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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation in part of our application Ser. No. 09/187,893, filed Nov. 6, 1998.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable.
BACKGROUND OF THE INVENTION
[0003] The invention of this application is described as applied to motorized conveyor pulleys, but it has application to dead shaft pulleys (those in which the shaft of a pulley is fixed against rotation, the drum of the pulley being mounted on bearings to rotate about the shaft) generally as well. Motorized conveyor pulleys have an electric motor inside a drum of the pulley, and a shaft with extensions at each end, fixed against rotation in mounting blocks mounted on a conveyer frame. Conveyer frames are welded structures that inherently do not have the positional accuracy required to mount machine components. Machining the frame structure to create a proper alignment is expensive and many conveyor structures are too large to be machined. In a motorized conveyor pulley a rigid mounting of the pulley in misalignment will cause excessive stress and lead to early failure of either the pulley or the frame. Thus, there must be some provision for aligning the shaft extensions and mounting blocks when the pulley is installed.
[0004] Conventionally, the shaft extensions of a motorized conveyor pulley are loosely fitted in mounting blocks in the form of yokes to allow for misalignment. Such a loose fit is noisy and leads to wear due to relative motion and impact loading. This is likely to cause early failure. For food and beverage service, the gap between the shaft and the mounting block can trap food.
[0005] One of the objects of this invention is to provide a mounting structure for a motorized conveyor pulley that accommodates misalignment but at the same time minimizes noise and relative motion, and provides a more sanitary arrangement for food and beverage service installations.
[0006] Other objects will become apparent to those skilled in the art in the light of the following description and accompanying drawings.
BRIEF SUMMARY OF THE INVENTION
[0007] In accordance with this invention, generally stated, a mounting for a dead shaft or motorized conveyor pulley is provided in which the shaft of the pulley is mounted at least one end in a pivot sphere, the sphere being mounted in a complementarily socketed block against rotation around the axis of rotation of the shaft when pulley is in use, but to permit angular movement in response to misalignment of the shaft from one end of the drum to another end during its installation. In a motorized pulley, the shaft is a composite, with shaft extensions extending from both ends of a pulley drum. Inasmuch as the extensions are part of the shaft as a whole, they are encompassed within the term “shaft” as used herein, when referring to the shaft's projecting from the drum. Preferably, each of the shaft extensions is mounted in a sphere against rotation. In both the dead shaft and motorized pulleys, the sphere is held against rotation around the axis of the shaft by clamping of the mounting block around the sphere. A positive restraint as a back-up can be provided in the form of a pin extending from the mounting block into a slot in the exterior of the sphere parallel to the axis of rotation of the pulley.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0008] In the drawings, FIG. 1 is a view in side elevation of a motorized conveyor pulley mounted in accordance with one illustrative embodiment of this invention. Shaft extensions 5 and 6 are shown as exaggeratedly misaligned in a vertical plane, to illustrate the capability of the mounting assembly in this invention;
[0009] [0009]FIG. 2 is a sectional view of a prior art mounting block and shaft;
[0010] [0010]FIG. 3 is a fragmentary sectional view of the shaft, sphere and mounting block shown on the right end of the pulley of FIG. 1;
[0011] [0011]FIG. 4 is a view in perspective of the mounting block and sphere and a shaft extension of this embodiment of the invention, with a threaded holding pin omitted;
[0012] [0012]FIG. 5 is a view in end elevation of the block shown in FIG. 4; and
[0013] [0013]FIG. 6 is a view in end elevation of the block shown in FIG. 2, being part of the prior art.
[0014] Corresponding reference numerals will be used throughout the several figures of the drawings.
DETAILED DESCRIPTION OF THE INVENTION
[0015] Referring now to the drawings for one illustrative embodiment of this invention, reference numeral 1 indicates a motorized conveyor pulley, which can be conventional as described in an application, now U.S. Pat. No. 6,117,318, co-pending with the parent of the present application Ser. No. 09/187,893, assigned to a common assignee. The pulley 1 is bolted to a support structure 2 , shown only fragmentarily, by means of bolts, as indicated at 16 in FIG. 6, the use of such bolts being conventional. The pulley includes a drum 3 and two shaft extensions, 5 and 6 , cylindrical through their central section, but provided at their projecting ends with flats 7 .
[0016] [0016]FIGS. 2 and 6 illustrate a conventional mounting, in which a shaft is loosely confined in a yoke 9 , within a slot defined by side walls 10 and a bottom wall 11 , which permits vertical misalignment, and a limited amount of horizontal angular misalignment, but suffers from the disadvantages described heretofore.
[0017] In the present invention, the shaft extensions 5 and 6 are mounted against rotation in spheres 20 . In the embodiment shown, the spheres 20 are made in the form of two hemispheres, a lower hemisphere 21 and an upper hemisphere or bearing cap 22 . The upper hemisphere 22 has, in this embodiment, an axial slot 23 in its uppermost surface, defined by parallel side walls and a bottom wall, as shown in FIG. 3. Each of the shafts 5 and 6 is mounted to fit closely in a seat defined by a flat bottom 24 and arcuate side walls 25 in the lower hemisphere and a flat upper wall 27 and arcuate side walls 28 in the upper hemisphere. The close fit substantially eliminates the noise and wear permitted by the conventional yoke. The spheres are mounted in mounting blocks 30 , and seated in sockets 32 formed in the mounting blocks 30 . The mounting blocks 30 are made in two parts, a lower seat part 34 and an upper seat part or bearing cap 46 . The lower seat part 34 has a base 35 from which ears 36 extend. Ears 36 have bolt holes 37 through them by which the mounting blocks are mounted on the support structure. The base 35 has bolt bosses 40 , from which bolts 42 , parallel to one another, project toward the upper seat part. The seats of the socket 32 are in the form of a semicircular groove or channel 44 in the lower seat part and 50 in the upper seat part 46 . The grooves 44 and 50 are aligned, to form an annular seat when the parts 34 and 46 are mounted, interrupted only by a narrow gap 60 between the seat parts 34 and 46 when the sphere is installed. The upper seat part 46 has bolt bosses 48 through which the bolts 42 extend, the bolts projecting from an upper surface of the bolt bosses sufficiently far to receive nuts 59 . The provision of the gap 60 permits the sphere to be gripped tightly between the seat parts to prevent rotation of the sphere when the nuts 59 on the bolts 42 are torqued down.
[0018] An internally threaded bolt hole 52 , extending radially through the upper seat 46 , is aligned with the slot 23 . A threaded pin 54 , mounted in the bolt hole 52 , extends into the slot 23 , closely adjacent but clear of the bottom wall of the slot, so as to permit angular movement of the shafts in a vertical plane, and is provided with sufficient clearance between the side walls of the slot 23 to permit angular movement of the sphere 20 about the pin 54 as a pivot in a horizontal plane. Thus the axis of rotation of the drum has freedom to pitch and yaw, but not to translate or roll.
[0019] As has been indicated, tightening the nuts 59 on the bolts 42 clamps the sphere between the upper and lower seat members 34 and 46 . In the embodiment described, if the clamping pressure should be unintentionally relaxed enough to permit rotation of the sphere, the sphere will be prevented from rotating around the axis of the shaft by the pin 54 , but it is intended that the clamping pressure be sufficient to prevent rotation after the pulley has been installed and the nuts 59 torqued down. The width of the gap 60 and the amount of torque applied to the nuts 59 will vary with the size of the pulley, hence the size of the spheres and mounting blocks.
[0020] In installing the pulley, the lower part of each mounting block is loosely mounted on a rail of a supporting structure, the spheres, in which the shaft extensions 5 and 6 are mounted, are seated in the lower part of the mounting block, and the upper part of the mounting block is put in place over the spheres, with the bolts 42 extending through the bosses 48 , and the nuts 59 started but not tightened. Bolts by which the housing is mounted on the structure extend through the bolt holes 37 , but are not initially tightened. The pulley is aligned, the loosely mounted housing itself and the untightened spheres permitting accurate alignment in spite of any structural inaccuracies of the support structure. The bolts by which the housing is mounted on the structure are then tightened. The nuts 59 on the bolts 42 are then torqued to a torque value producing predetermined pressure on the spheres 20 and 22 , that pressure being determined by the size and expected load of the pulley, but being readily calculable.
[0021] Numerous variations in the construction of the mounting assembly of this invention, within the scope of the appended claims, will occur to those skilled in the art in the light of the foregoing disclosure. For example, although the present arrangement is preferred, the sphere and socket mounting can be applied to only one end of the shaft or shaft extension. The pin and slot can be omitted entirely. A boss or pin in the outer surface of the sphere can be seated in a well or slot in the socket seat. An axial boss or bar or pin carried by the mounting block can be directed through an hourglass-shaped channel in the sphere or vice versa. The ends of the shafts can be differently formed, as, for example, polygonally or otherwise non-circularly instead of with flats. The flats and corresponding sphere seats can be oriented differently, as for example rotated ninety degrees from the position shown in FIGS. 1, 3, 4 and 5 . The sphere can be made in one piece and mounted on the shaft extension before it is mounted in the bearing housing. The socket can be made to enclose the sphere more completely, and the open end of the seat in which the shaft end is mounted can be closed, for food conveyor applications, although the construction shown is an improvement over the prior art in that respect. As has been indicated, the sphere assembly can be provided at one or both ends. These variations are merely illustrative.
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A dead shaft or motorized conveyor pulley in which a drum is mounted for rotation about an axis of rotation on a shaft mounted against rotation, has the shaft mounted in a pivot sphere. The sphere is mounted in a complementarily socketed block against rotation around the axis of rotation but to permit angular movement in response to misalignment of the shaft from one of the drum to the other end during installation.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to data communications and, more particularly, is directed to a highly efficient coding apparatus for compressing the number of bits of data required for each picture element of a digital television signal or the like.
2Description of the Prior Art
Among known methods of video signal coding, there are some highly efficient coding methods adapted to diminish the average bit number or sampling frequency of each picture element for purposes of narrowing the transmission band.
Applicants' Japanese Laid Open Patent Publication No. 61-144,989 discloses a highly efficient coding apparatus for determining a dynamic range from maximum and minimum values of a plurality of picture elements contained in a two-dimensional block and for performing a coding adapted to the dynamic range thus obtained. Further, Japanese Laid Open Patent Publication No. 62-92620 discloses a highly efficient coding apparatus for effecting coding adapted to a dynamic range determined with respect to a three-dimensional block formed of picture elements contained in areas of a plurality of frames. Moreover, Japanese Laid Open Patent Publication No. 62-128621 discloses a variable-length coding method for varying the quantization bit number as a function of the dynamic range so as to keep constant the maximum distortion occurring at the time of quantization.
Reference will be made to FIG. 1 in explaining a known adaptive dynamic range coding (ADRC) method. The dynamic range DR (difference between a maximum value MAX and a minimum value MIN) is calculated for every two-dimensional block formed of, for example, (8 lines ×8 pixels =64 pixels). The minimum level (minimum value) is removed from the input pixel data in the block. After removal of the minimum value, each picture element (pixel) is converted into a representative level. This quantization is for dividing the detected dynamic range DR into four level ranges A0 to A3 corresponding to a number of bits less than the bit number that would be required for an original quantization of the pixel data. Upon transmission, each pixel in the block is represented by a code signal indicative of the respective level range.
In FIG. 1, the dynamic range DR of the block is divided into four level ranges A0 to A3. Pixel data contained in the minimum level range A0 are coded as (00), pixel data contained in the level range A1 are coded as (01), pixel data contained in the level range A2 are coded as (10), and pixel data contained in the maximum level range A3 are coded as (11). Therefore, picture element data of 8 bits are compressed into 2 bits for efficient transmission.
In a receiver, such a received code signal is decoded into one of a plurality of representative levels L0 to L3 which are center levels of the level ranges A0 to A3, respectively.
The above described adaptive dynamic range coding method is disadvantageous in that a block distortion occurs because of a ringing or an impulsive noise as will be described with reference to FIG. 2. In FIG. 2, for the purpose of simplifying the explanation, variation in data in respect of a one-dimensional block, i.e., a block formed of a predetermined number of samples in a horizontal line or direction, is shown as an analog waveform, and values decoded by the receiver are shown by a broken line.
A low-level ringing is often produced in a picture output of a video camera near an edge where the level is changed abruptly, as shown in FIG. 2. In the block including such ringing, a peak value of the ringing is detected as a maximum value MAX1, and coding is carried out adaptively with reference to a dynamic range DR1 between the maximum value MAX1, and a minimum value MIN1. In a subsequent block, in which the ringing is converged, the maximum value is decreased to MAX2, and coding is effected adaptively with reference to a dynamic range DR2 between a minimum value MIN2 and the maximum value MAX2. Therefore, a difference in luminance level is indicated between these two blocks and this causes a block distortion. Also in the case of an impulsive noise, a block distortion occurs for the same reason. The difference in luminance level causing the block distortion is small but nevertheless is visually noticeable.
In order to overcome the problem of block distortion caused by a ringing or an impulsive noise, the present applicants have proposed a system for performing preliminary processing of input data converted into a block structure for example, as described in the Japanese Laid Open Patent Publication No. 63-59187. More specifically, an average value MAX' of the values of input data contained in a maximum level range (A3 in FIG. 1) and an average value MIN' of the input data contained in a minimum level range (A0 in FIG. 1) are detected, and then quantization is carried out so as to convert the average value MAX' and the minimum value MIN' into detected levels L3 and L0, respectively, as shown in FIG. 3. The quantization shown in FIG. 1 in which the representative levels L0 to L3 do not include the maximum value MAX and the minimum value MIN but indicate center values in respective level ranges, is called a non-edge matching. In contrast, the quantization shown in FIG. 3 in which the levels L0 to L3 do include the average values MAX' and MIN', is called an edge matching.
In the ADRC method which involves first performing the preliminary non-edge matching processing and then subsequently performing the edge matching quantization, the maximum value is converted into the average value MAX' and not into the ringing peak in a block including the ringing shown in FIG. 2. Similarly, the minimum value is converted into MIN'. Since the edge matching quantization is carried out in respect to the concealed dynamic range DR' determined by the values MAX' and MIN', the difference between the decoded level of a specific block including a ringing and a decoded level of an adjacent block is reduced, and generation of block distortion is prevented.
