in basic solution at -10° C. to +20° C. to form N-acetoacetyl-L-aspartic acid.
(b) dehydrating N-acetoacetyl-L-aspartic acid with a dehydrating agent to form N-acetoacetyl-L-aspartic anhydride.
(c) reacting N-acetoacetyl-L-aspartic anhydride with L-phenylalanine methyl ester to form N-acetoacetyl-α-L-aspartyl-L-phenylalanine.
(d) removing the N-acetoacetyl group from N-acetoacetyl-α-L-aspartyl-L-phenylalanine by reaction with hydroxylamine hydrochloride.
The preferable dehydrating agents are acetic anhydride in acetic acid or ethyl acetate or phosphorous trichloride in ethyl acetate/acetic acid.
Novel intermediates of the invention are
N-acetoacetyl-L-aspartic acid
N-acetoacetyl-L-aspartic anhydride
N-acetoacetyl-α-L-aspartyl-L-phenylalanine
DETAILED DESCRIPTION OF THE INVENTION
The above named novel intermediates are shown in Scheme I as structures 1, 2 and 3, respectively. Free carboxylic acid groups in these compounds can be converted to the respective salts such as sodium, potassium, calcium and the like by reaction with the appropriate base. Thus reaction mixtures which contain compound 1, 2 or 3 whether as the free base or acid or base salts are within the scope of the invention.
EXAMPLES
N-acetoacetyl-L-aspartic acid
L-aspartic acid, 13.3 parts, was added to 100 parts by volume of 2 N aqueous sodium hydroxide and the resulting solution was cooled to 0°-10° C. in an ice bath. Diketene, 8.4 parts, was added and the resulting two phase mixture was stirred for 2.5 hours at 0°-10° C. The homogeneous solution was washed twice with 100 parts by volume of ether and the aqueous layer was acidified with 16.6 parts by volume of concentrated hydrochloric acid. This solution was extracted three times with 100 parts by volume of ethyl acetate, the combined extracts were dried over sodium sulfate, filtered and the solvent evaporated under vacuum at 25°-30° C. to give 2.3 parts of N-acetoacetyl-L-aspartic acid, mp 127°-129.5° C.
Elemental analysis for C 8 H 11 NO 6 : Calc. C, 44.24; H, 5.10; N, 6.45. Found C, 44.59; H, 5.24; N, 6.10.
NMR (DMSO-D6): δ 2.18, 3H, s; 2.70, 2H,d; 3.38, 2H, s; 4.59, 1H, m; 8.40, 1H, m.
N-Acetoacetyl-L-Aspartic Anhydride
1.41 parts of N-acetoacetyl-L-aspartic acid were dissolved in 25 parts by volume of acetic acid, and 5 parts by volume of acetic anhydride were added and the mixture was stirred overnight under nitrogen. Solvent was removed under vacuum at 40°-45° C. 50 parts by volume of acetic acid were added and the evaporation repeated to form N-acetoacetyl-L-aspartic anhydride.
N-Acetoacetyl-L-Aspartyl-L-Phenylalanine Methyl Ester
The crude anhydride was stirred with 20 parts by volume of toluene and 5 parts by volume of acetic acid. 8 parts by volume of an 0.81 Molar solution of L-phenylalanine methyl ester in toluene was added and stirred overnight. The resulting solution was evaporated under vacuum to give an oil. The oil was stirred with 50 parts by volume of ether which resulted in formation of a solid. This solid was isolated by filtration, washed with ether and air dried to give 1.61 parts of N-acetoacetyl-L-aspartyl-L-phenylalanine methyl ester as a mixture of α and β isomers.
NMR (DMSO-D6): δ 2.13, 3H, s; 2.60, 2H, m; 3.02, 2H, m; 3.35, 2H, s; 3.60, 3H, s; 4.54, 1H, m; 7.25, 5H, s; 8.30, 2H, m.
L-Aspartyl-L-phenylalanine Methyl Ester
1.41 parts of N-acetoacetyl-L-aspartyl-L-phenylalanine methyl ester was dissolved in 50 parts by volume of 1:1 aqueous acetic acid, 0.259 parts of hydroxylamine hydrochloride was added and the solution stirred at ambient temperatures for 4 hours to provide a mixture of α and β isomers of L-aspartyl-L-phenylalanine methyl ester.
Preparation of Disodium N-Acetoacetylaspartate
8.1 parts of sodium hydroxide were dissolved in 100 parts by volume of water and the solution cooled to 0°-5° C. 13.3 parts of L-aspartic acid were added and stirred until all dissolved, then 15.8 parts by volume of diketene were added dropwise over 90 minutes, stirred at 0°-10° C. for an additional 2.5 hours, and filtered. The homogeneous solution was evaporated to dryness under vacuum at 35°-40° C. Disodium N-acetoacetylaspartate was obtained as a white foam.
Preparation of N-Acetoacetyl-L-Aspartyl-L-Phenylalanine Methyl Ester
Crude disodium N-acetoacetylaspartate, 28.51 parts, was stirred with 200 parts by volume of ethyl acetate and 11.7 parts by volume of acetic acid at 0°-5° C. under argon while 4.37 parts by volume of phosphorous trichloride was added dropwise. The resulting mixture was allowed to warm to ambient temperatures while stirring for 20 hours. To the resulting solution which contains N-acetoacetyl-L-aspartic anhydride was added dropwise over a 2 hour period 122 parts by volume of 0.9 M L-phenylalanine methyl ester in dioxane. After continued stirring for 20 hours, the solvent was evaporated under vacuum at 35°-40° C. Toluene, 200 parts by volume, was added to the residue and the evaporation was repeated, giving crude N-acetoacetyl-L-aspartyl-L-phenylalanine methyl ester as a semi-solid yellow residue.
L-Aspartyl-L-Phenylalanine Methyl Ester Hydrochloride Dihydrate
The crude N-acetoacetyl-L-aspartyl-L-phenylalanine methyl ester was dissolved in 100 parts by volume of water and 11.7 parts by volume of acetic acid. Toluene 200 parts by volume and 6.95 parts of hydroxylamine hydrochloride were added and the mixture stirred for 2.5 hours. The aqueous layer was separated and cooled to 0°-5° C. 15 parts by volume concentrated hydrochloric acid were added and the resulting mixture was cooled at 0°-5° C. overnight. The precipitate was collected on a filter and air dried for 3 hours to give 26.4 parts of α-L-aspartyl-L-phenylalanine methyl ester hydrochloride dihydrate.
α-L-Aspartyl-L-Phenylalanine Methyl Ester
12.5 parts of α-L-aspartyl-L-phenylalanine methyl ester hydrochloride dihydrate was dissolved in 100 parts by volume of water and aqueous sodium carbonate added to pH3, then heated to 60° C. and adjusted to pH4.6. The reaction mixture was cooled to 5° C. for three hours and the precipitate was collected on a filter and dried for 18 hours under vacuum at 60° C. to give 7.6 parts α-L-aspartyl-L-phenylalanine methyl ester.
Isolation and Characterization of N-Acetoacetyl-L-Aspartic Anhydride
2.0 parts of sodium hydroxide were dissolved in 25 parts by volume of water and cooled to 0°-10° C. Then 3.33 parts L-aspartic acid were added and the mixture stirred until all dissolved. To this mixture was added 3.95 parts by volume of diketene dropwise while maintaining temperature and continued stirring for 3 hours. The solvent was evaporated from the homogeneous solution under vacuum at 35°-40° C. until the mixture began to foam. 25 parts by volume of acetic acid was added and evaporation was repeated. This process was repeated twice to give 20.7 parts of clear solution. To this clear solution was added 12.5 parts by volume of ethyl acetate and 4.7 parts by volume of acetic anhydride. After about 1 hour a thick precipitate formed and stirring was continued for 18 hours. The solid was isolated by filtration, washed twice with 10 parts by volume of cold ethyl acetate and dried under vacuum at 35°-40° C. for 24 hours to give 9.85 parts of anhydride contaminated with sodium acetate/acetic acid. This material was stirred with 100 parts by volume of dioxane for 5 hours. After filtration to remove remaining solid, the dioxane was evaporated under vacuum at 35°-40° C. and the residue was dried under vacuum at the same temperature for 24 hours to give 1.08 parts of N-acetoacetyl-L-aspartic anhydride, mp 131.5°-135° C.:
Elemental analysis for C 8 H 9 NO 5 : Calc. C, 48.25; H, 4.55; N, 7.03. Found C, 48.42; H, 4.50; N, 6.72.
NMR (Dimethylformamide-D7) δ 2.23, 3H, s; 2.8-3.7, 2H, AB portion of ABX; 3.53, 2H, s; 4.99, 1H, m; 9.04, 1H, m.
Preparation and Isolation of N-Acetoacetyl-α-L-Aspartyl-L-Phenylalanine Methyl Ester
4.5 parts of diketene were added dropwise to a stirred suspension of 14.7 parts α-L-aspartyl-L-phenylalanine methyl ester in 400 parts by volume of tetrahydrofuran and stirred for 20 hours at ambient temperatures. An additional 4.2 parts of diketene was added. After 18 hours, the solvent was removed under vacuum and the residue was purified by chromotography on silica gel to give N-acetoacetyl-α-L-aspartyl-L-phenylalanine methyl ester, mp. 118.5°-121° C. which eluted in a 10:90:0.1 ethanol:methylene chloride:acetic acid mixture.
Elemental analysis for C 18 H 22 N 2 O 7 : Calc. C, 57.14; H, 5.86; N, 7.40. Found C, 56.91; H, 5.80; N, 7.31.
NMR (Dimethyl sulfoxide-D6): δ 2.13, 3H, s; 2.59, 2H, m; 3.02, 2H, m; 3.35, 2H, s; 3.60, 3H, s; 4.53, 2H, m; 7.24, 5H, s: 8.30, 2H, m.
N-Acetoacetyl-L-Aspartic Anhydride
21.72 parts of N-acetoacetyl-L-aspartic acid, 0.14 parts of magnesium acetate, and 9.5 parts by volume of acetic anhydride were mixed with 200 parts by volume of ethyl acetate and heated at 55±2° C. under argon for 24 hours.
N-Acetoacetyl-L-Aspartyl-L-Phenylalanine Methyl Ester
To the above mixture was added 60 parts by volume of a 1.67 M solution of L-phenylalanine methyl ester in ethyl acetate over 90 minutes. The resulting solution was stirred at ambient temperatures for 2 hours.
α-L-Aspartyl-L-Phenylalanine Methyl Ester
To the above solution was added 260 parts by volume of hexane, 336 parts by volume of water, 1.65 parts by volume of concentrated hydrochloric acid, and 6.95 parts of hydroxylamine hydrochloride. The resulting two-phase mixture was stirred at ambient temperatures for 2 hours. The aqueous layer was drawn off and treated with sodium carbonate to bring to pH 3.0. The solution was heated to 60° C. and sodium carbonate was again added to bring to pH 4.6. The solution was allowed to cool to 24° C. and was then stored at 0°-5° C. overnight. The precipitate was removed by filtration, washed with 75 parts by volume of cold water and pulled dry for 30 minutes, then dried under vacuum at 60° C. overnight to give 14.3 parts α-L-aspartyl-L-phenylalanine methyl ester.
N-Acetoacetyl-L-Aspartic Anhydride
2.17 parts of N-acetoacetyl-L-aspartic acid, 1.02 parts by volume of acetic anhydride, and 0.014 parts of magnesium acetate were mixed with 40 parts by volume of ethyl acetate and heated at 55±2° C. under nitrogen for 24 hours. 30 parts by volume of methanol was added and the mixture stirred at ambient temperatures for 5 hours. HPLC analysis of the resulting solution showed only 0.5% unreacted N-acetoacetyl-L-aspartic acid.
N-Acetoacetyl-L-Aspartic Acid in Methanol
Potassium hydroxide (90%), 49.9 parts, was dissolved in 250 parts by volume of methanol and the resulting solution was cooled to 25° C. L-aspartic acid, 53.2 parts, was added with good stirring and the resulting solution was cooled to 0° C. with a dry-ice-alcohol bath. Diketene, 35.2 parts, was added during about 20 minutes while maintaining the temperature at about -4° to 0° C. The solution was stirred at 0° C. for an additional 10 minutes and then was allowed to warm to 10°-15° C. Phosphoric acid (85%), 54.5 parts by volume, was added with continued stirring and cooling, the temperature being maintained at 10°-15° C. The mixture was stirred for an additional 30 minutes and then was filtered. The solid potassium dihydrogen phosphate was rinsed with about 200 parts by volume of methanol and the filtrates were combined. Methanol was distilled from the filtrate at a vacuum of 25- 50 mm Hg to leave a syrup containing N-acetoacetyl-L-aspartic acid and water. Water was removed from the product by evaporation under a higher vacuum (<1 mm Hg) at about 70° C. to leave a solid residue of 84.6 parts of N-acetoacetyl-L-aspartic acid.
N-Acetoacetyl-L-Aspartic Acid
L-aspartic acid, 53.2 parts, was slurried with 120 parts by volume of water and 41.1 parts by volume of 51.6% aqueous sodium hydroxide solution was added with stirring and cooling. The resulting solution was cooled to 0°-10° C. and 20 parts by volume of 2-butanone was added. Diketene, 35.2 parts, was added during about 20 minutes while maintaining the temperature at about 10° C. The mixture was stirred at about 10° C. for an additional 10 minutes and then was allowed to warm to 15°-20° C. Additional 2-butanone, 80 parts by volume, was added and the mixture was acidified by addition of 22.2 parts by volume of concentrated sulfuric acid. The temperature of the mixture was allowed to rise to 40°-45° C. to prevent crystallization of sodium sulfate. The 2-butanone layer was separated and the aqueous layer was extracted three times with 50 parts by volume portions of 2-butanone; the mixture was maintained at a temperature of 35°-40° C. during these extractions. The combined extracts were dried over sodium sulfate, filtered, and the 2-butanone was distilled under a vacuum of 25-30 mm Hg to leave a syrup containing water and N-acetoacetyl-L-aspartic acid. Water was removed from the product by evaporation under a higher vacuum (<1 mm Hg) at about 70° C. to leave a solid residue of about 79.4 parts of N-acetoacetyl-L-aspartic acid.
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This invention encompasses a method and intermediates for preparing a commercial sweetening agent, α-L-aspartyl-L-phenylalanine methyl ester. The process involves reacting L-aspartic acid with diketene to form N-acetoacetyl-L-aspartic acid which is converted to N-acetoacetyl-L-aspartic anhydride by reaction with acetic anhydride. N-acetoacetyl-L-aspartic anhydride is reacted with L-phenylalanine methyl ester to provide N-acetoacetyl-α-L-aspartyl-L-phenylalanine methyl ester which is converted to α-L-aspartyl-L-phenylalanine methyl ester by reaction with hydroxylamine hydrochloride.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority from copending provisional application No. 60/009,065 filed on Dec. 8, 1995.
FIELD OF THE INVENTION
[0002] The present invention relates generally to apparatus and methods for in situ construction of subsurface containment barriers for containing hazardous waste materials buried under the earth, and more particularly to a method of constructing a vault to encapsulate such hazardous materials so that contaminants are not released into the air or surrounding or underlying strata. The present invention further relates to a means for monitoring the continued integrity of the vault over many years and to a means for repairing any breaches which might occur over time.
BACKGROUND OF THE INVENTION
[0003] In the early days of the nuclear age, contaminated debris and undocumented low level radioactive waste were buried in shallow trenches. Other waste materials were placed in underground storage tanks. These burial areas are now considered to pose a unacceptable risk to the environment. Excavation and removal of these wastes is potentially dangerous and very expensive. The concern is that excavation of such sites could release airborne radioactive contaminants which would pose a substantial harm to personnel and nearby residents. There have been a number of solutions proposed for containing these sites. Some of these solutions include slant drilled jet grouting, soil freezing, soil dehydration, tunneling, and chemical grout permeation. Others have taught vertical drilling and hydraulic fracturing as a means of forming a bottom barrier.
[0004] U.S. Pat. Nos. 4,230,368 and 4,491,369 to Cleary and others have disclosed the concept of displacing soil blocks containing the contaminants. This is accomplished by making a narrow vertical trench around the perimeter of the soil and forming a horizontal fracture under the site through injection of a fluid under pressure. The horizontal fracture intersects the vertical perimeter trench. A seal is created along the surface areas of the vertical perimeter trench as continued injection of pressurized fluid into the horizontal fracture causes the block of soil within the perimeter to be lifted upwards.
[0005] The injected fluid may also become a sealant to produce a barrier surrounding the block like a basement. U.S. Pat. No. 4,230,368 to Cleary discloses that the density of the fluid is a factor in reducing the pressure needed to displace the block but does not contemplate use of fluid densities greater than those achievable with locally excavated soil materials in a clay slurry. This is by definition, less dense than soil. Gel strength of the fluid is mentioned as the primary means of sealing the perimeter opening. Such methods produce both the initial fracture and upward displacement by increasing hydrostatic pressure on the bottom of the block.
[0006] The problem with this approach is that hydrostatic pressure will cause fractures to propagate along the plane of least principal stresses. It is not possible to verify the final location and limits of such fractures in a radioactive waste site. The thickness and continuity of such fractures can not be verified. Because of the potential for uncontrolled fracturing into and beyond the contaminated material this method has not been used to produce any type of containment structure in radioactive waste sites.
[0007] The inventor's previous invention, U.S. Pat. No. 5,542,782, which is hereby incorporated by reference, describes a means of cutting vertical and horizontal barriers with high pressure jets of grout slurry and teaches the benefits of constructing such barriers from grout materials which are of a density equal to or greater than that of the overburden. This reference also teaches that the thickness of a horizontal grout barrier may be increased by introduction of a grout slurry which is sufficiently dense so as to result in net upward forces on the soil which heave the land surface upward, however few details of the method or apparatus to accomplish this are described.
SUMMARY OF THE INVENTION
[0008] The present invention is directed to improved methods and apparatus for constructing a thick horizontal barrier through buoyant block displacement. The present invention provides a new mews for cutting the soil with a cable saw and details a practical apparatus for introducing a block displacement fluid to multiple cuts under a large multi-acre site. The subject invention also provides an improved means of cutting a thin horizontal barrier with high pressure jetting apparatus, which is more practical for application of chemical grouts and has an improved means of joining adjacent cuts to previous ones and recovering from equipment breakage.
[0009] The present invention uses a combination of trenching, horizontal directional drilling, diamond wire quarry saw methods, or high pressure jetting to cut a thin gap under and around a block of soil containing the contamination. As this “cut” is formed, it is filled with a high-density, low-viscosity fluid grout. This thin channel of this dense fluid extends back to the surface and so exerts a hydrostatic head against the soil. This proprietary fluid is so heavy that the soil and rock will literally float on a thin layer of the fluid. This keeps the cut open and prevents the weight of the soil block from squeezing the fluid out from under it. After the block has been completely cut loose from the earth, additional dense fluid is pumped and poured into the cut. This additional fluid exerts a buoyant force on the block and causes it to rise out of the earth. The dense fluid is designed to slowly harden over a period of weeks to form an impermeable barrier. Use of the head of the dense grout fluid instead of attempting to pressurize the fluid to support the block is a subtle but important innovation. It eliminates the difficulties of sealing the vertical perimeter trench and also prevents uncontrolled fracturing of the grout into the waste burial area. If any of the grout fluid should find a crack in the active waste area it will do no more than fill it. It can not spurt up to the surface and form fountains of contaminated liquid, as it could do if it were under pressure. While the grout under the block is liquid an impermeable barrier sheet, such as HDPE (high density polyethylene extrusion), may be pulled under the floating block.
[0010] After the “moat-like” barrier around the soil block has hardened, a gravity-anchored, air-tight cap structure is built on top of it. The HOPE liner under the block may be fusion bonded to the HDPE liner in the cap to achieve a very high degree of containment integrity. Passive soil gas pressure sensors under the cap and similar sensors in the ground outside the cap monitor the air pressure changes inside the structure as a function of normal atmospheric pressure changes due to weather. This data allows passive monitoring of the integrity of not only the horizontal barrier but also the entire containment structure. Moisture, sound, and chemical tracer levels may be passively monitored as leak and leak location indicators. Repair of damage is also possible by flooding the structure with liquid grout.
[0011] A wire saw may also be used with molten paraffin grout to form a thin barrier roughly the thickness of the steel cable. This method maintains a circulating supply of molten paraffin in the pulling pipes which is ejected through holes in the pipe adjacent to the area being cut. The steel cable carries this molten paraffin into the cut and back to the surface. The paraffin is modified with additives that cause it to permeate into tight soils and form a barrier significantly thicker than the cut. Rapid cooling of the grout as the cut proceeds prevent excessive subsidence. An unlimited number of replacement jetting tubes or wire saw cables may be pulled into cutting position by the steel cables or the heated “pulling pipes” which are in the original directionally drilled holes. These may remelt a path through the previous cut.
[0012] Improvements on the inventor's previously disclosed method of forming a barrier by high pressure jetting from a long arcuate conduit are also described. The new method forms a very thin cut using chemical grout, such as molten paraffin or molten low density polyethylene, circulated through an catenary arcuate tube at high pressure and rate while the tube itself is reciprocated through directionally drilled holes to the advancing cut. Holes or hardened ports in the forward facing surface of the tube eject the heated liquid into the soil at high kinetic energy causing the soil to be eroded and substantially replaced by the molten paraffin. The tube is also able to perform abrasive cutting. An unlimited number of replacement jetting tubes or wire saw cables may be pulled into cutting position by the heated “pulling pipes” which are in the original directionally drilled holes.
[0013] Another improvement over prior art is the use of the above mentioned molten paraffin applied with conventional jet grouting apparatus. The preferred molten paraffin has a melting point between 120° and 180° F. and is modified by the addition of a surfactant which allows the molten paraffin to soak into soils which are already water wet or damp, as well as dry soils which have a very low permeability to water. The paraffin may also be replaced by or blended with a low density polyethylene homopolymer.
[0014] Previous inventions have addressed forming impermeable caps, vertical barriers and horizontal barriers but the present invention provides a totally integrated solution which results in total isolation of a waste site from the environment in a manner which is continually and passively verifiable. A subsurface “block” or volume of the earth defined by the ground level on its top and by a bottom comprised of a box-shaped or basin-shaped three dimensional mathematical “surface” which surrounds and underlies the block and rises upward to the ground level at the perimeter, forming a complete and continuous basin and top, frilly enclosing the volume of earth in an airtight, and water vapor-tight vault formed in situ around the block.
[0015] A liquid grout with viscosity comparable to motor oil, but which is of greater density than the subterranean “block” such that the block will float in the liquid grout, which will subsequently harden into an impermeable barrier material, and where the hardening of this grout is delayed for an extended period of 6 to 60 days while continuing to transmit hydrostatic pressure effectively. The length of set delay and the density and impermeability of this grout is significantly beyond the performance of the previous art.
[0016] Directionally drilled holes which traverse the lower surface of the block in roughly parallel paths and which rise to the ground level and level off to a near horizontal attitude at each end. Such holes being formed in a manner which leaves a tubular steel member or “pipe,” and one or more non-crossed steel cables, or two pipes and at least two non-crossed cables in each of the holes extending from ground level at one end of the block to ground level at the opposite end of the block. A mechanical earth cutting means consisting of a flexible length of abrasive tensile member such as a steel cable or chain. The catenary section of which is cooled, cleaned and lubricated by a flow of grout from one or more ports in the adjacent pipes which are moved at intervals in synchronous with the net advance of the cutting means, and which itself is joined end to end and reciprocated or circulated in a continuous substantially horizontal loop between the two adjacent holes by a power driven apparatus that maintains tension on the cutting means against the face of the cut. Prior art has not utilized an abrasive cable saw in curving directionally drilled holes and has not anticipated coolant lines advancing through the holes with the cut.
[0017] The initial cutting means and periodic replacement cutting means are pulled into the holes by means of the cables initially attached to the pulling pipes. Pipes which have one or more perforations and are used to convey pressurized grout to the arc of the cable saw cut being formed. Movement of such discharge point being accomplished by moving the pipe through the ground or by moving a smaller inner pipe discharging between straddle packers positioned over one or more holes nearest the arc of the cut.
[0018] A perimeter excavated trench filled with the dense grout covers each opening into the directionally drilled holes such that the grout may flow by gravity into those into the annulus between the pulling pipe and the hole and into any narrow cut between them formed by the cutting means. Grout may also flow out to relieve pressure. Flow from the grout filled trenches through the annulus to the cut area may be stimulated by a differential elevation of grout in the trench or the grout may flow from the pressurized grout pipe, which traverses the hole and discharges grout at any desired location along the length of the hole. Excess grout will flow up the annulus to the trench or will contribute to increasing the thickness of the barrier.
[0019] The cut through the soil along the lower surface of the block, is filled with a layer of the grout such that the overburden weight is supported by the buoyant force of the grout, and such that the thickness of the cut can be increased by adding additional grout to the excavations. The elevation increase of the block may be controlled by changing the elevation of grout in the trench or by changing the grout density. Restraining means such as steel cables or chains, attached between anchorages on the block and anchorages outside the perimeter trench which act to keep the block floating in the center of the excavation from which the block has been lifted, and to limit the elevation increase of any given section of the block.
[0020] While the block is floating flee on the layer of dense grout, an impermeable sheet, such as high density polyethylene extrusion (HDPE) heat-fusion-seamed together as is known in the art, is attached by chains or other flexible linkage to two or more of the pulling pipes such that the impermeable sheet may be pulled through the layer of liquid grout under the floating block by pulling the pipes from the opposite end until the sheet extends out of the grout filled perimeter trench on all sides. The sheet is preferably heat-fusion-seamed so as to be wide and long enough to underlie the entire block and the outside berm of the perimeter trench. The outermost portions of the sheet are permitted to pucker into undulating folds to compensate for differences in length of the paths under the block. Sites too large to move in one piece may be laid in the grout as unsealed strips with substantial overlap between strips. Separate sips of this material may be equipped with an slidable mechanical interlock, as is known in the art for vertical sheets such as the GSE Gundwall® Interlock, or Curtain Wall® made by GSE of Houston, Tex., such that one sheet may be slidably attached to adjacent sheets allowing one sheet to be pulled into place and sealed to its neighbor. A sealing compound may later be injected into this joint from the ends.
[0021] An air-tight above ground cap, is then constructed and sealed to the hardened surface of the perimeter trench of, and also preferably to the impermeable sheet. This completes an air-tight containment vault over, under and around the block. The top cap may have a layer of impermeable HDPE sheet which is heat-fusion-seam bonded to the bottom liner rising from the perimeter trench so as to form an air-tight seal between the two sheets. The cap is equipped with: air pressure, humidity, sound, and chemical sensors mounted both in the soil under the cap and on its exterior surface such that differential measurements may be performed and recorded on a continual basis in order to evaluate the degree of isolation between the environment inside the structure and the external environment. A standard data logger device records the data from the sensors may be periodically downloaded to a computer which graphically displays the relationship between internal conditions vs external conditions, as a function of time, temperature and rainfall conditions.
[0022] A catenary cutting means similar to the cable saw but operating by a reciprocating stroke implemented with standard construction equipment such as trackhoes may also be used to make the cuts between the directionally drilled holes. The apparatus consists of a flexible hollow tube of substantially uniform diameter extending from the surface down through the directionally drilled holes, joined in a catenary arc, through which high pressure fluid is circulated in a continuous loop, and from which at least a portion of this fluid exits the forward face of the tube through one or more holes or “jets”, such that the fluid jet helps erode and wet the soil in the path of the device and allows the fluid to displace substantially all of the soil. The orientation of such fluid jets being cyclically altered to increase the thickness and uniformity of the cut by reciprocating rotation of both ends of the tube an equal increment on each pulling stroke, or by other means substantially in unison such that all soil in the path of the tube can be impacted by one or more fixed jets. The surface of the catenary tube is abrasive and mechanically cuts the soil in its path as well as eroding it with fluid jets. An additional abrasive cable may be pulled into the cut by means of the color-coded, non-crossing cables on the pulling pipe. This cable can bypass the tube and perform an abrasive cutting job and then be withdrawn from either end. The entire cutting tube could also be circulated out of the ground and temporarily replaced by an abrasive cable or chain. If the tube is damaged it can also be replaced in the same manner. This is a major improvement over jet cutting methods which have no recourse when they strike a hard object or if the jets plug. If the jetting tube has substantial enlargements along its length or at the slurry discharge points then it can not be circulated out of the hole if a problem should develop. This ability to recover from a structural failure, jet plugging, or a hard obstruction is critical to commercial use of the process.
[0023] The grout material may be either a slow setting dense material capable of buoyantly supporting the overburden or may be a fast set or thermoplastic set material which sets before a large unsupported span exists. A low water, cementitious, latex polymer modified grout with iron oxide additives and a long term set retarder is preferred for buoyant barriers. A molten grouting material made from paraffin wax or polyethylene homopolymer and surfactant admixtures which enable it to mix with damp or wet soils and permeate farther into water impermeable soils is preferred for the non-buoyant process. Circulation of molten grout through the pulling pipes and the catenary tube can keep the material from setting during a work delay or even overnight. Paraffin supply lines from relatively hot and relatively cool but molten paraffin may be blended by a valve to rapidly adjust the temperature of the material with changing ground conditions. Blends of paraffin and polyethylene may also be used. A cap liner made of a similar polyethylene or paraffin mixture may be used in the top cap and heat fusion bonded to the bottom barrier to create a completely air tight seal of similar material. This cap material may be sprayed onto the surface of the cap as a liquid material and cured in place or it may be a pre-fabricated sheet.
[0024] The above mentioned grouts have desirable properties for block encapsulation of buried low level radioactive waste. The molten wax and surfactant blends offer superior permeation into non-homogenous trash as well as good bonding and encapsulation of organic sludges. They offer a desirable matrix to stabilize the waste while it remains in the ground and also prevent airborne dust release during future retrieval. Since they are fully combustible they add no volume to the final waste matrix of a vitrification melter process.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Other aspects and advantages of the present invention will become apparent upon reading the following detailed description and upon reference to the drawings in which:
[0026] [0026]FIG. 1 is a perspective view of a buried tank farm containing toxic waste illustrating directionally drilled holes being placed under the site and a quarry wire saw machine cutting between adjacent holes.
[0027] [0027]FIG. 2 is an illustration of the formation of an impermeable containment barrier under the tank farm shown in FIG. 1.
[0028] FIG, 3 is an illustration of a completed containment barrier under the tank farm shown in FIG. 1.
[0029] [0029]FIGS. 4A and 4B illustrate several of the steps performed in forming an impermeable containment barrier under a waste site.
[0030] [0030]FIGS. 5A and 5B illustrate the use of cables to keep a floating block containing the waste material centered in the excavation.
[0031] [0031]FIG. 6 is an elevation view of the completed containment vault illustrating the system for monitoring containment integrity.
[0032] [0032]FIGS. 7A and 78 illustrate the formation of barrier panels using an abrasive cable saw which cuts through the earth while molten grout is being supplied by pulling pipes to the cut region.
[0033] [0033]FIG. 8 is a illustration of an alternate method of forming a containment barrier under a buried tank.
[0034] FIGS. 9 A-F illustrate the steps in constructing a containment vault around a waste site.
[0035] [0035]FIG. 10 is a perspective view of the waste site shown in FIGS. 9 A-F being undercut and lifted.
[0036] [0036]FIG. 11 is a perspective view of a small test block being undercut by pull cables.
[0037] FIGS. 12 A-C illustrate the step of placing an impermeable liner sheet in the grout barrier under the block of soil containing the waste material.
[0038] [0038]FIG. 13 is a perspective view of the containment site illustrating the step of pulling a large one-piece sheet of impermeable material under the block of soil containing the waste material which is free floating in the dense grout fluid.
[0039] [0039]FIG. 14 is a perspective view of the containment site illustrating the step of interlocking adjacent impermeable liner sheets.
[0040] [0040]FIGS. 15A and B are a plan and cross-sectional view, respectively, illustrating a catenary cutting step used in one embodiment of the invention to cut and form an impermeable containment barrier.
[0041] [0041]FIG. 16 is a perspective view of the a completed containment vault with a sealed cap structure.
DETAILED DESCRIPTION OF THE INVENTION
[0042] Referring to FIG. 1, a shallow perimeter trench 7 is first excavated around the entire surface perimeter of the block to be isolated. A subsurface “block” or volume of the eat is defined by the ground level on its top and by a bottom comprised of a box-shaped or basin-shaped three dimensional mathematical “surface” which surrounds and underlies the block and rises upward to the ground level at the perimeter, forming a complete and continuous basin, fully enclosing the volume of earth.
[0043] A directional drilling machine 1 then drills rows of pilot holes under the site, which define the basin's elongated shape. A pulling pipe with two or more non-crossed cables strapped to it is connected to the drill pipe and pulled through the pilot holes. After this operation each pilot hole contains a pulling pipe and two or more color coded steel cables. Next, a diamond-wire saw machine 2 moves an abrasive cable 3 , formed by joined adjacent cables, through the pilot holes cutting a pathway between adjacent pilot holes. The abrasive cable 3 cuts the soil and assists the flow of the grout which carries soil particles to the surface. Pulling pipes 3 , 5 , and 8 remain in the pilot holes after the paths are cut.
[0044] A grout plant 4 pumps grout through one or both of a pair of adjacent pulling pipes to the arc of the cut and also fills the trench 7 with a high density fluid grout A grout panel 9 is formed as a pulling means, such as a dozer 10 , advances the wire saw 2 . The level of the grout in the trench 7 and its density applies a hydrostatic force to the bottom of the block.
[0045] [0045]FIG. 2 shows the pulling pipes 11 are in place defining a basin. Each pulling pipe 11 has one or more accompanying steel cables which are joined at the cutting end and threaded through a wire saw machine 13 at the other end. The wire saw machine 13 is pulled by a dozer 12 . A grout plant 15 supplies pressurized grout to the surface perimeter trench 16 and to one or more of the pulling pipes 11 through the flexible hose 14 . The grout exits the pulling pipes 11 through ports 18 . The grout cools and lubricates the cable saw 19 , and carries cuttings back to the surface perimeter trench 16 . The cut 17 is filled with the dense liquid grout, which supports the weight of the overburden soil.
[0046] Referring to FIG. 3, as the grout plant 21 , continues to fill the perimeter trench to an elevation 22 , below the elevation of an outer berm 24 , the thickness of the cut increases due to buoyancy as the block rises out of the ground. Existing fractures and fissures inside the block will fill with grout but will not extend even in planes of weakness because the hydrostatic forces on the block are balanced. Fissures in the earth outside the block will also be filled with the grout.
[0047] [0047]FIG. 4 shows a directional drilling machine 2 $ placing a drill pipe in the ground defining the lower surface of the vault. Long “pulling pipes” are prepared with several steel cables running parallel along the length of the pipe and secured to the pipe by a temporary fastener such as steel bands on the ends and masking tape in the midpoint. The cables have color coded ends and do not cross one another. These pulling pipes are attached to the drill pipe in the holes and pulled into position 31 by a dozer 29 , which pulls on the original drill pipe. One of the cables from each adjacent pipe 32 is joined together and threaded through a wire saw machine 35 . The cable may be used to draw a more specialized diamond-wire saw cable 33 into the cut. Circulation of this cable and tension applied by the wire saw machine carves a catenary cut through the earth as a supply of grout is pumped down the pulling pipe and exit ports 34 in the vicinity of the cut to cool, lubricate and carry away cuttings. This pipe may be pulled along through the ground as the location of the cut advances. The grout buoyantly increases the thickness of the cut such that a chain or other type of mechanical proving instrument may be pulled through one or more sections of the cut under the now floating block to verify that the barrier is continuous. Additional lengths of pipe are added to the end of the pipe as it is pulled under the block, so that a pipe always remains in position. A roll of a synthetic impermeable sheet, e.g., a high density polyethylene extrusion sheet 27 is then pulled through the liquid grout under the floating block. This may be interlocking sheets pulled in separately, as further explained below, or one large continuous sheet with numerous wrinkles.
[0048] [0048]FIG. 5B shows a block 38 floating on a layer of grout may not be of uniform density and due to its size may behave somewhat elastically. Steel cables or chains, 36 and 37 , may be secured to anchor posts in the block and surrounding it to limit the total upward movement of the block as well as provide a centering effect 41 , as the block reaches full elevation. Grout from the plant 42 may fill the trench 40 at one end of the block but due to viscosity and friction effects may not initially fill the trench at the other end 39 , thus causing one end of the block to lift first. However, after a period of time the fluid levels will equalize and the block will level.
[0049] A cap structure is sealed to the hardened grout wall 43 with a resilient material 44 (such as an elastomer or wax) to create an airtight vault, as shown in FIG. 6. Additionally, the impermeable polyethylene sheet 53 , is fusion bonded to a similar polyethylene sheet 45 , in the cap structure. This top sheet is covered with layers of sand, concrete 46 , clay 47 , and topsoil, as is known in the art. The clay and sand are doped with bitter tasting additives to discourage plants, animals and insects from burrowing into it Air pressure, humidity, temperature, sound and chemical sensors 48 , 49 , 50 , and 51 are buried in the clean perimeter soil inside the vault and also outside the vault. These sensors allow passive measurement of the vault's integrity over time. A port may also be provided to introduce tracer gas into the containment structure.
[0050] In an alternate embodiment, the device shown in FIGS. 1 and 2 is modified to include a circulating loop of molten paraffin grout, as shown in FIG. 7A, The molten paraffin grout 55 is circulated by a pump 56 to one of the pulling pipes 57 to a connecting pipe 63 or hose, back through the other pulling pipe and through a hose back to the tanker truck. Holes or jets 59 in the pulling pipe spray the grout into the cutting area to cool and lubricate the cut and to carry away cuttings back to the surface along the annulus outside the pulling pipes. The cutting cable 60 is pulled through the cut by the wire saw 61 . The wire saw and the pulling pipes are all attached to a sled which is periodically pulled forward by a dozer. The paraffin grout displaces the soil and hardens a few meters behind the cut of the wire saw, before the length of the cut is wide enough to allow subsidence of the overburden. The paraffin grout is capable of soaking several inches into soils before it hardens and thus the final barrier may be several inches thick. Paraffin supply lines from relatively hot and relatively cool but molten paraffin may be blended by a simple valve to rapidly adjust the temperate of the material with changing ground conditions.
[0051] Once the panels are complete the perimeter trench may be excavated by conventional means and filled with molten grout. If the paraffin grout is made sufficiently dense, by addition of iron oxide powder, to provide buoyant force on the block then a perimeter trench may be maintained with molten grout to produce a thick barrier as in FIG. 3. The pulling pipes 66 and cable assembly have a length 65 , which is enough to allow one complete pass under the block with the end still exposed.
[0052] In another alternate embodiment according to the present invention, a directional drilling machines 67 place a pipe down into the earth encircling the perimeter of a contaminated soil site below the tank, and then back to the surface, as shown in FIG. 8. Using a cutting means similar to the one shown in FIG. 7, a layer of high density fluid grout from a grout plant 70 is placed in a plane 72 below the tank 71 . A perimeter trench is then excavated 68 around the tanks to partial depth and is filled with high density fluid grout. The remaining depth is excavated with a clamshell or trackhoe excavator 69 releasing the block of ground containing the tank which floats upward as the grout flows into the plane under the tank.
[0053] FIGS. 9 A-F show a cross-sectional view of a long narrow burial site 73 being undercut and lifted by the method according to the present invention wherein a single pair of pilot holes 74 is employed. First, a wire saw 75 cuts between directionally drilled holes with a dense fluid to form a horizontal out under a burial trench, as shown in FIG. 9A. Second, a vertical perimeter trench 76 is excavated, as shown in FIG. 9B. Next, the perimeter trench 76 is filled with dense grout 77 , as shown in FIG. 9C. The soil block 78 then becomes buoyant and displaces upward to its final position 79 , with higher external soil berms in place, as shown in FIGS. 9D and 9E. Lastly, the airtight cap structure 81 is bonded to the below ground barrier, as shown in FIG. 9F.
[0054] In FIG. 10, a long waste site, similar to the one shown in FIG. 9, is being undercut and lifted. An excavator 83 digs a perimeter trench to full depth. A pair of holes are drilled and cased, intersecting one end of the trench and a wire saw cable is looped around the entire block. This could also be done with another trench, but would require more grout. The trench is then filled with a dense liquid grout. A wire saw machine 82 makes a cut 84 , which is filled by the grout from the trench, which buoyantly supports the weight of the block. As the cut progresses, the block buoyantly lifts upward to its fill floating position.
[0055] In FIG. 11, a small test block is being undercut by the direct pull cable method. The dozer 89 pulls the cable 88 through the soil while the trench 87 is filled with the dense fluid grout supplied by the grout plant 90 .
[0056] FIGS. 12 A-C show the steps of sealing the block with a synthetic impermeable layer. This is accomplished as follows. While the block of soil is floating free on a thick layer of dense grout; a dozer 93 pulls on pulling pipes 92 , which in turn pull an impermeable liner sheet 91 completely under the block, as shown in FIG. 12A. The impermeable liner sheet 94 is pulled under the block until it extends over berms on the perimeter, as shown in FIG. 12B. An impermeable top sheet 95 is fusion bonded 96 to the bottom sheet all around the perimeter of the block producing an airtight containment vault, as shown in FIG. 12C.
[0057] In one embodiment, one large sheet 99 is pulled under the free floating block by one or more dozers 98 , as shown in FIG. 13. In this embodiment, the pulling pipes 100 are elastically attached 103 to the sheet at intervals. The edges of the sheet are allowed to pucker 102 to compensate for the differences in lengths.
[0058] In another embodiment, multiple interlocking sheets of the impermeable liner material 105 are pulled under the free floating block by pulling pipes 108 , as shown in FIG. 14. The interlock 106 joins the sheets while allowing relative movement as the sheets are pulled through the liquid grout 104 .
[0059] FIGS. 15 A-B show another alternate embodiment of the basic method. This embodiment illustrates a catenary cutting method using a uniform tubular abrasive member 110 and a circulating pressurized fluid 55 directed at the cut as the tubular member is reciprocated around the arc of the cut by the motion of two hydraulic excavator trackhoes. The ends of the tubular member are rotated to allow a single fixed jet to sweep through at least 450 of arc so that it may strike substantially all of the soil in the path of the tubular member, as shown in FIG. 15B. In this embodiment, the tubular member is a flexible high pressure tube of substantially uniform diameter extending from the surface down through the pilot holes and joined in a catenary arc. The high pressure fluid is circulated in a continuous loop and at least a portion of the fluid exits the forward face of the tube through one or more holes or jets such that the fluid jet helps erode and wet the soil in the path of the device and allows the fluid to displace substantially all of the soil. The orientation of such fluid jets being cyclically altered to increase the thickness and uniformity of the cut by reciprocating rotation of both ends of the tube an equal increment on each pulling stroke, or by other means substantially in unison such that all soil in the path of the tube can be impacted by one or more fixed jets.
[0060] A completed containment structure with the final cap in place is shown in FIG. 16.
[0061] Further details of the present invention are described below.
[0062] A directional drilling machine 1 , such as those used by Eastman Cherrington Co, Houston, Tex., or direct push type machines such as those made by Charles Machine Works, which is known in the art, is used to drill a series of roughly parallel (in plan view) pilot holes 8 , under the site. The pilot holes may typically be spaced from 20 to 100 feet apart and do not have to be parallel or equidistant. They need only define the geometry of the barrier to be constructed. The holes typically enter the ground within the trench at an angle, descend to the desired depth, level off and run substantially horizontal, and then rise back to the trench at the opposite end of the block. Steering and verification of the position of such holes is well known in the art. Several such pilot holes would be drilled at intervals across the width of the site at various depths to trace an elongated basin-shaped surface which is substantially below the contaminated rock/soil layer but rises nearly to the surface on the sides and each end, where it intersects the perimeter trench. This perimeter trench may be excavated with a backhoe in conventional manner.
[0063] During drilling of these pilot holes any drilling fluid which returns to the surface may be used to verify that the holes are located in uncontaminated soil. If contamination is found, the hole may be plugged and a deeper pilot hole installed. Portions of the hole in unconsolidated soils may optionally be cased with a thin plastic sleeve 5 .
[0064] After drilling is complete, a pair of saw cables 6 , (or jetting tubes, 110 ) and a “pulling pipe” 7 , may be introduced into each pilot hole as the drill pipe 8 , is extracted. These two cables (or tubes) are affixed to both ends of the steel pipe. This arrangement helps prevent the cables from crossing each other and provides a means of running replacement cables or injecting grout. The pipes extend up through the trench and over a soil berm to a horizontal position on each end. The steel pipes are preferably 2-⅜ inch oil well tubing with threaded connections as is known in the art. The steel pipe may have one or more small holes drilled in it at intervals. The pipe may optionally be used to convey dense fluid or super dense grout to points along the pilot hole. A smaller pipe with a straddle packer may be moved within the pulling pipe to direct liquid flow to any desired point along the pipe. Preferably the fluid may also be directed to any point by moving the pipe through the ground such that the holes are at the desired position. The pipe may also be used to draw additional wire saw cable into place if a cable breaks in service. The pipes may also be used to pull larger or more powerful wire saw cables or cutting devices or proving bars through the cut after the initial cut is made.
[0065] A diamond-wire saw quarry saw such as the Pellegrini TDD 100 G, Verona, Italy, made for the extraction of granite blocks, is set up at one end of the directionally drilled pilot holes. These machines have been in use for many years. The diamond-wire saw is essentially a steel cable with abrasive materials bonded to it at intervals. The wire saw machine is a large power driven cable sheave which maintains tension on the cable and pulls a continuous loop of cable through the cut like a band saw. The diamond-wire saw steel cable from the first hole is joined in a loop back through the second hole to the wire saw machine and joined into a continuous cable. The method of joining steel cables may include a reweaving process which is known in the trade. The cable machine causes the cable to move in a continuous loop through the holes and places tension on the cable to cut a pathway between the first two pilot holes. Diamond abrasive sections of the cable do the cutting in rock, and also cut soil. In applications where rock is not anticipated, the cable abrasives may be optimized for fast soil cutting. A standard aircraft grade steel cable may also be used without abrasives to cut through soft soils. In this specification, the words cable saw, cable, diamond-wire saw, diamond-wire saw quarry saw, and wire saw are used interchangeable to refer to a mechanical cutting means. The cutting fluid may optionally contain a clay dispersing additive such as sodium lignosulphonate or salt, to keep the clay from sticking to the cable. A high pressure fluid jet or mechanical brushes may be set up to continuously clean the cable as it comes out of the ground.
[0066] The shallow perimeter trench at each end of the pilot holes is filled with a special cutting fluid or grout which has a density greater than the average density of the waste site soil and a low viscosity. Cutting fluid is circulated through the cut to remove cuttings, cool and lubricate the cable. The cutting fluid is preferably sufficiently dense to support the overburden and prevent the cut from subsiding and also to provide significant net lifting force as well. This fluid may be made from a gelled water combined with a powdered iron oxide to increase its density, or it may be a dense iron oxide modified cement grout with set retarder. The fluid may be introduced into the pilot holes by pumping it down the pulling pipes in the pilot holes to the area of the cut. At this point the fluid exits the pulling pipe through small holes and flows back to the surface, applying a hydrostatic head to the area of the cut, As the wire saw cable moves, it circulates this fluid from the entry side of the cut to the exit side and back to the surface trench. The wire saw cable also carries this fluid into the cut where it picks up cuttings and then returns to the surface trench with the returning cable. The used fluid may be picked up from the exit area of the trench and re-conditioned before placing it back into the trench. The fluid's density and the hydrostatic head from the space trenches provide a balancing force which prevents the overburden soils from collapsing into the cut which the wire saw makes. The fluid is designed to flow into permeable soils and rock to a very limited degree, while forming a filter cake which the hydrostatic force may act against and support the overburden. The principal is similar to that of a deep horizontal oil well drilled through unconsolidated sands.
[0067] If the soil and rock is very abrasive, the cable may be changed several times during a single cut. Broken cables may be replaced by pulling a new set of cables through that pair of holes with the steel pulling pipe which is left in the hole. After the first wire saw cut is complete, the next cut may begin. Each cut has its own cables so if multiple wire saw machines are available many cuts could be completed at the same time. The cable will tend to cut through most rocks and debris in soil. Hard rocks in softer soils may get pushed up or pushed down by the cable. In either case the dense fluid will fill whatever gap is created. For large scale applications a larger diameter cable could be used to make longer and wider cuts.
[0068] After the initial cuts have been formed in a given area additional grout may be added to the trench and injected through the pipes. The level of the grout fluid in the trench is gradually increased, which causes more grout fluid to flow into the cut and buoyantly lift the overburden soil as the thickness of the cut slowly and uniformly increases. The concept is like floating a ship out of dry dock. Addition of grout continues until the soil block has risen about 3 feet. See FIG. 2A. At this point the barrier thickness is also about 3 feet. The steel pipes which lie in the tracks of the pilot holes can now be utilized to pull a chain type proving bar or a High Density Polyethylene Extrusion (HDPE) liner under the floating block. See FIG. 5. A large sheet of HDPE could be fabricated by field fusion bonding techniques and pulled under the entire site in one motion. A reinforcing mesh of composite fiber could also be installed in this manner to increase the strength of cement based grout. Post tension cables or nondestructive testing devices could also be installed in the same manner.
[0069] Earthen berms may be built up around the outer perimeter of the trench to allow higher grout levels to increase the lift of the block or to allow lift of a site with surface structures, or heavy objects. Anchored cables may be used to provide a force to keep the block floating in the geometric center of the liquid perimeter. See FIG. 6.
[0070] Grout Properties and Composition
[0071] The proprietary grout will remain fluid for several weeks and then harden into a rock with physical and chemical properties similar to ceramic tile. Properties of this fluid are tailored for the site and are sufficiently “filter cake-forming”, that the fluid does not leak into the soil or rock excessively. Permeability of the preferred grout has been demonstrated to be approximately 10 −8 cm/sec. Compressive strength after 6 months is greater than 5000 psi. This grout has near zero shrinkage on set and is highly impermeable. It is suitable for both wet and desert dry conditions. As a liquid the grout has a marsh funnel viscosity less than 120 seconds and typically less than 70 seconds. The grout is inorganic and resistant to nitrate salt migration. A nonhardening version of the grout is also available for use as a cutting fluid in the wire saw operations. When mixed with the hardening version of the grout this dense cutting fluid will also harden.
[0072] The special super dense grout is preferably composed of a type K other zero expansion cement to minimize the potential for stress cracking, mixed with water to an initial density of 12 to 20 pounds per gallon. A high density additive, such as barite, brass or copper powder, uranium ore, or steel shot, but preferably iron oxide powder (hematite) such as is known in the art of oil well cementing and drilling fluids, is added to increase the final density to 20 to 30 pounds per gallon, A viscosity reducing admixture such as condensed polynaphthalene sulfonate, but preferably a salt-tolerant high range water reducer such as Halliburton CFR-3, available from Halliburton Services, in Houston, Tex. is added at a concentration of 0.5 to 2 percent. A set retarding admixture, based on lignosufonates, borates or gluconic acids, which are known in the art, but preferably an organic phosphonic acid such as Amino Tri Methylene Phosphonic Acid, which is made by Monsanto Chemical as a anti-scale additive. Other preferred additives include Fumed Silica, epoxy resins, and butadiene styrene latex emulsion. The above grout formulation, properly proportioned, will form a nonsettling slurry which will remain liquid for several weeks and have a viscosity comparable to butter milk After several weeks the slurry will harden. After curing for several months it will develop a high compressive strength.
[0073] An example of such a slurry is as follows: 90 to 110 parts water (by weight), 150 parts type K cement, 300 to 400 parts powdered hematite (iron oxide), 20 to 40 parts finned silica, 25 to 35 parts Latex emulsion, 30 to 60 parts CFR-3, and 0.2 to 0.8 parts organic phosphonic acid. This grout has a very low water content and produces a final product which can withstand very dry environments.
[0074] An alternative slurry may be used if the site characteristics require a flexible barrier material. This slurry would be similar to the above slurry but the cement content would be reduced to 50 parts cement and the water replaced with a 6 to 8 percent prehydrated bentonite slurry modified with 1 percent sodium lignosufonate in place of the other set retarder. This formula will form a dense clay-like grout which will have plasticity similar to native clay.
[0075] Another alternative grout may be made by adding powdered hematite or a cement grout slurry containing hematite to an epoxy resin grout. The preferred epoxy would be CARBRAY 100, distributed by Carter Technologies, Sugar land, Tex. This epoxy has a very low viscosity and can be diluted with water or bentonite slurry. The material, cures to a rubbery product which is stable in a variety of moist environments. This epoxy may also be mixed with dry bentonite and powdered hematite to form a lower cost, but still flexible, product.
[0076] Another useful grout material is molten paraffin or molten low density polyethylene. These materials will melt at temperatures below the boiling point of water and thus can be applied in field operations with relative ease of cleanup. They can both be modified with surfactants to make them wet the soil better, even when the soil is already wet.
[0077] Air-Tight Barometric Cap, for all Methods
[0078] After the below ground portions of the barrier vault are completed by either method, an above ground cap would be constructed and later covered with soil. This cap is of conventional concrete, clay, and HDPE construction but is designed to be air-tight and would be equipped with passive air pressure sensors on its inner and outer surface. These sensors allow air pressure differentials between the vault and the surroundings to be monitored and recorded. Dry soils are relatively permeable to air pressure. A breach in the vault will allow external air pressure to slowly equalize in the vault. This cap is equipped with pressure sensors which monitor external atmospheric pressure, external soil gas pressure, and internal soil gas pressure under the cap. By comparing these three pressures over time the integrity of the barrier may be verified. Manually operated vent pipes would allow periodic venting of any pressure which accumulates in the structure due to gas generation by the contents. Trace gasses may be introduced to aid in crack detection, location and repair. See FIG. 7. Introducing a small amount of Freon or other suitable tracer gasses into the containment structure should allow any subsurface cracks to be detected by soil gas probes placed around the perimeter. Injecting an odor producing chemical would allow S regular monitoring by trained dogs. Dogs can be trained to dig at the source of the leak,
[0079] Moisture levels and sound levels inside versus outside the barrier may also be used to monitor leakage. The moisture levels inside the barrier should not change when the exterior levels change. The interior moisture levels may be reduced by circulating dry air through the interior of the structure. Passive sound sensors inside the containment structure can detect stress cracking of the rock-like barrier material as it occurs, Four buried acoustic transducers outside the structure alternately sweeping frequencies from 20 to 60,000 cycles per second would allow several acoustic sensors inside and outside the structure to pick up information that could indicate both the location and magnitude of a crack. The attenuation of different frequencies can indicate the size of a crack.
[0080] The preferred method of construction varies greatly according to the size and environmental conditions. An example of such construction for a 300 foot by 300 foot cap in Idaho is as follows. The hardened surface of the perimeter trench is smoothed and a resilient rubbery material such as Carbray 100 epoxy, or silicone caulk is layered on to its surface. A layer of permeable sand is placed within the boundary of the perimeter trench to a depth of 1 foot on the edges sloping to 3 foot deep in the center. A geo-textile high density polyethylene top liner sheet fabricated by fusion bonding methods is placed over the site extending over the seal material and fusion bonded to the bottom liner extending out of the perimeter trench. A geo-textile is installed on top of the top HDPE liner with post tensioning and reinforcing installed above. A layer of sand with bitter tasting additives like pepper, alum, and borax is spread over the liner and a Low permeability concrete is cast on top of it to further discourage insects, plants, and rodents. A clay and soil cap is constructed above using these same additives to bury the concrete cap well below the frost line.
[0081] In the event of a breach, ports into the finished vault can be used to inject a small amount of tracer gas such as common R-12 Freon or R-134 or similar fluorocarbons, which will diffuse through the entire vault. Leakage of even trace amounts of this gas through the wall can be sensed by an inexpensive portable detector at the perimeter surface and on the top cap, thus indicating the general area of the leak. An odor producing chemical could also be introduced into the vault. Trained dogs can then be used to routinely inspect the cap and perimeter areas. It is well established that dogs can detect concentrations of oderants more reliably, and in smaller concentrations than currently available instruments. Moisture levels could also be used to verify isolation. Hollow pipes, placed into the wall and floor of the vault while in the liquid state may be used to perform radio frequency, electro-resistivity, or acoustic logging in the walls of the vault to locate cracks even if they do not cause a leak. Several acoustic transducers outside the vault sweeping from 20 to 60,000 cycles per second picked up by sensors buried in the interior of the structure could be used to locate cracks, Stress cracks will make sounds as they occur and can be passively detected. The preferred grout material would have a low electrical conductivity to allow resistive logging between the inside and the outside of the containment structure.