Since the above-described adaptive to a dynamic range coding (ADRC) method can largely compress the amount of data to be transmitted, it is suitable for use in a digital VTR. Although variable-length ADRC can increase the compression rate, variable-length ADRC causes variation in the amount of transmitted data with the contents of the picture, so that a buffering process is required when using a transmission path having a fixed rate, such as, a digital VTR configured to record a predetermined amount of data in each track.
A buffering system for variable-length ADRC has been proposed by the present applicants, for example, as disclosed in Japanese Laid Open Patent Publication No. 63-111781. In this system, an integrating type frequency distribution table of dynamic ranges is formed and a threshold value is preliminarily obtained from the frequency distribution table for determining an assigned bit number, whereupon the generated amount of information in a predetermined period, such as one frame period, is obtained, so that the generated information amount does not surpass a target value.
When using variable-length ADRC in the above-mentioned ADRC method which involves preliminary processing using the non-edge matching quantization and subsequent performing of the edge matching quantization, a problem arises by reason of mismatching between the encoder and the decoder because, while the assigned bit number is established based on an original dynamic range DR, a different dynamic range DR' is transmitted to the receiver side.
More specifically, in order to control the generated information amount, a frequency distribution table for a predetermined period, e.g., one frame period, of dynamic ranges DR is prepared, and the frequency distribution table is converted into an integrating type frequency distribution table to which threshold values T1, T2, T3 and T4 (T1<T2<T3<T4) are adapted. In case of (DR<T1), the assigned bit number n is set at 0 (this means that no code signal is transmitted). In case of (T1≦DR<T2), the assigned bit number is set at (n=1). In case of (T2≦DR<T3), the assigned bit number is set at (n=2). In case of (T3<=DR<T4), the assigned bit number is set at (n=3). In case of (T4=<DR), the assigned bit number is set at (n=4).
As described above, for the relationship of (MAX' MIN'-MIN'=DR'), quantization is performed in respect to the concealed dynamic range DR', and the dynamic range DR' is transmitted. If the relationships of (T2<DR<T3) and (T2 DR'<T3) are established for the dynamic range of a certain block, the bit number (n=2) set at the encoder also exhibits (n=2) at the decoder, and no problem occurs. However, since the relationship of (DR>DR') exists, the decoder may erroneously regard the bit number as being (n=1) in the case of T1≦DR'<T2), and this causes a problem in that proper decoding is not effected.
OBJECTS AND SUMMARY OF THE INVENTION
It is, therefore, an object of the invention to provide a highly efficient coding apparatus which prevents mismatching between bit numbers used in encoding and decoding by reason of a difference between an original dynamic range and a concealed dynamic range which is transmitted.
In order to achieve the above object, the invention proposes a highly efficient coding apparatus for coding digital video data in a block format allowing video data compression for transmission using a data transmitter having a predetermined transmission capacity, the coding apparatus comprising a first detector for detecting a maximum value of the digital video data of plural picture elements in a block; a second detector for detecting a minimum value of the digital video data of plural picture elements in the same block; a first averaging circuit for averaging the digital video data having a value between the maximum value and a first value which is a first predetermined level lower than the maximum value, and for generating a modified maximum value; a second averaging circuit for averaging the digital video data having a value between the minimum value and a second value which is a second predetermined level higher than the minimum value, and for generating a modified minimum value; a subtracter for subtracting the modified minimum value from the digital video data for each of the picture elements to generate modified digital video data; a circuit for generating modified dynamic range information from the modified maximum and minimum values; a bit number deciding circuit for determining an encoding bit number for each block during a predetermined period from the predetermined transmission capacity of the data transmitter; an edge-match encoder for encoding the modified digital video data with the encoding bit number; and a transmission circuit for transmitting an output of the encoder, a first additional code for each block formed of at least two of the modified maximum and minimum values and a signal based on the modified dynamic range information, and a second additional code for each predetermined period referred to above.
The features of this invention which are believed to be new are set forth with particularity in the appended claims. The invention itself, however, together with further objects and advantages thereof may best be understood by reference to the following description when taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1, 2 and 3 are schematic diagrams to which reference is made in describing examples of quantization employed in prior art highly efficient coding apparatus, respectively;
FIGS. 4A and 4B are a block diagram of a transmitter according to one embodiment of this invention;
FIG. 5 is a schematic diagram of a block used as a unit in an encoding process in the transmitter of FIG. 4;
FIG. 6 is a block diagram of a receiver corresponding to the transmitter shown in FIG. 4;
FIG. 7 is a block diagram of a buffering circuit included in the transmitter of FIG. 4;
FIG. 8 is a flow chart for use in explaining the operation of the buffering circuit of FIG. 7;
FIGS. 9A and 9B are schematic diagrams showing distribution tables of dynamic range information;
FIGS. 10A and 10B are a block diagram of a transmitter according to a second embodiment of the invention;
FIG. 11 is a block diagram showing a receiver corresponding to the transmitter shown in FIG. 10;
FIGS. 12A, 12B, 13A and 13B are block diagrams of third and fourth embodiments of this invention, respectively;
FIGS. 14A1, 14A2 and 14B are a block diagram of fifth embodiment of this 10 invention;
FIGS. 15A, 15B, 15C and 15D are schematic diagrams to which reference will be made in describing examples of quantization used in the embodiment of FIG. 14; and
FIGS. 16A, 16B, 16C, 16D and 16E are schematic diagrams showing distribution tables of dynamic range information.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIGS. 4A and 4B, which together comprise FIG. 4, generally show the arrangement of a transmitter or recorder in accordance with a first embodiment of the invention. A digital video signal (digital luminance signal) in which one sample is quantized with eight bits, for example, is supplied through an input terminal 1 to a block segmentation circuit 2.
In the block segmentation circuit 2, the input digital video signal is converted into successive signals for each two-dimensional block which is the unit of coding. In this embodiment each block is 8 lines ×8 pixels =64 pixels, as shown in FIG. 5. An output signal of the block segmentation circuit 2 is supplied to a maximum/minimum value detector circuit 3 and a delay circuit 4. The maximum/minimum value detector 3 detects a minimum value MIN and a maximum value MAX of each block. The delay circuit 4 delays the input data by a time equivalent to that required for detecting the maximum value and the minimum value. Pixel data from the delay circuit 4 are supplied to comparator circuits 5 and 6.
The maximum value MAX from the maximum/minimum value detector 3 is fed to a subtracter circuit 7, and the minimum value MIN is supplied to an adder circuit 8. A value Δ equal to one quantization step width at the time of variable-length non-edge matching quantization is supplied from a bit shift circuit 9 to the subtracter 7 and the adder 8. The bit shift circuit 9 is configured to shift a dynamic range DR by n bits so as to perform subtraction of (DR/2 n ) when the assigned bit number is n. From the subtracter 7 is obtained a threshold value of (MAX-Δ), and from the adder 8 is obtained a threshold value of (MIN+Δ). These threshold vales from the subtracter 7 and the adder 8 are fed to the comparators 5 and 6, respectively.
An output signal of the comparator 5 is supplied to an AND gate 10, and an output signal of the comparator 6 is fed to an AND gate 11. The delayed pixel data from the delay circuit 4 are also supplied to the AND gates 10 and 11. The output signal of the comparator 5 represents a high level when the input data is larger than the threshold level (MAX-Δ). Therefore, at the output terminal of the AND gate 10, there is extracted that pixel data of the input data which is contained in the maximum level range of (MAX to MAX-Δ). The output signal of the comparator 6 represents a high level when the input data is smaller than the threshold level (MIN+Δ). Therefore, at the output terminal of the AND gate Il there is extracted that pixel data of the input which is contained in the minimum level range of (MIN to MIN+Δ).
An output signal of the AND gate 10 is supplied to an averaging circuit 12, and an output signal of the AND gate 11 is fed to an averaging circuit 13. These averaging circuits 12 and 13 each calculate an average value for each block, and a reset signal is supplied at block intervals to the averaging circuits 12 and 13 from a terminal 14. From the averaging circuit 12 is obtained an average value MAX' of the pixel data belonging to the maximum level range of (MAX to MAX-Δ), and from the averaging circuit 13 is obtained an average value MIN' of the pixel data belonging to the minimum level range of (MIN to MIN+Δ). The average value MIN' is subtracted from the average value MAX' by a subtracter circuit 15 (FIG. 4B), and a concealed dynamic range DR' is obtained from the subtracter 15.
Further, the average value MIN' is supplied to a subtracter circuit 16 in which the average value MIN' is subtracted from the input data supplied to the subtracter 16 through a delay circuit 17, thereby forming data PD1. The data PD1 and the concealed dynamic range DR' are supplied to a quantizer circuit 18. This embodiment performs edge-match quantization which is a variable-length ADRC in which the bit number n assigned to the quantization is either 0 bit (no code signal is transmitted), 1 bit, 2 bits, 3 bits or 4 bits. The assigned bit number n is determined for each block by a bit number deciding circuit 19, and data representing such bit number n are supplied to the quantizer 18.
To the bit number deciding circuit 19 is supplied an output signal of a comparator circuit 22. The comparator 22 is supplied with the original dynamic range DR (=MAX-MIN) from a subtracter circuit 20, and threshold values T1 to T4 (T1<T2 T3<T4) from a buffering circuit 21. The assigned bit number n is determined on the basis of the relationship between the magnitude of the dynamic range DR and the magnitudes of the threshold values T1 to T4.
The variable-length ADRC can perform efficient coding by decreasing the assigned bit number n in blocks in which the dynamic range DR is smaller and by increasing the assigned bit number n in blocks where the dynamic range DR is larger. More specifically, in a block in which DR<T1, the bit number n is set as 0 and no code signal is transmitted, and the dynamic range DR' and the average value MIN' alone are transmitted. In blocks in which T1≦DR<T2, the bit number is set as (n=1). In blocks in which T2≦DR<T3, the bit number is set as (n=2). In blocks in which T3≦DR<T4, the bit number is set as (n=3). In blocks in which DR≧T4 the bit number is set as (n=4). The assigned bit number n determined in this manner and the concealed dynamic range DR' are supplied to the quantizer 18, and edge-match quantization is carried out.
In such variable-length ADRC, the amount of generated information can be controlled (so-called buffering) by varying the threshold values T1 to T4. Therefore, variable-length ADRC may be adapted to a transmissions path, e.g. a digital VTR, which requires that the amount of generated information for each field or each frame be maintained at a predetermined value.
In FIG. 4, reference numeral 21 designates a buffering circuit which determines the threshold values T1 to T4 for limiting the generated information amount to a predetermined value. In the buffering circuit 21, a plurality of, for example, 32 sets of threshold values (T1, T2, T3 and T4) are prepared as will be referred to later, and these sets of threshold values are discriminated or identified by a parameter code Pi (i=0, 1, 2, . . . , 31). As the number i of the parameter code Pi increases, the amount of generated information decreases. However, as the amount of generated information decreases, the decoded picture quality is deteriorated.
In the comparator 22 to which threshold values T1 to T4 from the buffering circuit 21 and the dynamic range DR from the subtracter circuit 20 are applied, respective threshold values are compared with the dynamic range DR, and comparison outputs are supplied to the bit number deciding circuit 19 which determines therefrom the assigned bit number n of the block. In the quantizer 18, the data PD1, from which the minimum value MIN' has been removed, is converted into a code signal DT by edge-match quantization using the concealed dynamic range DR' and the assigned bit number n. The quantizer 18 is formed of, for example, a ROM.
A flag F is formed in a comparator circuit 23 for use at the receiver side in properly setting the assigned bit number n. The comparator circuit 23 is supplied with the original dynamic range DR, the concealed dynamic range DR' and a threshold value Ti selected by a selector 24. The selector 24 is supplied with the threshold values T1 to T4 formed in the buffering circuit 21 and information of the assigned bit number n from the bit number deciding circuit 19. A lower threshold value Ti for deciding the assigned bit number n of the block is selected by the selector 24. For example, in case of (n=2), the threshold value T2 is selected by the selector 24.
In the case of the relationship (DR≧Ti>DR') which causes a mismatching such that the bit number assigned on the part of the encoder is regarded as (n-1) with respect to the bit number n assigned on the part of the decoder, the comparator circuit 23 generates a flag F indicating "1", and when the described relationship is not established, it generates a flag F indicating "0".
In order to ensure that the variation of the assigned bit number caused by a difference between the original dynamic range DR and the concealed dynamic range DR' does not exceed 1 bit (that is, in order to prevent a variation of 2 bits), the threshold values T1 to T4 are set to satisfy the following relationship.
T2≧2T1T3≧6/8×T2, T4≧6/14×T3
The concealed dynamic range DR', the average value MIN', the code signal DT, the parameter code Pi indicative of a specific set of threshold values, and the flag F are all supplied to a frame segmentation circuit 25. Data to be transmitted and which have been converted into serial data are taken out at an output terminal 26 of the frame segmentation circuit 25. In the frame segmentation circuit 25, a coding of an error correction code is carried out, if necessary, and a synchronizing signal is added.
FIG. 6 shows a construction of a receiver (or reproducer) which is complementary to the transmitter of FIG. 4. Received data from an input terminal 31 are fed to a frame separation circuit 32. The code signal DT and the added codes DR', MIN', Pi and F are separated from the received data and undergo an error correction processing in the frame separation circuit 32.
The code signal DT is fed to a decoder circuit 33, and the parameter code Pi is applied to a ROM 34. The ROM 34 generates a set of threshold values T1 to T4 indicated by the parameter code Pi, and the set of threshold values is supplied to a comparator circuit 35. The concealed dynamic range DR' is fed to the comparator circuit 35, and an output signal of the comparator circuit 35 is applied to a bit number deciding circuit 36. The bit number deciding circuit 36 decides an assigned bit number for the block based on the relationship between the concealed dynamic range DR' and the threshold values, and generates data corresponding to the bit number. An output of the bit number deciding circuit 36 is fed to an adder circuit 37 and there added to the flag F.
As described above, since the flag F represents "1" when the assigned bit number decided by the bit number deciding circuit 36 is less by 1 bit than that assigned on the part of the encoder by the bit number deciding circuit 19, a proper assigned bit number is obtained at the output of the adder circuit 37. The proper assigned bit number from the adder circuit 37 and the concealed dynamic range DR' are fed to the decoder 33. The average value MIN' is applied to an adder circuit 38. The adder 38 is supplied with an output signal of the decoder 33, and an output signal of the adder 38 is applied to a block separation circuit 39. The decoder 33 carries out a processing opposite to the processing performed by the quantizer 18 in the transmitter. More specifically, in the decoder 33, the code signal DT is decoded into a plurality of representative levels each including MAX' and MIN', and the resulting data and the average value MIN' of 8 bits are added by the adder 38, thereby to decode the original pixel data.