[0082] Significant damage to the cap of the vault could be repaired by conventional means including epoxy crack injection. Damage to side walls could be repaired by excavating a narrow trench along the wall and casting new concrete in place. Traditional chemical grouting methods could also be used. Damage to the floor of the vault could be repaired by flooding the vault with a water-thin chemical grout such as sodium silicate, polyacrylamide, or epoxy. It should also be possible to construct an entirely new containment barrier under an existing one.
[0083] Variations of the Method
[0084] Bottom First Burial Trench Method
[0085] There are a number of burial trenches in Idaho which are approximately 20 feet wide by 15 feet deep by 500 to 1700 feet long. These trenches are typically parallel and about 30 feet apart. They contain randomly dumped undocumented low level waste. The trenches were cut with a dozer down to a basalt rock layer. This basalt rock layer is about 500 feet thick but is located over the Snake River aquifer, The rock is fractured and is not considered to be a long term confining layer.
[0086] Directionally drilled holes would be placed along the bottom outboard edges of a trench at the desired depth. This could be well into the basalt rock layer. These pilot holes would curve back to the surface on each end of the burial trench. Diamond wire quarry saw cables, attached to both ends of a pipe, preferably 2-⅜ inch oil well steel tubing, would be pulled into each hole as the drill pipe is removed.
[0087] The cables from one hole to another would be joined at the surface into a continuous length and threaded through the wire saw machine. Two separate, bermed, elevated pits “A” and “B” would be constructed around each of the pilot hole openings on the wire saw machine end of the burial trench. A single trench “C” would be constructed connecting both of the pilot holes on the opposite end of the burial trench. A dense drilling fluid pumped into the “A” pit will flow through the number 1 pilot hole to the “C” trench and back through the number 2 pilot hole to pit “B”. The fluid arriving in pit “B” would be reprocessed and placed back in pit “A”. Grout could also be pumped through the pipes as described above.
[0088] After this continuous flow is established the wire saw machine would feed cable into the number one pilot hole while pulling the cable from the number 2 pilot hole. The cut would begin at the “C” trench and proceed toward the wire saw machine, as the machine moves backward along its tracks. Periodically a new wire saw cable would be spliced into the system. The steel pipes can be used to pull additional cables into position if a cable breaks in service, or to provide a flow of cutting fluid to a specific area. As the cut progresses the entire burial trench will be undercut and supported on a half inch thick layer of the dense cutting fluid.
[0089] The properties and stability of this fluid are, of course critical to the process. The fluid must have a density greater than the soil and rock above it and be fluid enough that it flows and transmits hydrostatic pressure effectively through a half inch thick cut. It's fluid loss characteristics must also be tailored to plug small fissures in the permeable rock without plugging the half inch thick cut, Large vertical cracks and fissures are a common feature in the basaltic rock of Idaho. If the wiresaw encounters cracks which cannot be filled, one or more of the pulling pipes will be used to inject a sodium silicate solution into the cut. This material will cause the grout to become viscous very rapidly and plug large openings.
[0090] After completion of the bottom cut, sidewall trenches would be excavated by conventional means such as backhoes under a slurry of low viscosity dense grout. These trenches would begin at one end and proceed down both sides at once to construct a trench around the entire perimeter. When the sidewall trench intersects the bottom cut the dense grout will flow into the bottom cut and provide a net positive lifting force on the order of 1 to 5 pounds per square foot, (Not enough to shear the soil and rock but enough to lift it once it is no longer restrained.) As the sidewall cuts proceed down the length of the burial trench the elasticity of the soil and rock will allow the block to lift out of the ground on the free end. Once the entire length of the block is free floating, additional grout could be added to increase the thickness of the grout layer. In very long trenches the soil block may rise to full design elevation before the excavators reach the far end of the site. See FIG. 10.
[0091] Side First Burial Trench Method
[0092] An alternate method of construction may be used in soil or rock which may be cut more rapidly. This method is expected to be useful in hard soil in which a trench will stand open without support and has little chance of large fractures or voids. In this method the vertical perimeter trench is first excavated to fall depth. The wire sawing equipment is then positioned in the trench to cut loose the base of the block on a horizontal plane. This may be accomplished by placing cable pulleys in the trench or by entering the base of one end of the trench with directional drilled holes, through which the cable saw is threaded. The trench will be filled with a super dense grout which is denser than the soil block and which is designed to remain fluid during the duration of the work. As the cut begins, the super dense grout fills the trench and enters the gap cut by the wire saw to provide solids removal, cooling and buoyancy for the block. The cable saw for this work may require diamond abrasives in rock but in soil may use steel cable or steel chain cutting elements, In this method the grout will fill the void behind the cable as it cuts.
[0093] As the wire saw undercuts the block, buoyancy of the super dense grout will cause the end of the block which has been undercut to rise slightly as the grout flows into the horizontal cut. Additional grout will be added to the trench to maintain a level sufficient to cause a small but measurable rise in the free end of the block After the under-cutting process is complete additional grout will be added to the trench to cause the entire block to rise to the desired elevation. (18 to 36 inches typical) Berms may be constructed around the outer perimeter of the trench to allow greater lift height.
[0094] In this method the set properties of the super dense grout must be delayed until the cut is complete, This method may not require directional drilling at sites where deep conventional excavation of the perimeter trench is possible. This method forms a rectangular block instead of a gently curved basin structure, Additional sloping excavations on each end could be added to facilitate introduction of a plastic liner material.
[0095] Direct Pull Cable Method
[0096] A special variation of this method is possible in very soft soil or in a small test site. A trench is excavated dry in a U shape with the ends of the U tapering back to the surface and a cross ditch in the fall depth portion such that the waste area is surrounded. A steel cable is laid in the bottom of the trench with ends extending from the bottom of the U and connecting to a pulling means such as a large dozer. The tapering portion of the trench is backfilled to hold the cables in place. The remaining trench is filled with a grout that is more dense than the soil but still fluid. The dozer pulls the cable through the soft soil like a cheese slicer, making a cut which is instantly filled with grout. This action forms a continuous layer of grout under the soil block which thickens as the grout displaces the block upward. Anchor cables keep the soil block centered in the excavation. When the grout hardens it will form a seamless basement structure.
[0097] Vertical Cylindrical Block Method
[0098] Another alternate method involves forming a directionally drilled hole which enters the ground outside the waste area perimeter, descends to depth and levels off, proceeds around the perimeter of the area to be isolated, (completely encircling it), and then returns to the surface near the point of entry. The wire saw cable is drawn through this circular path as the drill is withdrawn As the wire saw tightens it cuts under the area to be isolated. A large circular cut is formed under the site. See FIG. 8. The cut is filled with dense fluid a it is cut, as is done in the preferred method. This dense fluid fills the cut and the directionally drilled holes back to the surface to provide hydrostatic support for the block of soil. This dense fluid may be a nonhardening material which could remain in place for many months before the next phase of the project. The fluid would be designed to be slightly heavier or lighter than the grout and would have the ability to seal off small leak pathways or permeable formations.
[0099] After the bottom horizontal cut is formed, a perimeter trench is conventionally excavated within the boundaries of the horizontal circular cut and through it. This trench may be rectangular or curved according to the capability of the excavating equipment. This trench may be cut “dry” or excavated under a super dense grout slurry. If excavated dry, the dense fluid will flow out of the horizontal cut and allow the cut to close near the trench. This also provides visual evidence that the horizontal cut has been intersected. If the trench is excavated under a super dense grout slurry the slurry will balance the hydrostatic pressure of the dense fluid in the horizontal cut, or overcome it and flow into the horizontal cut. Optionally both methods be used at the same time on opposite sides of the block. As the slurry filled perimeter trench cuts through the horizontal cut its super dense grout will enter the horizontal cut and cause the block to lift. It may also be desirable to cut to a percentage of full depth with a dry trench, and then complete the intersection with the trench filled with super dense grout.
[0100] Forming Barriers with Molten Paraffin
[0101] Wiresaw cuts may also be made using a molten paraffin which is pumped into the cut through the pulling pipes in the same manner as with dense grout. Pulling pipes may include circulation loops to keep paraffin from hardening around the pipes. In this method the paraffin hardens only a few feet behind the cutting cable. The liquid area is a thin arc between the pilot holes, typically from 1 to 3 inches thick. Tis limits the overburden stress on the soil so that the barrier does not get pinched out. These grouts can also be modified with powdered iron oxide to make them more dense than the soil to facilitate a buoyant lift barrier. However it is also possible to use a thermoplastic material like paraffin to construct a thin barrier which relies on rapid hardening to prevent subsidence. Subsidence forces are managed by keeping the one horizontal dimension of the cut sufficiently narrow that the structural strength of the soil overburden is enough to prevent collapse. A two component chemical grout may also be applied in a similar manner with the pulling pipe containing a concentric inner pipe supplying the second component and a nozzle constructed so as to receive flow of both components and mix them together. This could also be done with two separate pipes tethered together or inside a larger pipe. The grout need only be injected on the side of the cut from which the cable moves inward. The movement of the cable through the ground creates a pumping action which causes the greater portion of the grout to follow the movement of the cable around the catenary arc of the cut and back to the surface trench.
[0102] Molten paraffin, circulated through a catenary arcuate tube at high pressure and rate while the tube itself is reciprocated through directionally drilled holes to the advancing cut. Typical pressures would be from 2,000 psi to 10,000 psi controlled by a spring loaded pinch valve on the recirculation line which automatically limits the pressure in the line. Circulation rates are sufficient to prevent particles from settling out and to keep temperature uniform. Holes or hardened ports in the forward facing surface of the tube eject the heated liquid into the soil at high kinetic energy causing the soil to be eroded and substantially replaced by the molten paraffin. This allows the tube to advance forward laterally. These ports, or “jets” may be fabricated by brazing a tungsten carbide nozzle flush with the surface of the tube. Portions of the surface of the tube may be covered with an abrasive grit such as tungsten carbide imbedded in an epoxy coating, or by weld deposited hard facing. Rotating both ends of the tube slightly after each pulling stroke allows for a single jet to cut a path wider than the tube. An example of such a rotation sequence would be 0°, +5°, 0°, −5°, 0°,+5° By rotating the tube in small increments it is possible to sweep the entire soil area in front of the tube with a fixed position jet. In previous tests of soil jetting devices the inventor has noted that the width of the-cut formed by a single jet varies significantly with soil type and jetting factors, If the jets do not make a cut at least as thick as the diameter of the tube then the device can not advance except by mechanical abrasion. The ends of the pipe may be automatically rotated by a mechanical “J-Slot” mechanism such as is common in the art of oil well down-hole tools. The mechanism rotates one increment each time the tube is placed in tension and released.
[0103] As the tube passes laterally through the ground, the paraffin both permeates into the soil and cools to a solid state. Paraffin which fractures away from the barrier will undergo rapid cooling and will harden and seal off. The injection temperature, and the cooling rate are such that the paraffin hardens before a large enough liquid area of the cut exists to allow subsidence of the overburden to pinch out the barrier. Since fresh molten paraffin is always circulating through the tube, the immediate area of the cut will always remain molten even if reciprocation stops. If the pipe breaks or becomes stuck a new tube may be pulled into position by melting a path through the previous cut. An unlimited number of replacement jetting tubes or wire saw cables may be pulled into cutting position by the heated “pulling pipes” which are in the original directionally drilled holes. An abrasive wire saw cable or chain, may also precede the jetting tube by a few feet to cut through hard objects and reduce the stress on the tube.
[0104] Another improvement over prior art is the use of the above mentioned molten paraffin applied with conventional jet grouting apparatus. The preferred molten paraffin has a melting point between 120° and 180° F. and is modified by the addition of a surfactant which allows the molten paraffin to soak into soils which are already water wet or damp, as well as dry soils which have a very low permeability to water. An example of such a surfactant includes Fluoroaliphatic polymeric esters such as Flourad™ FC430 made by the 3M company of St. Paul, Minn. Another useful surfactant blend can be formed from a blend of 9 parts by weight oleic acid, 6 parts alkanolamine, and 6 parts nonionic surfactant such as nonyl phenol ethoxylate. The surfactant, along with an optional oil soluble dye may be added to a tanker track of molten paraffin which directly feeds the jet grouting equipment. Optionally a bad tasting or bad smelling substance may be added to increase the resistance to rodent and insect damage. When mixed with the soil by the jet grouting process, it produces a water impermeable product. Hot water is pumped through the system prior to the paraffin to heat the piping and also afterward to clean the system. Molten low density polyethylene Homopolymer such as Marcus 4040 which melts at 181.4° F. may be utilized in a similar manner to the paraffin to increase chemical resistance properties. It may also be modified to enhance its performance in wet soils by the additions of surfactant blends. An example of a nonionic blend is 7 parts by weight ethoxylated alcohol, 0.56 parts potassium hydroxide, and 0.21 parts sodium bisulphite. An ionic blend could be made with equal parts by weight of oleic acid and an amine. If polyethylene is used as the primary grout, the HDPE top liner may be fusion bonded directly to the bottom barrier. This material may also be used as a hot melt glue to bond the paraffin to an HDPE top liner. The low density polyethylene homopolymers may be blended with the paraffin wax at a concentration of from 2 to 10 percent weight percent to improve its wetting properties, impermeability, and chemical resistance.
[0105] Molten paraffin may be especially useful for constructing barrier vaults in rock which has large cracks or fissures such as the basalt rock layers which exist in Idaho. As the molten wax enters a fissure and begins to escape from the area where the barrier is to be formed it loses heat and solidifies quickly. This tends to seal off the fissure. This approach should work in both water saturated and vadose zones.
[0106] Those skilled in the art who now have the benefit of the present disclosure will appreciate that the present invention may take many forms and embodiments, Some embodiments have been described so as to give an understanding of the invention. It is intended that these embodiments should be illustrative, and not limiting of the present invention, Rather, it is intended that the invention cover all modifications, equivalents and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
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A method is disclosed for constructing, verifying, and maintaining underground vaults that isolate and contain radioactive burial sites. The method employs a buoyant lift technique to isolate a block of soil containing the contaminates from the surrounding soil. An impermeable synthetic liner is embedded in the vault to enhance the integrity of the system. The integrity of the vault is monitored by a system of sensors placed both inside and outside of the sealed vault. The method eliminates the need to excavate or drill in the contaminated areas.
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RELATED APPLICATION
This application is a continuation of U.S. patent application Ser. No. 11/503,662 filed Aug. 14, 2006, which claims the benefit of and priority to U.S. Provisional Application No. 60/708,445, filed on Aug. 16, 2005, both of which are owned by the assignee of the instant application and the disclosures of which are incorporated herein by reference in their entireties.
BACKGROUND
Ozone is useful for numerous applications that require a high level of oxidation. For example, ozone is useful for disinfection of drinking water and has been used for water treatment since the early 1900s. More recently, ozone has been used for semiconductor device processing. One application for ozone in semiconductor device processing is forming insulating layers on semiconductor wafers by growing insulating films or by oxidizing thin films on the wafer. For example, high deposition rate chemical vapor deposition of high quality SiO 2 can be accomplished by using a TEOS/ozone process.
Another application for ozone in semiconductor device processing is for cleaning semiconductor wafers and the processing chambers of semiconductor processing equipment. Ozone is particularly useful for removing hydrocarbons from the surface of semiconductor wafers or from processing chambers. Using ozone for cleaning is advantageous because it avoids the use of dangerous chemicals which require costly disposal. In contrast, ozone does not present a toxic waste disposal problem because ozone decays to oxygen without residues.
SUMMARY
Ozone can be generated from oxygen according to a so-called “silent discharge principle.” For instance, ozone can be generated by exposing high purity oxygen to an electrical discharge or an electrical flux. The discharge or flux excites the oxygen molecules, breaking them into their atomic state. The atoms then recombine into a mixture of ozone (O 3 ) and oxygen (O 2 ).
Ozone (O 3 ) is typically produced by passing oxygen through an ozone cell where it is acted upon by an electrical discharge causing the dissolution and recombination of the oxygen atoms into ozone molecules. The electrical discharge or electrical flux needed for ozone generation is produced by applying a high voltage AC power across opposing plates of the ozone cell. The high voltage AC power is produced from transformer-based power oscillators.
Disadvantages of a transformer-based power supply (an oscillator) typically include high cost, limited reliability, and limited range of operation. For example, the high cost is typically due to the high-voltage transformer with multiple windings and special potting requirements for cooling and insulation. Limited reliability is typically due to the topology of the self-oscillator, high voltage corona caused by the dependence of the potting quality, and use of single source unique parts. Limited range of operation with respect to the regulated output voltage is typically due to the self-oscillator topology and use of transformer feedback for the transistor's gate drive.
The present invention is directed to a method and apparatus for supplying power using a power supply including transformer-less high voltage power oscillators for ozone generation. Embodiments of the present invention can reduce cost, increase reliability and operation range of ozone generators.
One embodiment includes a power supply having a power source and a resonant circuit coupled to the power source, the power source providing a first AC voltage to the resonant circuit, the resonant circuit providing a second AC voltage for use by an ozone generating unit, the second AC voltage being greater than the first AC voltage. The resonant circuit can apply a substantially resonant voltage to the ozone generating unit in response to the first AC voltage having a frequency substantially close to the resonant frequency of the resonant circuit.
In some embodiments, the resonant circuit can be a series resonant circuit including a resonant inductor coupled in series with a resonant capacitor. The resonant capacitor can be an individual capacitor, a natural capacitance of the ozone generating unit, or a combination of both an individual capacitor and natural capacitance of the ozone generating unit. The resonant circuit has a q-factor greater than or equal to 10. In other embodiments, the resonant circuit can be a parallel resonant circuit including a resonant inductor coupled in parallel with a resonant capacitor. The resonant capacitor can be an individual capacitor, a natural capacitance of the ozone generating unit, or a combination of both an individual capacitor and natural capacitance of the ozone generating unit.
The power source can be a half bridge inverter, a full bridge inverter, and/or a switching power source. The switching elements can be MOSFETs, BJTs, IGBTs, and/or any other type of switching elements.
The power supply can further include a controller providing signals to the power source that cause the power source to modulate the first AC voltage, resulting in the second AC voltage having a desired voltage magnitude. The first AC voltage can be modulated using pulse width modulation and/or frequency modulation. The controller can provide signals to the power source that allows the resonant circuit to operate at its maximum operating resonant frequency. The controller can tune to the maximum operating frequency of the resonant circuit by comparing a sensed input DC current to a set point input current. The controller can control a resonant voltage of the ozone generating unit during self-tuning to the maximum operating frequency of the resonant circuit by comparing a sensed resonant current to a set point resonant current.
Embodiments of the invention also include a power supply for ozone generation. Other embodiments of the invention may be applied for supplying power for generation of any reactive gases.
Advantages of the embodiments of the invention include reduced cost and increased reliability and operation range of ozone generators by eliminating the need for a transformer.
Using a high Q resonant circuit (Q≧10 typically for an ozone generator) instead of a transformer implies that the circuit resonant frequency peak is narrow. Since its center frequency depends on circuit elements with tolerances often wider than the resonance peak width, control of such a circuit can be a problem. A circuit to control high Q resonant circuits allows realization of the advantages above in both ozone generators and in resonant power supplies for other applications.
BRIEF DESCRIPTIONS OF THE DRAWINGS
The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.
FIG. 1 is a diagram illustrating a typical ozone generator;
FIG. 2 is a diagram that illustrates a transformer-based power supply used in an ozone generator according to the prior art;
FIG. 3 is a diagram illustrating a power supply having a transformer-less power oscillator for ozone generation in a single ozone cell according to one embodiment;
FIG. 4 is a diagram illustrating a power supply having a transformer-less power oscillator for ozone generation in a single ozone cell according to a particular embodiment;
FIG. 5A shows a detailed schematic of one embodiment of a frequency modulation controller;
FIG. 5B shows a detailed schematic of one embodiment of a pulse-width modulation controller;
FIG. 6 shows a graph showing the relationship between set point power and resonant frequency;
FIG. 7 is a diagram illustrating a power supply having multiple transformer-less power oscillators for ozone generation across multiple ozone cells according to one embodiment; and
FIGS. 8A and 8B are diagrams illustrating a power supply having a transformer-less power oscillator for ozone generation in a single ozone cell according to other particular embodiments.
DETAILED DESCRIPTION
FIG. 1 is a diagram illustrating a typical ozone generator 100 . The ozone generator 100 includes a bank of ozone generating units, referred to herein as ozone cells 110 a . . . 110 n . Oxygen (O 2 ) is supplied to each ozone cell 110 through an oxygen inlet 120 for conversion into a mixture of ozone (O 3 ) and oxygen (O 2 ). The resulting ozone mixture flows out of the ozone generator 100 through an ozone outlet 130 .
Components of the ozone cell 110 typically include opposing electrode plates (not shown) and a dielectric barrier (not shown). The dielectric barrier is positioned against one of the electrode plates, forming a channel between the dielectric barrier and the opposing electrode plate. In operation, oxygen (O 2 ) passing through the channel is acted upon by an electrical discharge causing the dissolution and recombination of the oxygen atoms into ozone molecules. To cause the electrical discharge or flux, high voltage AC power is applied across the opposing electrode plates of each ozone cell 110 .
The high voltage AC power is provided by a bank of power oscillators 140 a . . . 140 n with each oscillator 140 supplying power to a respective ozone cell 110 . The power oscillators 140 are coupled to a common DC power supply 150 that can convert single-phase or three-phase AC line voltage 152 into a regulated DC voltage (Vdc). Each oscillator 140 , in turn, converts the regulated DC voltage (Vdc) into high voltage AC power that is supplied to a corresponding/respective ozone cell 110 , resulting in the electrical discharge or electrical flux needed for ozone generation. An exemplary embodiment of the ozone cell 110 can be found in U.S. Pat. No. 5,932,180, the entire contents of which are incorporated herein by reference.
Generally, the power oscillators 140 are implemented using transformers to generate high voltage AC power. FIG. 2 is a diagram that illustrates a transformer-based power supply 200 used in an ozone generator according to the prior art. The illustrated power supply 200 consists of a DC power supply 210 and two additional stages: (1) a buck converter 220 for regulation of output power and (2) a self oscillating push-pull converter 230 that includes a transformer 232 to generate the high voltage AC power across the ozone cell 110 .
FIG. 3 is a diagram illustrating a power supply 300 having a transformer-less power oscillator 310 for ozone generation in a single ozone cell 110 according to one embodiment. The power oscillator 310 includes a power source 320 coupled to a resonant circuit 330 . The resonant circuit 330 is coupled, in turn, to the ozone cell 110 . The power source 320 can be a switching power source.
In operation, the power source 320 converts a regulated DC voltage (Vdc) from a DC voltage source 210 into a first AC voltage that is supplied to the resonant circuit 330 . Preferably, the first AC voltage from the power source 320 has a frequency substantially close to the resonant frequency of the resonant circuit 330 . In response, the resonant circuit 330 applies a substantially resonant second AC voltage to the ozone cell 110 causing an electrical discharge or flux within the ozone cell 110 . Thus, by coupling the resonant circuit 330 to the power source 320 , the power supply 300 is able to provide high voltage AC power (a second AC voltage) needed for ozone generation in the ozone cell 110 without the use of a transformer.
With reference to FIG. 3 , a controller 340 provides control signals to the power source 320 that cause the power source 320 to modulate the frequency and/or duty cycle of the first AC voltage resulting in the resonant circuit 330 providing a substantially second AC resonant voltage having a desired magnitude to the ozone cell 110 . In some embodiments the second resonant AC voltage can be 4.5 kVpk at 30 kHz.
In operation, the controller 340 compares a reference current REF with a sensed input current at the power source 320 and sends control signals (gate control signals) to the power source 320 to make adjustments to the operating frequency or duty cycle of the power source 320 to obtain the desired magnitude. The first AC voltage can be modulated by the controller 340 using pulse-width modulation and/or frequency modulation. In some embodiments, the controller 340 can be configured to sense voltage, current, or a combination thereof to determine and control the desired resonant voltage.
FIG. 4 is a diagram illustrating a power supply 400 having a transformer-less power oscillator 404 for ozone generation in a single ozone cell 110 according to a particular embodiment. In the illustrated embodiment, the resonant circuit 420 is a series resonant circuit including a resonant inductor 422 coupled in series with a resonant capacitor 424 The ozone cell 110 is coupled in parallel with the resonant capacitor 424 . The resonant capacitor 424 can be a separate individual capacitor, the natural capacitance of the ozone cell 110 , or a combination thereof. In the illustrated embodiment, the power source 410 is a half bridge inverter including two switching elements 412 a , 412 b connected in series. The switching elements 412 a , 412 b can be MOSFETs, BJTs, IGBTs and/or any other type switching elements known in the art. The electrical connection between the switching elements 412 a , 412 b is connected to the resonant circuit 420 . The power source 410 can also be a full bridge inverter as shown in FIGS. 8A and 8B .
In operation, a DC power supply 210 supplies a regulated DC voltage (Vdc) to the power source/half bridge inverter 410 . Control signals from the controller 340 are provided to a gate driver 540 ( FIGS. 5A and 5B ) that causes the switches 412 a , 412 b to turn on and off resulting in the half bridge inverter 410 supplying the first AC voltage having a frequency substantially close to the resonant frequency of the series resonant circuit 420 . Particularly, the first AC voltage applied to the resonant circuit 420 can be square wave pulses with a controlled duty cycle. The control signals can also change the duty cycle of the half bridge inverter 410 to alter the magnitude of the second resonant AC voltage applied to the ozone cell 110 . In response to receiving the first AC voltage from the half bridge inverter 410 , the series resonant circuit 420 provides a resonant or substantially second resonant AC voltage across the ozone cell 110 such that an electrical discharge or flux is provided within the cell to effect conversion of oxygen (O 2 ) to ozone (O 3 ). Particularly, the resonant circuit 420 converts the applied square wave pulses with a controlled duty cycle to a high voltage sine wave of controlled amplitude. According to one embodiment, the frequency and magnitude of the second resonant AC voltage is approximately 4.5 kVpk at 30 kHz.
The ratio of ozone (O 3 ) to oxygen (O 2 ) depends on the amount of power supplied to the ozone cells 110 . The power applied to the ozone cell 110 increases in proportion to the voltage applied to the ozone cell 110 and is regulated by the controller 340 in accordance with the reference signal REF as described above. Thus, by changing the operating frequency or duty cycle of the half bridge inverter 410 , the controller 340 can alter the concentration of ozone. Further, the resonant frequency changes with even a small variation in inductance and capacitance. Thus, the resonant circuit 420 should have a high Q factor (greater than or equal to 10) to eliminate the need for transformer. Therefore, the controller 340 should be independent of the resonant component variation.
FIGS. 5A and 5B show a detailed schematic of embodiments of a controller 500 . The major components of the controller 500 include a pulse-width modulated integrated circuit (PWM IC) 510 , a first operational/error amplifier 520 , a second operational/error amplifier 530 , a gate driver circuit 540 , a first resistor 550 , and a second resistor 560 .
FIG. 5 A shows one embodiment of a frequency modulated controller 500 ′. In operation, the operational amplifier/error amplifier 520 compares the sensed DC input current 522 with the set point DC current 524 . The resistors 550 , 560 control the frequency of the PWM IC 510 . The output of the error amplifier 520 controls the current flowing through the resistor 550 by pulling it up or down and thus controls the frequency of the controller 510 . The controller 500 ′ includes an auto tuning circuit that ensures the initial frequency generated by the error amplifier 520 is the maximum operating frequency of the resonant circuit 420 ( FIG. 4 ).
The tuning circuit includes a resistor 526 , a capacitor 528 , and a small offset voltage at the sensed input of the error amplifier 520 . In operation, when the tuning circuit powers up, the DC current set point 524 slowly increases from zero to its set point through a delay created by the resistor 526 and capacitor 528 . In that time, the offset voltage at the error amplifier 520 ensures that the frequency generated by the error amplifier is the maximum operating frequency of the circuit. The maximum resonant frequency is determined by considering the maximum tolerance on the resonant circuit elements and the capacity of the switching devices.
FIG. 6 shows a graph showing the relationship between the set point power and the resonant frequency. As shown, as the set point power increases, the pulse-width modulation frequency starts reducing from its maximum value toward maximum power. That is, pulse-width modulation frequency walks over the resonant curve to achieve the maximum power.
It is important to control the ozone cell 110 voltage because the ozone cell 110 voltage can rise to a very high voltage during auto-tuning of the frequency for maximum power. Thus, the controller 500 ′ includes a second operational amplifier/error amplifier 530 . The error amplifier 530 controls the resonant voltage of the ozone cell 110 by comparing the sensed resonant current 532 to the set point resonant current 534 .