The output signal of the adder 38 is fed to the block separation circuit 39. The block separation circuit 39 is a circuit which, contrary to the block segmentation circuit 2 in the transmitter, converts the decoded data in the order of blocks into a different order which is the same as the television signal scanning order. At an output terminal 40 of the block separation circuit 39 is obtained a decoded video signal.
FIG. 7 shows an example of the buffering circuit 21. In order to form a frequency distribution table and an integrating type frequency distribution table, a memory (RAM) shown at 41 is provided in the buffering circuit 21, and an address signal is supplied to the memory 41 via a multiplexer 42. The dynamic range DR is supplied from an input terminal 43 as one of the inputs to the multiplexer 42, and an address from an address generator circuit 50 is fed as the other input of the multiplexer 42. Data to be written in the memory 41 is supplied to an input thereof from an output of an adder circuit 44, and data read out of the memory 41 and an output of a multiplexer 45 are added in the adder circuit 44.
The output of the adder circuit 44 is fed to a register 46, and an output of the register 46 is supplied to the multiplexer 45 and to a comparator circuit 47. The multiplexer 45 is supplied with data representing 0 and +1 in addition to the output of the register 46. When an operation for computing the amount of generated information is carried out, an information amount Ai generated in one frame period, for example, is obtained at the output of the register 46.
The generated information amount Ai and a target value Q from a terminal 48 are compared in the comparator 47, and an output signal of the comparator 47 is fed to a parameter code generator circuit 49. The parameter code Pi from the parameter code generator 49 is applied to the address generator 50 and a register 51. The parameter code Pi output from the register 51 is fed not only to the frame segmentation circuit 25, as described before, but also to a ROM 52. The ROM 52 generates a set of threshold values (T1i, T2i, T3i and T4i) corresponding to the parameter code Pi entered in the ROM as an address. The threshold values are fed to the comparator 22 as described before.
FIG. 8 is a flow chart which shows an operation of the buffering circuit 21. In the first step shown at 61, the memory 41 and the register 46 are cleared to zero. Because of the zero clearance of the memory 41, the multiplexer 42 selects an address generated in the address generator 50, and the output of the adder circuit 44 is continuously held at zero. The address varies in the order of (0, 1, 2, . . . , 255), and zero (0) data is written into all addresses of the memory 41.
In next step at 62, a frequency distribution table of dynamic ranges DR in one frame, which is a unit period for buffering, is formed in the memory 41. The multiplexer 42 selects the dynamic ranges DR from the terminal 43, and the multiplexer 45 selects +1. Therefore, when the one-frame period expires, occurrence frequencies of respective dynamic ranges DR are stored in respective addresses of the memory 41 corresponding to the dynamic ranges DR. An example of a frequency distribution table of the memory 41 is as shown in FIG. 9A, in which the DR is plotted along the abscissa and the frequency of occurrence of each DR is plotted along the ordinate.
Subsequently, in step 63, the frequency distribution table is converted into an integrating type frequency distribution table. For forming of the integrating type frequency distribution table, the multiplexer 42 selects an address from the address generator 50, and the multiplexer 45 selects the output of the register 46. The address signal supplied to the memory 41 sequentially decrements from 255 toward 0. The read-out output of the memory 41 is fed to the adder 44, and it is there added to the contents of the register 46 supplied through the multiplexer 45 to the adder 44. An output of the adder 44 is written into the same address of the memory 41 as the address from which reading is then occurring, and the contents of the register 46 are renewed by the output of the adder 44. Thus, the frequencies of occurrence of the several dynamic ranges DR are accumulated at the respective addresses of the memory 41. In the initial condition where the address of the memory 41 is 255, the register 46 is cleared into zero (0). An integrating frequency distribution table, for example, as shown in FIG. 9B, is formed in the memory 41 when occurrences are accumulated for all the addresses of the memory 41 as described above.
The amount of generated information Ai at the time when the set of threshold values (T1i, T2i, T3i and T4i) is adapted to the integrating type frequency distribution table is computed in step 64. For the computation of the generated information amount Ai, the multiplexer 42 selects the output of the address generator 50, and the multiplexer 45 selects the output of the register 46. The parameter code generator 49 generates a parameter code which sequentially varies from P0 to P31. The parameter code Pi is fed to the address generator 50, and addresses corresponding to the respective threshold values (T1i, T2i, T3i and T4i) are successively generated. Values read out of the addresses of the memory 41 corresponding to the respective threshold values are accumulated in the adder 44 and the register 46. This integrated value corresponds to the generated information amount Ai at the time when the set of threshold values indicated by the parameter code Pi is adapted. More specifically, in the integrating type frequency distribution table of FIG. 9B, the value which is obtained by multiplying the total value (A1+A2+A3+A4) of the respective values A1, A2, A3 and A4 read out of the addresses corresponding to the threshold values T1, T2, T3 and T4 by the number of picture elements (64) in the block is the generated information amount (bit number). However, since the number of picture elements is constant, the process of multiplying the total of A1+A2+A3+A4 by 64 is omitted in the buffering circuit 21 of FIG. 7.
In the next step 65, the comparator circuit 47 compares the generated information amount Ai with the target value Q. An output of the comparator circuit 47 generated when the relationship (Ai≦Q) is determined to exist in step 65 is fed to the parameter code generator 49. As a result, incrementing of the parameter code Pi is stopped, and the parameter code Pi is fed into the register 51. The parameter code Pi from the register 51 and a corresponding set of threshold values generated in the ROM 52 are discussed in the next step 66.
If the relationship (Ai≦Q) is not established in the judging step 65 by the comparator 47, the program returns to step 64 through a step 67 in which the parameter code Pi is updated or changed into a subsequent code Pi+1 corresponding to an updated set of threshold values, and an address corresponding to Pi+1 is generated by the address generator 50. In the same manner as described above, a generated information amount Ai+1 is computed, and it is compared to the target value Q in the comparator 47. This operation is repeated until the relationship of (Ai≦Q) is established.
In the above described embodiment of the invention, the code signal DT, the concealed dynamic range DR' and average value MIN' are transmitted. In lieu of the concealed dynamic range, the average value MAX' and a quantization step width may be transmitted as additional codes.
A second embodiment of the invention is described below, with reference to FIGS. 10A and 10B which together constitute FIG. 10 in which elements equivalent to those of the first embodiment of FIG. 4 are denoted by the same reference numerals and their detailed explanation is omitted accordingly.
In the embodiment of FIG. 4, the data PDI is quantized adaptively to the concealed dynamic range DR' according to the bit number n decided in the bit number deciding circuit 19. Therefore, under the above-indicated relationship between the original dynamic range DR and the concealed dynamic range DR', since mismatching occurs between the bit number n on the part of the transmitter and the bit number obtained on the part of the receiver by comparing the transmitted dynamic range DR' with the threshold value Ti generated on the basis of the transmitted parameter code Pi, a flag F is also transmitted to insure proper decoding.
In the second embodiment shown in FIG. 10, in order to omit transmission of the flag F, information concerning the threshold values T1 to T4 obtained by the buffering circuit 21 is compared with the concealed dynamic range DR' in a comparator circuit 28, and a bit number deciding circuit 27 decides a bit number n' for quantization on the basis of, a comparison output of the comparator 28, whereupon, the data PDI are quantized by the quantizer 18 according to the bit number n'. Under this arrangement, quantizing bit numbers employed in the transmitter and the receiver, respectively never fail to coincide, and transmission of the flag F is not necessary.
An arrangement in a receiver for receiving data transmitted from the transmitter of FIG. 10 is explained below with reference to FIG. 11 in which elements equivalent to those in the receiver shown in FIG. 6 are designated by the same reference numerals. As described above, since the transmitter shown in fig. 10 performs quantization using the bit number n' which is obtained by comparing the concealed dynamic range DR' with the threshold value information T1 to T4 obtained in the buffering circuit 21, the receiver can readily decode the quantizing bit number n' from the transmitted parameter code Pi and the concealed dynamic range DR'. Decoding of the quantizing bit number n' is effected in a decoder circuit 33 in the arrangement of FIG. 11. Its detail, however, is omitted. Data DT are decoded based on the decoder bit number information n' and the dynamic range DR'. Other operations of the arrangement of FIG. 11 are equal to those of the arrangement of FIG. 6, and their detailed explanation is omitted.
A third embodiment of the invention is explained below with reference to FIG. 12 comprised of FIGS. 12A and 12B and in which some elements equivalent to those of FIGS. 4 and 10 are designated by the same reference numerals, and a detailed explanation thereof is omitted in the following description.
In the third embodiment of FIG. 12, edge-match quantization using a fixed bit number is first performed as a preliminary processing. After this, by averaging data belonging to the maximum and minimum bit planes, new values MAX' and MIN' are obtained. The quantizing bit number is decided by effecting a buffering based on a concealed dynamic range DR' obtained from the values MAX' and MIN'. Therefore, by performing fixed-bit shifting of a dynamic range DR of an output of the maximum/minimum detector 3 in the bit shift circuit 9, a value of one quantizing step width (Δ=1/16 DR) is obtained. Subsequent processings are the same as in the first and second embodiments. The concealed dynamic range DR' obtained in the subtractor 15 is supplied to the buffering circuit 21. The buffering circuit 21 in FIG. 12B may have the same arrangement as the buffering circuit shown in FIG. 7 and, its operation is the same as that explained with reference to the flow chart shown in FIG. 8. The threshold values T1 to T4 obtained in the buffering circuit 21 on FIG. 12B are supplied to the comparator 22 for comparison with the concealed dynamic range DR' supplied thereto through a delay circuit 122 and, based on an output of the comparator 22, the bit number deciding circuit 19 decides the quantizing bit number n. The quantizer 18 is responsive to the quantizing bit number n to quantize the data PDI after passing through a delay circuit 123 adaptively to the dynamic range DR'. As a result, quantized data DT are obtained. The quantized data DT, the average value MIN' delayed in a delay circuit 124, the concealed dynamic range DR' delayed by the delay circuit 122, and the parameter code Pi are supplied to the frame segmentation circuit 25. Delay circuits 122, 123 and 124 are used to delay respective signals by a time required for processing in the buffering circuit.
The same arrangement as that in the receiver apparatus shown in FIG. 11 may be employed for receiving data transmitted from the transmitter apparatus according to the third embodiment of FIG. 12.
FIG. 13 shows a fourth embodiment which is basically analogous to the third embodiment of FIG. 12 except that, while the embodiment of FIG. 12 obtains the one quantizing step width Δ by fixed-bit shifting of the original dynamic range DR, the embodiment of FIG. 13 is configured to enter a fixed value Δ from a terminal 9 and to subtract that value Δ from the maximum value MAX and add the value Δ to the minimum value MIN. The fixed value Δ preferably corresponds to the noise level. Other arrangements and operations of the embodiment of FIG. 13 are the same as those in the embodiment of FIG. 12.
In the first embodiment of FIG. 4 heretofore referred to, flag information is required as additional information. In the second embodiment of FIG. 10, since the buffering itself is based on the original dynamic range and the quantizing bit number is decided upon from the resulting threshold value information and the concealed dynamic range DR' so that the quantization is performed accordingly, such a low efficiency may result that the actual information amount is greater than the allowable maximum information amount. In the third embodiment of FIG. 12 and in the fourth embodiment of FIG. 13, since non-edge matching quantization using the fixed bit number is performed as a preliminary processing regardless of any value of the original dynamic range DR, they are also not optimum from the viewpoint of efficiency.
A fifth embodiment removing these drawbacks is explained below with reference to FIGS. 14A and 14B which, although connected actually, are drawn separately on account of the limited area of each drawing sheet.
In FIG. 14A, a digital video signal (video luminance signal) in which one sample is quantized with eight bits, for example, is supplied through an input terminal 1 to a block segmentation circuit 2.
In the block segmentation circuit 2, the input digital video signal is converted into successive signals for each two-dimensional block which is the unit of coding. In this embodiment, each block is comprised of 8 lines ×8 pixels =64 pixels, as shown in FIG. 5. An output signal of the block segmentation circuit 2 is supplied to a maximum/minimum value detector circuit 3 and a delay circuit 4. The maximum/minimum value detector 3 detects a minimum value MIN and a maximum value MAX of each block. The delay circuit 4 delays the input data by a time required for detecting the maximum value and the minimum value. Pixel data from the delay circuit 4 are supplied to comparator circuits 5A, 5B, 5C and 5D and to comparator circuits 6A, 6B, 6C and 6D.
The maximum value MAX from the maximum/minimum value detector 3 is fed to subtracter circuits 7A, 7B, 7C and 7D and to adder circuits 8A, 8B, 8C and 8D. The subtracter circuits 7A, 7B, 7C and 7D and the adder circuits 8A, 8B, 8C and 8D are supplied from bit shift circuits 9A, 9B, 9C and 9D with values Δ4=1/16DR, Δ3=1/8DR, Δ2=1/4DR and Δ1/2DR, respectively, of one quantization step width at the time of non-edge matching quantization using respective bit numbers, that is 4 bits, 3 bits, 2 bits and 1 bit, respectively. The bit shift circuits 9A, 9B, 9C and 9D are configured to shift a dynamic range DR by 4 bits, 3 bits, 2 bits and 1 bits, respectively, so as to perform these subtractions. From the subtracters 7A, 7B, 7C and 7D are obtained threshold values of MAX-Δ4, MAX-Δ3, MAX-Δ2 and MAX-Δ1, respectively, and from the adders 8A, 8B, 8C and 8D, threshold values of MIN+Δ4, MIN+Δ3, MIN+Δ2 and MIN+Δ1, respectively, are obtained. These threshold values from the subtracters 7A, 7B, 7C and 7D and from the adders 8A, 8B, 8C and 8D are fed to the comparators 5A, 5B, 5C and 5D and to comparator circuits 6A, 6B, 6C and 6D, respectively, for comparison therein with the pixel data from delay circuit 4.