The resonant current can also be controlled by using pulse-width modulation. FIG. 5B shows one embodiment of a pulse-width modulation controller 500 ″. The operation of the pulse-width modulation controller 500 ″ is similar to the operation with respect to the frequency modulated controller 500 ′ as described above.
FIG. 7 is a diagram illustrating a power supply 600 having multiple transformer-less power oscillators 404 a . . . 404 n for ozone generation across multiple ozone cells 110 a . . . 110 n according to one embodiment. In the illustrated embodiment, the regulated DC voltage (Vdc) (e.g. approximately 400V) is provided by a known full bridge high frequency converter 610 . The high frequency converter 610 includes a rectifier stage 612 , a full bridge switching stage 614 , a transformer stage 616 , and a filter stage 618 . Other circuits known to those skilled in the art can also be implemented to provide the regulated DC voltage. The power oscillators 404 a . . . 404 n are coupled to a corresponding/respective ozone cell 110 a . . . 110 n to provide the high voltage AC power. Each oscillator 404 includes a power source 410 coupled to a resonant circuit 420 . In the illustrated embodiment, the power sources 410 are half bridge inverters implemented using MOSFET switching devices 412 a , 412 b . Other switching devices known to those skilled in the art may also be utilized. Also, mixed implementations of half-bridge oscillators, full-bridge oscillators, and other known devices may be employed. The operation of the illustrated embodiment is similar to the operation described with respect to FIGS. 1 and 4 .
FIGS. 8A and 8B are diagrams illustrating a power supply 700 having a transformer-less power oscillator for ozone generation in a single ozone cell 110 according to other particular embodiments. In both embodiments, the power source 710 is implemented as a full bridge converter with four switching elements 712 a , 712 b , 712 c , 712 d coupled as shown.
As shown in FIG. 8A , a voltage supply 210 supplies regulated DC voltage (Vdc) to the full bridge converter 710 . The full bridge converter 710 is coupled to a series resonant circuit 720 having a resonant inductor 722 coupled in series with a resonant capacitor 724 . The resonant circuit 720 is coupled, in turn, to an ozone cell 110 as shown.
As shown in FIG. 8B , a current supply 730 supplies a regulated DC current (Idc) to the full bridge converter 710 . The full bridge converter 710 is coupled to a parallel resonant circuit 740 having a resonant inductor 742 coupled in parallel to a resonant capacitor 744 . The resonant circuit 740 is coupled, in turn, to an ozone cell 110 as shown.
In either embodiment, the resonant capacitor can be a separate individual capacitor or can be the natural capacitance of the ozone cell 110 or combination of both an individual capacitor and natural capacitance of the cell.
While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.
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A transformer-less power supply is provided for ozone generation. The power supply advantageously reduces costs and increases reliability of ozone generators. The power supply provides a first AC voltage from a power source to a resonant circuit and the resonant circuit provides a second AC voltage to the ozone generating unit, the second AC voltage being greater than the first AC voltage. A controller for the power supply that adapts to the resonance of the circuit to provide control with a wide tolerance for the high Q circuit component values of the circuit.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation application of U.S. application Ser. No. 10/405,368 filed Apr. 3, 2003, now abandoned, the subject matter of which is incorporated herein by reference. This application claims the benefit of Japanese Patent Application 2002-100735 filed on Apr. 3, 2002, the disclosure of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
The present invention relates to a cellular phone comprising a central processing unit (CPU).
A hand-held terminal or mobile terminal, for switching the frequency of a clock signal delivered from the side of an application program, is disclosed in JP-A NO. 73237/1999 (Heisei 11).
Further, in JP-A No. 148475/2000, there is disclosed a computer for a mobile unit, capable of switching a clock frequency to a high-speed mode frequency higher than a normal frequency when conditions, such as power source voltage, ambient temperature, and so forth, are satisfied.
In the case of the conventional technology described above, speed control of a clock signal has been implemented by an application program or has been dependent on the conditions such as power source voltage, ambient temperature, and so forth, so that there is no room for interposition of the will of a user in switching the speed of the clock signal. Further, if the CPU is driven at a high frequency, there has been a tendency toward an increase in current consumption although a processing speed is enhanced. With a cellular phone, in particular, since its battery capacity is small, there has been a risk of premature depletion of the battery capacity occurring when the clock signal has been automatically switched over to the high-speed side without knowledge of the user.
SUMMARY OF THE INVENTION
To attain both enhancement in processing speed and reduction in current consumption, it is an object of the invention to provide a mobile terminal comprising clock control means capable of changing the frequency of a clock signal received from an oscillator under control by a central processing unit, and converting an operation frequency of the central processing unit to a different frequency, wherein a clock signal at the different frequency as converted by the clock control means becomes a clock signal of the central processing unit.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram showing the configuration of a first embodiment of a cellular phone according to the invention;
FIG. 2 is a block diagram showing the configuration of a second embodiment of a cellular phone according to the invention;
FIG. 3 is a block diagram showing the configuration of a third embodiment of a cellular phone according to the invention;
FIG. 4 is a block diagram showing the configuration of a fourth embodiment of a cellular phone according to the invention; and
FIG. 5 is a graph showing the relationship between an operation frequency of a central processing unit of the cellular phone according to the first to fourth embodiments, respectively, and current consumption.
Other and further objects, features and advantages of the invention will appear more fully from the following description.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
A first embodiment of a cellular phone according to the invention is described hereinafter with reference to FIGS. 1 and 5 . FIG. 1 is a block diagram showing the internal configuration of the cellular phone according to the first embodiment.
A central processing unit (CPU) 100 controls the operation of the cellular phone in accordance with a control program stored in a memory 110 . The CPU 100 performs operation in accordance with an input pushbutton as pressed via an operation panel (input pushbutton group) 120 , executing processing in response to the input pushbutton as pressed.
Upon dialing, a telephone number as inputted from the operation panel 120 is shown on a display unit 130 , a speech signal delivered from a speech input unit (microphone) 140 is sent out in the form of radio waves from an antenna 160 to the outside via a transmit/receive unit 150 in accordance with a transmission directive delivered from the operation panel 120 .
At the time of signal reception, radio waves from the outside are received by the antenna 160 , and upon recognition by the transmit/receive unit 150 that the radio waves received are radio waves corresponding to a telephone number dedicated to the present cellular phone, speech is delivered from a speech output unit (speaker) 170 .
The CPU 100 receives a clock signal from an oscillator 180 through the intermediary of a clock controller 200 . Because an operation frequency of the CPU 100 is dependent on the frequency of the clock signal as received, a processing speed of the CPU 100 is regulated by the frequency of the clock signal. The clock controller 200 converts the frequency of the clock signal into any suitable frequency by use of a PLL (Phase Locked Loop) circuit under control by the CPU 100 , and the clock signal is delivered to the CPU 100 as a clock signal of the CPU 100 . The frequency of the clock signal delivered to the CPU 100 becomes the operation frequency of the CPU 100 .
FIG. 5 is a graph showing the relationship between the operation frequency and current consumption. In proportion as the frequency of the clock signal is changed to a higher frequency, the operation frequency of the CPU 100 becomes higher, thereby enhancing the processing speed of the CPU 100 although current consumption increases.
With the present embodiment, when executing a specific processing, the frequency of the clock signal of the CPU 100 is caused to change to a higher frequency, thereby enhancing the processing speed. Upon completion of the execution of the specific processing, the frequency of the clock signal of the CPU 100 is caused to change to a lower frequency, thereby reducing current consumption. In the initial condition at the time when power is turned on, the frequency of the clock signal of the CPU 100 is set to a low frequency in order to reduce current consumption.
Herein, the specific processing refers to, for example, processing for image decoding, address retrieval processing, and application processing such as kana-kanji conversion processing used in entering characters. These processing often have effects on the response of the user.
With the present embodiment, the user can change the operation frequency of the CPU 100 by changing the output frequency of the clock controller 200 at will with the use of a clock manipulation unit 300 connected with the CPU 100 .
If the user enters a request for change via the clock manipulation unit 300 , the CPU 100 receives an input from the clock manipulation unit 300 , and controls the clock controller 200 , thereby controlling a clock frequency to be fed to the CPU 100 . That is, in response to the input from the clock manipulation unit 300 , the frequency of the clock signal to be fed to the CPU 100 is set.
Further, with the present embodiment, depending on an application to be used, and use environments, the user can change the frequency of the clock signal in every processing. For example, if the user wants to increase the processing speed of the CPU 100 , the frequency of the clock signal can be raised, and if the user wants to reduce current consumption, the frequency of the clock signal can be changed to a lower frequency. By virtue of such a function as described, the user can set the frequency of the clock signal as appropriate at will depending on the user's use environments, such as the user' desire to execute high speed processing, or to use the cellular phone for many hours, the amount of the actual battery capacity that remains in a battery being small, and so forth, so that operability can be enhanced.
In FIG. 1 , the clock manipulation unit 300 is shown as a single pushbutton (clock manipulation pushbutton), but may be made up of a plurality of keys instead. In order to implement the clock manipulation unit 300 with the single pushbutton, for example, the lowest frequency is set as the initial condition of the frequency of the clock signal, thereby carrying out control such that every time when the single pushbutton is once operated, the frequency of the clock signal of the CPU 100 is changed to sequentially higher frequencies by stages. The frequency is changed cyclically, and if the frequency of the clock signal of the CPU 100 is changed to the highest frequency, upon operation of the single pushbutton the next time, the frequency of the clock signal of the CPU 100 reverts to the lowest frequency. Thus, every time when the single pushbutton is operated, the output frequency of the clock controller 200 can be changed, thereby enabling the operation frequency of the CPU 100 to be changed.
The CPU 100 causes the display unit 130 to display a numerical value of the frequency after changed in such a way as to explicitly advise the user of the frequency of the clock signal after changed. Since it is sufficient for such display to indicate simply which stage the processing speed of the CPU 100 is in, indication of a specific numerical value of the frequency is not necessarily required. Numbers to indicate respective stages, such as 1, 2 , 3 . . . , or characters such as high, middle, low, etc. may be displayed. Alternatively, the respective stages of the processing speed may be displayed in number of stars, exhibiting one star on the display unit 130 for the lowest speed, increasing the number of stars exhibited on the display unit 130 in ascending order of the stage. Otherwise, the status of the processing speed may be displayed with the use of a bar graph, icons, and so forth.
Further, for changing the output frequency of the clock controller 200 at the user's will, there may be adopted a method whereby an operation menu directing change of the frequency of the clock signal is caused to be displayed on the display unit 130 without the use of the clock manipulation pushbutton, and the user selects or directs at will the output frequency of the clock controller 200 by use of the operation panel 120 , thereby changing the operation frequency of the CPU 100 . In such a case, the operation panel 120 functions as the clock manipulation unit 300 , so that the clock manipulation unit 300 can be omitted.
Now, a second embodiment of a cellular phone according to the invention is described hereinafter with reference to FIG. 2 . FIG. 2 is a block diagram showing the internal configuration of the cellular phone according to the second embodiment.
With the present embodiment, a central processing unit (CPU) is made up so as to be divided into a first central processing unit 400 concerned with transmit/receive of signals, and a second central processing unit 410 handling processing that has effects on the response of a user. In FIG. 2 , blocks denoted by the same reference numerals as those in FIG. 1 correspond to those blocks of the first embodiment, having the same functions.
The first central processing unit 400 controls operation concerned with transmit/receive by the cellular phone in accordance with a control program stored in a first memory 420 , and the second central processing unit 410 controls operation concerned with processing that has effects on the response of a user in accordance with a control program stored in a second memory 430 . More specifically, the second central processing unit 410 controls operation concerned with processing of an application program.
A clock signal from an oscillator 180 is directly delivered to the first central processing unit 400 as a clock signal. Meanwhile, a clock signal at any suitable frequency converted by control of the second central processing unit 410 is delivered to the second central processing unit 410 through the intermediary of a clock controller 200 .
With such a configuration as described, when executing a specific processing, the frequency of the clock signal delivered to the second central processing unit 410 can be changed to a high frequency, thereby enhancing a processing speed, and upon completion of execution of the processing that has effects on the response of the user, the frequency of the clock signal delivered to the second central processing unit 410 can be changed to a low frequency, thereby reducing current consumption.
For example, during a standby (waiting) period for communications by the cellular phone, the first central processing unit 400 is in intermittent operation to receive radio waves from the outside via an antenna 160 , executing processing for recognition by the transmit/receive unit 150 that the radio waves received are radio waves corresponding to a telephone number dedicated to the present cellular phone. In this case, the frequency of the clock signal delivered to the second central processing unit 410 is changed to a low frequency to thereby reduce current consumption. As shown FIG. 5 , the relationship between an operation frequency and current consumption is such that in proportion as the operation frequency becomes higher, the current consumption increases while in proportion as the operation frequency becomes lower, the current consumption decreases.
The cellular phone shown in FIG. 2 further comprises a power supply controller 500 . The power supply controller 500 controls power to be supplied from a battery 510 to the second central processing unit 410 in response to control by the first central processing unit 400 . For example, during a standby (waiting) period for communications by the cellular phone or upon completion of the processing by the second central processing unit 410 , the power supply controller 500 can turn off power to be supplied to the second central processing unit 410 in response to control by the first central processing unit 400 . Since the second central processing unit 410 handles application, its power consumption at the time of processing is large, and consequently, effective saving in power can be attained by controlling the power supplied.
Next, a third embodiment of a cellular phone according to the invention is described hereinafter with reference to FIG. 3 .
The cellular phone shown in FIG. 3 comprises a battery voltage detector 600 in place of the power supply controller 500 incorporated in the cellular phone shown in FIG. 2 . In FIG. 3 , blocks denoted by the same reference numerals as those in FIG. 2 have the same functions as those of the blocks of the second embodiment, omitting therefore description thereof.
The battery voltage detector 600 detects a voltage of a battery 510 . A first central processing unit 400 determines whether or not the voltage detected is lower than a predetermined value. In the case where it is determined that the amount of the actual battery capacity that remains in the battery 510 is less than a predetermined amount, the frequency of a clock signal delivered to a second central processing unit 410 is changed to a lower frequency even when executing a specific processing, thereby reduging current consumption. Hence, it is possible to effect control so as to reduce current consumption in case that the amount of the actual battery capacity that remains in the battery becomes small, thereby prolonging operable time of the cellular phone.
Further, a fourth embodiment of a cellular phone according to the invention is described hereinafter with reference to FIG. 4 . FIG. 4 is a block diagram showing the internal configuration of the cellular phone of a folded structure, according to the fourth embodiment. In FIG. 4 , blocks denoted by the same reference numerals as those in FIGS. 2 and 3 , respectively, have the same functions as those of the blocks of the second and third embodiments, respectively, omitting therefore description thereof.
The cellular phone shown in FIG. 4 comprises a folding condition detector 700 for detecting whether the cellular phone is in a folded (closed) condition or in an unfolded (open) condition.
With the cellular phone according to the present embodiment, a first display unit 710 and a second display unit 720 are added to a first central processing unit 400 and a second central processing unit 410 , respectively. The first display unit 710 is disposed at a position as can be seen by a user even in the folded condition. The second display unit 720 is disposed at the folded-down side of the cellular phone.
Since the operation of the cellular phone in the open condition is the same as that of the cellular phone according to the second and third embodiments, respectively, the operation of the cellular phone in the closed condition is described hereinafter.
Normally, in the closed condition, the cellular phone is often on standby (waiting) for cellular phone communications, and the first central processing unit 400 is in intermittent operation to receive radio waves from the outside via an antenna 160 , executing processing for recognition through the intermediary of a transmit/receive unit 150 that the radio waves received are radio waves corresponding to a telephone number dedicated to the present cellular phone. Meanwhile, since a load on the second central processing unit 410 is light at this point in time, the frequency of a clock signal delivered to the second central processing unit 410 can be changed to a low frequency, thereby reducing power consumption. When executing a specific processing even in the closed condition, the frequency of the clock signal delivered to the second central processing unit 410 is caused to change to a higher frequency, thereby enhancing a processing speed, and upon completion of execution of the specific processing, the frequency of the clock signal is caused to change to a low frequency, thereby reducing current consumption.
Further, in the closed condition, the user is unable to see the second display unit 720 . Accordingly, as for processing concerning the second display unit 720 , upon detection of the closed condition, the frequency of the clock signal delivered to the second central processing unit 410 is caused to change to a low frequency, thereby enabling current consumption to be reduced.
Furthermore, even when executing the specific processing, the frequency of the clock signal delivered to the second central processing unit 410 may be changed to a low frequency in the case of the closed condition. In the case of the cellular phone being in the closed condition, the user does not look at a display screen of the cellular phone, and is often in no hurry to do processing. Accordingly, in the case of the closed condition, processing can be executed while reducing power consumption by changing the frequency of the clock signal to a lower frequency. When the cellular phone is shifted to the open condition, the processing speed is enhanced by changing the frequency of the clock signal delivered to the second central processing unit 410 to a higher frequency.
The cellular phone shown in FIG. 4 further comprises a lighting controller 800 for controlling backlight of the second display unit 720 . Since the user is unable to see the second display unit 720 in the folded condition, further reduction in power consumption can be attained by turning off the backlight of the second display unit 720 .
In addition, the power supply controller 500 shown in FIG. 2 or the battery voltage detector 600 shown in FIG. 3 may be added to the cellular phone according to the present embodiment. In such a case, when the amount of the actual battery capacity that remains in the battery 510 is less than a predetermined amount, power consumption can be reduced and waiting time can be extended by implementing control such that the backlight of the second display 720 is turned off even in the open condition.
Still further, the operability of the cellular phone can be improved by providing the cellular phone shown in FIGS. 2 through 4 , respectively, with the clock manipulation unit 300 shown FIG. 1 , thereby enabling the user to change the frequency of the clock signal as with the case of the first embodiment. Also, the operation panel 120 may have the function of the clock manipulation unit 300 .
The respective embodiments described hereinbefore may be carried out singly or in combination as appropriate.
With the embodiments described hereinbefore, the clock controller, the memories, and so forth are disposed outside of the central processing unit, however, these components together with the central processing unit may be integrated so as to be incorporated in one chip.
As described in the foregoing, with the embodiments of the invention, it is possible to attain both enhancement in the processing speed and reduction in the power consumption.
The foregoing invention has been described in terms of preferred embodiments. However, those skilled, in the art will recognize that many variations of such embodiments exist. Such variations are intended to be within the scope of the present invention and the appended claims.
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There is provided a cellular phone taking into consideration enhancement in processing speed and reduction in current consumption, and the cellular phone comprises a processing unit capable of executing plural kinds of processing, an oscillator for generating a clock signal to be fed to the processing unit, and a clock controller for converting the frequency of the clock signal received from the oscillator, wherein the clock controller changes the frequency of the clock signal for each of the plural kinds of the processing in response to the control by the central processing unit.
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CLAIM OF PRIORITY
[0001] This application claims priority to U.S. Provisional Patent Application No. 61/716,203, filed Oct. 19, 2012, the contents of which are hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] The present technology relates to work stations for use in applying pulling heads to the ends of wires that have been wound onto a single reel for installation into a conduit.
DESCRIPTION OF RELATED ART
[0003] Pulling heads have been developed that allow multiple cables, sometimes referred to as wires or conductors, to be simultaneously pulled through a conduit. Such pulling heads include a plurality of lugs attached to lanyards of varying lengths, and the lanyards all attach to a single pulling head. A pulling rope running through the conduit is attached to a pulling head, which is in turn attached to each cable by separate pulling lugs, and the rope is pulled through the conduit, drawing the multiple conductor cabling from spools or other delivery mechanism and through the conduit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] Specific examples have been chosen for purposes of illustration and description, and are shown in the accompanying drawings, forming a part of the specification. The drawings are not drawn to scale. Accordingly, the dimensions or proportions of particular elements, or the relationships between those different elements, as shown in the drawings are chosen only for convenience of description, but do not limit possible implementations of this disclosure. Like numerals represent like elements throughout the several figures.
[0005] FIG. 1 is a top plan view of an embodiment a pulling head work station of the present technology.
[0006] FIG. 2 is a side elevational view of a stripper that can be used with a pulling head work station of FIG. 1 .
[0007] FIG. 3 is a perspective view of a crimping head that can be used with a pulling head work station of FIG. 1 .
[0008] FIG. 4 is a perspective view of a plurality of cables placed into cable receiving jigs of the pulling head work station of FIG. 1 .
[0009] FIG. 5 is an end elevational view of a cable receiving jig of the pulling head work station of FIG. 1 .
[0010] FIG. 6 is a top plan view of a portion of a cable receiving jig of the pulling head work station of FIG. 1 .
[0011] FIG. 7 is an end elevational view of cable receiving jigs of the pulling head work station of FIG. 1 , in an open position and in a clamped position.
[0012] FIG. 8 is a top plan view of a single cable being fed to the pulling head work station of FIG. 1 .
[0013] FIGS. 9A-9C are top plan views illustrating one of the cables of FIG. 8 being fed into a cable receiving jig of the pulling head work station of FIG. 1 .
[0014] FIG. 10 is a top plan view of the pulling head work station of FIG. 1 , with the chop saw in a first position.
[0015] FIG. 11 is a top plan view of the pulling head work station of FIG. 1 , with the chop saw in a second position.
[0016] FIG. 12 is a top plan view of the pulling head work station of FIG. 1 , with the chop saw in a third position.
[0017] FIG. 13 is a top plan view of the pulling head work station of FIG. 1 , with the chop saw in a fourth position.
[0018] FIG. 14 is a top plan view of an embodiment of a chop saw that can be used with the pulling head work station of FIG. 1 illustrating alternative positions.
[0019] FIG. 15 is a top plan view of the chop saw of FIG. 14 illustrating movement between the alternative positions of FIG. 14 .
[0020] FIG. 16 is a top plan view of the pulling head work station of FIG. 1 , with the chop saw in a rest position.
[0021] FIG. 17 is a top plan view of the pulling head work station of FIG. 1 , with the stripper of FIG. 2 in use.
[0022] FIGS. 18A-18C are side elevational views of a pulling lug that can be used with the present technology being placed onto the stripped end portion of a cable.
[0023] FIGS. 19A-19C are side elevational views of the stripper of FIG. 2 being used to strip an end portion of a cable.
[0024] FIG. 20 is a perspective view of the crimper of FIG. 3 being positioned with respect to a pulling lug on a cable.
[0025] FIG. 21 is a perspective view the crimper of FIG. 20 in place with respect to the pulling lug on a cable.
[0026] FIG. 22 is a perspective view of the crimper of FIGS. 20 and 21 crimping the pulling lug onto the cable.
[0027] FIG. 23 is a perspective view of the crimper of FIGS. 20-22 being removed from the cable.
[0028] FIG. 24 is a top plan view of the pulling head work station of FIG. 1 with the chop saw in a retracted position and the crimper in use.
[0029] FIG. 25 is a perspective view of a pulling lug crimped onto a cable after use of the present technology.
[0030] FIG. 26 is a perspective view of a reel with cables having pulling lugs attached thereto after use of after use of the present technology.
DETAILED DESCRIPTION
[0031] FIG. 1 illustrates an embodiment of a pulling head work station 100 of the present invention. The pulling head work station 100 includes a base 102 having a work surface 104 . The work surface 104 is preferably horizontal and level. The additional components of the pulling head work station 100 are mounted on the base 102 of the pulling head work station 100 . The pulling head work station 100 can include a plurality of cable receiving jigs 106 a - 106 d mounted to the work surface 104 of the base 102 . Each cable receiving jig can have a first end 108 and a second end 110 . A first cable clamp 112 a - 112 d can be mounted at the first end 108 of each cable receiving jig 106 a - 106 d, and a second cable clamp 114 a - 114 d can be mounted at the second end 110 of each cable receiving jig 106 a - 106 d.
[0032] As illustrated in FIG. 1 , the length of cable receiving jig 106 a is less than the length of cable receiving jig 106 b . The length of cable receiving jig 106 b is less than the length of cable receiving jig 106 c. the length of cable receiving jig 106 c is less than cable receiving jig 106 d. As a result, while jig first ends 108 are in horizontal alignment, the jig second ends 110 are staggered (i.e. not in horizontal alignment with one another). As explained below, this permits the cables to be automatically and conveniently cut in a staggered fashion after they are clamped in the jigs 106 a - 106 d.
[0033] It should be noted that while four jigs are illustrated in the figures and described below, the work station could feature an alternative number of jigs and associated components.
[0034] In methods of the present technology, a reel 200 including at least one cable 202 a can be provided, and the pulling head work station 100 can be used to attach a pulling lug 300 a - 300 c to each cable 202 a - 202 d. To that end, the pulling head work station 100 can include a number of tools that can be used to cut cables 202 a - 202 d , strip the end portions 204 of the cables 202 a - 202 d, and secure pulling lugs 300 a - 300 c to the stripped end portions 204 of the cables 202 a - 202 d. For example, the pulling head work station 100 can include a chop saw 116 slidably mounted to the base 102 via track 103 , a stripper 118 removably mounted to the base 102 , and a crimping head 120 slidably mounted to the base, also by track 103 . The track 103 is mounted to the work surface 104 of the base 102 .
[0035] The pulling head work station 100 can also include a power supply system 500 that supplies power to at least one of the chop saw 116 (via line 504 ), the stripper 118 and/or the crimping head 120 (via line 502 ). In one example, the power supply system 500 can include a self contained power source, such as a battery, that provides power to the work station tools. In another example, power supply system 500 can include a power cord that can connect to an electrical outlet to transfer power to the power supply system 500 . In a third example, a power supply system 500 could include both a self-contained power source and at least one power cord, to ensure that power can be provided to the power supply system 500 under various circumstances.
[0036] FIG. 2 illustrates one example of a stripper 118 that can be used with a pulling head work station 100 . The stripper 118 can be a portable device, and can be removably mounted to the base 102 of the pulling head work station 100 . The stripper can be a cordless device, which can be electrically connected to the power supply system 500 to be recharged when it is mounted to the base 102 of the pulling head work station 100 . Alternatively, the stripper 118 can include a power cord that is connected to the power supply system 500 .
[0037] FIG. 3 illustrates one example of a crimping head 120 that can be used with a pulling head work station 100 . The crimping head 120 can be slidably mounted to the base 102 of the work station 100 via track 103 and a carriage. As will be explained in greater detail below, in the illustrated embodiment, the crimping head 120 is slidable in two directions with respect to the work surface 104 , such as lengthwise and across within the plane defined by the X and Y arrows of FIG. 1 . The crimping head 120 is also illustrated as being mounted to the base 102 of the work station in parallel with the chop saw 116 .
[0038] FIGS. 4-7 illustrate a plurality of cables 202 a - 202 d placed into cable receiving jigs 106 a - 106 d of the pulling head work station 100 and clamped with first clamps 112 a - 112 d ( FIG. 1 ) and second clamps 114 a - 114 d. As illustrated, the cable receiving jigs 106 a - 106 d can be mounted parallel to each other with the ends 110 featuring a staggered configuration due to the differing lengths of jigs 106 a - 106 d . Additionally, as shown in FIGS. 5 and 7 , each cable receiving jig 106 can have a V-shaped cross section.
[0039] FIG. 7 illustrates second clamps 114 a and 114 b in a clamped position and in an open position, respectively. Each of the first clamps 112 a - 112 d and second clamps 114 a - 114 d has an open position and a clamped position, and can function in the same manner illustrated in FIG. 7 .
[0040] A method of using a pulling head work station 100 of the present technology can include placing a portion of each cable 202 a - 202 d onto a corresponding cable receiving jig 106 a - 106 d mounted to the work surface 104 of to pulling head work station 100 . As discussed above, each cable receiving jig 106 a - 106 d can have a first end 108 and a second end 110 . The method can also include clamping the placed portion of each cable 202 with a first cable clamp 112 mounted at the first end 108 of each cable receiving jig 106 and a second cable clamp 114 mounted at the second end 114 of each cable receiving jig 106 .
[0041] After the cables 202 a - 202 d are clamped into their corresponding jigs 106 a - 106 d, the method can include cutting each cable 202 a - 202 d to a desired length using a chop saw 116 slidably mounted to the pulling head work station 100 to produce a cut cable.
[0042] The method can then include removing at least one cable layer, such as the cable jacket and/or insulation, from an end portion 204 of each cut cable with a stripper 118 removably mounted to the pulling head work station 100 .
[0043] Once the end portion 204 of the cable is stripped, a pulling lug 300 can be placed onto each stripped end portion 204 . The method can then include crimping a pulling lug 300 onto each end portion 204 using a crimping head 120 slidably mounted to the base 102 . Once the pulling lugs have been secured to the cables 202 by crimping, the method can include unclamping each cable 202 from each cable receiving jig 106 .
[0044] FIGS. 8 and 9 illustrate placing a portion of each cable from roll 200 into a cable receiving jig 106 a - 106 d, and clamping the placed portion of each cable with a first cable clamp 112 mounted at the first end 108 of each cable receiving jig 106 a - 106 d and a second cable clamp 114 mounted at the second end 110 of each cable receiving jig. Specifically, as shown in FIGS. 9A-9C , a cable 202 a can be fed into a cable receiving jig 106 a of a pulling head work station 100 , in the direction of the arrows 203 and 205 of FIG. 9B as illustrated, and then clamped by clamping each of the first clamp 112 a and second clamp 114 a.
[0045] FIGS. 10-16 illustrate one example of use of the chop saw 116 to cut, in serial, each cable 202 a - 202 d to a desired length. As illustrated in FIG. 10 , the chop saw 116 can be positioned with respect to a first cable 202 a via a track 103 and a carriage 105 to cut the cable. The carriage 105 of FIG. 10 slides along the track 103 in the direction of arrows 207 . Furthermore, the chop saw 116 is mounted at one end of slide bar 107 . Slide bar 107 slides with respect to the carriage 105 in the directions indicated by arrows 209 of FIG. 10 .
[0046] As a result, as illustrated in FIGS. 11-15 , the chop saw 116 can be repositioned with respect to a second cable 202 b, a third cable 202 c, and a fourth cable 202 d by sliding it incrementally in a lengthwise and a crosswise direction with respect to the work surface 104 of the pulling head work station 100 via track 103 , carriage 105 and slide bar 107 . As noted previously, the cables are automatically and conveniently cut to the desired lengths in a staggered fashion due to the staggered configuration of the ends 110 of the jigs 106 a - 106 d.
[0047] As illustrated in FIG. 16 , once each cable 202 a - 202 d has been cut to a desired length, the chop saw 116 can be returned to a rest position.
[0048] FIGS. 17-19 illustrate removing at least one cable layer from cable 202 d , such as the cable jacket and/or insulation, from an end portion 204 d of cut cable 202 d with a stripper 118 , and placing a pulling lug 300 d onto the stripped end 204 d of cable 202 d. A similar procedure is followed for cables 202 a - 202 c (of FIG. 17 ).
[0049] FIGS. 20-25 illustrate crimping a pulling lug 300 d onto the end portion of cut and stripped cable 202 d using the crimping head 120 . As illustrated in FIG. 24 , the crimping head 120 can be positioned with respect to cable 202 d via a track 103 and a carriage 111 to cut the cable. The carriage 111 of FIG. 24 slides along the track 103 in the direction of arrows 215 . Furthermore, the crimping head 120 is mounted at one end of slide bar 113 . The slide bar 113 slides with respect to the carriage 111 in the directions indicated by arrows 217 of FIG. 24 .
[0050] As a result, as shown in FIGS. 20-21 , the crimping head 120 can be slidably positioned, in the direction of arrow 211 in FIG. 20 , over a pulling lug 300 d that has been placed over the stripped end portion of cable 202 d. As shown in FIG. 22 , the crimping head then is activated to crimp the pulling lug 300 d onto the stripped end portion of cable 202 d, preferably in two locations, such as first crimping location 304 and second crimping location 305 illustrated in FIG. 25 . As shown in FIG. 23 , the crimping head can be slidably removed in the direction of the arrow 219 after the crimping process. A similar procedure is followed for cables 202 a - 202 c and pulling lugs 300 a - 300 c (of FIGS. 24 and 26 ).
[0051] FIG. 26 illustrates a reel 200 having a plurality of cables 202 a - 202 d after the pulling lugs 300 a - 300 d have been attached in accordance with the above.
[0052] While the preferred embodiments of the invention have been shown and described, it will be apparent to those skilled in the art that changes and modifications may be made therein without departing from the spirit of the invention, the scope of which is defined by the appended claims.
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A pulling head work station for attaching the lugs of pulling heads to cables, so that the cables may be pulled simultaneously through a conduit. The pulling head work station includes staggered cable receiving jigs, each jig having two clamps to hold a corresponding cable in place during attachment of a pulling lug. A chop saw to cut the cables and a crimper to secure a pulling lug to each stripped end portion of a cable may be slidably mounted to a work surface of the work station. A wire stripper may be removably attached to the work station.
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BACKGROUND OF THE RELATED ART
[0001] Since the introduction of the first personal computer (“PC”), technological advances to make PCs more useful have continued at an amazing rate. Microprocessors that control PCs have become faster and faster, with operational speeds eclipsing the gigahertz (one billion operations per second) and continuing well beyond.
[0002] Productivity has also increased tremendously because of the explosion in development of software applications. In the early days of the PC, people who could write their own programs were practically the only ones who could make productive use of their computers. Today, there are thousands of software applications ranging from games to word processors and from voice recognition to web browsers.
[0003] Not surprisingly, the increasing complexity of computers and software applications has presented technologists with some challenging obstacles along the way. One such obstacle is the continual increase in the amount of computing power needed to run increasingly large and complex software applications. Increased computing power is also needed to enable networked computer systems to provide services such as file and printer sharing to larger numbers of users in a cost effective manner.
[0004] One way to increase computing power has been to design computer systems that are capable of processing data faster. Computers may use clock signals to synchronize the processing of data. Bits of data in the form of electrical signals that represent “0s” and “1s” (logical lows and highs) may be clocked into integrated circuit devices, which may process the 0s and 1s to do useful work. Data signals may be passed through a data buffer circuit before being latched and stored in a device known as a register, which may also be known as a latch or flip-flop. A clock signal, which may be an electrical signal in the form of a square wave, may be used to latch data bits into the register. Registers are incorporated into an integrated circuit device to receive data bits and hold them for further processing by the internal workings of the integrated circuit device. The registers may be designed to receive a new data bit with each rising edge (or falling edge) of the clock signal. A rising edge of the clock occurs when the clock signal transitions from a relatively low level to a relatively high level. A falling clock edge occurs when the clock signal transitions from a relatively high level to a relatively low level.
[0005] If the speed of the clock is increased, data is processed at a faster rate, with a corresponding increase in computing power. For example, if data bits are being clocked into data buffers for further processing on each rising edge of a system clock, twice as much data may be clocked into the registers if the clock rate is doubled. A potential problem may arise, however, because, as clock speed increases, there is less time during each clock cycle to perform work.
[0006] One problem faced by designers of input buffer circuits as clock speeds increase is insufficient data setup time. Setup time refers to the length of time that a data signal should be stable to guarantee that it will be clocked into an input register by the relevant edge of a clock signal. Setup time is potentially a problem because electrical data signals transition rapidly and may take time to settle after a transition (for example a transition from a logical “0” to a logical “1” and vice versa). As clock speeds get faster, the time in which data signals have to stabilize or settle gets shorter. If a data signal is not stable when the relevant clock edge latches the signal into a register, the signal may be incorrectly interpreted. For example, a logical “0” may be mistakenly latched into the register as a logical “1” or vice versa. If data is incorrectly latched into a register, the performance of the computer system is degraded.
[0007] Another factor that may affect the clocking of data into a register is the synchronization of the clock signal across multiple data inputs. In many integrated circuit devices, multiple data bits may be clocked in parallel into their respective registers by a single clock signal. Many factors may introduce small variations into the synchronization of the clock signal with respect to when each of the multiple data bits is latched into its register. One factor may be a difference in length that the clock signal has to travel to actuate the registers of different data inputs. Another factor may be that the registers that receive the data have differing voltages at which they are actuated by the clock signal. These differences may result from variations in integrated circuit processing or temperature, among others. A system that may reduce the effects of these variations may be desirable.
SUMMARY
[0008] The disclosed embodiments relate to buffer circuits and methods. One embodiment is a buffer circuit that receives a data signal, a first clock signal and a second clock signal, the buffer circuit comprising circuitry to latch the data signal with the first clock signal to produce a first latched signal, circuitry to latch the data signal with the second clock signal to produce a second latched signal, and circuitry that selects the first latched signal or the second latched signal depending on a transition of the data signal in a previous clock cycle.
[0009] Another embodiment is a computer system having at least one integrated circuit that includes a buffer circuit. The buffer circuit receives a data signal, a first clock signal and a second clock signal. The buffer circuit comprises circuitry to latch the data signal with the first clock signal to produce a first latched signal, circuitry to latch the data signal with the second clock signal to produce a second latched signal, and circuitry that selects the first latched signal or the second latched signal depending on a transition of the data signal in a previous clock cycle.
[0010] Yet another embodiment is a method of operating a buffer circuit that receives a data signal, a first clock signal and a second clock signal. The method comprises receiving a data signal, storing a first latched data signal using a first clock signal, storing a second latched data signal using a second clock signal, selecting the first latched signal or the second latched signal depending on a transition of the data signal in a previous clock cycle.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Advantages of the invention may become apparent upon reading the following detailed description and upon reference to the drawings in which:
[0012] [0012]FIG. 1 is a block diagram illustrating a computer system in which embodiments of the present invention may be employed;
[0013] [0013]FIG. 2 is a block diagram of an embodiment of a single-ended input buffer circuit in which the embodiments of the present invention may be employed;
[0014] [0014]FIG. 3 is a block diagram of an input buffer circuit according to embodiments of the present invention; and
[0015] [0015]FIG. 4 is a process flow diagram according to embodiments of the present invention.
DETAILED DESCRIPTION
[0016] [0016]FIG. 1 is a block diagram illustrating a computer system in which embodiments of the present invention may be employed. A computer system is generally indicated by the numeral 100 and may comprise a processor complex 102 (which may include a plurality of central processing units (“CPUs”)). The computer system 100 may also include core logic 104 (or north bridge), system random access memory (“RAM”) 106 , a video graphics controller(s) 110 , a video display(s) 112 , a PCI/SCSI bus adapter 114 , a PCI/EISA/ISA bridge 116 , and a PCI/ATA controller 118 . Single or multilevel cache memory (not illustrated) may also be included in the computer system 100 according to the current art of microprocessor computer systems. Integrated circuit components that make up the processor complex 102 , the core logic 104 , the RAM 106 , for example, may include a plurality of data buffers and registers that are adapted to receive data via a clock or strobe signal.
[0017] The processor complex 102 may be connected to the core logic 104 through a host bus 103 . The system RAM 106 is connected to the core logic 104 through a memory bus 105 . The video graphics controller(s) 110 is connected to the core logic 104 through an AGP bus 107 (or other bus for transporting video data). The PCI/SCSI bus adapter 114 , PCI/EISA/LPC bridge 116 , and PCI/ATA controller 1 18 is connected to the core logic 104 through a primary PCI bus 109 . Those of ordinary skill in the art will appreciate that a PCI-X bus or Infiniband bus is substituted for the primary PCI bus 109 .
[0018] Also connected to the PCI bus 109 may be a network interface card (“NIC”) 122 and a PCI/PCI bridge 124 . Some of the PCI devices such as the NIC 122 and PCI/PCI bridge 124 may plug into PCI connectors on the computer system 100 motherboard (not illustrated). The PCI/PCI bridge 124 may provide an additional PCI bus 117 .
[0019] Hard disk 130 and tape drive 132 may be connected to the PCI/SCSI bus adapter 114 through a SCSI bus 111 . The NIC 122 may be connected to a local area network 119 . The PCI/EISA/LPC bridge 116 may connect over an EISA or LPC bus 113 to a non-volatile random access memory (NVRAM) 142 , modem 120 , and input-output controller 126 . The NVRAM 142 may store the system BIOS and/or other programming and may include flash memory. Additionally, the NVRAM may be contained in a programmable logic array (“PAL”) or any other type of programmable non-volatile storage. The modem 120 may connect to a telephone line 121 . The input-output controller 126 may interface with a keyboard 146 , CD-ROM drive 144 , mouse 148 , floppy disk drive (“FDD”) 150 , serial/parallel ports 152 , and/or a real time clock (“RTC”) 154 .
[0020] Many of the devices shown in FIG. 1 may be implemented as integrated circuit devices that employ buffer circuits according to embodiments of the present invention. The operation of buffer circuits is explained with reference to FIG. 2.
[0021] [0021]FIG. 2 is a block diagram of an embodiment of a single-ended input buffer circuit in which embodiments of the present invention may be employed. The buffer circuit is generally identified by the reference numeral 200 . Single ended data signaling is typically used to minimize the number of wires and pins required for data transfer, with a concomitant reduction in the associated design cost.
[0022] The buffer circuit 200 comprises a single-ended data buffer 202 , which is adapted to receive a data signal D 0 , and a single-ended data buffer 206 , which is adapted to receive a data signal D 1 . The data signal D 0 that may be delivered to the input buffer 202 is illustrated as a waveform 204 , which is shown as transitioning from a logical low level to a logical high level. The data signal D 1 that may be delivered to the input buffer 206 is illustrated as a waveform 208 , which is shown as transitioning from a logical high level to a logical low level. To correctly operate, the data buffers 202 , 206 utilize data signals 204 , 208 which are stable for a setup time, shown as tSU, prior to being latched. The imposition of the setup time tSU helps to ensure that the data presented to the data buffers 202 , 206 is correctly received.
[0023] A single-ended clock buffer 210 is adapted to receive a clock signal 212 , which may be a square wave. The clock buffer 210 is adapted to deliver the clock signal 212 to a register 214 and a register 216 . Transparent latches may be used instead of the registers 214 , 216 depending on design considerations. The buffer circuit 200 may employ single-pumped, rising-clock-edge triggered signaling, double-pumped clock signaling designs, or any other appropriate clocking technology.
[0024] For illustrative purposes, the clock signal 212 is used to clock data into the registers 214 and 216 on a rising edge, as illustrated by the clock signal 212 . The rising edge of the clock signal 212 is synchronized to occur after the end of the setup time tSU. This synchronization may help to ensure the valid data is clocked into the registers 214 and 216 . Data that is presented to the D input of the registers 214 , 216 may be latched on the rising edge of the clock signal 212 and delivered to the Q output of the registers 214 , 216 where it is retrieved for further processing by the internal workings of an integrated circuit device.
[0025] The data buffers 202 , 206 may have a threshold voltage, which is the voltage level at which the buffer recognizes the transition from a logical low to a logical high and vice versa. Variation in the threshold voltage may negatively impact setup time for the data signals 204 , 208 . For example, if an input buffer has a higher-than-nominal threshold voltage, the buffer may tend to recognize a rising edge later (with respect to a buffer with a nominal threshold voltage). Similarly, the input buffer with the higher-than-nominal threshold voltage may also tend to recognize falling edges earlier as compared to an input buffer with a lower than nominal threshold voltage. Such variations in threshold voltages may open up timing ambiguity if a buffer recognizes such transitions in the data, and thus reduce setup timing margin. If the buffer has a single-ended clock buffer, the problem may be compounded by similar ambiguity in the timing of the clock or strobe. In such a case, embodiments of the present invention may be employed to advantage.
[0026] [0026]FIG. 3 is a block diagram of an input buffer circuit according to embodiments of the present invention. The buffer circuit, which is generally identified by the reference numeral 300 , provides relatively improved clock timing. The buffer circuit 300 comprises a single-ended data buffer 302 , which is adapted to receive a data signal D 0 , and a single-ended data buffer 306 , which is adapted to receive a data signal D 1 . The data signal D 0 delivered to the input buffer 302 is illustrated as a waveform 304 , which is shown as transitioning from a logical low level to a logical high level. The data signal D 1 to the input buffer 306 is illustrated as a waveform 308 , which is shown as transitioning from a logical high level to a logical low level. To operate correctly, the data buffers 302 , 306 employ data signals 304 , 308 which are stable for a setup time, shown as tSU, prior to being latched. The imposition of the setup time tSU helps to ensure that the data presented to the data buffers 302 , 306 is correctly received.
[0027] The input buffer 302 delivers the data signal D 0 as an input to a pair of registers 328 and 330 via a signal path 318 . The input buffer 306 delivers the data signal D 1 as an input to a pair of registers 332 and 334 via a signal path 320 . As set forth below, the buffer circuit 300 is designed to select the output of the register pair for each data signal that will provide the most synchronized timing. In other words, the buffer circuit 300 selects the output of the registers 328 or 330 for further processing depending on which of the registers 328 or 330 will provide the best timing for the data signal D 0 . The data value stored by the register 328 may be referred to as a first latched signal and the data value stored by the register 330 may be referred to as a second latched signal. Similarly, the buffer circuit 300 selects the output of the registers 332 or 334 for further processing depending on which of the registers 332 or 334 will provide the best timing for the data signal D 1 . The data value stored by the register 332 may be referred to as a first latched signal and the data value stored by the register 334 may be referred to as a second latched signal.
[0028] In the embodiment of FIG. 3, a single-ended clock buffer 310 is adapted to receive a clock high (CLK_H) signal 312 , which may be a square wave. For illustrative purposes, the clock high signal 312 is shown as transitioning from a low state to a high state. The clock buffer 310 may be adapted to deliver the clock high signal 312 to the register 328 and the register 332 via a signal path 322 . Transparent latches may be used instead of the registers 328 , 332 depending on design considerations. The buffer circuit 300 may employ single-pumped, rising-clock-edge triggered signaling, double-pumped clock signaling designs, or any other appropriate clocking technology.
[0029] A single-ended clock buffer 314 is adapted to receive a clock low (CLK_L) signal 316 , which may be a square wave. For illustrative purposes, the clock low signal 316 is shown as transitioning from a high state to a low state. The clock buffer 314 is adapted to deliver the clock low signal 316 to the register 330 and the register 334 via a signal path 324 . As illustrated in FIG. 3, the output of the clock buffer 314 is negated prior to being delivered as the clock signal to the registers 330 , 334 . Transparent latches may be used instead of the registers 330 , 334 depending on design considerations.
[0030] The output of the clock buffers 310 , 314 is delivered as inputs to a logic component 326 , which may be an OR gate. The clock low signal is negated before being delivered as the input to the logic component 326 . The output of the logic component 326 is used as a clock signal for a register 340 and a register 342 via a signal path 327 . The data input to the register 340 is provided as the output of a multiplexor 336 , and the data outputs of the registers 328 , 330 are provided as inputs to the multiplexor 336 . The output of the register 340 is used to select which of the inputs of the multiplexor 336 is delivered as the input of the register 340 and also provided as the data to the internal workings of an integrated circuit component via a data path 344 . The output of the register 342 is used to select which of the inputs of the multiplexor 338 is delivered as the input of the register 342 and also provided as the data to the internal workings of an integrated circuit component via a data path 346 .
[0031] The buffer circuit 300 exploits the fact that multiple receiving buffers implemented on the same IC wafer tend to have well-matched voltage activation thresholds. This may be true because buffers on the same integrated circuit device may share a common process, voltage, and temperature characteristics.
[0032] In a system that employs single-ended clocking and enforces a setup time prior to an active edge transition of the clock or strobe, there may be two different scenarios. Either (1) the data transition and clock/strobe transition are both in the same direction (i.e. both rising or both falling), or (2) the data transition and clock/strobe transition are in opposite directions (i.e. one transition is rising and the other transition is falling). In case 1, uncertainty in the voltage thresholds of the data buffers tends to cancel each other out. For example, if the threshold voltage levels are lower than nominal and both signals are rising, then both the clock/strobe and data may tend to be recognized early, but their relative timing is not altered.
[0033] The “canceling out” effect described with respect to case 1 may be effective if the edge rates of the data signals and clock/strobe signals are well matched to each other. Thus, the buffer circuit 300 may be well suited for use in connection with data busses on which the device sourcing the data also sources the clock or strobe. Performance may also be improved in cases in which the data signaling circuitry and clock circuitry has similar pad designs, topology, termination schemes, and board routing constraints.
[0034] In case 2, uncertainty in the voltage thresholds of the data buffers tends to cause one signal transition to be recognized relatively early with respect to the other transition. For example, if the voltage threshold levels are lower than nominal with the data transition falling and the clock/strobe transition is rising, the data transition may be recognized late, while the clock/strobe transition may be recognized relatively early. This combination may reduce the amount of setup time at the input to an input buffer, potentially causing a timing violation and/or data corruption.
[0035] The buffer circuit may reduce or eliminate the timing error that results from case 2 by helping to ensure that, if a given data bit transitions during any particular clock cycle, the data buffer that subsequently samples that data bit is clocked from a single-ended clock/strobe signal that is switching in the same direction as the transition in the data bit. In cases where a data bit does not transition in a given clock cycle, the polarity of the clock/strobe signal that samples it is immaterial.
[0036] In the buffer circuit 300 , the data signals D 0 ( 304 ) and D 1 ( 308 ) may be received, respectively, by the input buffers 302 and 308 . The data signals are then each clocked into two different registers, one of which is controlled by the clock high signal 312 and the other of which is controlled by the clock low signal 316 . As shown in FIG. 3, the data signal D 0 ( 304 ) is clocked into the register 328 by the clock high signal 312 via the signal path 322 . The data signal D 0 ( 304 ) is also clocked into the register 330 by the clock low signal 316 via the signal path 324 . Similarly, the data signal D 1 ( 308 ) is clocked into the register 332 by the clock high signal 312 via the signal path 322 . The data signal D 1 ( 308 ) is also clocked into the register 334 by the clock low signal 316 via the signal path 324 . Thus, each of the data signals D 0 and D 1 is clocked into a first register by a rising edge clock transition (clock high signal 312 ) and into a second register by a falling edge clock transition (clock low signal 316 ).
[0037] If the logical value of a data signal (e.g. the data signals D 0 or D 1 ) does not transition between two successive active clock edges (i.e., the value of the data signal stays at the same logical level for two clock active edge transitions instead of either transitioning from a logical low to a logical high or vice versa), then it may be immaterial for timing purposes whether the data is sampled by the clock signal with a falling edge transition (clock low signal 316 ) or a rising edge transition (clock high signal 312 ). This is true because the data signal being sampled has virtually an entire clock cycle of setup time since it does not transition in the interim. In such a case, the setup time tSU is easily met.
[0038] If the logical value of one of the data signals does transition (e.g. from a logical low to a logical high or vice versa) in a given clock cycle, the data may be sampled by two registers close to simultaneously. One register may sample the data based on the rising clock high signal 312 , and the other register may sample the data based on the falling clock low signal 316 . Whichever of the clock signals switches the same direction as the data (i.e. high to low or low-to-high) is deemed to be more reliable. The data sampled by the other clock signal may be untrustworthy and possibly metastable. The buffer circuit 300 helps to ensure that the data sample that is actually sampled by the associated integrated circuit is the data that is sampled by the clock signal that transitions in the same direction as the data in cases where the data has transitioned since the previous active clock edge.
[0039] The multiplexor 336 receives both data samples of the data signal D 0 304 via the registers 328 and 330 . The register 328 delivers the sample that is obtained on the rising edge of the clock high signal 312 and the register 330 delivers the sample that is obtained on the falling edge of the clock low signal 316 . Similarly, the multiplexor 338 receives both data samples of the data signal D 1 308 via the registers 332 and 334 . The register 332 delivers the sample that is obtained on the rising edge of the clock high signal 312 and the register 334 delivers the sample that is obtained on the falling edge of the clock low signal 316 .
[0040] The register 340 controls which data sample is selected from the multiplexor 336 and the register 342 controls which data sample is selected from the multiplexor 338 . The buffer circuit 300 is designed in such a way that the registers 340 and 342 select the multiplexor input that corresponds to the data that is sampled by the clock signal that transitions in the same direction as the corresponding data signal. To accomplish this, the register 340 and the register 342 store the data from the corresponding clock cycle for comparison. Specifically, the register 340 stores the data symbol or value that the data signal D 0 represented at the previous active clock transition and the register 342 stores the data symbol or value that the data signal D 1 represented at the previous active clock transition. Moreover, the registers 340 and 342 comprise circuitry that stores a value corresponding to the respective data signals in a previous clock cycle. Those stored values are then used to select between the first latched signal and the second latched signal for each data input.
[0041] The Q output of the register 340 , which may correspond to the data symbol or value from the previous active clock transition, selects the input of the multiplexor 336 that corresponds to the data sample clocked by the rising clock edge of the clock high signal 312 if the data symbol or value of the data signal Do 304 transitioned from a logical low level to a logical high level. The Q output of the register 340 selects the input of the multiplexor 336 that corresponds to the data sample clocked by the falling clock edge of the clock low signal 316 if the data symbol or value of the data signal D 0 304 transitioned from a logical high level to a logical low level. If the data symbol or value of the data signal D 0 304 does not transition between active clock edges, the multiplexor output selected by the register 340 is irrelevant for timing purposes. The output of the multiplexor 336 may be delivered to the internal workings of an integrated circuit device for further processing via a signal path 344 .
[0042] The Q output of the register 342 , which may correspond to the data symbol or value from the previous active clock transition, selects the input of the multiplexor 338 that corresponds to the data sample clocked by the rising clock edge of the clock high signal 312 if the data symbol or value of the data signal D 1 308 transitioned from a logical low level to a logical high level. The output of the register 342 selects the input of the multiplexor 338 that corresponds to the data sample clocked by the falling clock edge of the clock low signal 316 if the data symbol or value of the data signal D 1 308 transitioned from a logical high level to a logical low level. If the data symbol or value of the data signal D 1 308 does not transition between active clock edges, the multiplexor output selected by the register 342 is irrelevant for timing purposes. The output of the multiplexor 338 may be delivered to the internal workings of an integrated circuit device for further processing via a signal path 346 .
[0043] The logic component 326 may help to ensure correct operation of the buffer circuit 300 . A possible design consideration is meeting a hold time at the input of the register 340 and the register 342 . Skew between the rising clock high signal 312 and the falling clock low signal 316 could potentially cause hold time violations at the input of the register 340 or the register 342 , if those registers were clocked by the clock high signal 312 or the clock low signal 316 . The logic component 326 , which receives both the clock high signal 312 and the negation of the clock low signal 316 , helps to ensure that the registers 340 and 342 recognize only the earlier of the two clock signals.
[0044] Ideally, the drivers and terminators driving a bus are symmetrical, with rising and falling edges having the same clock-to-output delay and slew rate. In practice there are several factors that may tend to make rising and falling edges have unequal timings and edge rates. Some of those factors may include:
[0045] 1. Difficulty sizing positive field effect transistors (“PFETs”) and negative field effect transistors (“NFETs”)for identical drive characteristics.
[0046] 2. Asymmetries in termination (e.g., in busses requiring pull-ups).
[0047] 3. Asymmetries in ground/power pin counts in driving chip.
[0048] 4. Asymmetrical ground bounce because more lines switch one way than the other in any given clock cycle.
[0049] Each of these factors may tend to give rising and falling edges unequal delays and edge rates. Each of these factors may also tend to effect multiple simultaneously same-direction switching signals identically. By sampling rising data lines with rising clock/strobes, and falling data lines with falling clock/strobes, the buffer circuit 300 may also reduce the setup time margin degradation associated with each of these effects.
[0050] [0050]FIG. 4 is a process flow diagram according to embodiments of the present techniques. The process is generally referred to by the reference numeral 400 . At block 402 , the process begins. At block 404 , a data signal is received by an input buffer circuit such as the buffer circuit 300 (FIG. 3).
[0051] The data signal is clocked by two separate clock signals as set forth at block 406 . The first and second clock signals may transition in opposite directions, as do the clock high signal 312 and the clock low signal 316 (FIG. 3). If the data signal transitioned in the same direction as the first clock signal (block 410 ), then the data is latched by the first clock signal, as shown at block 416 . If the data signal transitioned in the same direction as the second clock signal (block 412 ), then the data is latched by the second clock signal, as shown at block 414 . If the data signal does not transition (i.e. the data remains at the same value for successive clock cycles), the data signal may be latched by either the first or second clock signal without significantly impacting timing synchronization (block 408 ). At block 418 , the process ends.
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The disclosed embodiments relate to buffer circuits and methods. One embodiment is a buffer circuit that receives a data signal, a first clock signal and a second clock signal, the buffer circuit comprising circuitry to latch the data signal with the first clock signal to produce a first latched signal, circuitry to latch the data signal with the second clock signal to produce a second latched signal, and circuitry that selects the first latched signal or the second latched signal depending on a transition of the data signal in a previous clock cycle.
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RELATED APPLICATIONS
This application is related to Disclosure Document Number 416964, filed Mar. 19, 1997.
FIELD OF THE INVENTION
The invention finds applicability in the field of molding and casting.