Output signals of the comparators 5A, 5B, 5C and 5D are supplied to AND gates 10A, 10B, 10C and 10D, and output signals of the comparators 6A, 6B, 6C and 6D are fed to AND gates 11A, 11B, 11C and 11D, respectively. The pixel data from the delay circuit 4 is also supplied to the AND gates 10A, 10B, 10C and 10D and to the AND gates 11A, 11B, 11C and 11D. The output signals of the comparators 5A, 5B, 5C and 5D represent high levels when the input data from delay circuit 4 is larger than the threshold levels from subtracters 7A, 7B, 7C and 7D, respectively. Therefore, at the output terminals of the AND gates 10A, 10B, 10C and 10D are extracted the pixel data of the input data which are contained in the maximum level ranges of MAX to MAX-Δ4, MAX to MAX-Δ3, MAX to MAX-≢2, and MAX to MAX-Δ1, respectively. The output signals of the comparators 6A, 6B, 6C and 6D represent low levels when the input data from delay circuit 4 is smaller than the levels from adder circuits 8A, 8B, 8C and 8D, respectively. Therefore, at the output terminals of the AND gates 11A, 11B, 11C and 11D are extracted the pixel data of the input data which are contained in the minimum level ranges of MIN to MIN+Δ4, MIN to MIN+Δ3, MIN to MIN+Δ2, and MIN to MIN +Δ1, respectively.
Output signals of the AND gates 10A, 10B, 10C and 10D are supplied to averaging circuits 12A, 12B, 12C and 12D, and output signals of the AND gates 11A, 11B, 11C and 11D are fed to averaging circuits 13A, 13B, 13C and 13D. These averaging circuits 12A, 12B, 12C, 12D, 13A, 13B, 13C and 13D each calculate an average value for each block, and reset signals appearing at the block intervals are supplied to the averaging circuits 12A, 12B, 12C, 12D, 13A, 13B, 13C and 13D from a terminal 14. From the averaging circuit 12A is obtained a maximum average value MAX4 of the pixel data belonging to the maximum level range of MAX to MAX-Δ4 and, from the averaging circuits 12B, 12C and 12D, there are obtained maximum average values MAX3, MAX2, and MAX1 of the pixel data belonging to the maximum level ranges of MAX to MAX-Δ3, MAX to MAX-Δ2, and MAX to MAX-Δ1, respectively. From the averaging circuits 13A, 13B, 13C and 13D are obtained minimum average values MIN4, MIN3, MIN2 and MIN1 of the pixel data belonging to the minimum level ranges of MIN to MIN+Δ4, MIN to MIN+Δ3, MIN to MIN+Δ2 and MIN to MIN+Δ1, respectively. Representative sets of corresponding maximum and minimum average values under subtraction from each other in subtracter circuits 15A, 15B, 15C and 15D, respectively, and concealed dynamic ranges DR4, DR3, DR2 and DR1 are obtained from the subtracters 15A, 15B, 15C and 15D.
FIGS. 15A to 15D are diagrams for explaining formation of the dynamic ranges DR4, DR3, DR2 and DR1. As shown in FIG. 15A, the bit shift circuit 9A divides the original dynamic range DR into 16 equal parts and forms the quantizing step width Δ4. Average values of pixel data present in the maximum level range (MAX-Δ4) and in the minimum level range (MIN+Δ4) are used as the maximum value MAX4 and the minimum value MIN4. As shown in FIG. 15B, the bit shift circuit 9B divides the original dynamic range DR into 8 equal parts and forms the quantizing step width Δ3. Average values of pixel data present in the maximum level range (MAX-Δ3) and in the minimum level range (MIN+Δ3) are used as the maximum value MAX3 and the minimum value MIN3. Using the quantizing step width Δ2 which is formed in the bit shift circuit 9C, the maximum value MAX2 and the minimum value MIN2 are formed as shown in FIG. 15C. Using the quantizing step width Δ1 which is formed in the bit shift circuit 9D, the maximum value MAXi and the minimum value MIN1 are formed as shown in FIG. 15D.
As shown in FIG. 14B, the average values MIN4, MIN3, MIN2, and MIN1 are supplied to subtracter circuits 216A, 216B, 216C and 216D which subtract the average minimum values MIN4, MIN3, MIN2, and MIN1, respectively, from the input data PD arriving through a delay circuit 17 to form data PDI after removal of the minimum values. These data PDI and the concealed dynamic ranges DR4 to DR1 are supplied to quantizer circuits 218A, 218B, 218C and 21BD, respectively. This embodiment performs edge-match quantization which is a variable-length ADRC in which the bit number n assigned to the quantization is either 0 bit (no code signal is transmitted), 1 bit, 2 bits, 3 bits or 4 bits. The quantizers 218A, 218B, 218C and 218D each consist of, for example, a ROM, and their output signals are supplied to a selector 219.
A code signal selected by the selector 219 is transmitted as a coding output DT. There is provided a further selector 220 which is supplied with the concealed dynamic ranges DR4 to DR1 and the minimum values MIN4 to MIN1. The selectors 219 and 220 are controlled by a bit number code Bn which is read out of a ROM 221. The assigned bit number n indicated by the bit number code Bn is decided for each block by the ROM 221, and the bit number code Bn is supplied to the quantizers 218A, 218B, 218C and 218D. Variable-length ADRC performs efficient coding by decreasing the assigned bit number n in a block where the dynamic range DR is smaller and by increasing the assigned bit number n is a block where the dynamic range DR is larger. More specifically, assuming that the threshold values used deciding the bit number n are T1 to T4 (T1<T2<T3<T4), no code signal is transmitted in blocks of (DR<T1), and information only as to the dynamic range DR1 is transmitted. In blocks of (T1≦DR2<T2, the bit number is set as (n=1). In blocks of (T2≦=DR3<T3, the bit number is set as (n=2). In blocks of (T3≦=DR4<T4, the bit number is set as (n=3). In blocks of (DR4 ≧T4), the bit number is set as (n=4).
The ROM 221 is supplied with comparison output signals from comparator circuits 222A, 222B, 222C and 222D as addresses. The comparator 222A compares the dynamic range DR4 with the threshold value T4, the comparator 222B compares the dynamic range DR3 with the threshold value T3, the comparator 222C compares the dynamic range DR2 with the threshold value T2, and the comparator 222D compares the dynamic range DR1 with the threshold value T1. These comparators supply output signals of "1" (high level) for the condition Drn>Tn, in which n=0, 1, 2, 3 or 4. Assuming the comparison output signals of the comparators 222A, 222B, 222C and 222D are a, b, c and d, respectively, the ROM 221 produces the output signal Bn of 3 bits according to the following table.
______________________________________a 1 0 0 0 0b 1 1 0 0 0c 1 1 1 0 0d 1 1 1 1 0Bn 4 3 2 1 0______________________________________
When (Bn=4) is established, the selector 219 selects the output signal of the quantizer 218A, and the selector 220 selects DR4 and MIN4. In case of (Bn=3), the selector 219 selects the output signal of the quantizer 218B, and the selector 200 selects DR3 and MIN3. In case of (Bn=2), the selector 219 selects the output signal of the quantizer 218C, and the selector 220 selects DR2 and MIN2. In case of (Bn=1), the selector 219 selects the output signal of the quantizer 218B, and the selector 220 selects DR2 and MIN2. In case of (Bn=0), the selector 219 does not supply any code signal, and the selector 220 selectively supplies DR1 and MIN1.
The code signal DT selected by the selector 219, the dynamic range Drn and the average value MINn both selected by the selector 220, and a parameter code Pi (FIG. 14A-2) indicative of a specific set of threshold values are supplied to a frame segmentation circuit (not shown). The frame segmentation circuit performs a coding of an error correcting code, if necessary, and adds a synchronizing signal. At an output terminal of the frame segmentation circuit, transmitted data converted into serial data is taken out.
Variable-length ADRC can control the generated information amount by varying the threshold values T1 to T4, that is, by so-called buffering. Therefore, variable-length ADRC is useful in a transmission path, e.g., a digital VTR, which requires the amount of generated information for each field or each frame to be a predetermined value.
The embodiment of FIG. 14 uses distribution table generator circuits 223A, 223B, 223C and 223D as shown in FIG. 14A-2 in order to compute amounts of generated information. The distribution table generator 223A is supplied with the concealed dynamic range DR4 from the subtracter 15A. The distribution table generators 223B, 223C and 223D are similarly supplied with the dynamic ranges DR3, DR2 and DR1 from the subtracters 15B, 15C and 15D, respectively. The distribution table generator 223A creates in a memory a table corresponding to an occurrence frequency distribution graph as shown in FIG. 16A which indicates the dynamic range DR4 in the abscissa and the occurrence frequencies in the ordinate. The distribution table generators 223B, 223C and 223D similarly create, in respective memories, tables corresponding to occurrence frequency distribution graphs shown in FIGS. 16B, 16C and 16D, respectively. The occurrence frequency table is formed for each predetermined period, e.g., every frame period or every two frame periods. After the tables are formed, the distribution table generators 223A, 223B, 223C and 223D are supplied with the threshold values T4, T3, T2 and T1, respectively, from a threshold value table 224 which may be formed of a ROM.
In the threshold value table 224, plural sets e.g., 32 sets, of threshold values (T1, T2, T3 and T4) are prepared and these sets of threshold values are discriminated or identified by a parameter code Pi (i=0, 1, 2, . . . , 31). As the number i of the parameter code Pi increases, the amount of generated information decreases. However, as the generated information amount decreases, the decoded picture quality is deteriorated.
When the threshold value T4 is applied to the distribution table generator 223A, it aggregates the number of blocks including dynamic ranges DR4 larger than the threshold value T4 as shown by hatched lines in FIG. 16A, and supplies an aggregated value S4. The aggregated value S4 is the total number of blocks to which the bit number of 4 bits is assigned. When the threshold value T3 is applied to the distribution table generator 223B, it aggregates the number of blocks including dynamic ranges DR3 larger than the threshold value T3 as shown by hatched lines in FIG. 16B, and supplies an aggregated value S3. The distribution table generators 223C and 223D similarly supply aggregated values S2 and S1 of blocks including dynamic ranges larger than the threshold values T2 and T1, respectively, as shown by hatched lines in FIGS. 16C and 16D. In FIGS. 16B, 16C and 16D, regions discriminated by different threshold values are shown by different hatched lines.
The aggregated value S4 is the total number of blocks whose assigned bit number is 4 bits. The aggregated value S3 is the total number of blocks whose assigned bit number is 3 bits or more. The aggregated value S2 is the total number of blocks whose assigned bit number is 2 bits or more. The aggregated value S1 is the total number of blocks whose assigned bit number is 1 bit or more. Therefore, a value obtained by multiplying the sum of the aggregated values obtained from an adder circuit 226 by the number of picture elements in one block (64 in this embodiment) is the total of the bit numbers in a predetermined period. However, since the number of picture elements is constant, multiplication by 64 is omitted in this embodiment.
An output signal of the adder circuit 226 is supplied to a comparator circuit 227, and it is there compared with a target value from a terminal 228. When the generated information amount is equal to or less than the target value, the amount of data transmitted in a predetermined period is deemed to be within the capacity of the transmission path. An output signal of the comparator 227 is supplied to a read-out control circuit 225. The read-out control circuit 225 controls the reading of the threshold values T4 to T1 from the threshold value table 224. When, for example, there are sets of threshold values T4 to T1 stored in the threshold value table 224, they are selectively read out of the threshold value table 224 along with the parameter code Pi.
In this case, the sets of threshold values are sequentially read out, starting from a set with which the amount of generated information is increased. A set of threshold values read out at the time when the generated information amount from the adder circuit 226 comes under the target value is decided to be the optimum set. This optimum set of threshold values is supplied to the comparators 222A to 222D (FIG. 14B). Additionally, the parameter code Pi indicative of the selected set of threshold values is supplied from the table 224 to the frame segmentation circuit (not shown) and transmitted to the receiver.
Referring to FIGS. 16A to 16D, in respect of obtaining aggregated values S4 to S1 of the number of blocks larger than the threshold values T4 to T1, the distribution table is preferably converted into an integrating type in order to ensure quick generation of the aggregated values when the threshold value is changed. Taking the distribution table of FIG. 16A as an example, an integrating type distribution table shown in FIG. 16E is obtained by sequentially integrating occurrence frequencies from the maximum value of the dynamic range DR4 toward the minimum value thereof. In the integrating type distribution table, the integrating type occurrence frequency, at the time when the threshold value T4 is given, is just the aggregated value S4. The other aggregated values S3, S2 and S1 can readily be obtained from integrating type distribution tables in the same manner.
The embodiment of FIG. 14A et seq. may be used in combination with a receiver having the same arrangement as that of FIG. 11.
According to the invention, it is possible to prevent block distortion in a block including a ringing, an impulsive noise, or the like. The invention can perform an effective coding using a variable length ADRC, and can prevent mismatching that causes the assigned bit number n to be different for the encoder and the decoder because of a difference in dynamic ranges used for control of the amount of generated information and quantization. Further, upon obtaining a new dynamic range Drn, the maximum levels MAXn and the minimum levels MINn are in the form of average values of pixel data present in the maximum level range and in the minimum level range corresponding to a specific bit number. Therefore, as compared to other systems in which the maximum level range and the minimum level range are fixed at constant values regardless of the assigned bit number, the invention can effectively prevent block distortion.
Although illustrative embodiments of the invention have been described in detail herein with reference to the accompanying drawings, it is to be noted that the invention is not limited thereto, and that various changes and modifications may be effected therein by a person skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
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In a highly efficient coding apparatus, for coding digital video data in a block format and allowing video data compression for transmission using a data transmitter having a predetermined transmission capacity; maximum and minimum values of the digital video data of plural picture elements in a block are detected, the digital video data having values between the maximum value and a first value which is a first predetermined level lower than the maximum value are averaged for generating a modified maximum value, the digital video data having values between the minimum value and a second predetermined level higher than the minimum value are averaged for generating a modified minimum value, the modified minimum value is subtracted from the digital video data for each of the picture elements to generate modified digital video data, modified dynamic range information is generated from the modified maximum and minimum values, an encoding bit number is determined for each block during a predetermined period from the predetermined transmission capacity of the data transmitter, the modified digital video data is subjected to edge-match encoding with the encoding bit number, and an output of the encoder, a first additional code for each block formed of at least two of the modified maximum and minimum values and a signal based on the modified dynamic range information, and a second additional code for each predetermined period referred to above are transmitted.
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PRIORITY CLAIM
[0001] The present application claims priority to U.S. Provisional Application No. 60/471,053 entitled, “GOLF PUTTER WITH ERROR VARIANCE REDUCING INSERT,” filed May 16, 2003, and herein incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The invention relates generally to a golf putter. In particular, the invention relates to a golf putter having an error-variance-reducing hitting surface that is constructed to dampen the impact force of a golf ball by specific proportions over the typical range of forces commonly used in putting the ball.
BACKGROUND OF THE INVENTION
[0003] Throughout the history of golf, various techniques have been used to enhance and alter the hitting characteristics of golf club heads. There are many different head designs, which are intended to alleviate some of the most common swing problems or are specifically tailored for situations a golfer can encounter on a golf course. In addition, a player's physical characteristics, for example, height, weight, build, stroke mechanics, stance, gender, left-handed or right-handed, along with course conditions such as grass conditions, and moisture content, are also factors in determining how an individual will hit a putter.
[0004] Golf club heads, including inserts for at least a portion of the desired striking area, have been used at least as far back as the 1880s, when leather-faced irons were manufactured in Scotland. Golfers in the 1890s were able to purchase putters with faces composed of gutta percha. More recently, inserts composed of various materials in a variety of shapes have been put forth by the golf industry to provide golfers with purported better feel and control of the golf ball.
[0005] Many putter heads made today have what is commonly referred to as a “face insert,” which is placed in a desired impact area on the club head face to provide a certain feel when striking a golf ball. Face inserts may be formed of polymers such as polyurethane while the remaining portion of the putter head is typically formed of a metal such as steel or bronze. Generally, a cavity having a desired shape and depth is provided in the impact area on the putter head face. The face insert is installed in the cavity by either one of two well-known methods. In one method, synthetic resin in a liquid state is poured into the cavity and is then cured so that the face insert is tightly bonded to the cavity. In another method, the face insert is preformed and glued into the cavity by using a suitable adhesive such as epoxy. In both methods, the putter head may be milled after the face insert has been installed to provide a flat face across the club head. A drawback of both of these methods is that they are time consuming and costly.
[0006] The development of insert materials has lead artisans to try and use such materials to develop putter heads that provide better putting results. In the United States, the only constraint guiding selection of potential insert materials is the United States Golf Association (USGA) rule that the striking surface of a putter insert be fairly hard (90 durometer or more on the Shore A scale). Although one finds many suggestions encompassing a wide variety of materials and constructions to improve the feel and accuracy of ball striking, these ideas have no actual basis in research or derivation from accepted science to support claims of actual improvement in putting performance.
[0007] The material used for face inserts in conventional putters is usually a metal or a polymer. The softer feel attributed to some of these materials is preferred by some golfers for various reasons. Most often, golfers suggest that the softer feel increases comfort and results in less vibration when striking the ball. It has been suggested that the softer feel when putting may increase putting accuracy in some way though there has been no actual basis or research to support such a claim. Alternatively, putters have been designed for a harder feel, with the idea that increased vibration from ball impact may help putting accuracy in some way.
[0008] U.S. Pat. No. 4,793,616, issued to Fernandez describes a club head, which is constructed of a molded lightweight composite material. The design is intended to provide improved weight and mass distribution for better ball striking. As disclosed, the invention does nothing to improve compression or feel.
[0009] U.S. Pat. No. 5,403,281 describes a shock-absorbing casing of a magnesium alloy and an elastic plate of an aluminum alloy, a titanium alloy or a ceramic material. This elastic plate is fastened to an open end of the hollow casing such that the elastic plate forms the ball striking surface of the club head. The shock absorbing elastic plate of this invention does not control compression impact or the feel associated with striking the golf ball.
[0010] U.S. Pat. No. 5,340,107 describes a putter of silicon nitride, and construction technique for the same. The putter does not have a layered hitting area, does not control compression impact and does not control the feel of striking the golf ball.
[0011] U.S. patents by Huggens (U.S. Pat. No. 4,156,526) and Douglass (U.S. Pat. No. 5,083,778) disclose how the shape of the insert response may reduce lateral deflection off the striking face of a putter insert. These inventions both suggest that an elliptical-shaped insert is optimal for controlling the direction of ball-rebound off the face, however, these elliptical inserts do not relate to distance control or improved feel.
[0012] Several patents, such as Webb (U.S. Pat. No. 6,270,423), Delaney (U.S. Pat. No. 6,001,030) and Rohrer (U.S. Pat. No. 6,431,997) describe clubs with interchangeable face pads and face inserts that an individual golfer can change himself to influence the feel of the club. However, these inserts do not address distance control.
[0013] While a variety of prior art references have been discussed and mentioned, there has yet to be introduced a golf putter hitting surface that demonstratably improves the forward distance accuracy problems associated with putting a golf ball. The history of golf putter designs, as well as patents disclosing various golf putter designs, reveals no prior mention or awareness of designing a putter head that demonstratably increases putting accuracy through the application of proportional impact damping to reduce putting distance error variability. As such, there is a present need to provide for a golf putter that applies the physics of proportional impact damping to improve distance accuracy associated with golf putting.
SUMMARY OF THE INVENTION
[0014] The golf club of the present invention goes beyond the past and current artisanship of simply trying differing materials for ball striking components to improve the feel of the golf putter. Instead, the present invention provides a demonstratable way of increasing putting accuracy through the use of materials selected to have proportional compression damping characteristics such that the overall error variance associated with putts is reduced.
[0015] The golf club of the present invention reduces forward, line-of-sight distance accuracy problems found in conventional golf putters. Through the use of proportional damping materials under a hard hitting surface, a golf putter provides a damping effect on ball rebound that is proportional to the ball striking force. By varying the construction techniques and selected materials, a proportional damping insert can be configured to have a specific Error Variability Reduction (EVR) profile. The EVR effect is produced by damping hard striking forces more than light striking forces, with the damping effect being proportional to the striking force. The consequence of proportional damping is an increase in forward distance control by reducing the variability of a set of distance measurements around their mean. The proportional damping insert decreases the variability of the distance measures around their mean by the damping proportion of the damping insert, for example EVR proportion=damping proportion. Consequently, missed putts will, on average, end up closer to the hole than is the case with conventional golf putters.
[0016] In one aspect, the present invention comprises a golf putter having an EVR insert. The EVR insert comprises at least one internal proportional damping layer and a hard hitting surface. The internal proportional damping layer can comprise a foam material, such as a vinyl or urethane foam, while the hard hitting surface comprises a material sufficiently hard enough to pass the USGA hardness test. An Ultra High Molecular Weigh (UHMW) polyethylene is one example of a polymer suitable for use as the hard hitting surface. The golf putter further comprises a putter head in which the EVR insert can be fixedly or removably mounted. The golf putter further comprises a shaft attached to the putter head.
[0017] In another aspect, the present invention comprises a putter head having an EVR insert. The putting head includes a cavity for fixedly or removably mounting the EVR insert to the putter head. In an embodiment including a removable EVR insert, a backplate can be used to retain and mount the EVR inset in the putter head.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] [0018]FIG. 1 is a side perspective view of a putter in accordance with the present invention;
[0019] [0019]FIG. 2 is a top perspective view of a putter head in accordance with the present invention;
[0020] [0020]FIG. 3 is a front perspective view of a putter head in accordance with the present invention;
[0021] [0021]FIG. 4 is a top view of a putter head in accordance with the present invention;
[0022] [0022]FIG. 5 is a top sectional view of the club head;
[0023] [0023]FIG. 6 is a graph illustrating an Error Variability Reducing profile for various Error Variability Reducing Inserts of the present invention;
[0024] [0024]FIG. 7 is a front side view of an embodiment of a golf putter with a configurable EVR putter head;
[0025] [0025]FIG. 8 is a rear side view of the golf putter of FIG. 7;
[0026] [0026]FIG. 9 is a rear side view of a head cavity within the golf putter of FIG. 7;
[0027] [0027]FIG. 10 is a front perspective view of the head cavity within the golf putter of FIG. 7;
[0028] [0028]FIG. 11 is a rear perspective view of the head cavity within the golf putter of FIG. 7;
[0029] [0029]FIG. 12 is a top perspective view of an embodiment of an EVR insert assembly;
[0030] [0030]FIG. 13 is a top section view of the EVR insert assembly of FIG. 12;
[0031] [0031]FIG. 14 is a top section view of a configurable EVR putter head;
[0032] [0032]FIG. 15 is a top section view of an embodiment of an EVR insert assembly;
[0033] [0033]FIG. 16 is a rear view of an embodiment of a backplate;
[0034] [0034]FIG. 17 is a rear view of an embodiment of a backplate; and
[0035] [0035]FIG. 18 is a rear view of an embodiment of a backplate.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0036] Referring to FIG. 1, an embodiment of a golf putter 10 in accordance with the present invention is shown. The putter 10 includes a shaft 12 having a top end 14 and a bottom end 16 . Shaft 12 can be constructed of any of the industry standard shaft materials, for example, stainless steel, graphite or other composite materials. Shaft 12 includes a hand grip 18 located at top end 14 . Operably attached to bottom end 16 of shaft 12 is a putter head 20 .
[0037] As depicted in FIGS. 2, 3 and 4 , head 20 includes a front side or face 22 , a rear surface or heel 24 , a forward surface or toe 26 , a rear side 28 , a bottom surface 30 and a top surface 32 . Located on face 22 is a proportional EVR insert 34 . Bottom surface 30 has a slightly arcuate shape from face 22 to rear side 28 for the purpose of avoiding accidental grounding of head 20 during a swing as well as to reduce dragging of head 20 on the ground surface. Top surface 32 includes an alignment groove 36 in perpendicular alignment with the plain of face 22 . In the present invention, alignment groove 36 has a width 38 greater than is typical in current putter designs. Alignment groove 36 is further accentuated through the application of a highly visible coating 40 . Coating 40 , most typically paint, is chosen to distinguish from the color of head 20 . Typical colors for coating 40 can include white, yellow and orange though other colors having similar distinguishing characteristics can be used as well. The body of head 20 can be constructed of any of the common materials currently used in golf putters such as aluminum, bronze, nickel, steel, titanium and other suitable materials.
[0038] Referring to FIG. 5, an EVR insert 34 comprises a multi-layer configuration including an outer striking surface 42 and at least one proportional damping layer 44 . Striking surface 42 can comprise a variety of materials such as stainless steel, bronze, nickel, titanium or suitable polymers. In one embodiment, an Ultra High Molecular Weight (UHMW) polymer, for example UHMW polyethylene with a molecular weight of between 3 million and 6 million can be used. In a preferred embodiment, striking surface 42 is selected to meet a minimum hardness requirement of 90 durometer or greater on the Shore A scale as dictated by rules of the United States Golf Association. Proportional damping layer 44 typically comprises a damping material and has no hardness requirement. Examples of suitable damping materials include polymers and polymeric foams. In an embodiment, a proportional damping layer 44 can comprise a vinyl or urethane foam such as those manufactured by Aero Specialty Composites of Indianapolis, Ind. or Rogers Corp. of Woodstock, Conn. Proportional damping layer 44 can also comprise a plurality of layers, each layer imparting its own damping characteristic. In one embodiment, striking surface 42 and proportional damping layer 44 have material properties that allow for quick and permanent bonding, for example through the use of thermal processes, adhesive processes, molding processes or other suitable bonding processes.
[0039] Generally, face 22 includes a recess 46 in which EVR insert 34 is inserted and attached. Attachment of EVR insert 34 within recess 46 can be permanent through adhesive, thermal or pressing means or EVR insert 34 can be removable attachable through the use of screws or other suitable fasteners. In the case of EVR insert 34 being removably attached with in the recess 46 , a user can alter the proportional damping properties of putter 10 by swapping a first EVR insert with a second EVR insert having an alternative damping proportion.
[0040] In use, a golfer grips putter 10 using the handgrip 18 . The golfer aligns himself, the putter 10 and the ball relative to the target, most commonly a golf hole. Using alignment groove 36 , the golfer positions the face 22 in a perpendicular arrangement to the desired line for the putt. The golfer then swings the putter 10 with a generally parallel swing such that EVR insert 34 , and more specifically the striking surface 42 , contacts the ball and propels it toward the hole. While the use of putter 10 is simple to describe, putting a golf ball consistently and accurately is one of the most difficult skills to acquire when learning the sport of golf. Consistency is difficult as many variables such as putt length, body mechanics, green contours, weather conditions and course conditions make each putt different.
[0041] Through the use of a multi-layer design including proportional damping layer 44 , EVR insert 34 has a proportional damping characteristic that is proportional to the impact energy supplied by putter 10 . Statistically, the use of EVR insert 34 including the proportional damping characteristic reduces overall distance variability of putts around a target as compared to typical solid metal putters or putters having hard polymer inserts that lack proportional damping qualities.
[0042] An EVR insert 34 can be constructed to exhibit optimum proportional damping qualities at a desired range of putt distances, for example 10-20 feet. Similarly, a maximum EVR effect for EVR insert 34 can be constructed specifically for short putts, mid-range putts and longer putts. Even when putt distances are outside the design range of EVR insert 34 , a damping effect will occur that reduces the effects of common swing mistakes such as those typically encountered with very short putts.
[0043] In actual use, an EVR insert 34 can be constructed using a specifically selected proportional damping layer 44 to impart an overall damping proportion of 0.30 or other desired damping proportions. In other words, the impact energy imparted to the golf ball through the EVR insert 34 is reduced by 30% over the desired range of putt distances. A golfer with a 30% EVR putter will have to hit the ball 30% harder to hit the ball comparatively the same distance than when using a putter without any proportional damping qualities. Golfers readily adjust their swings to compensate for a required increase in impact energy as they routinely make similar adjustments to putter weight, green speeds, wet greens and other environmental variables that are experienced between golf courses.
[0044] Referring now to FIGS. 7 and 8, an alternative embodiment of a golf putter 200 including EVR properties is depicted. Similarly to putter 10 , golf putter 200 includes a shaft 202 having a top end 204 and a bottom end 206 . Shaft 202 includes a handgrip 208 located at top end 204 . Operably connected to shaft 202 at bottom end 206 is a configurable EVR head 210 .
[0045] As illustrated in FIGS. 7, 8, 9 , 10 and 11 , configurable EVR head 210 comprises a head body 212 and an EVR insert assembly 214 . Head body 212 is generally defined by a top surface 216 , a bottom surface 218 , a front surface or toe 220 , a rear surface 222 , a front side 224 and a rear side 226 . As shown in FIGS. 10 and 11, a head cavity 228 extends between front side 224 and rear side 226 . Head cavity 228 is defined by a top cavity surface 230 , a bottom cavity surface 232 and a pair of side cavity surfaces 234 a , 234 b , a front opening 236 and a rear opening 238 . Front opening 236 is undersized as compared to rear opening 238 such that a front cavity surface 240 surrounds the perimeter of front opening 236 . Front cavity surface 240 includes a pair of head bores 242 a , 242 b extending into head body 212 such that the head bores 242 a , 242 b do not extend to the front side 224 . Head bores 242 a , 242 b can include an internal thread or other suitable attachment means.