Terms Used Herein:
DIE CASTING MACHINE is a machine that injects molten metal into a die (mold) to form a casting, or castings.
ROBOT is a programmable, automated device that is adapted to unload die casting machines and set the casting assemblage (Gate) down in an organized, predictable fashion.
GATE is the casting assemblage, consisting of the casting or castings, with the runners and the sprue, all tied together.
DEGATING is a process for removing the waste portion or gate remnant from the casting.
DEGATE-AND-TRIM MACHINE is a machine that utilizes a complex punch and die set to separate the good casting or castings from the gate, and then trim away the flash and/or overflow.
CASTING is the desired product resulting after degating.
GATE REMNANT is the portion of the gate that is separated from the castings by the degating and trim process.
BACKGROUND OF THE INVENTION
Modern die casting plants employ a number of die casting machines with a degate-and-trim machine alongside each casting machine. The die casting machines, in the larger sizes, are usually attended by a robot, and can thus run unmanned. The degate-and-trim machines are rarely automated as to loading and unloading, and thus require labor to operate.
In rare, high volume instances where degate-and-trim machines have been automated, the buildup of scrap (broken-off pieces of the gate, flash and overflows) inevitably hinders the proper working of the machine. This is the main reason that most degate-and-trim machines were never automated.
Objects of the Invention
A main object of this invention is to produce a machine which will automatically and efficiently separate the casting from waste material.
A significant object of this invention is to produce a machine for separating castings from scrap requiring a minimum amount of manpower.
Another object of this invention is to produce an efficient means for determining imperfections in different sets of castings.
A still further object is to produce a machine which will efficiently return scrap separated from the casting for recycling.
These and other objects of the present invention will become apparent from a reading of the following specification taken in conjunction with the enclosed drawings.
Problem Solved By This Invention
This invention completely solves the problem of scrap buildup, and permits easy interface with the robot that unloads the die casting machine. This permits seamless, unmanned operation between the two machines, namely, the mold and the degate and trim machine. Additionally, this invention provides a means for progressively removing parts from the gate while the die casting machine is making its next shot, thus the degate-and-trim machine does not have to be as big or expensive as that of the prior art.
BRIEF SUMMARY OF THE INVENTION
The invention covers a general purpose machine which will run unmanned to automatically remove die castings from their gates, trim the castings and send the trimmed castings to a parts container or bin. The scrap remnants and trim are automatically removed for remelting and use to manufacture additional castings.
The automated degate-and-trim machine works in the following manner. First, the robot grabs the gate while the gate is still hot and in the casting machine. A typical gate, and the robot's grippers might grab the casting around the sprue. The robot then brings the gate to the automated degate-and-trim machine (A.D. & T.M.) and sets the castings onto lower male fixtures positioned on the degating plate or platform. The A.D. & T.M.'s press then actuates, trimming and separating the castings from the gate. The press then opens, lifting the castings with a female die, and an unloading plate or parts catcher slides in from below to receive the castings released onto it. The unloading plate containing the castings slides and ejects the casting into parts chutes, from whence they slide into the parts bins. After this process the robot picks up a gate again and moves the gate ahead so that the second castings set is degated and trimmed. The process can be repeated until all castings are removed and trimmed. After the castings have been degated and trimmed, the gate plate slides back and tips up, dumping all scrap, i.e., the gate remnant, flash and overflows, into the scrap conveyor, thus leaving the machine clean and clear for the next shot.
In its broadest aspect, the herein disclosed invention involves an automatic degate and trim machine comprising a means for receiving and positioning a gate, for example a male fixture. Said gate comprising a casting and gate remnant. With the gate positioned in registry with a female die having ejecting means disposed therein, said female die along with a ram descend with force onto the gate to yieldably engage the casting, as well as, separate the gate remnant from the casting while leaving the gate remnant on a gate plate. Once the gate remnant is separated from the casting, the ram and the female die yieldably engaging the casting are raised to allow a parts catcher to come into position under the female die. With the parts catcher in position said ejecting means is actuated causing the casting to be ejected from the female die onto said parts catcher which delivers the casting into a parts bin for receiving said casting. With the casting out of the way of said gate remnant, a gate plate containing said gate remnant is tilted causing the gate remnant to fall into a scrap bin. The automatic degate and trim machine can have the casting deposited onto a chute prior to delivery to said parts bin and the gate remnant can be deposited onto a chute or conveyor prior to deposit into said scrap bin. Once the cycle is complete the machine can repeat the cycle.
Viewed another way, the invention encompasses an automatic degate and trim machine having as its main components:
a ram,
a female die with ejecting means disposed therein,
a male die or fixture for receiving a gate comprising a casting,
a gate plate and
a parts catcher,
wherein said gate plate has disposed thereon said with male fixture for receiving a gate, said ram and female die with ejecting means positioned in a raised position over the male fixture being powered and operating reciprocally such that the ram and female die can be lowered with force to cut and separate the casting from said gate leaving a gate remnant and with the female die yieldably retaining said casting within the female portion of the die. With the female die raised the female die can release the casting into a parts catcher and then into a parts bin,
the gate plate having received the gate remnant delivers the gate remnant to a scrap bin for recycling. Once the cycle is complete the machine can repeat the cycle.
In its broadest aspect, this invention involves an automated method for removing and separating castings from a gate containing the same comprising placing a gate onto a gate plate wherein a ram and a female die with ejecting means disposed therein descends with force onto the casting of said gate to yieldable engage the castings to separate and trim away gate remnant form the casting, leaving the gate remnant on said gate plate, with the gate remnant separated from the castings, the castings are separated and deposited into individual groups for deposit into separate bins and the gate remnant is removed from the gate plate for placement into scrap. This method allows for ready determination of imperfections in the different castings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a pictorial view of the automated degate and trim machine displaying a greatly enlarged gate (casting assemblage).
FIG. 2 is a plan view showing the gate received on the gate plate. The gate plate is supported on a gate plate support or lower platen shown in dashed lines.
FIG. 3 is an exploded view showing the components making up the gate plate and male projections, gate plate support and their relationship to the gate, female dies and punch.
FIGS. 4-8 is a series of views showing the casting being severed and received into the female die and at a proper time released therefrom. The end of the female die and the end of the casting have been removed to show the inner mechanism of the female die and how the casting sits on the male fixture.
FIG. 9 is a view of the female dies having released the castings into the parts catcher.
FIG. 10 is a view showing the parts shunted onto a parts chute.
FIG. 11 is a schematic view of the castings being released from the dies and then shunted onto a parts chute.
FIG. 12 is a view of a finished casting.
FIG. 13 is a view of the casting received on the gate plate, with the chain in a relaxed position.
FIG. 14 is a view of the gate plate translating and depositing the gate remnant into a scrap bin after the casting has been separated. The chain is in a taut position.
FIG. 15 is a front view schematic representation of an automatic degate and trim machine disposing of gate remnant and shunting the finished castings into a chute and then to the parts bin.
FIGS. 16-20 are a series of views describing the procedural steps by which the machine operates.
DESCRIPTION
With reference to FIG. 1 the automated degate and trim machine 10 for receiving a gate 12 onto a degate plate 14 (arrow) has disposed thereon a set of male fixtures or lower dies 16 for positioning the gate 12 . Above the male fixtures is a set of female dies 18 . The female dies 18 function in cooperation with a parts catcher 20 and a chute 22 (explained below). The degate plate 14 functions with a chain 26 to drop gate remnant 34 into a chute or recycling bin 28 (explained below). The gate 12 is composed of castings 28 , a sprue or biscuit 30 and runners 32 . The sprue 30 is the opening through which molten metal is poured into the mold. As used herein the sprue is a waste piece of metal which the robot (not shown) can grasp and hold onto. The runners 32 are composed of metal which was poured into the mold.
Referring to FIGS. 1 and 2 in operation a robot (not shown) brings the gate 12 and places the castings 28 within the gate 12 onto lower die or male positioning means 16 which are attached to a lower platen, explained below. Once the gate castings 28 are positioned on the male positioning means 16 the castings will be in registry with female dies 18 mounted above the castings 28 . As shown in FIGS. 4-8, the female dies 18 descend onto the castings 28 , and with the sharp edges of the die, as well as with pressure exerted by ram or punch 36 through the hydraulic system sever the castings 28 from the gate leaving gate remnant 34 on the degate plate 14 . The ram or punch 36 , as well as the female dies, are attached to an upper platen 37 which, in turn, is driven by a fluid or air cylinder (not shown).
With reference to FIG. 3, there is shown an exploded view of the ram 36 and female dies 18 , the gate 12 , the degate plate 14 and the gate plate support or lower platen 46 . The degate plate support or platen 46 is stationary while the degate plate is able to translate from right to left to dump the gate remnant and return to its original position (explained below). The degate plate support or lower platen 46 is shown with male fixtures or lower dies 16 disposed thereon, as well as guide slot 48 for receiving projection 50 under the degate plate. Guide slot 48 in conjunction with projection 50 may help stabilize the translation and return of the degate plate or stabilization can be attained by separate ways, guide rods or guide rails. Projection 50 also retains the chain. Open cut-outs 52 in the gate plate accommodate the male fixtures 16 . In addition, the cut-out access 52 allows for the degate plate 14 to translate while the degate plate support or platen remains stationary. The male fixtures or male dies are placed on the stationary degate plate or platen support and receive a major amount of force from the thrust of the ram and female dies. As an alternative embodiment, the male and female dies can be, and sometimes are, reversed in position.
More specifically, referring to FIGS. 4-8, a female die 18 shown with its end removed has disposed in the top compartment 45 of the die 18 , a pad 39 on the first end of a shaft 41 with the second end the shaft joined to a pad lift cylinder guide 42 . A spring 43 is positioned around the shaft 41 with the ends of the spring 43 abutting the pad 39 and the top of the die compartment 45 . As shown in FIG. 4 prior to the descent of the die 18 , the pad lift cylinder (not shown) is relaxed, the spring 43 is extended in a relaxed position. Once the ram cylinder (not shown) is actuated, the female die 18 descends (arrow) upon the gate 12 with the casting 28 shown with end removed in the gate 12 (FIG. 5 ). In FIG. 5 the casting is trimmed. During this step the pad 39 has remained in contact with the descent of the upper platen 37 . This holds the casting firmly on the lower male die or fixture. Note particularly that in FIGS. 4-8 the male die or fixture 16 is shown with a square shoulder 17 which is able to more securely position the casting 28 for severing and trimming. The male die 28 with the square shoulder is a preferred embodiment of this invention. After the casting has been severed (FIG. 6) the pad 39 is lifted leaving a gap 47 . This gap is brought about by the hydraulic cylinder raising the pad off of the casting. This release of the pad (gap) is necessary; otherwise, the spring would push the casting out of the female die as soon as the ascent began. With ascent (arrow) of the die (FIG. 7) the casting is wedged in the female die so that the die lifts the casting as the upper platen 37 ascends. The pad lift cylinder (not shown) is retracted, holding the spring 43 back. Note that in FIGS. 5-7 spring 43 is compressed. As a final step (FIG. 8) the pad lift cylinder relaxes causing the spring 43 and pad to push the casting 28 out of the upper die 18 (arrow). However, in operation, prior to the casting being ejected from the female die, parts catcher 20 moves under the female die to catch the casting 28 being ejected as explained below.
As described by FIGS. 9-11, the female dies 18 , employed to sever the casting 28 from the gate 12 , are made so as to yieldably grasp and retain the casting 28 . This is normally effected in that the castings once trimmed will naturally fit snuggly inside the female die. Once castings are severed the female dies retaining the castings therein are raised through means of the hydraulic press (ram) which opens lifting the castings with the female die. Referring specifically to FIG. 11, an unloading plate or parts catcher 20 slides in below the castings held in the female dies to receive the castings which are released onto the parts catcher 20 . The arrows in FIGS. 9-11 show direction of movement of the castings 28 .
Referring specifically to FIG. 11, upon release from the dies 18 the castings 28 drop into the parts catcher 20 shown on the left in slashed lines (FIG. 11 ). The parts catcher is made to move rapidly to the right (shown by arrow) striking into its stops 49 and coming to an abrupt halt. At the end of the guide rails or rods is a rubber sleeve or bumper which takes up shock when the guide rail comes to the end of its travel. The parts catcher 20 is attached to a rod 21 which, in turn, is attached to the hydraulic system (not shown). Since the castings 28 cannot stop as fast as the parts catcher 20 stops the castings are thrown by their momentum to the right and onto receiving chutes 22 shown by arrows for delivery to a parts bin. The motion of the parts catcher is controlled by guide rods and sleeves shown in FIGS. 1 and 9 - 11 . The motive force is produced through hydraulic or air cylinders. Attention is directed to the fact that the castings are delivered to two separate baskets on the parts catcher 20 . Two separate chutes 22 and two separate parts bins for receiving parts are employed. The advantage of two separate chutes is that the parts can be separately examined for flaws based on the individual parts in the bin and adjustments can be made for each individual line run. This segregation is particularly useful where multiple, and particularly more than two, castings are being dealt with. While the invention has been described as the finished castings being deposited into a chute and then a parts bin, the finished product could have been deposited directly into the parts bin.
With reference to FIG. 12, there is shown the finished casting 28 . The casting shown is a cast part of a door closer. It is obvious that the automated degate and trim machine could handle castings of unlimited shapes and sizes and the invention is not limited to any particular casting configuration.
With reference to FIGS. 13-15, once the casting is separated from the gate 12 there remains a gate remnant 34 on the degate plate 14 . The gate remnant is removed from the degate plate by the degate plate 14 translating to the left in a straight line until a slack chain 26 (shown in FIGS. 13-15) becomes taut causing the degate plate 14 which is hinged (not shown) to tilt dropping the gate remnant onto a scrap bin 44 where the remnant can be recycled. Instead of the scrap being placed in bin 44 , it can be placed onto a conveyor 53 as shown in FIGS. 16-18. With degate plate unloaded it is returned to its original position and the cycle can be repeated. Detail of the degate plate 14 and degate plate support are shown in FIGS. 2 and 3. In FIGS. 13-15 a chain 26 is shown, however, the chain could be substituted with a cable or like device.
Referring more specifically to FIGS. 13-15, the gate plate 14 is able to translate from right to left and dump gate remnant 34 onto scrap bin 44 . The mechanism by which translation and dumping takes place is that the hydraulic system drives shaft attached to brace 55 which, in turn, is attached to guide shaft 56 . The left end of the gate plate 14 is hinged at the juncture of brace 55 and guide shaft 56 . As previously pointed out, the scrap placed onto a conveyor is more convenient since the conveyor can facilitate recycling.
Referring to FIG. 15 there are shown auxiliary gate remnant deflectors 51 which direct stray pieces of remnant onto a chute, conveyor or scrap bin. For ease of recycling, a conveyor is preferred because with a conveyor the process will be more continuous. The conveyor can lead directly to the furnace.
FIGS. 16-20 briefly describe the steps of the machine process. FIG. 16 shows the machine with the gate 12 on the lower dies 16 . Scrap conveyor 53 carries scrap to the scrap bin 44 . With reference to FIG. 17 the female die 18 grasp the castings after the gate 12 is broken. The castings 28 are shown in dashed lines and arrow shows direction of the die. The dies are raised (arrow) with the castings and the castings are released into a parts catcher (not shown) (FIG. 18 ). Referring to FIG. 19, the gate remnant 34 is deposited into a scrap bin 44 and the castings into the parts bin. Arrows show the reciprocal action of the parts catcher. The tilt of the gate plate and its translation are shown by arrows. With the cycle complete the machine is ready for the next gate (FIG. 20 ).
An alternative embodiment of this invention is the combination of a gate plate support and a gate plate comprising said gate plate support having male fixtures on the top surface of the gate plate support, said gate plate having slots through which said male fixtures protrude and also allow the gate plate to translate, said gate plate being able to translate and tilt to dispose of gate remnant on the gate plate, said male fixtures being able to receive a casting in a gate. The mechanism to cause the gate plate to translate is a chain and sprocket arrangement. The gate plate can be made to tilt by a hinge and tension on a chain attached to the gate plate. With the slack taken out of the chain, the gate plate will tilt, dumping the gate remnant as herein disclosed.
As an alternative embodiment, the gate plate could be cleared of gate remnants by a wiper, such as a windshield wiper, or the scraps could be removed by magnetic attraction.
The female dies and ram are actuated by hydraulic means, however, other motive forces known to those skilled in the art could be used to operate the dies and ram.
The invention has been described in the context of twin castings. It is obvious that the machine could be fashioned to accept a greater number of castings, or could be fashioned to accept a single casting.
CONTROL SEQUENCE
The control is an ordinary action-reaction type control, using an ordinary Programmable Logic Controller. The program is basically the same for all castings being run. All program-initiated actuation are via solenoid valves, to cause motion in hydraulic or air cylinders.
The machine cycle starts as a robot brings the gate over from the die casting machine and sets it (the gate) onto the lower (male) fixtures. At this point, a spring-loaded pin is depressed, actuating a part-present sensor that is an input to the control:
Control Input
Subsequent Control Output
Part present
Program →
Solenoid valve is shifted to
sensor is made
dictates
send the ram and female
dies onto its downward
journey
Mechanical: The ram or punch extends downward until it “bottoms out” at its stall point. Before bottoming out, a pressure pad inside the female die(s) will have firmly pressed the castings onto the male fixture(s), thus locating the casting firmly, and then an instant later the female die trims away all the flash, overflows and gate remnants. The casting is now “stuck” inside the female (upper) die(s).
Ram “down”
Program →
Solenoid is shifted to lift the
sensor is made
dictates
pressure pad that pushes
down on the trimmed
castings.
Mechanical: The pressure pad lifts against the spring.
Pressure pad lift
Program →
Solenoid is eneegized to
sensor is made
dictates
lift the ram.
Mechanical: The ram and female dies ascend, with the castings stuck inside the dies. Ram cylinder bottoms out.
Ram “up” sensor is made
Program →
Solenoid for scrap plate
dictates.
is energized.
Solenoid for parts
catcher is energized.
Mechanical: The scrap plate translates to the left (in a straight line) until the chain slack is taken up, whereupon further leftward motion causes the scrap plate to tip up. Eventually, the actuating cylinder bottoms out.
Meanwhile, the parts catcher mechanism has translated in (from right to left) until the parts catchers themselves are directly under the castings. The actuating cylinder bottoms out.
Two sensors are
Program →
Solenoid for scrap plate is
made, one for each
dictates
reversed.
of the foregoing
Solenoid for parts,
motions
catcher is reversed.
Mechanical: scrap plate flops back down and translates back to its original (R.H.) position.
And, the parts catcher moves rapidly to the right, striking into its stop and coming to an abrupt halt. The castings cannot stop that fast, so they are thrown to the right and end up going down the chutes.
Two sensors are
Program →
End of program. Await new
made, one for each
signal from part present
of the foregoing
sensor to start next sequence.
motions
Note that all actuating cylinders run to, and are arrested by, stops. These stops are rubber rings that also act as shock absorbers.
While the invention employs hydraulic or air cylinders for motive force, other power sources readily apparent to those skilled in the art are envisioned by this invention.
ADVANTAGES
Many advantages accrue to the automatic degate and trim machine of this invention.
The machine will operate with conventional robots of the type that are used in die casting plants.
The machine is able to keep itself clean.
The machine will trim progressively if desired, so that it does not have to be as big as conventional degate and trim machines presently in use. This permits use of smaller capacity equipment requiring less space. Thus, the machine of this invention will be able to trim and dispose of large pieces of gate remnant, as well as small scrap that ordinarily would build up to impeded the functioning of the machine.
The robot does not need to be involved during the processing of the last castings set, nor during gage plate dump, freeing it (the robot) to return to the die casting machine for the next gate.
Obviously, many modifications may be made without departing from the basic spirit of the present invention. Accordingly, it will be appreciated by those skilled in the art that within the scope of the appended claims, the invention may be practiced other than has been specifically described herein.
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A general purpose molding and casting machine which will run unmanned to receive a casting assemblage and then separate the runners and sprue from the casting. Once the separation has taken place the casting is carried to the finished parts area and runners and sprue remnants are delivered to the scrap area for reuse.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to techniques in the field of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). The present invention also relates to techniques for measuring the spatial distribution of the electrical properties of substances such as electrolyte solutions, the tissues of a living body and human tissues by the use of MRI or MRS. The present invention relates also to techniques for measuring the spatial distributions of the currents within these substances.
2. Description of the Prior Art
Magnetic resonance signals are high-frequency signals, typically on the order of microvolts, which have weak frequencies produced by the precession of atomic nuclei (spins) in a static magnetic field. The frequency of the precession is determined by the magnetic field strength and the type of nucleus in question. The spins are aligned by the homogenous static magnetic field, and are excited by the application of an RF field, with the resulting magnetic resonance signals being detected as a voltage with a resonant coil (antenna).
An MR image is abbreviated MRI, and the method for acquiring it is called MR imaging which is abbreviated MRI. Further, MR spectral curve is referred to as an MR spectrum which is abbreviated MRS, and the acquisition of it or the method for acquiring it is called MR spectroscopy, which is abbreviated MRS.
Since R. Damadian found in the early 1970s that the spin-lattice relaxation time T 1 and the spin-spin relaxation time T 2 vary with tissues significantly, and tumorous tissues have extremely longer relaxation times than normal tissues (R. Damadian, “Tissue detection by nuclear magnetic resonance.” Science vol. 171: pp. 1151-1153, published in 1971), the relaxation times T 1 and T 2 have been recognized as very important parameters in developing and designing magnetic resonance imaging systems and obtaining and evaluating magnetic resonance images and spectra.
The relaxation time T 1 is the time constant required for the spins excited in a static magnetic field to return to their initial state in which they can be excited again. Accordingly, if T 1 of the tissues of a living body or the like (examination subject) is particularly long, then a correspondingly longer time is needed for obtaining the magnetic resonance signals by repeating the excitation, returning the spins to the initial state, and for obtaining MRI or MRS by performing calculations such as two-dimensional Fourier transform or one-dimensional Fourier transform with a computer. In case of a clinical MRI apparatus, the patient, who is not allowed to move during the image pickup, is more burdened. Further, the number of patients who can be imaged over a given time is decreased. Accordingly, it is generally considered better for T 1 to be shorter.
The relaxation time T 2 is the time constant from a time when many spins are excited in resonance with the RF field (i.e., the field having the same frequency as the frequency of the precession relative to the magnetic flux density of the static magnetic field around the spins), so that the phases of the precessions are uniform and can be detected macroscopically as an induced electromotive force by an external resonance coil, to when the phases become irregular and non-uniform, so that the spins cannot detected. Accordingly, in order to obtain the signals, it is better in many cases for T 2 to be long, but there are also many cases where, even if T 2 is short, it suffices if the signals are obtained, by an appropriate signal obtaining technique, for instance immediately after the excitation thereof.
Typically, T 1 of the gray matter of the brain of the human body is 1.0 when it is measured in a magnetic field of 1T. Further, typically, T 2 of the gray matter of the human brain is 0.1. It has been conventionally believed that there is no method or means for changing these relaxation times T 1 and T 2 in a given static magnetic field (of 1.0 T, 1.5 T or the like) and at a given temperature (substantially 37° C. of the human body) unless some chemical substance or the like is introduced into the human body.
More specifically, it is known that the ions of a magnetic material such as a transition metal and lanthanide ions have unpaired electronic spins which have magnetic moments several hundreds of times as large as protons, and thus have strong relaxation effects. As an application example of such substances, the injection of a gadolinium compound, which is a paramagnetic material, into the circulatory system of an examination subject is widely practiced in the field of clinical MRI. If a gadolinium compound is introduced into the tissue of a living body, it has a relatively larger shortening effect on T 1 , which is originally long, than on T 2 which is originally short.
In other words, if the gadolinium compound is introduced into a vein, then it is absorbed into the blood or the brain tissue or the like if the cerebral blood vessel barrier has been destroyed by a cerebral infarction or the like. This selectively shortens the T 1 of the tissue, so that the site of disease or the like can be selectively imaged or depicted in a T 1 -weighted image (that is, an image which is generated, by obtaining successive sets of magnetic resonance signals by repeating the excitation after each return of the spins to the initial state.) In such an image a substance which has a short T 1 and is therefore apt to return to the initial state in which, even if previously excited, it can be excited again, produces a higher amplitude signal and thus appears brighter in the image.
A T 2 -weighted image is generated from a signal that is not obtained immediately after the excitation, but is obtained as a dark signal after waiting for a substance with a shorter T 2 to become irregular and non-uniform in phase by the T 2 relaxation and become undetectable.
Further, in the middle 1960's, E. O. Stejskal and J. E. Tanner developed a diffusion measurement method by nuclear magnetic resonance that uses a motion probing gradient (MPG) pulses. [E. O. Stejskal and J. E. Tanner, “Spin diffusion measurements: spin-echoes in the presence of time-dependent field gradient.” J. Chem. Phys. Vol. 42: pp. 288-292, published in 1965].
This is a method of measuring the magnitude of the movement of spins as a diffusion coefficient by utilizing the fact that, as long as the spins perform a precession at a stationary position, no influence is exerted even if two gradient magnetic fields which are identical in magnitude but opposite in direction are successively applied as MPG pulses, but, if the spins are moved by the diffusion, then the phases are made irregular and non-uniform eventually by the application of the MPG pulses. The MPG pulses may be applied by making them identical with each other in magnitude and direction and putting 180° RF pulses between them.
Further, D. Le Bihan, etc. introduced MRI techniques that incorporate MPG pulses into imaging sequences of MRI in mid-1980s. [D. Le Bihan, E. Breton, D. Lallemand, P. Granier, E. Cabanis and M. Laval-Jeantet, “MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurological disorders.” Radiology Vol. 161: pp. 401-407, published in 1986].
Since then, the diffusion-weighted MRI techniques have been widely used as a very important imaging methods because, for important lesions like acute cerebral infarctions which cannot be depicted, unless two or three days lapse after the beginning of the disease, by T 1 -weighted imaging or T 2 -weighted imaging. Using diffusion-weighted imaging, these important lesions are imaged 20 to 30 minutes after the development of the disease.
The diffusion of certain molecules in the same substance, such as water molecules diffusing in water, is called self-diffusion. Accordingly, the diffusion coefficient of a substance itself refers to the self-diffusion coefficient. Self-diffusion is originally isotropic. However, among the movements of spins in living bodies, etc., not only do movements due to diffusion occur, but also some movements due to blood flow occur. More precisely, therefore, the measured diffusion coefficient of the water molecules is called the apparent diffusion coefficient (ADC). In particular, if the gradient factor attenuation value (which is sometimes abbreviated b-factor) that is determined dependent on the magnitude, the length in time and the pulse interval of each of the MPG pulses) is very small, the detection of only the movement due to the diffusion of the spins is very difficult, because the movement of the spins due to the blood flow, etc. also is detected. However, MPG pulses of such a degree that are in practical use in ordinary diffusion-weighted imaging sequences in clinical MRI, etc. at present can make the ADC value almost equal to the diffusion coefficient by sufficiently increasing the b-factor. Concerning the b-factor, details are given in the above-mentioned literature of Le Bihan, etc.
Further, a method of making a measurement by magnetic resonance while flowing an electric current through an electrolyte solution, is disclosed in U.S. Pat. No. 5,757,185.
The aforementioned patent states that by flowing an electric current, changing with time, the motion of the ions or molecules caused only by the electric current can be detected by nuclear resonance, with respect to the direction in which the gradient magnetic field is applied. Motion caused by diffusion is not detected.
There is no discussion in the aforementioned patent that applying an electric current through an electrolyte solution has any effect on T 1 or T 2 . Moreover, the technique according to the aforementioned patent for detecting the motion of the ions or molecules produced by an electric field and thus differs from known techniques for detecting the self-diffusion that develops isotropically.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a technique for markedly shortening T 1 or T 2 of a water-containing substance such as an electrolyte solution, the tissues of a living body or human tissues without using an intravenous injection or the like of a paramagnetic material such as a gadolinium compound or the like.
Another object of the present invention is to provide a technique for markedly increasing the ADC of a water-containing substance, so that the diffusion-weighted sensitivity is enhanced, in the context of a diffusion-weighted MRI or diffusion-weighted MRS.
Still another object of the present invention is to provide a technique for measuring the spatial distribution of the electrical properties of a water-containing substance by the use of MRI or MRS.
Still another object of the present invention is to provide a technique for measuring the spatial distribution of the electric currents in the interior of a water-containing substance by the use of MRI or MRS.