[0046] As illustrated in FIGS. 12 and 13, EVR insert assembly 214 comprises a striking layer 244 , a proportional damping layer 246 and a backplate 248 . Striking layer 244 has a striking surface 250 projecting from a flange surface 252 . Striking surface 250 is sized and shaped to fit snugly within front opening 236 . Proportional damping layer 246 is constructed to have a perimeter equivalent to flanged surface 252 . Backplate 248 has a plate surface 254 and a pair of projecting arms 256 a , 256 b . Projecting arms 256 a , 256 b include arm flanges 257 a , 257 b and insert bores 258 a , 258 b . Projecting arms 256 a , 256 b and plate surface 254 are dimensioned to snugly accommodate the striking layer 244 and the flange surface 252 of striking layer 244 . Projecting arms 256 a , 256 b are dimensioned such that the distance between insert bores 258 a , 258 b corresponds to the distance between head bores 242 a , 242 b.
[0047] To assemble EVR head 210 , EVR insert assembly 214 is positioned such that striking surface 250 fits within front opening 236 as shown in FIG. 14. When properly positioned, striking surface 250 and head body 212 form the substantially smooth and uninterrupted front side 224 . When striking surface 250 is positioned within the front opening 236 , flange surface 252 and arm flanges 257 a , 257 b are in contact with front cavity surface 240 such that head bore 242 a is aligned with insert bore 258 a and head bore 242 b is aligned with insert bore 258 b . Finally, a pair of fasteners 260 a , 260 b , such as a pair of screws, is directed into the insert bores 258 a , 258 b and subsequently into head bores 242 a , 242 b to operably couple the EVR insert assembly 214 and the head body 212 .
[0048] Due to the ability to attach and remove the EVR insert assembly 214 from the head body 212 , it is possible for a golfer to specifically configure the golf putter 200 to have a desired EVR profile, for example High Gain EVR, Low EVR profile or High EVR profile. A golfer can replace a first EVR insert assembly with a second EVR assembly wherein the second EVR insert assembly has a selected proportional damping layer 246 different from that of the first EVR insert assembly. In another alternative embodiment, a golfer could replace EVR insert assembly 214 with EVR insert assembly 262 illustrated in FIG. 15 such that the proportional damping layer 246 is replaced with a first damping layer 264 and a second damping layer 266 . In another alternative embodiment, the EVR properties of the EVR insert assembly 214 can be specifically tailored by removing mass from the plate surface 254 as shown in FIGS. 16, 17 and 18 . As shown, a plurality of perforations 268 , such as channels or spheres, can be fabricated as part of plate surface 254 .
[0049] In order to illustrate the effect of proportional impact damping on putt length variability, an experiment is conducted in which a golfer hits 10 twelve-foot putts with a standard hard (either metallic or polymer) striking surface. The golfer fails to make any of the putts but instead, the putts are distributed around the hole, half being long and half being short. With respect to the distribution, the average length is twelve feet, the range is 8 feet and the standard deviation is 2.74 feet as shown in Column A of Table 1 below.
[0050] When the same 10 golf balls are putted with a proportional damping putter having a damping proportion of 0.30, the corresponding putt lengths and variability are as indicated in Column B of Table 1. Note that the measures of putt average, putt range and putt deviation are 30% less than the values displayed in Column A.
[0051] The average length of Column B putts is only 8.4 feet, which is 3.6 feet short of the required 12 foot required putt length. However, this is not the expected result of using a proportional damping putter. Instead, golfers quickly adapt and learn to hit an EVR putter harder, just as golfers quickly learn to swing harder on slower greens as opposed to fast greens, to swing harder on wet greens as opposed to dry greens, and to swing harder with a light putter as opposed to a heavy putter.
[0052] Column C shows the results wherein a golfer using a proportional damping putter hits the 10 twelve-foot putts 30% harder, on average, than with the standard metal or polymeric faced putter. The average 30% increase in swing force required to distribute the 30% damped putts around the 12 foot target results in an average of 3.6 feet being added to putt lengths shown in Column B to produced the distribution of putts in Column C. Note that the variability measures of the Column C putts are 30% less than the original putts in Column A. Thus, hitting putts harder as required by an EVR putter, does not reduce the accuracy gained with using the EVR putter.
TABLE 1 Column A Non- Column B Column C Proportionally Proportionally Force-Adjusted Putt Damped Putts Damped Putts Damped Putts 1 8 ft 5.6 ft 9.2 ft 2 9 ft 6.3 ft 9.9 ft 3 10 ft 7.0 ft 10.6 ft 4 10 ft 7.0 ft 10.6 ft 5 11 ft 7.7 ft 11.3 ft 6 13 ft 9.1 ft 12.7 ft 7 14 ft 9.8 ft 13.4 ft 8 14 ft 9.8 ft 13.4 ft 9 15 ft 10.5 ft 14.1 ft 10 16 ft 11.2 ft 14.8 ft Average 12 ft 8.4 ft 12.0 ft Range 8 ft 5.6 ft 5.6 ft Standard Deviation 2.74 ft 1.92 ft 1.92 ft
[0053] Quantitatively, putting accuracy with an EVR putter improves by ρ, on average, over putting accuracy with a comparable non-EVR putter where accuracy is measured by standard deviation, where S c =1−ρ (S A ).
[0054] S C : Standard deviation of putts with a proportional damping putter
[0055] S A : Standard deviation of putts with a comparably non-EVR putter
[0056] ρ: The damping proportion.
[0057] A second experiment was conducted as described above with putters having different damping constructions to illustrate that using different damping materials results in EVR putters with differing EVR profiles. FIG. 6 presents EVR measurements for the three EVR insert configurations used in the experiment.
[0058] The experiment was conducted using a putting machine programmed with seven putting force levels. Each of four putters hit eight matching golf balls at each force level. The putters were identical in construction with respect to putter length, head weight and striking surface. The putting machine hit the golf balls on a moderately fast putting green with a green speed stimpmeter reading of 11.3 feet. The only variable between each of the four putters was the insert construction as described below:
[0059] Putter 1 : A putter similar to putter 10 including an insert consisting of a UHMW polyethylene striking surface meeting the USGA hardness standard.
[0060] Putter 2 : A putter similar to putter 10 including an insert with the same striking surface used in Putter 1 backed with a 0.03 inch thick layer of urethane foam (Part Number 4701-50-30031-04, produced by Rogers Corp. of Woodstock, Conn.).
[0061] Putter 3 : A putter similar to putter 200 including an insert with the same striking surface used in Putters 1 and 2 backed with a 0.03 inch thick layer of less dense urethane foam (Part Number 4701-30-25031-04, produced by Rogers Corp. of Woodstock, Conn.), and with the insert backplate cut-out in the fashion depicted in FIG. 16.
[0062] Putter 4 : A putter similar to putter 10 including an insert with the same striking surface used in Putter 1 , 2 and 3 backed by a 0.03 inch thick layer of soft urethane foam (Part Number 4701-30-25031-04, produced by Rogers Corp. of Woodstock, Conn.).
[0063] The EVR profiles displayed in FIG. 6 indicate the EVR obtained at the impact force levels required to propel a golf ball the distances indicated on the abscissa. EVR data points for the EVR putters were determined at a given impact force level by comparing the error variance (standard deviation) for a given EVR putter with the error variance (standard deviation) for the standard putter and plotting the percentage difference (error variance reduction) at that level. Best fit trend lines were drawn through the data points for each putter/insert configuration and are shown in FIG. 6 for each configuration.
[0064] The EVR of each of the EVR inserts was determined at a given impact force level by comparing the average ball distance travel produced by the damping inserts as compared to the average ball distance travel produced by the standard non-EVR insert at that same force level. The procedure was repeated at each of the seven force levels, producing the EVR profiles for each of the four putter as shown in FIG. 6. A best-fit trend line was drawn through the data points for each insert configuration. These trend lines are also shown in FIG. 6.
[0065] The EVR profile for Putter 2 presents a generally linear decreasing EVR, from 9% at 4.5 feet to 3.5% at 18.4 feet.
[0066] The EVR profile for Putter 3 shows a steep rate of EVR decrease from 18% at 4.5 feet to 9% at 12 feet and then a shallower linear decrease to 4.5% for putts at 18.4 feet.
[0067] The EVR profile of Putter 4 shows a rate of EVR decrease accelerating from 16% at 4.5 feet to 7% for putts at 18 feet.
[0068] The results shown in FIG. 6 demonstrate the feasibility of designing putters with differing EVR profiles. The EVR profiles for Putters 2 , 3 and 4 in FIG. 6 show the greatest accuracy gain for short and medium length putts. These particular EVR profiles would be most helpful to golfers who have trouble with short distance putts. More specifically, Putter 3 would be the most helpful for golfers who jerk or yip their stroke on short putts.
[0069] In addition to the EVR profiles demonstrated with Putters 2 , 3 and 4 of FIG. 6, putter inserts that that produce level or increasing EVR with increasing putt lengths can be created by layering materials with different damping characteristics.
[0070] The present invention has been described above with reference to a preferred embodiment. However, those skilled in the art will recognize that changes and modifications may be made to the preferred embodiments without departing from the spirit and scope of the present invention.
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A golf putter includes a putter head having an error variability reducing insert that imparts proportional damping properties such that the distance accuracy problems of conventional golf putters are statistically reduced. Through the use of a proportional damping insert comprising at least one exterior striking layer in combination with at least one interior proportional damping layer, the golf putter increases forward distance control by decreasing the distance error consequences of putting swing force errors. The statistical advantage of an error variability reducing insert having proportional damping properties results in missed putts, on average, ending up closer to the hole as compared to conventional putter designs. The exterior striking layer can have a hardness exceeding the level required by the United States Golf Association.
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BACKGROUND
1. TECHNICAL FIELD
This invention relates generally to thermal regulation circuits for power dissipating electronic circuit elements, and more specifically to power regulation and thermal management for power transistors as, for example, in battery charging applications.
2. BACKGROUND ART
FIG. 1 illustrates a simple battery charger 100 that is well known in the art. The charger 100 consists of a power supply 101 , a linear regulator 102 , a pass element 103 and a battery cell 104 . The power supply 101 provides voltage and current to the battery cell 104 . The voltage and current must be regulated by the pass element 103 so as to avoid charging the battery cell 104 too rapidly. The linear regulator 102 performs this regulation by dissipating as heat the difference between the power generated by the power supply 101 and the power stored by the battery cell 104 .
The problem with this prior art solution is that the pass element 103 can overheat. This is best explained by way of example. For a typical single-cell, lithium battery application, a fully charged battery cell 104 typically registers about 4.1 volts. Thus, to fully charge the battery cell 104 , and to give enough headroom for parasitic power losses in the pass element 103 and connecting circuitry, the power supply must be capable of supplying at least 5 volts. A typical battery cell 104 will charge optimally at a current of roughly 1 amp.
The problem arises with the battery cell 104 is fully discharged. A discharged battery cell 104 may register only 2 volts. As the power supply 101 would supply energy at a rate of 5 volts at 1 amp, or 5 watts, and the battery cell 104 stores energy at a rate of 2 volts at 1 amp, or 2 watts, the pass element 103 must dissipate energy at a rate of 3 watts. As typical pass elements 103 may come in a TO-220 package, 3 watts for extended periods of time may make the pass element 103 quite warm. Extended periods of heat my actually jeopardize reliability by approaching—or surpassing—the threshold junction temperature of the pass element 103 .
The problem is exacerbated when an incompatible power supply 101 is coupled to the circuit. For example, if someone accidentally couples a 12-volt supply to the charger, the pass element 103 may have to dissipate 10 watts! This can eventually lead to thermal destruction of the pass element 103 .
One solution to this problem is recited in U.S. Pat. No. 5,815,382, issued to Saint-Pierre et al. entitled “Tracking Circuit for Power Supply Output Control”. This solution provides a means of reducing the output voltage of a power supply when the battery is in a discharged state, thereby reducing the total output power of the power supply. This, in turn, reduces the amount of power a pass element would need to dissipate.
While this is a very effective solution to the problem, it requires a power supply that both includes a feedback input and is responsive to the input by changing the output voltage. The electronics associated with an adjustable power supply can be more expensive that those found is a simple linear transformer power supply.
There is thus a need for an improved means of regulating temperature in a power-dissipating element like those employed as pass elements in battery charging applications.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an illustration of a prior art charging circuit.
FIG. 2A is an illustration of the characteristic output of a constant current, constant voltage power supply.
FIG. 2B illustrates a danger zone of operation in accordance with the invention.
FIG. 3A is an illustration of the characteristic output of a wall transformer power supply.
FIG. 3B illustrates a danger zone of operation in accordance with the invention.
FIG. 4 is a plot of the voltage across a pass element versus the charge current in accordance with the invention.
FIG. 5 is a schematic diagram of a preferred embodiment in accordance with the invention.
FIG. 6 is a piecewise, linear approximation of FIG. 4 in accordance with the invention.
FIG. 7 is an alternate embodiment of a voltage sensing circuit in accordance with the invention.
FIG. 8 is one embodiment of a temperature sensing circuit in accordance with the invention.
FIG. 9 is a block diagram of an alternate embodiment in accordance with the invention.
FIG. 10 is a schematic block diagram of a power management and temperature regulation circuit in accordance with the invention.
DETAILED DESCRIPTION OF THE INVENTION
A preferred embodiment of the invention is now described in detail. Referring to the drawings, like numbers indicate like parts throughout the views. As used in the description herein and throughout the claims, the following terms take the meanings explicitly associated herein, unless the context clearly dictates otherwise the meaning of “a,” “an,” and “the” includes plural reference, the meaning of “in” includes “in” and “on.”
Prior to turning to the specifics of the invention, it is well to briefly examine the operating regions in which there is a risk of thermal damage to a pass element. This is best explained by looking at battery charging applications, although it will be obvious to those of ordinary skill in the art that the invention may be equally applied to other applications as well.
Referring now to FIG. 2A, illustrated therein is the output characteristic 200 of a “constant-voltage-constant-current”, or “CCCV”, power supply. Such supplies are known in the art, as recited by U.S. Pat. No. 5,023,541, entitled “Power Supply Control Circuit Having Constant Voltage and Constant Current Modes”. Another such supply is taught in the application notes for the TL494 control IC manufactured by On-Semiconductor. Segment 201 illustrates a constant voltage of Vmax that is supplied for all load currents less than Imax. Once the load current attempts to exceed Imax, segment 202 represents the maximum current, Imax, that is delivered as the voltage tapers from Vmax to zero.
Referring now to FIG. 2B, illustrated therein is a charging characteristic 203 of the circuit of FIG. 1 when a CCCV source is employed as the power supply. The characteristic 203 is represented as voltage versus percentage of charge. Presuming that an initially discharged battery cell is coupled to the supply, the charging curve begins at Vlow 204 , which essentially represents the voltage of the discharged battery cell. The power supply, by contrast, begins at Vmax 205 . Consequently, there is a difference Vmax 205 minus Vlow 204 that proportionally corresponds to the power that must be dissipated by the pass element. Experimental and theoretical results have shown that a threshold exists, Vok 206 , above which standard pass elements are capable of dissipating power for a given charge rate. However, when the battery cell voltage is below Vok 206 , the pass element is called upon to dissipate more power than it can withstand. Thus, the shaded region 207 represents the “danger zone” for the pass element. Note that the current is below Imax for the voltage to be Vmax.
Referring now to FIG. 3A, illustrated therein is the output characteristic 300 for another common power supply, the common linear transformer. It may be seen from segment 301 that voltage generally rolls off as current increases. A small peak at segment 302 may be caused by rectification circuitry that includes filter capacitors. In any event, the battery charges between the levels Vbatmin 303 and Vbatmax 304 .
Referring now to FIG. 3B, illustrated therein is the power generated by the circuit of FIG. 1 when a linear transformer is employed as the power supply. When the battery cell voltage approaches its termination point, Vbatmax 304 of FIG. 3A, the voltage of the transformer continues to increase while the battery voltage stays relatively constant. This means that the pass element must be able to dissipate the extra power that results from this increasing voltage differential. As a result of the extra power, a pass element danger zone for linear transformers exists in the shaded region 306 .
To summarize the preceding discussion, there are regions of operation in which a battery charger having a pass element works well with no temperature compensation. There are other danger zones, however, where pass element reliability may be compromised. It is one object of this invention to provide a circuit that prevents pass elements or other power dissipating elements from entering danger zones.
Referring again to FIG. 1, the power dissipated in the pass element 103 may be expressed as the voltage of the power supply 101 , minus the voltage of the battery cell 104 , multiplied by the charge current. If the pass element 103 comprises a PNP bipolar junction transistor, as is common in the art, the voltage of the power supply 101 , minus the voltage of the battery cell 104 may simply be represented as Vce, the voltage difference between the emitter 106 voltage and the collector 107 voltage. Thus, the power is given as:
P=Vce*Ichg (EQ.1)
The threshold junction temperature, Tj, of the pass element 103 transistor is the temperature above which the transistor integrity begins to degrade. In other words, if the pass element 103 gets hotter than its threshold junction temperature, it will probably stop working properly. The threshold junction temperature may be represented as:
Tj=P*k+Tamb (EQ. 2)
where P is the power dissipated in the pass element, k is a constant dependent upon the physical Thus, if the ambient temperature is 35 degrees C. and the threshold junction temperature is 150 degrees C, a power dissipation temperature of 115 degrees may be tolerated while still ensuring proper pass element operation.
Substituting EQ. 1 into EQ. 2 yields:
Tj=Vce*Ichg*k+Tamb (EQ. 3)
Solving for Ichg yields:
Ichg= ( Tj−Tamb )/( Vce*k ) (EQ. 4)
Referring now to FIG. 4, illustrated therein is a plot of Vce versus Ichg. In this particular plot, Tj is presumed to be 150 degrees C. as this is common in transistors when used as power dissipating components. Additionally, Tamb is set at a maximum, for example 50 degrees C. as this presents a worst case (i.e. minimum) temperature rise allowed by power dissipation. It will be clear to those of ordinary skill in the art that any number of different plots could be generated by varying these assumptions to fit a particular application.
It is one object of this invention to keep the temperature of the pass element below the threshold junction temperature by reducing Ichg prior to the pass element entering a danger zone. In so doing, the invention provides a safeguard against component failure in battery charging applications.
Referring now to FIG. 5, illustrated therein is one preferred embodiment of a power regulation and thermal management circuit in accordance with the invention. A power supply 501 provides power to the circuit. The power supply 501 may be any of a number of power supply types, including but not limited to CCCV and linear transformers. The power supply 501 is coupled to a pass element 502 . In this preferred embodiment the pass element is a PNP bipolar junction transistor, although a large number of other types of pass elements may be substituted. The pass element 502 in this embodiment includes an emitter 504 and a collector 505 .
A voltage sensing circuit 503 senses the voltage from collector 505 to emitter 504 , Vce. In one preferred embodiment, the voltage sensing circuit includes an op-amp 506 with a preset gain. The voltage sensing circuit 503 delivers a voltage output 507 that is proportional to Vce. The voltage output 507 is coupled to a plurality of comparators 508 , 509 , 510 , each having a distinct reference voltage 511 , 512 , 513 . The reference voltages 511 , 512 , 513 are easily set by resistor dividers. The number of comparators and corresponding reference voltages depends upon the resolution desired. It will be clear to those of ordinary skill in the art that the number of comparators may vary by application. It will also be obvious that the voltage references may be set in linear intervals, e.g. Vref, Vref* 2 , Vref* 3 , etc., as well as in non-linear intervals, e.g. Vref, Vref*a, Vref*b, etc.
A particular comparator will be selected based upon the level of the voltage sense output 507 . Once actuated, the comparator will turn on a corresponding current switching transistor 514 , 515 , 516 . The particular current switch transistor then couples the charging current through a current sensing resistor 517 , 518 , 519 . The resultant current then flows through the cell 520 .
The current is regulated by the current regulator 521 , which in turn provides feedback to the pass element 502 to reduce or increase current accordingly. This is accomplished by comparing the voltage generated by current flowing through the current sensing resistors 517 , 518 , 519 to a reference by way of the current regulator 521 . The values of the current sensing resistors 517 , 518 , 519 , will of course have different values, each corresponding to a different level of current that should be allowed by the current regulator 521 . The current regulator 521 then couples feedback to the pass element 502 to reduce current when the pass element 502 is in a danger zone. In this manner, the circuit facilitates charging at a constant power level (with respect to the pass element 502 ) by reducing current based upon the voltage across the pass element 502 . The circuit is actuated in the danger zones, where Vce*ichg is too large.
Note that the current regulator 521 is essentially dominantly, analog “OR” coupled with a conventional linear regulator 522 . The OR connection 523 allows the current regulator to override the conventional linear regulator 522 when the pass element 502 is in a danger zone. At other, safe operating ranges, the pass element 502 is allowed to remain saturated to allow maximum charge current to flow in accordance with the conventional linear regulator 522 .
By way of example, the circuit was constructed in the lab to charge a single cell lithium battery having a termination voltage of 4.0 volts. The threshold junction temperature was set at 150 degrees C. and the maximum ambient was set at 50 degrees C. Typical power supplies found in electronics stores range from 7 to 25 volts, so these were presumed as realistic limits on input voltage. For a maximum pass element power dissipation of 600 mW, and a tolerance resolution of 15%, a total of 13 comparators and current switch transistors were employed. The component values and input values are shown in Table 1. It should be noted that the “Current Sense Resistor” corresponds to elements 517 , 518 , 519 in FIG. 5, and the Voltage Set Resistors corrrespond to the resistor dividers coupled to the comparators 508 , 509 , 510 , respectively. R1 is coupled to the reference voltage and R2 is coupled to ground. The cell voltage is 4.0 volts.
TABLE 1
Pass
Power
element
Current
Supply
Ichg
power
sense
Voltage Set
Voltage Set
Comparator
Voltage
Vce
(mA)
(mW)
resistor
Resistor R1
Resistor R2
0.00
0.00
0.00
0.00
1
7.00
3.00
0.20
600
3.33
1000
136
1
7.00
3.00
0.17
510
3.33
1000
136
2
7.53
3.52
0.17
600
3.92
1000
164
2
7.53
3.52
0.15
510
3.92
1000
164
3
8.15
4.15
0.15
600
4.61
1000
199
3
8.15
4.15
0.122
510
4.61
1000
199
4
8.89
4.88
0.122
600
5.42
1000
243
4
8.89
4.88
0.104
510
5.42
1000
243
5
9.75
5.75
0.104
600
6.38
1000
299
5
9.75
5.75
0.088
510
6.38
1000
299
6
10.76
6.76
0.088
600
7.51
1000
371
6
10.76
6.76
0.075
510
7.51
1000
371
7
11.96
7.95
0.075
600
8.83
1000
467
7
11.96
7.95
0.064
510
8.83
1000
467
8
13.36
9.35
0.064
600
10.39
1000
598
8
13.36
9.35
0.054
510
10.39
1000
598
9
15.01
11.01
0.054
600
12.23
1000
787
9
15.01
11.01
0.046
510
12.23
1000
787
10
16.95
12.95
0.046
600
14.39
1000
1075
10
16.95
12.95
0.039
510
14.39
1000
1075
11
19.24
15.24
0.039
600
16.93
1000
1562
11
19.24
15.24
0.033
510
16.93
1000
1562
12
21.93
17.93
0.033
600
19.22
1000
2536
12
21.93
17.93
0.028
510
19.22
1000
2536
13
25.09
21.09
0.028
600
23.51
1000
5402
When the circuit is actuated, the 13 comparators yield 13 different currents for 13 different Vce values, each effectively yielding a total power dissipation in the pass element of less than or equal to 600 mW. The circuit thus yields a piecewise linear approximation of the Vce versus Ichg curve shown in FIG. 4 . This piecewise linear charging curve is shown in FIG. 6 .
While the circuit of FIG. 5 is one preferred embodiment of a regulation circuit designed to keep a pass element at a constant power dissipation level during danger zones, it will be clear to those of ordinary skill in the art that the circuit is not so limited. Any number of equivalent circuits that account for voltage, current, ambient temperature and threshold junction temperature of a pass element would also suffice.
Turning now to FIG. 7, one such alternative embodiment will be described. In FIG. 7, a circuit 700 that computes the difference between cell voltage 701 and the power supply voltage 702 completes the voltage sensing function. Recall from the discussion above that danger zones can occur when the power supply voltage 702 is much greater than the cell voltage 701 . Here, a comparator 703 generates a signal 705 proportional to the difference between the power supply voltage 702 and the cell voltage 701 . This signal 705 is coupled to a plurality of comparators 704 , each having a corresponding reference voltage 706 . In this manner, the plurality of comparators 704 selects a voltage range 707 .
Referring now to FIG. 8, illustrated therein is an analogous circuit 800 for sensing temperature. In this circuit 800 , a thermistor 801 generates a voltage that is compared to a plurality of references 802 . Just as a plurality of comparators creates a voltage range in FIG. 7, here, a plurality of comparators 804 generates a temperature range 803 .
Referring now to FIG. 9, the temperature range 803 and voltage range 707 may then be coupled into a selection matrix 901 . The selection matrix 901 may comprise analog circuitry, programmable logic, a memory look-up table, or other equivalent device. The output 902 is then coupled to a current sensing matrix 903 to select the proper gain for the current regulator 521 . The current regulator 521 is then coupled to a conventional regulator 502 to override the conventional regulator 522 when the pass element 502 is in a danger zone.
The invention could equally be carried out with a microprocessor having voltage, current and temperature. inputs. The microprocessor could then use a memory look-up table to select from a plurality of current limiting elements to set the proper gain for the current regulator, thereby ensuring the proper current during danger zone operation. The microprocessor could also solve EQN. 4 directly to select the proper current limiting element for the proper charge current to keep the pass element at a constant power dissipation level in the danger zones.
Referring now to FIG. 10, illustrated therein is a general embodiment 1000 of the invention. The general embodiment 1000 includes a power source 1010 , pass element 1020 and load 1030 as herein described. A voltage sense circuit 1040 senses voltage across the pass element 1020 . A current sense circuit 1050 senses current flowing through the pass element 1020 to the load 1030 . A conventional charge regulator 1050 is provided for non-danger zone operation. A power threshold circuit 1060 is provided that receives the current sense and voltage sense. The power threshold circuit 1060 has stored intemally a predetermined threshold junction temperature threshold. The power threshold circuit 1060 thus computes a current level sufficient to keep the power of the pass element 1020 constant during danger zone operation, and overrides the conventional charge regulator 1050 when necessary. If a predetermined maximum temperature is not desirable, a real time temperature sensor 1070 may optionally be coupled to the power threshold circuit 1060 as well.
While the preferred embodiments of the invention have been illustrated and described, it is clear that the invention is not so limited. Numerous modifications, changes, variations, substitutions, and equivalents will occur to those skilled in the art without departing from the spirit and scope of the present invention as defined by the following claims. For example, while a preferred embodiment included a battery charging application, it will be clear that the circuit may be applied to any number of applications where power dissipating elements require threshold junction temperature protection.
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This invention provides a means of protecting power dissipating pass elements from exceeding their predetermined thermal limits. In one preferred embodiment, the circuit protects a pass element in a battery charging circuit from exceeding its threshold junction temperature by predicting temperature based upon the voltage across the pass element and the current flowing through it. From this predicted temperature, current is reduced to provide charging of a battery at a constant power. The circuit includes a voltage sensing circuit and a plurality of comparators for selecting a predetermined current based upon the output of the voltage sensing circuit. The circuit provides a piecewise linear approximation of proper pass element voltage and current values to maintain a suitable threshold junction temperature.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a pulp mill recovery system. More specifically, the present invention relates to a low temperature kraft spent liquor recovery system utilizing separate reactors for pyrolysis, combustion and sulfate reduction.
2. Description of the Prior Art
The central piece of equipment for recovery of cooking chemicals and energy from kraft black liquor is the so-called Tomlinson furnace. Black liquor at about 65% dry solids content is sprayed into the furnace. During their descent, the black liquor droplets lose the remaining water by evaporation and the solids pyrolyze to form a char bed at the bottom of the furnace. The char bed burns under reducing conditions at a temperature of about 750°-1050° C. and the recovered chemicals, mainly Na 2 CO 3 and Na 2 S, are drained from the furnace as a smelt. The smelt is dissolved in water to produce so-called green liquor, the precursor of the cooking liquor called white liquor. The gases generated during pyrolysis and burning of the char are fully combusted at a higher location in the furnace. The furnace is provided with suitable heat exchange means to recover heat from the hot combustion gases for steam and electricity generation.