The first object is achieved in accordance with the present invention wherein, by applying an electric current through a water-containing substance, T 1 or T 2 of the substance is reduced.
The first object also is achieved in accordance with the present invention in a method for obtaining magnetic resonance images or spectra wherein a water-containing substance is placed in a static magnetic field, and, by a radio-frequency magnetic field, nuclear spins in the substance are excited to generate magnetic resonance signals, and wherein, by applying an electric current through said substance, the T 1 or T 2 of the substance is reduced.
The second object is achieved in accordance with the present invention wherein by applying an electric current through a water-containing substance, the apparent diffusion coefficient (ADC) of the substance is increased.
The second object also is achieved in accordance with the present invention also lies in a method for obtaining a magnetic resonance image or spectrum wherein a water-containing substance is placed in a homogeneous static magnetic field, and, by a radio-frequency magnetic field, nuclear spins in the substance are excited to generate magnetic resonance signals, and wherein, by applying an electric current through the substance, the ADC of the substance is increased.
The third and fourth objects are achieved in accordance with the present invention in a method for obtaining a magnetic resonance image or spatial information representing an electrical property of a water-containing substance wherein a T 1 -weighted, T 2 -weighted or diffusion-weighted magnetic resonance image, or localized magnetic resonance spectra is/are obtained,while applying an electric current through the substance, and wherein these images or spectra are compared to images or localized spectra obtained without applying the electric current.
The water-containing substance can be an electrolyte solution or the tissues of a living body.
The first object also is achieved in accordance with the present invention in an apparatus for obtaining a magnetic resonance image of a water-containing substance having a basic field magnet which generates a homogeneous static magnetic field, an RF system which generates a radio-frequency field, a gradient system which generates gradient magnetic fields, and a computer which generates an image from the received magnetic resonance signals and an arrangement for applying an electric current through the substance while the nuclear spins are processing, to reduce T 1 or T 2 of the substance.
A further embodiment of the present invention is an apparatus for obtaining a magnetic resonance image of a water-containing substance having a basic field magnet which generates a homogeneous static magnetic field, an RF system which generates a radio-frequency magnetic field, a gradient system which generates gradient magnetic fields, and a computer which generates an image from the received magnetic resonance signals, and an arrangement for applying motion probing gradient (MPG) pulses through the substance, and an arrangement for applying an electric current through the substance, to increase the ADC of the substance as the magnetic resonance signals are being generated and received.
A further embodiment of the present invention is a method for obtaining spatial information, by magnetic resonance, representing the internal electric current evoked in a water-containing substance, wherein T 1 -weighted or T 2 -weighted or diffusion-weighted magnetic resonance images or localized magnetic resonance spectra while an internal current is caused to flow in the substance, and wherein images or localized spectra are obtained without an internal current flowing in the substance, which are compared to the images or the localized spectra obtained with the internal current.
Even if the internal current is evoked in the tissue of a living body instead of being externally applied, the present invention can be practiced. In particular, even if the electric current in the tissue of a living body is evoked by an external stimulus to the living body tissues or by the internal brain activity in the living body, the present invention can be practiced.
The main cause for the relaxation phenomenon of the spins excited in water lies in the dipole-dipole interaction. One water molecule has two protons. Each rotates with a positive charge, as a result of which a magnetic field is emitted as a magnetic dipole having an N pole and an S pole. Moreover, the individual protons are each disposed within the magnetic fields emitted by surrounding protons. Further, each water molecule is experiencing thermodynamic molecular motion (Brownian motion). The correlation time (i.e., the time constant when the state at a certain instant is lost by the thermodynamic molecular motion, which becomes shorter as the thermodynamic molecular motion increases of the thermodynamic molecular motion of water existing as a liquid is much shorter than the cyclical period of the spin precession.
If the correlation time of the thermodynamic molecular motion reaches the same order as that of the cyclical period of the spin precession, many protons are subjected to radio-frequency magnetic fields generated by the other protons, on the same order as that of the precessions, and accordingly on the same order as the resonance frequencies but having various frequencies on the same order as the precessions, and accordingly on the same order as that of the resonance frequencies, but the protons exhibit various frequencies, like white noise. Then, the spins excited by the radio-frequency magnetic fields with a single resonant frequency from the outside cannot keep the excitation state any longer and thus become relaxed. This is the T 1 relaxation caused by the dipole-dipole interaction.
Further, if the correlation time of the thermodynamic molecular motion becomes very long, then one proton also is disposed in a static magnetic field produced by the magnetic fields emitted from the other protons, so that the precession which would otherwise occur at a cyclical period due to the constant external magnetic field, is disturbed by the existence of many surrounding protons, and thus becomes irregular and non-uniform. This is the T 2 relaxation caused by the dipole-dipole interaction.
On the other hand, one water molecule has two protons which have positive charges and one oxygen nucleus which has a negative charge, bonded at an angle of about 105°, and therefore, the molecule itself is a weak electric dipole. For example, in saline solution, sodium and chlorine exist in an ionized state, and the electric dipoles of the water molecule are attracted or repulsed by the dissociated ions, forming, around the individual electrolytic ions, many semi-stable structures, called hydration shells, containing many water molecules. Semi-stability refers to the state in which the total number of the electric dipoles does not change significantly with time, but replacement of the dipoles by surrounding dipoles is constantly taking place. Also in human body tissue, sodium ions of about 150 mM exist in the extracellular fluid and potassium ions of about 150 mM exist in the intracellular fluid, so that, around these ions, hydration shells are formed.
When an electric current is applied, the electrolytic ions move together with the hydration shells in a manner taking many water molecules with them. It is believed that, in this case, the thermodynamic molecular motion of the water molecules is restricted by the movement of the electrolytic ions, so that the correlation time is changed. As a result, the above-mentioned T 1 relaxation and T 2 relaxation based on the above-mentioned dipole-dipole interaction are caused, and T 1 and T 2 become markedly shorter.
Further, it is believed that, if an electric current is applied, the electrolytic ions move with the hydration shells in a manner taking many water molecules with them, as a result of which the movement of the water molecules is caused, and thus the ADC is remarkably increased. Here, the important feature pertaining to the increase of the ADC in the present invention is that the increase is developed isotropically. The mechanism therefor is believed to be in that the replacement, in a direction perpendicular to the movement, of the water molecules with the surrounding water molecules, which is caused by the movement of the hydration shells, occurs isotropically. Therefore, it is believed that the increase of the ADC in the present invention is also due to the fact that the diffusion coefficient substantially increases.
Further, T 1 -weighted or T 2 -weighted images or diffusion-weighted images can be obtained while applying an electric current through a water-containing substance, and a comparison is made between these images and corresponding control images obtained without applying an electric current. Such a comparison can be subtraction or division of attributes the images, or image calculations such as statistical inspection, etc. among many images. The tissues through which the electric current flow is higher exhibit a greater T 1 shortening effect or T 2 shortening effect or ADC increasing effect according to the present invention. Therefore, images in which the distribution of the electrical conductivity is represented can be obtained.
Further, according to the present invention, T 1 -weighted images can be obtained while applying an electric current through a water-containing substance, then T 1 is shortened, as a result of which the intensity of the signals obtained is markedly high, and therefore the obtained images are bright. Alternatively, a T 1 -weighted image can be obtained with a “conventional” brightness but the scan can be completed in a shorter time as a whole in connection with MRI or MRS. Accordingly, in a clinical MRI apparatus, the stores the patients can be markedly reduced and patient throughput can be increased.
Further, according to the present invention, diffusion-weighted images can be obtained, while applying an electric current through a water-containing substance, causing the ADC to be markedly increased, as a result of which images in which the contrast of the signals obtained is markedly strong are obtained.
The present invention is based on the finding that, when an electric current exists in a water-containing substance, T 1 or T 2 is shortened, or ADC is increased. The electric current which yields such effects need not be applied from outside the subject, but can be evoked internally, such as in the case of the water-containing substance being tissue in a living body, such as brain tissue.
More specifically, the brain evokes an electric current internally in response to an external stimulus or by internal brain activity. In a living body, the nerve tissues of the brain or the like are relatively easy to supply with an electric current, and as a result of the application of the electric current, a natural biomagnetic field is generated. The intensity of such electric fields emitted in the surrounding electrolyte, however, is small. Further, the duration of the electrical activities is very short in many cases.
Thus, T 1 -weighted or T 2 -weighted or diffusion-weighted magnetic resonance images or local magnetic resonance spectra are obtained when an internal electric current exists and when no internal electric current exists, and, between the data obtained when the internal electric current exists and the data obtained when no internal electric current exists, a comparison is made by performing subtractions and divisions or, among many datasets, a comparison is made by performing statistical inspection, etc. This allows information pertaining the spatial distribution of the internal currents and/or magnetic resonance images which represent the spatial distribution of the internal currents to be obtained.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram showing the structure of the apparatus according to an embodiment.
FIG. 2 is a chart showing an example of the diffusion-weighted spin echo imaging sequence according to an embodiment of the present invention.
FIG. 3 is a chart showing an example of the diffusion-weighted MRS obtaining sequence according to an embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 is a block diagram showing the basic structure of an apparatus according to an embodiment of the present invention.
Referring to FIG. 1, a phantom sample of an electrolyte solution 5 is placed in the static magnetic field of a horizontal superconducting magnet 1 of an MRI apparatus. The phantom sample 5 is connected to a current source 6 through a lead wire 7 . The MRI apparatus also has a gradient magnetic field coil assembly 2 and a radio-frequency coil 4 . The gradient magnetic field coil assembly 2 is supplied with an electric current from an electrical power supply 3 for the gradient magnetic field coil or coils, and produces gradient magnetic fields in the homogeneous static magnetic field volume of the magnet 1 .
The gradient magnetic field power supply 3 is operated by a command sent from an unillustrated man-machine interface. Power is supplied to the radio-frequency coil 4 in a transmit mode via a transmit/receive changeover switch 8 from a radio-frequency amplifier 10 , causing spins to be excited in the phantom sample 5 . Conversely, in a reception mode the magnetic resonance signals generated by the proton spins are detected as an induced electromotive force by the radio-frequency coil 4 and are sent to a computer 11 through the transmit/receive changeover switch 8 and an amplifier stage 9 (for example a pre-amplifier and an intermediate amplifier). After known data processing such as Fourier transformation, etc., In the computer 11 , data are supplied to a display 12 as MRI or MRS data. The radio-frequency amplifier 9 is also operated by the command sent from the man-machine interface.
According to the present invention, the electrical current applied from outside to a tested subject (in case of FIG. 1, the phantom sample 5 ) is an alternating current of 10 Hz or below, preferably 2 Hz or below, or a direct electric current. The lower the frequency, the larger the T 1 shortening effect, the T 2 shorting effect and the ADC increasing effect become, and the use of DC current is the most effective. In case of cellular tissues constituting a living body, AC currents are easier to conduct than DC currents, and a suitable frequency range thereof is 0.1 to 1.0 Hz.
In the present invention, if the subject is a human body the density of the electric current applied from the outside must be set to 50 mA/cm 2 or below to avoid a possible danger. The current density should preferably is 10 mA/cm 2 or below and more preferably is 5 mA/cm 2 or below for non-invasion measurement.
On the other hand, in most cases the higher the current density is, the larger the T 1 shortening effect and the ADC increasing effect will be. The practical current density range is 0.02 to 2.0 mA/cm 2 and preferably is 0.05 to 1.0 mA/cm 2 However, these current values should be set to lower values for safety if the invention is applied to a human body in the medical field, since the brain and the heart are organs which generate currents by themselves. Also in the fields of biology, veterinary medicine, botany, etc., the present invention exhibits marked effects as long as a water-containing substance is the subject, for shortening T 1 or T 2 or increasing ADC to perform MRI or MRS. When the present invention is employed for measuring the physical properties of water-containing substances other than the human body, allowable current values appropriate for the respective substances may of course be employed.
In the present invention, an electric current can be applied through an electrically conductive paste by the use, as electrodes, of non-magnetic metal foils, graphite plates or carbon powder-containing rubber plates. Where the tested subject is covered by an electrically conductive body, then radio-frequency eddy currents are caused to flow though the conductive body by the external radio-frequency field used for the excitation of spins, and thus the external RF field does not reach the interior of the tested subject. In an exemplary embodiment of the inventive method, an electrically conductive rubber band is placed around the wrist as one electrode, and another electrically conductive rubber band is placed around the upper arm as the other electrode, and an electric current is caused to flow between the wrist and the upper arm.
An external DC or low-frequency AC power source unit for this current, which has a magnetic component, cannot be brought near the MRI apparatus or MRS apparatus. A current-regulated power source would produce a location at the tested subject, at which the electric current flows in a concentrated manner, and thus for safety a voltage regulated power source is better in many cases. The wire extending from the power source to the electrode in the strong magnetic field will experience a force according to Fleming's left-hand rule depending on the magnitude of the electric current, and therefore this conductor is preferably a twisted pair so that the current flows in opposite directions parallel to the static magnetic field as much as possible, or the conductor can be rigidly fixed in the magnetic field.
In order to obtain diffusion-weighted image data, it is necessary to use MPG pulses as shown in, e.g., FIG. 2 . Referring to FIG. 2, RF indicates the RF pulses. Further, Gs indicates the output of the gradient magnetic field coil for slice selection. Further, Gr indicates the output of the gradient magnetic field coil for reading-out signals. Gp indicates the output of the gradient magnetic field coil for phase encoding. EC indicates the electric current applied though the tested subject.
Referring to FIG. 2, the RF pulses are applied in a direction perpendicular to the static magnetic field. If so, the many individually processing spins existing in the water-containing substance, which were directed as a whole in the direction of the static magnetic field, flip by 90° as a whole in resonance with the RF pulses. This is the first 90° pulse shown in FIG. 2 .
If the second pulse (a 180° pulse twice having twice the amplitude of the 90° pulse in the example of FIG. 2) is applied to the spins thus excited, then an echo signal is generated for the same time as the time Te/2 ranging from the application of the first excitation pulse (i.e., the 90° pulse) to the application of the second pulse and after a time Te lapses from the application of the first excitation pulse. This echo signal is called spin echo, and the time Te is called echo time.
At the instant when the 90° pulse or the 180° pulse is applied, pulses of the gradient magnetic field Gs for slice selection are applied. As is known as gradient magnetic field is a magnetic field which gives a linear gradient to the static magnetic field, and the spins perform precessions only at the frequency determined depending on the magnetic field intensity. Thus, it follows that, with respect to the radio-frequency field having a fixed frequency, the excitation by the 90° pulse and the generation of the echo signal by the 180° pulse each take place only at specific position with respect to one axis in space. This is the slice selection achieved by the gradient magnetic field Gs.
Next, when the echo signal which is generated after the time Te lapses is read out (in other words, the echo signal is detected as an induced electromotive force by the radio-frequency coil 4 ), the gradient magnetic field Gr is applied. This gradient magnetic field Gr is applied to the signal source, i.e., all the spins are differently spatially distributed. The gradient magnetic field Gr is a magnetic field which gives a linear gradient to the second spatial axis (i.e., an axis different from the axis for which the slice selection was made).
By the gradient magnetic field Gr, the echo signal from a specific slice is modulated with the frequency determined depending on the second spatial axis, and the radio-frequency coil 4 detects the echo signal as one signal containing the various frequencies of all of the spins in the slice. This signal is a signal on a time axis, that is, a signal which varies with time. When this signal is Fourier-transformed by the computer ii, then it is represented as a signal on a frequency axis. The frequency axis corresponds to the second spatial axis, so that the distribution of the spins along the second axis is identified.
Referring to FIG. 2, the MPG pulses are applied, by the use of the gradient magnetic field Gr, in the same direction with the 180° pulse interposed there between. The MPG pulses have a function as already mentioned. When readout of the echo signal is completed, the 90° pulse is applied again. The time from the application of the first 90° pulse to the application of the second 90° pulse is the repetition time Tr.
During the period from the excitation by the second 90° pulse to the second readout, the gradient magnetic field Gp is applied for a fixed time with a size changed by a fixed amount from the size applied at the first time. If the gradient magnetic field Gp is applied for a fixed time to the spins which perform precessions at a fixed frequency, then the precessions of the spins advance by a phase determined by the magnitude of the gradient magnetic field Gp. This gradient magnetic field Gp is a gradient magnetic field in the direction of the third spatial axis.
If signals are obtained repeatedly, the changes in the phase of the echo signal read out in each repetition represents the spatial distribution of the spins with respect to the direction of the third axis. Thus, if a Fourier transformation is made by the computer 11 with respect to the direction of the third axis, the phase axis corresponds to the third spatial axis, and thus the distribution of the spins along the third axis is identified. This is the diffusion-weighted spin echo imaging sequence.
The computer 11 performs a two-dimensional Fourier transformation with respect to one dataset comprising several echo signals measured repeatedly, and supplies the result to the display 12 as a magnetic resonance image.
It will be understood that if diffusions are not to be detected, the MPG pulses are not applied.
Next, referring to FIG. 3, three gradient magnetic fields Gx, Gy and Gz correspond to three directions in space and are for specifying one rectangular parallelepiped in the interior of the tested subject. Referring to FIG. 3, three 90° pulses are applied. If three 90° pulses are applied as mentioned above, then, after the application of the third 90° pulse, an echo signal is generated for the same time as the time Te/2 ranging from the application of the first 90° pulse to the application of the second 90° pulse and after the time, Te+Tm, from the application of the first excitation pulse. This echo signal is called a stimulated echo and this stimulated echo is detected as an induced electromotive force by the radio-frequency coil 4 . The time Tm ranging from the application of the second 90° pulse and the application of the third 90° pulse is called the mixing time.
Every time three 90° pulses are applied, one of the gradient magnetic fields Gx, Gy and Gz in the three spatial directions is applied. In this way, slice selection is performed with respect to the three axes in space, and the stimulated echo signals obtained are those only from within the rectangular parallelepiped in which the slices in three directions intersect each other, and, from this sequence, a diffusion-weighted localized MR spectrum is obtained.
In FIG. 3 EC again designates the electric current applied through the tested subject. Referring to FIG. 3, the MPG pulses are applied to the gradient magnetic field Gx, with two pulses applied with the same magnitude but in opposite directions. The function of these MPG pulses is as described above. Again, if no diffusion is to be detected, no MPG pulse is applied.
In the present invention, in order to detect a diffusion developing isotropically, the b-factor of the MPG should be set to 0.02 to 2,000 s/mm 2 and preferably to 0.2 to 200 s/mm 2 . This is because, if the b-factor is small, the influence by the flow of ions or molecules can be contained. If the b-factor is large, then the burden in the manufacture and use of hardware such as the gradient magnetic field coil, etc. is increased.
The embodiment of the present invention will be further described, with reference to a few examples.
EXAMPLE 1
An acrylic column with a 26 mm inner diameter and 45 mm in length was filled with physiological saline solution. The column was placed as the phantom sample 5 in the magnetic field of an MRI machine of 1.5 T shown in FIG. 1 . Further, the column was connected to the electric current source 6 through the lead wire 7 .
T 1 values were measured by an inversion recovery (IR) sequence, applying an electric current to the phantom sample. Further, T 2 values were measured by a Carr-Purcell-Meiboom-Gill (CPMG) sequence. The measurement was made with respect to the whole solution in the column as the subject, applying a direct electric current via platinum planer electrodes of both ends of the column.
When the current density was 0.0 mA/cm 2 (in other words, when no current was applied), T 1 and T 2 were 2.8 and 2.1 seconds respectively. When the current density was 1.0 mA/cm 2 , T 1 and T 2 were 2.2 and 1.7 seconds respectively. When the current density was 2.0 mA/cM 2 , T 1 and T 2 were 1.8 and 1.5 seconds respectively.
In this case, the results obtained when the electric current was applied in parallel to the static magnetic field (i.e., the length direction of the column was set in parallel to the static magnetic field) and when the electric current was applied perpendicular to the static magnetic field (i.e., the length direction of the column was set perpendicular to the static magnetic field), and when the electric current was applied in a direction oblique to the static magnetic field, were the same. Thus, it has also been shown that the T 1 shortening effect and the T 2 shortening effect of the electric current in the present invention are isotropic.
EXAMPLE 2
The acrylic column with a 26 mm inner diameter and 45 mm in length was filled with physiological saline solution. This column was placed in the magnetic field of the MRI machine of 1.5 T, wherein the length direction of the column was set in parallel to the static magnetic field. An MRI image was obtained by the use of a T 1 -weighted spin echo imaging sequence with a repetition time Tr=300 and an echo time Te=25 ms, applying a direct electric current via platinum planer electrodes of both ends the column.
It was confirmed that the image of which the surface perpendicular to the static magnetic field was a section, the image of which the surface parallel to the static magnetic field was a section, and the image of which a surface oblique to the static magnetic field was a section were all markedly brighter than the images obtained under the same conditions without the application of an electric current, and, in the former, T 1 was shortened and isotropically shortened.
Similar imaging experiments were conducted with a repetition time Tr=225 ms, applying an electric current. As a result, the signal intensities of the images obtained were comparable to the signal intensities of the images obtained with application of no electric current and with Tr=300 ms, whereby the imaging time as a whole was reduced by ¼ with the electric current.
EXAMPLE 3
Two aluminum plate electrodes of each 25 cm 2 were attached with conductive glue to both anterior and posterior sides of a human forearm, and the outer side thereof were wound with a cotton bandage. An MRI image was obtained by the use of a T 1 -weighted spin echo imaging sequence with a repetition time Tr=300 ms and an echo time Te=25 ms, applying a direct electric voltage of 8.0 V to the forearm via the electrodes.
It was confirmed that the muscle region where an electric current was allowed to flow through, produced signals brighter than the image obtained under the same condition without applying any electric current; and the T 1 was shortened.
EXAMPLE 4
The acrylic column with a 26 mm inner diameter and 45 mm in length was filled with physiological saline solution. The column was placed as the phantom sample 5 in the magnetic field of the MRI machine of 1.5 T as shown in FIG. 1 . The ADC was measured by a spin echo imaging sequence with a set of MPG pulses as shown in FIG. 2 , with Tr=5000 ms and Te=60 ms, applying a direct electric current via the platinum planer electrodes of both ends of the column. The MPG pulses were applied using a Gr gradient magnetic field as shown in FIG. 2, and the gradient factor attenuation value (b-factor) was set to 25 s/mm 2 .
When the current density was 0.0 mA/cm 2 (that is, when no current was applied), the ADC was 0.0021 mm 2 /s. When the current density was 0.2 mA/cm 2 , the ADC was 0.020 mm 2 /s. When the current density was 0.5 mA/cm 2 , the ADC was 0.079 mm 2 /s. In this case, the same result was obtained when the electric current was applied in parallel to the static magnetic field, when they were applied perpendicular to the static magnetic field, and when it was applied in a direction oblique to the static magnetic field. Thus, it was also proved that the ADC increasing effect according to the present invention was isotropic.
EXAMPLE 5
The acrylic column with a 26 mm inner diameter and 45 mm in length was filled with physiological saline solution. The column was placed in the magnetic field of the MRI machine of 1.5 T, wherein the length direction of the column was set in parallel to the static magnetic field. MRI images were obtained by a diffusion-weighted spin echo imaging sequence with MPG pulses and with Tr=5000 ms and Te=60 ms, applying a direct electric current of 0.2 mA/cm 2 via the platinum planer electrodes of both ends of the column. The gradient factor attenuation value of the MPG was set to 25 s/mm 2 .
The image of which the surface perpendicular to the static magnetic field was a section, the image of which the surface parallel to the static magnetic field was a section, and the image of which a surface oblique to the static magnetic field was a section, were all remarkably darker than the images obtained under the same conditions without application of an electric current; and thus it was confirmed that the ADC was remarkably increased and isotropically increased.
EXAMPLE 6
Two aluminum plate electrodes of each 25 cm were attached with conductive glue to both anterior and posterior sides of a human forearm, and the outer side thereof was wound with a cotton bandage. An MRI image was obtained by a diffusion-weighted spin echo imaging sequence with MPG pulses and with Tr=5000 ms and Te=60 ms, applying a direct electric voltage of 8.0 V to the forearm via the electrodes. The MPG gradient factor attenuation value of the MPG was set to 42 s/mm 2 .
It was confirmed that the muscle region where the electric current was allowed to flow through, produced signals markedly darker-intensity than the image obtained under the same conditions without applying an electric current; and the ADC was markedly increased.
EXAMPLE 7
A spherical glass phantom of 18 cm in inner diameter was filled with physiological saline solution. An electrical dipole of 4 cm in length, both ends of which were positive and negative electrodes, was installed in a submerged state at the center of the phantom. Lead-wires were led out from the center and twisted in the phantom so that electromagnetic effects of external currents were canceled. By applying electric voltage from outside, an electric current of 1 mA was made to flow through the spherical saline solution phantom directly from the electrical dipole. T 1 -weighted (Tr=300 ms, Te=25 ms), T 2 -weighted (Tr=5000 ms, Te=60 ms) and diffusion-weighted (Tr 5000 ms, Te=60 ms, and MPG Gradient Factor Attenuation b=25 s/mm 2 ) spin echo magnetic resonance images were obtained.
As a result, it was confirmed that, in case an electric voltage was applied to an electrical dipole, representing the distribution of an electric current around the electrical dipole, T 1 and T 2 reduction and diffusion increase were clearly exhibited, as compared with the case where no electric voltage was applied to the electrical dipole.
As mentioned above, according to the present invention, the T 1 and T 2 of a water-containing substance can be remarkably shortened without using a paramagnetic material or the like such as a gadolinium compound or the like. By shortening the T 1 , the measuring time of MRI or MRS can be shortened. Further, by the present invention, the ADC of a water-containing substance can be markedly increased.
Further, according to the present invention, the spatial distribution of the electrical properties of a water-containing substance can be measured. Further, according to the present invention, the spatial distribution of the electric currents in the interior of a water-containing substance can be measured. The above-mentioned measurements can all be performed in a non-invasion manner in case a living body is used as the tested subject.
Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventors to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within the scope of their contribution to the art.
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In a method and apparatus for obtaining magnetic resonance data from water-containing substance, nuclear spins are excited in the substance in the presence of a homogenous static magnetic field, while an electrical current is flowing in the subject. The electrical current flowing in the subject shortens the spin-spin relaxation time and the spin-lattice relaxation time, and lengthens the apparent diffusion coefficient of the substance.
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TECHNICAL FIELD
[0001] The present invention relates to improvements in the field of solid materials decontamination treatment. In particular, the invention relates to processes for microorganisms deactivation and/or destruction in solid materials. Such processes can be useful for treating various types of solid materials, such as sludges. They also permit deactivation and/or destruction of various types of pathogenic microorganisms.
BACKGROUND OF THE INVENTION
[0002] The management and reclamation of municipal sludge generated by wastewater treatment require a beforehand dewatering and pathogens reduction.
[0003] The principal microorganisms representative and indicators of treatment efficiency for pathogens reduction are: fecal coliforms or Salmonella sp., enteric viruses and viable helminth ova (US EPA, 2003. Control of Pathogens and Vector Attraction in Sewage Sludge. Environmental Regulations and technology . United States Environmental Protection Agency. EPA/625/R-92/013. Revised July 2003). All those microorganisms are likely to be present at various degrees in municipal sludge.
[0004] According to US EPA (1993), the aim of class A processes is to reduce pathogen densities below the following detection limits: less than 3 most probable number (MPN) per 4 grams of total solid (dry weight basis) for Salmonella sp.; less than 1 plaque-forming unit (PFU) per 4 grams of total solids (dry weight basis) for enteric viruses and less than 1 viable helminth ova per 4 grams of total solid (dry weight basis). For fecal coliforms, used as indicator organism, the aim is to reduce them to less than 1000 most probable number (MPN) per 1 gram of total solid (dry weight basis).
[0005] Other microorganisms like Clostridium perfringens , aerobic and facultative anaerobic heterotrophic bacteria, total coliforms, enterococus and coliphages can be used as indicator organisms. Coliphages (bacteriophages) are viruses that infect bacteria. Thanks to their characteristics, coliphages are considered by researchers as indicators of fecal pollution and are proposed as a model to follow the fate of enteric viruses in various hydrous environment and wastewater treatment plant.
[0006] Actual technologies for sludge sanitization rely essentially on thermal treatment, heat drying and heat treatment, high pH combined to high temperature process (alkaline treatment), thermophilic digestion, beta and gamma ray irradiation, pasteurization and composting.
[0007] It is thus highly desirable to be provided with an alternative to the solutions proposed so far.
SUMMARY OF THE INVENTION
[0008] According to one aspect of the invention, there is provided a process for at least partially deactivating microorganisms in a solid material. The process comprises submitting the solid material to an electric current having a voltage gradient of at least 3 volts per centimeter of solid material to be treated, and a current density of at least 2 mA per cm 2 with respect to the surface of electrodes used for generating the current.
[0009] It was found that such a process is very useful to treat solid materials in order to at least partially deactivate the microorganisms contained therein or even destroy the microorganisms contained therein. The process represents an economic and simple manner to decontaminate or to permit hygienization of solid materials. The process can permit to deactivate and/or destroy a plurality of microorganisms such as fecal coliforms, Salmonella spp., enteric viruses, viable helminth ova, enterococus, aerobic and facultative anaerobic heterotrophic bacteria, total coliforms, Escherichia coli, Clostridium perfringens , somatic coliphages and F-specific coliphages. The efficiency of the process is quite impressive since it can permit to considerably decrease the amount of microorganisms present in the solid material. The costs and problems related to the disposal of a solid material contaminated with microorganisms can thus be avoided by using such a process.
[0010] According to another aspect of the invention, there is provided a process for at least partially deactivating microorganisms in a solid material, and dewatering the solid material. The process comprises submitting the solid material to an electric current having a voltage gradient of at least 3 volts per centimeter of solid material to be treated, and a current density of at least 2 mA per cm 2 with respect to the surface of electrodes used for generating the current density and compacting the solid material.
[0011] It was found that such a process is very useful to treat solid materials in order to dewater it and to at least partially reduce the amount of microorganisms contained therein or even destroy the microorganisms contained therein. The process represents an economic and simple manner to dewater and decontaminate or to permit hygienization of solid materials. The process can permit to reduce or eliminate a plurality of microorganisms such as fecal coliforms, Salmonella spp., enteric viruses, viable helminth ova, enterococus, aerobic and facultative anaerobic heterotrophic bacteria, total coliforms, Escherichia coli, Clostridium perfringens , somatic coliphages and F-specific coliphages. The process can permit to at least partially eliminate or decrease the amount of microorganisms present in the solid material. Thus, such a process is very useful since it can convert a contaminated solid material having a considerable volume of water or solution i.e. low dryness into a dewatered solid material with higher dryness, reduced volume and in which the amount of microorganisms has been considerably reduced or in which the microorganisms have been eliminated. Therefore, the costs and difficulties to dispose and handle a solid material are considerably lowered when the solid material is treated with such a process.
[0012] The expression “deactivating microorganisms” as used herein refers to preventing the microorganisms from being active and causing undesired effects. For example, “deactivating microorganisms” can refer to preventing the microorganisms from metabolizing and/or multiply. Deactivation of microorganisms can also include reduction, elimination or destruction of the microorganisms.
[0013] The voltage gradient can be at least 4 V/cm, at least 5 V/cm, at least 6 V/cm, at least 7 V/cm, at least 8 V/cm, at least 9 V/cm, at least 10 V/cm, at least 12 V/cm, at least 14 V/cm, at least 16 V/cm, at least 18 V/cm at least 20 V/cm, at least 22 V/cm, at least 24 V/cm, at least 26 V/cm, at least 28 V/cm, or at least 30 V/cm. Alternatively, the voltage gradient can be about 3 V/cm to about 50 V/cm, 3 V/cm to about 60 V/cm, 3 V/cm to about 80 V/cm or about 15 V/cm to about 30 V/cm. The current can have an average current density of at least 3 mA/cm 2 , at least 4 mA/cm 2 , at least 5 mA/cm 2 at least 6 mA/cm 2 , at least 7 mA/cm 2 , at least 8 mA/cm 2 , at least 9 mA/cm 2 , at least 10 mA/cm 2 , at least 12 mA/cm 2 , at least 14 mA/cm 2 , at least 16 mA/cm 2 , at least 18 mA/cm 2 , at least 20 mA/cm 2 , at least 25 mA/cm 2 or at least 30 mA/cm 2 . Alternatively, the average current density can be of about 6 mA/cm 2 to about 70 mA/cm 2 or of about 10 mA/cm 2 to about 45 mA/cm 2 .
[0014] The current can be applied to the solid material for a period of at least 5 minutes, at least 12 minutes, at least 20 minutes, or at least 25 minutes. The solid material can be submitted to the electrical current and compacted simultaneously. The solid material can be compacted by a pressure applied to it, the pressure varying according to the consistency of the solid material, the pressure increasing when the solid material consistency is increasing. The pressure applied to the solid material can be substantially non-existent at the beginning of the process, and then, the pressure is progressively increased. A pressure of at least about 0.1 bar can be applied to the solid material in order to compact it while submitting it to the electric current. The pressure can also be about 0.15 bar to about 5 bars. Alternatively, the pressure applied to the solid material can be constant.
[0015] The solid material can be compressed by maintaining a contact substantially constant between at least one electrode and the solid material when the solid material is submitted to the electric current.
[0016] The solid material, before the treatment, can have a dryness of at least 25%. The dryness can also be about 2% to about 25%. For example, the solid material, after the treatment, can have a dryness increased of at least 10% as compared to the dryness of the solid material before the treatment.
[0017] The processes of the present invention can further comprise imparting a rotation movement to the solid material while the material is being compacted and submitted to the electrical current.
[0018] Alternatively, the solid material can be moved in a predetermined direction, and the solid material can be compacted by applying a pressure to the solid material in a direction which is substantially perpendicular to the predetermined direction.
[0019] The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, at least 99.99%, at least 99.999%, or at least 99.9996% the content of Escherichia coli in the solid material. The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, at least 99.99%, at least 99.999%, or at least 99.9999 the content of Salmonella spp. in the solid material. The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, or at least 99.99% the content of enterococus in the solid material. The processes can permit to reduce of at least 70%, at least 97%, at least 99%, or at least 99.99% the content of aerobic and facultative anaerobic heterotrophic bacteria in the solid material. The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, at least 99.99%, at least 99.999%, or at least 99.9999% the content of total coliforms in the solid material. The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, at least 99.99%, at least 99.999%, or at least 99.9999% the content of fecal coliforms in the solid material. The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, at least 99.99%, or at least 99.999% the content of Clostrodium perfringens in the solid material. The processes can permit to reduce of at least 70%, at least 99%, or at least 99.9% the content of somatic coliphages in the solid material. The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, or at least 99.99% the content of F-specific coliphages in the solid material. The processes can permit to reduce of at least 70%, at least 94%, at least 99.9%, at least 99.99%, or at least 99.9999% the content of enteric viruses in the solid material. The processes can permit to reduce of at least 70%, at least 99%, at least 99.9%, at least 99.99%, at least 99.999% or at least 99.9999% the content of helminths ova in the solid material. The processes can also permit to eliminate helminths ova in the solid material.
[0020] The processes can permit to substantially prevent the microorganisms from metabolizing and/or multiply and/or to substantially reduce or eliminate the presence of microorganisms in the solid material. Moreover, the processes can permit to substantially destroy microorganisms in the solid material.
[0021] One way to meet the Class A pathogen reduction requirements is to treat sewage sludge in a process equivalent to the processes to further reduce pathogens (US EPA, 2003. Control of Pathogens and Vector Attraction in Sewage Sludge. Environmental Regulations and technology . United States Environmental Protection Agency. EPA/625/R-92/013. Revised July 2003). One of the processes to further reduce pathogens (PFRP) is pasteurization that involves heating sewage sludge to above a predetermined temperature for a minimum time period. During pasteurization, sludge temperature is maintained at 70° C. or higher for 30 minutes or longer.
[0022] During the treatment, the processes of the present invention can permit to submit the solid material to a temperature higher than 70° C. For example, the processes can be considered as equivalent to a process to further reduce pathogens (PFRP) if they comprise certain parameters. The two following examples represent such processes.
[0023] Firstly, the processes can comprise submitting the solid material to an electric current having a voltage gradient of at least 3 volts per centimeter of solid material to be treated, and a current density of at least 2 mA per cm 2 with respect to the surface of electrodes used for generating the current density, and compacting the solid material and submitting the solid material to a temperature of at least 70° C. for at least 30 minutes.
[0024] Secondly, the processes can comprise submitting the solid material to an electric current having a voltage gradient of at least 3 volts per centimeter of solid material to be treated, and a current density of at least 2 mA per cm 2 with respect to the surface of electrodes used for generating the current density, and compacting the solid material and submitting the solid material to a temperature of at least 70° C. for a time period t 1 , wherein t 1 ≦30 minutes. A system, for maintaining the temperature of the solid material at 70° C. or more, can then be added at the end of the treatment. The solid material is thus subjected to a temperature of 70° C. or more during a time period t 2 (t 2 30 minutes) in such a way that the time period t 3 (t 3 =t 1 +t 2 ) is at least 30 minutes. Alternatively, t 1 <30 minutes; and t 2 <30 minutes.
[0025] According to another aspect of the invention, there is provided a process for at least partially deactivating microorganisms in a solid material, the process comprising submitting the solid material to an electric current having a voltage gradient of at least 0.5 volt per centimeter of solid material to be treated, and a current density of at least 2 mA per cm 2 with respect to the surface of electrodes used for generating the current.
[0026] According to another aspect of the invention, there is provided a process for at least partially deactivating microorganisms in a solid material and dewatering the solid material, the process comprising submitting the solid material to an electric current having a voltage gradient of at least 0.5 volt per centimeter of solid material to be treated, and a current density of at least 2 mA per cm 2 with respect to the surface of electrodes used for generating the current density.
DETAILED DESCRIPTION OF THE INVENTION
[0027] Further features and advantages of the invention will become more readily apparent from the following non-limiting examples.
EXAMPLES
[0028] For Examples 1 to 4 treatments were made on a pilot scale in an activated sludge wastewater treatment plant.
[0029] The apparatus that was used in Examples 1 to 4 was an apparatus similar to the apparatus illustrated in FIGS. 13 to 18 of US 2005/0199499 and described in pages 5 to 7 of the latter document. US 2005/0199499 is hereby incorporated by reference in its entirety.
Example 1
[0030] The process was carried out on the sludge with the previously mentioned apparatus, but with the specific parameters described in Table 1. In fact, the specific values of voltage gradient, current density, and time of treatment described in Table 1 were applied in the process and superior results in term of microorganisms deactivation were unexpectedly obtained as compared to those mentioned in US 2005/0199499. At the end of the treatment or process, a considerable increase of the sludge dryness was observed as indicated in Table 2. The electric current induced a temperature elevation. Temperatures measured in the treated sludge, at the outlet of the apparatus, varied from 70.0 to 76.3° C. Moreover, as shown in Table 3, the treatment permitted to considerably reduce the amount of microorganisms present in the sludge and event eliminate certain types of microorganisms.
[0000]
TABLE 1
Treatment parameters
Average voltage
Current density
Treatment time
gradient (V/cm)
(mA/cm 2 )
(minutes)
18.7
6.6
49
[0000]
TABLE 2
Sludge characteristics
Properties
Before treatment
After treatment
pH
7.7
5.7
Dryness (%)
17
33
[0000]
TABLE 3
Microorganisms reduction
Before
After
Microorganisms
Units
treatment
treatment
Escherichia coli
MPN/g dry weight
94 × 10 3
<7
Salmonella spp.
MPN/4 g dry weight
71
<3
Enterococus
CFU/g dry weight
447 × 10 3
<32
Aerobic and facultative
CFU/g dry weight
101 × 10 6
27 × 10 5
anaerobic heterotrophic
bacteria
Total coliforms
MPN/g dry weight
94 × 10 3
<7
Clostridium perfringens
CFU/g dry weight
Absence
Absence
Somatic coliphages
PFU/4 g dry weight
3576
<2
F-specific coliphages
PFU/4 g dry weight
29412
<2
Enteric viruses
PFU/4 g dry weight
<0.47
<0.24
Enteric viruses
MPNIP 1 /4 g dry
<0.94
<0.24
(immunoperoxydase
weight
method)
Viable helminth ova
Ova/4 g dry weight
Absence
Absence
1 MPNIP: Most probable number by immunoperoxidase
[0031] As it can be seen from Table 3, E. coli and Salmonella spp. levels where reduced below detection limits. For E. coli , a decrease of at least 4.13 log units was obtained, which corresponds to at least 99.99% reduction. A reduction below detection limits was obtained for: enterococus (decrease of at least 4.14 log units corresponding to at least 99.99% reduction), total coliforms (decrease of at least 4.12 log units corresponding to at least 99.99% reduction), somatic coliphages (decrease of at least 3.25 log units corresponding to at least 99.94% reduction) and F-specific coliphages (decrease of at least 4.17 log units corresponding to at least 99.99% reduction). For aerobic and facultative anaerobic heterotrophic bacteria, a decrease of 1.57 log units, corresponding to a 97.33% reduction, was obtained.
Example 2
[0032] The sludge was treated in a similar manner as described in Example 1, but with the specific parameters described in Table 4. In fact, the specific values of voltage gradient, current density, and time of treatment described in Table 4, were applied in the process. At the end of the treatment or process, a considerable increase of the sludge dryness was observed as indicated in Table 5. The temperatures measured in the treated sludge, at the outlet of the apparatus, varied from 77.5 to 96.2° C. Table 6 shows that the treatment permitted to considerably reduce the amount of microorganisms present in the sludge and event eliminate certain types of microorganisms.
[0000]
TABLE 4
Treatment parameters
Average voltage
Maximum current
Minimum Current
Average current
Treatment time
gradient (V/cm)
density (mA/cm 2 )
density (mA/cm 2 )
density (mA/cm 2 )
(minutes)
25
13.6
11
12.7
25
[0000]
TABLE 5
Sludge characteristics
Properties
Before treatment
After treatment
pH
—
6.6
Dryness (%)
16
32
[0000]
TABLE 6
Microorganisms reduction
Before
After
Microorganisms
Units
treatment
treatment
Escherichia coli
MPN/g dry weight
19 × 10 5
<7
Salmonella spp.
MPN/4 g dry weight
<5
<3
Enterococus
CFU/g dry weight
38 × 10 4
<32
Aerobic and facultative
CFU/g dry weight
4250 × 10 3
4750
anaerobic heterotrophic
bacteria
Total coliforms
MPN/g dry weight
31 × 10 6
<7
Clostridium perfringens
CFU/g dry weight
775 × 10 4
63
Somatic coliphages
PFU/4 g dry weight
1750
<2.5
F-specific coliphages
PFU/4 g dry weight
6400
<2.5
Enteric viruses
PFU/4 g dry weight
<0.5
<0.25
Enteric viruses
MPNIP 2 /4 g dry
1.75
<0.25
(immunoperoxydase
weight
method)
Viable helminth ova
Ova/4 g dry weight
Absence
Absence
[0033] During this treatment, E. coli level was reduced below detection limit. A decrease of at least 5.43 log units corresponding to at least 99.9996% was obtained. Moreover, a decrease of at least 6.65 log units was obtained for total coliforms corresponding to at least 99.9999%. For Clostridium perfringens , the results indicated a decrease of 5.09 log units, corresponding to 99.999% reduction. Enteric viruses were reduced to below the detectable limit. For aerobic and facultative anaerobic heterotrophic bacteria a decrease of 2.95 log units corresponding to 99.89% reduction was obtained by the treatment.
Example 3
[0034] The sludge was treated in a similar manner as described in Example 1, but with the specific parameters described in Table 7. In fact, the specific values of voltage gradient, current density, and time of treatment described in Table 7, were applied in the process. At the end of the treatment or process, a considerable increase of the sludge dryness was observed as indicated in Table 8. The temperatures measured in the treated sludge, at the outlet of the apparatus, varied from 96.5 to 98.7° C. As shown in Table 9, the treatment permitted to considerably reduce the amount of microorganisms present in the sludge and event eliminate certain types of microorganisms.
[0000]
TABLE 7
Treatment parameters
Average voltage
Maximum current
Minimum current
Average current
Treatment time
gradient (V/cm)
density (mA/cm 2 )
density (mA/cm 2 )
density (mA/cm 2 )
(minutes)
25.4
12.8
10.9
11.8
12.6
[0000]
TABLE 8
Sludge characteristics
Properties
Before treatment
After treatment
pH
7.5
6.6
Dryness (%)
15
26
[0000]
TABLE 9
Microorganisms reduction
Before
After
Microorganisms
Units
treatment
treatment
Escherichia coli
MPN/g dry weight
33 × 10 3
<8
Salmonella spp.
MPN/4 g dry weight
5
<3
Enterococus
CFU/g dry weight
15 × 10 5
<38
Aerobic and facultative
CFU/g dry weight
547 × 10 5
46 × 10 2
anaerobic heterotrophic
bacteria
Total coliforms
MPN/g dry weight
>107 × 10 3
<8
Clostridium perfringens
CFU/g dry weight
550 × 10 4
327 × 10 2
Somatic coliphages
PFU/4 g dry weight
67 × 10 3
<3
F-specific coliphages
PFU/4 g dry weight
26 × 10 3
<3
Enteric viruses
PFU/4 g dry weight
0.53
<0.3
Enteric viruses
MPNIP 2 /4 g dry
5.33
<0.3
(immunoperoxydase
weight
method)
Viable helminth ova
Ova/4 g dry weight
Absence
Absence
[0035] In this example, enteric viruses are detected and reduced to below detection limits. For aerobic and facultative anaerobic heterotrophic bacteria, a decrease of 4.07 log units, corresponding to 99.99% reduction was obtained.
Example 4
[0036] The sludge was treated in a similar manner as described in Example 1, but with the specific parameters described in Table 10. In fact, the specific values of voltage gradient, current density, and time of treatment described in Table 10, were applied in the process. At the end of the treatment or process, a considerable increase of the sludge dryness was observed as indicated in Table 11. As shown in Table 12, the treatment permitted to considerably reduce the fecal coliforms present in the sludge.
[0000]
TABLE 10
Treatment parameters
Average voltage
Maximum current
Minimum current
Average current
Treatment time
gradient (V/cm)
density (mA/cm 2 )
density (mA/cm 2 )
density (mA/cm 2 )
(minutes)
25
13.4
10.6
11.6
38
[0000]
TABLE 11
Sludge characteristics
Properties
Before treatment
After treatment
Dryness (%)
15
30
[0000]
TABLE 12
Microorganisms reduction
Before
After
Microorganisms
Units
treatment
treatment
Fecal coliforms
MPN/g dry
>110000
37
weight
[0037] A reduction of fecal coliforms of at least 3.47 log units corresponding to at least 99.97% reduction was obtained by the treatment.
Example 5
[0038] In examples 1 to 3, the analyzed samples were free of helminths ova. To show the effect of the process on helminths ova, tests were made on an activated sludge from wastewater treatment plant, which was voluntarily contaminated with helminths ova ( Ascaris suis ) isolated from pig faeces Wisconsin method (double centrifugation in water and after in saturated sugar solution) was used to isolate Ascaris ova (Foreyt, 2001. Veterinary Parasitology Reference Manual. 5th edition. Iowa State University Press) The solution used for sludge contamination contained approximately 1000 eggs/ml.
[0039] The apparatus used for Example 5 is an apparatus similar to the one illustrated in FIG. 2, of US 2005/0016870 and described in pages 3 and 4 of the latter document. US 2005/0016870 is hereby incorporated by reference in its entirety.
[0040] The process was carried out on the sludge with the previously mentioned apparatus but with the specific parameters described in Table 13. In fact, the specific values of voltage gradient, current density, and time of treatment described in Table 13, were applied in the process and superior results in term of microorganisms reduction were unexpectedly obtained as compared to those reported in US 2005/0016870. At the end of the treatment or process, a considerable increase of the sludge dryness was observed as indicated in Table 13. Table 13, also demonstrates that the treatment permitted to considerably reduce the amount of helminthes ova present in the sludge and even eliminate them.
[0000]
TABLE 13
Results
Treatment time
Average voltage
Max. current
Min. current
Average current
Initial
Final
Helminths
(minutes)
Treatment
gradient (V/cm)
density (mA/cm 2 )
density (mA/cm 2 )
density (mA/cm 2 )
dryness (%)
dryness (%)
Ova/10 g
13
Treatment 1
24.9
88
10
39.4
14.14
35.31
0
Treatment 2
24.9
88
10
40
14.14
33.41
0
Treatment 3
24.9
95
8
37.8
14.14
31.78
0
17
Treatment 4
24.9
95
10
35.3
14.14
39.09
0
Treatment 5
24.8
93
10
30.8
14.14
34.16
0
Treatment 6
24.8
95
9
32.9
14.14
43.79
0
—
Untreated
—
—
14.14
—
60
sample
[0041] Wisconsin method was used for detecting Ascaris ova in treated and untreated samples. Microscopic examination of the untreated sample shows 60 eggs of helminthes ova ( Ascaris suis ) by 10 grams of sludge. For treated samples (treatment 1 to 6), microscopic examination shows no eggs. These results demonstrate that such a process can permit the complete destruction or elimination of helminths ova. To check the viability of helminths ova, a culture at ambient temperature was made with eggs taken from the untreated sample. The culture showed that larval development was induced for 64% of the eggs.
Example 6
[0042] The effluent issued from a sludge, treated with an apparatus similar to the one illustrated in FIG. 2, of US 2005/0016870 and described in pages 3 and 4 of the latter document, has been analyzed for fecal coliforms. The analysis shows less than 10 Colony Forming Unit per 100 mL. The so-obtained effluent may be used for example as a fertilizer.
[0000]
TABLE 14
Treatment parameters
Treatment time
Gradient
Maximum current
minimum current
Average current
(minutes)
voltage (V/cm)
density (mA/cm 2 )
density (mA/cm 2 )
density (mA/cm 2 )
15
22.7
79
40
53
[0000]
TABLE 15
Sludge characteristics
Properties
Before treatment
After treatment
Dryness (%)
16.37
38.9
Example 7
[0043] Table 16 is presented in the example 7 in order to show the variation of the current densities during the treatment. Data were collected from a cell of an apparatus similar to the apparatus illustrated in FIGS. 13 to 18 of US 2005/0199499 and described in pages 5 to 7 of the latter document.
[0000]
TABLE 16
Current density variation during a treatment
Current density
Time (minutes)
(mA/cm 2 )
0
14.0
1
19.0
2
20.5
3
15.0
4
9.0
5
2.7
6
1.2
7
3.8
8
12.5
9
16.4
10
17.3
11
21.8
12
14.4
13
5.5
Average current
12.5
density
Example 8
[0044] In this example, municipal secondary sludge was treated. The apparatus that was used in Examples 8 was an apparatus similar to the apparatus illustrated in FIGS. 1 to 7 of PCT/CA2007/001052 filed on Jun. 13, 2007 and described in pages 14 to 23 of the latter document. PCT/CA2007/001052 is hereby incorporated by reference in its entirety. The total treatment process took about 15 minutes. The applied voltage gradient was about 28.6 V/cm.
[0045] During the sludge treatment, three sampling were performed. For each sampling, untreated sludge, treated sludge and generated effluent were sampled for salmonella and fecal coliforms analyses.
[0046] Tables 17 and 18 show monitoring results and various parameters obtained during the treatment of the sludge sampled at the first sampling, and for each of the five anode-units. Table 19 to 21 show microorganisms reduction for the samples taken during the first, second and third sampling.
First Sampling
[0047]
[0000]
TABLE 17
Parameters used for the first, second and third anode-unit
Anode-unit 1
Anode-unit 2
Anode-unit 3
Pres-
Current
Pres-
Current
Pres-
Current
Time
sure
density
Time
sure
density
Time
sure
density
(s)
(PSI)
(s)
(PSI)
(s)
(PSI)
0
15.3
32.5
190
10.0
40
370
10.0
17.5
10
15.0
33
200
10.0
40
380
10.5
16
20
15.1
33.5
210
10.3
37
390
10.5
14.5
30
15.1
34.5
220
10.3
34.5
400
10.4
13.5
40
15.1
35
230
10.3
32.5
410
10.5
13
50
15.1
35.5
240
10.3
31
420
10.4
12.5
60
15.1
36
250
10.3
28.5
430
10.4
12.5
70
15.0
37
260
10.2
27
440
10.4
12
80
15.1
38.5
270
10.2
25.5
450
10.3
11.5
90
15.1
39
280
10.2
23.5
460
10.3
11.5
100
15.0
40
290
10.2
21.5
470
10.3
11.5
110
15.0
40
300
10.2
21
480
10.3
11
120
15.1
40
310
10.2
20.5
490
10.3
11
130
15.1
40
320
10.1
19.5
500
10.2
10.5
140
14.8
40
330
10.0
18.5
510
10.1
10.5
150
14.8
40
340
10.0
17.5
520
10.1
10.5
160
14.8
40
350
10.0
17.0
530
10.1
10.5
170
14.8
40
360
10.0
17.0
540
10.0
10.5
180
14.8
40
—
—
—
—
—
—
indicates data missing or illegible when filed
[0000]
TABLE 18
Parameters used for the forth, and fifth anode-unit
Anode-unit 4
Anode-unit 5
Time
Pressure
Current
Time
Pressure
Current
(s)
(PSI)
density (mA/cm 2
(s)
(PSI)
density (mA/cm 2
550
9.2
26.7
730
10.6
12.5
560
9.2
20.0
740
10.4
14.0
570
9.3
13.5
750
10.3
12.5
580
9.2
11.5
760
10.2
10.5
590
9.9
10.5
770
10.2
9.5
600
9.8
10.0
780
13.1
9.0
610
9.7
9.5
790
13.0
9.5
620
9.7
10.0
800
13.0
9.0
630
9.5
9.5
810
13.0
8.5
640
9.5
9.0
820
13.0
8.0
650
9.5
9.0
830
12.9
8.0
660
9.5
8.5
840
12.9
7.5
670
9.3
8.5
850
12.8
7.5
680
9.2
8.5
860
12.8
7.2
690
9.1
8.0
870
12.7
7.0
700
9.2
8.5
880
12.7
7.0
710
9.7
8.0
890
12.6
7.0
720
9.8
8.5
900
12.7
7.0
[0000]
TABLE 19
Microorganisms reduction
Microorganisms
Untreated sludge
Treated sludge
Generated effluent
Fecal coliforms
>10000 MPN/g dry weight
<9 MPN/g dry weight
<10 CFU/100 ml
Salmonella spp.
<3 MPN/4 g dry weight
<3 MPN/4 g dry weight
<2 MPN/100 ml
Second Sampling
[0048]
[0000]
TABLE 20
Microorganisms reduction
Microorganisms
Untreated sludge
Treated sludge
Generated effluent
Fecal coliforms
>11000 MPN/g dry weight
10 MPN/g dry weight
<10 CFU/100 ml
Salmonella spp.
293 MPN/4 g dry weight
<3 MPN/4 g dry weight
<2 MPN/100 ml
Third Sampling
[0049]
[0000]
TABLE 21
Microorganisms reduction
Microorganisms
Untreated sludge
Treated sludge
Generated effluent
Fecal coliforms
>11000 MPN/g dry weight
<2 MPN/g dry weight
<10 CFU/100 ml
Salmonella spp.
80 MPN/4 g dry weight
<3 MPN/4 g dry weight
<2 MPN/100 ml
[0050] Examples 1 to 5, 6 and 8 thus clearly demonstrate that the processes of the present invention permit the at least partial deactivation, reduction and/or destruction of microorganisms such as E. Coli, Salmonella spp., fecal coliforms, enteric viruses and helminths ova.
[0051] The processes of the present invention can thus be useful for micoorganisms reduction or elimination in solid materials. They can also be useful for dewatering these solid materials. The solid materials can be, for example, municipal sludge, agro-alimentary sludge, industrial sludge, etc.
[0052] The processes of the present invention can also be useful for treating and/or dewatering various types of solid materials such as sediment, soil, biosolids, organic and/or inorganic sludge such as colloidal sludge, sludge from pulp and paper industries, agroalimentary sludge, sludge issued from a chemical or biological treatment, sludge from a dairy, sludge from a slaughterhouse, sludge from liquid or semi-liquid manure such as pork manure, and sludge from wastewater treatment plant. These processes can be used in industrial applications as well as for protecting environment.
[0053] While the invention has been described with particular reference to the illustrated embodiment, it will be understood that numerous modifications thereto will appear to those skilled in the art, without however departing from the scope of the claims. Accordingly, the above description and examples should be taken as illustrative of the invention and not in a limiting sense.
|
There is provided a process for at least partially deactivating microorganisms in a solid material. The process comprising submitting the solid material to an electric current having a voltage gradient of at least 3 volts per centimeter of solid material to be treated, and a current density of at least 2 mA per cm 2 with respect to the surface of electrodes used for generating the current.
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