Although the objective of the recovery of chemicals and energy is adequately achieved in present commercial operations, the use of the Tomlinson furnace presents a number of problems. For example, inadvertant contact between water and the inorganic smelt has resulted in serious explosions. Also, high char bed temperatures lead to increasing emission of sodium salts and excessive fouling of the steam pipes in the upper part of the furnace.
To solve these problems, and also to reduce capital investment and increase the energy efficiency of the recovery operation, a number of kraft recovery alternatives have been described. In some of these alternatives the smelt-water explosion hazard is eliminated and the emission of sodium salts reduced by keeping the inorganic chemicals in solid rather than molten form. This principle was used by Copeland et al., U.S. Pat. No. 3,309,262, where spent liquor is concentrated and introduced by atomization into a fluidized bed reactor. The resulting waste liquor spray encounters residual inorganic chemicals derived from the combustion of previous spent liquors. Additionally, the fluidized bed reactor may contain inert materials such as silica grains in admixture with the inorganic chemicals. In the fluidized bed reactor, operated with excess air, all the organic material is combusted below the fusion point of the inorganic salt mixture. The sodium sulfate in the inorganic pellets are reduced with hydrogen in a second fluidized bed (Arnold, Can. Pat. 828,654). Alternatively, the first fluid bed can be used as a means to provide incremental recovery capacity, while the reduction of sodium sulfate is achieved by injecting the pellets into the conventional recovery furnace (Tomlinson II, U.S. Pat. No. 4,011,129).
Flood, U.S. Pat. No. 3,322,492, describes a two-stage fluid bed process where weak black liquor at about 20% solids content is dried to solid granules in the first bed at a temperature of about 175° C. The sodium sulfate in the granules is reduced to sodium sulfide by virtue of carbon monoxide derived from decomposition of the organic matter in the second bed. The operating temperature of the second fluid bed is about 800° C.
Osterman, U.S. Pat. No. 3,523,864, presents a three-zone fluid bed reactor which would replace the conventional chemical recovery furnace and lime kiln. Black liquor is dried and burned under reducing conditions at about 650°-700° C. in the intermediate zone. The reducing gas from the intermediate zone is burned and serves as fluidizing medium for the top fluidized bed. Here predried CaCO 3 is introduced to be calcined to CaO pellets. These CaO pellets overflow first to the intermediate zone and then subsequently to the lower bed with a coating of mainly char, Na 2 SO 4 and Na 2 CO 3 from the burned black liquor. The reduction of Na 2 SO 4 is said to take place in the lower fluidized bed at about 700°-760° C. with air and/or combustion gases as a fluidizing medium.
In the process of Shah, U.S. Pat. No. 3,574,051, kraft black liquor is concentrated by contact with a stream of heated air. The resulting concentrated black liquor is then burned with excess air in a fluidized bed reactor while the bed temperature is maintained at about 250°-600° C. The solid salts are then passed through another reactor and subjected to a reducing gas stream containing mainly carbon monoxide. It is claimed that in the range of 250°-500° C. the sodium sulfate is reduced to sodium sulfide. Green liquor is produced by dissolution of the salts in water.
Lange, Can. patent 1,089,162, presents a low temperature process where the organic portion of black liquor is gasified in a fluidized bed, operating not in excess of 760° C. so as to keep the inorganic portion of black liquor in the solid state. The solid particles leaving the bed will typically contain 90% Na 2 CO 3 , 9% Na 2 S, less than 1% Na 2 SO 4 , and less than 1% carbon. After dissolving the solids in water, and separation of the carbon, the liquor will be used to remove H 2 S from the gas produced in the fluidized bed reactor. The spent absorbing medium can then be treated to form the cooking liquor which is returned to the digestion process.
In all the above alternatives to the conventional kraft recovery process (except for the process of Tomlinson II, U.S. Pat. No. 4,011,129), Na 2 S and Na 2 CO 3 are produced from black liquor in reactors operating below the fusion point of the inorganic salt mixture. As far as is known, only the Copeland process is used on a commercial scale. However, in this process the end products are pellets consisting of mainly Na 2 SO 4 and Na 2 CO 3 rather than mainly Na 2 S and Na 2 CO 3 . There are two main reasons for the absence of commercial utilization of these low temperature processes. First, the relatively high temperature required for fast and complete conversion of Na 2 SO 4 to Na 2 S and, secondly, the ease of formation of H 2 S when Na 2 S is contacted with combustion gases below the melting point of the inorganic salts. So, while the reduction is favored by a high temperature, the above alternative processes require a relatively low temperature just below the melting point of the inorganic salt mixture. The consequence is that in fluid bed processes operating in the reducing mode, most of the formed Na 2 S is rapidly converted to H 2 S (and some COS) according to the overall reaction
Na.sub.2 S+CO.sub.2 +H.sub.2 O→Na.sub.2 CO.sub.3 +H.sub.2 S
resulting in a low yield of solid Na 2 S.
It is an object of this invention to provide a kraft recovery process whereby Na 2 CO 3 and Na 2 S are formed below the melting point of the inorganic pulping chemicals with a minimum production of sulfurous gases.
It is a further object of this invention to provide an assembly for carrying out the process, more especially an assembly of reactors.
SUMMARY OF THE INVENTION
The process of the invention provides for the recovery of energy and kraft pulping chemicals in a system of multiple reactors, all operating below the melting point of the mixture of inorganic pulping chemicals.
In accordance with one aspect of the invention there is provided a process for the treatment of kraft black liquor which comprises i) pyrolyzing black liquor which contains inorganic salts, including an oxysulphur component and a carbonate component, at a temperature of not more than 600° C. to produce a char; ii) subjecting the char to reducing conditions effective to reduce the oxysulphur component to a sulphide salt component inside the char; the reduction is carried out at a temperature above 600° C. and below the melting temperature of the salts in the char in an atmosphere generated by the reduction itself; iii) cooling the resulting char; iv) leaching the cooled resulting char from iii) with an aqueous leaching liquid to leach inorganic salts from the char; and v) recovering the aqueous liquid bearing the salts from iv) as a green liquor.
In a particular embodiment of the process volatile components from the pyrolysis and reduction stages, for example pyrolysis gases, are combusted in a fluid bed reactor and the heat energy of combustion is recovered. The leached char may also be passed to the fluid bed reactor.
In another aspect of the invention there is provided an apparatus for the treatment of kraft black liquor which comprises a pyrolyzer, a reduction reactor, a char leacher and a fluid bed combustor for carrying out the several stages of the process of the invention. Flow lines are provided between the several parts of the apparatus, in particular a first line between the pyrolyzer and the reduction reactor, a second line between the reduction reactor and the char leacher, a third line for green liquor from the char leacher, a fourth line from the pyrolyzer to the fluid bed combustor, and a fifth line from the reduction reactor to the fluid bed combustor.
The inorganic salts are in particular sodium salts, especially sodium carbonate and sodium salts of oxysulphur acids, for example sodium sulphate, sulphite and thiosulphate.
Thus in a particular embodiment the present invention employs a fluidized bed pyrolyzer where black liquor at 30-100% dry solids, but preferably 60-100% dry solids, is pyrolized with hot combustion gases and some air. It is preferred that the black liquor is previously oxidized. Air is premixed with the combustion gases and used for temperature control. The temperature of the solids in the reactor is 600° C. or lower. This minimizes the formation of Na 2 S and subsequent formation of sulfurous gases from the decomposition of Na 2 S. The resulting char, containing Na 2 CO 3 and Na 2 SO 4 but mostly free of Na 2 S, is separated from the pyrolysis gases and introduced in a reactor where reduction of Na 2 SO 4 to Na 2 S takes place under an atmosphere generated by the reduction itself. The low partial pressures of H 2 O and CO 2 , the presence of carbon, and a temperature above 600° C. but preferably slightly below the onset of smelt formation, favor conversion of Na 2 SO 4 to Na 2 S with minimum production of H 2 S or other sulfur containing gases. The char leaving this reduction reactor is cooled and contacted with water to produce green liquor and leached char. The leached char and gases from the pyrolysis and reduction reactors are burned in a fluid bed combustion unit operating below the melting point of the mixture of Na 2 CO 3 and Na 2 SO 4 . The fluid bed pellets, consisting mainly of Na 2 CO 3 and Na 2 SO 4 , serve to remove the gaseous oxidized sulfur species formed by combustion of the sulfurous components produced in the reduction and pyrolysis reactor. The overflow of pellets is ground and mixed with the black liquor feed. Alternatively, the leached char could be combusted in a typical coal fired furnace. In this case, flue gas cleaning equipment must be added to minimize sulfur emission.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a schematic representation of a recovery process for kraft black liquor of the invention.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 is a schematic illustration of one form of the present invention. As shown in FIG. 1, the present invention includes as main pieces of equipment the fluid bed pyrolyzer 5, the indirect heated reducer 10, the char leacher 14, and the fluid bed combustor 25. Strongly oxidized black liquor is fed via line 1 to the fluid bed pyrolyzer and sprayed onto the fluid bed particles. The fluid bed particles are either black liquor char pellets or inert particles like sand or Al 2 O 3 coated with black liquor char. The black liquor may contain 30-100% solids and, in the case of high dry solids content, the black liquor solids are injected under the surface of the fluidized bed with a carrier gas. The carrier gas can be air and/or cooled combustion gas. Air in line 2, mixed with combustion gas in line 3 from the fluid bed combustor 25 is used as a fluidizing medium in the fluid bed pyrolyzer 5. The temperature in pyrolyzer 5 is controlled by air flow rate in line 2 and the temperature of the combustion gases in line 3. Additionally, the pyrolyzer can be indirectly cooled or heated to obtain the required fluid bed temperature. The temperature of the fluid bed pyrolyzer is kept below about 600° C. to minimize formation of Na 2 S and subsequent formation of sulfurous gases from the decomposition of Na 2 S. The flue gases leaving the pyrolyzer 5 via line 4 also contain high boiling point organic compounds and elutriated black liquor char particles. The particles are separated from the gas in cyclone 6 operating at essentially the same temperature as the fluid bed pyrolyzer 5. The char is transported by gravity or mechanical means via line 7 to reduction reactor 10. Alternatively, the char pellets may be removed directly from the fluid bed and transported to the reduction reactor. Reactor 10 is indirectly heated by the flue gases in line 26 from the fluid bed combustor 25 or heated by other means. The temperature in the reduction reactor is about 750° C., i.e. slightly below the value where the onset of smelt formation occurs. A relative motion between the char and internal surface of reactor 10 is maintained by either internal mechanical agitation or rotation/oscillation of the reactor 10 itself. The gases produced in reactor 10 are vented via line 9 to the fluid bed combustor 25. The admission of gases which contain CO 2 or H 2 O to reactor 10 should be minimized to reduce the formation of sulfurous gases from Na 2 S. The addition of CO to reactor 10 on the other hand is favorable for suppression of sodium emission from reactor 10. Thus the gas in reactor 10 is, preferably, high in CO content and low in H 2 O and CO 2 content. The char leaving the reduction reactor 10 contains mainly Na 2 CO 3 and Na 2 S as the inorganic salts. The char is fed via line 11 to a steam producing heat exchanger 31, and subsequently to the char leacher 14 via line 12. Water is added via line 15 to remove, to a large extent, the inorganic salts from the char. The extracted char is separated from the resulting green liquor and enters a filter press 19 via line 17. In the filter press additional green liquor is removed from the char and combined with main green liquor streams in line 16. The leached and dewatered char is transported via line 39 to the fluid bed combustor 25. The particles in the fluid bed combustor consist mainly of Na 2 CO 3 and Na 2 SO 4 originating from Na 2 CO 3 and Na 2 S remaining in the char after the filter press 19. Air enters reactor 25 and is mixed with the gas streams 8 and 9. The energy, generated by combustion of carbon, volatile organics, CO and H 2 in the fluid bed reactor 25 is used to generate steam leaving via line 20. The combustion products of sulfurous gases combine with Na 2 CO 3 to form Na 2 SO 4 . The overflow of particles from the fluid bed combustor 25 are ground and mixed with heavy black liquor to be reintroduced in the present process. Part of the combustion gases from reactor 25 are recycled to reactor 5 and a part is vented to atmosphere after particulate removal in cyclone 32 and heat exchange in reactor 10 and heat exchanger 30. Alternatively, the leached and dewatered char in line 39 could be combusted in a typical coal fired furnace. In this case, flue gas cleaning might be added to minimize the emission of sulfur and sodium containing species. Finally, in order to increase the throughput through the reactors 5, 10 and 25, the gas pressure in the reactors can be increased to levels considerably above atmosperic.
EXAMPLE 1
Black liquor was obtained by cooking black spruce chips at 170° C. with white liquor at a liquor-to-wood ratio of 4 L/kg o.d. chips. The heat-up time from 80° to 170° C. was 90 minutes and the time at 170° C. was 45 minutes. The white liquor had a sulfidity of 29.82% and an effective alkali concentration of 30.07 g/L. After completion of the cook, the cooking liquor was blown from the digester and separated from the chips. The kappa number of the chips was 104. The black liquor was subsequently strongly oxidized in a continuously stirred batch pressurized reactor operating at 130° C., by bubbling air through the liquor for 180 minutes. Some of the liquor was then transferred to an Al 2 O 3 dish and dried under I.R. lamps for 7 hours. The dried black liquor solids were put in an Al 2 O 3 boat which was subsequently inserted in the quartz tube of a tube furnace preheated to 600° C. The volatiles produced during pyrolysis of black liquor solids were removed by a flow of 0.55 L/min (at room temperature) of 90% helium and 10% CO. The boat was removed from the furnace after 30 minutes at 600° C. Samples were taken for analysis and the boat was reintroduced in the tube furnace which was now increased in temperature to 750° C. The flow of 90% helium and 10% CO was maintained at 0.55 L/min. After 45 or 60 minutes at 750° C., the boat was again removed from the furnace and the black liquor char was analyzed for total sulfur, sulfide, oxy-sulfur and carbonate ion content. The analysis of the black liquor solids, the 600° C. pyrolyzed char and the char treated at 750° C. are shown for the two samples in Tables 1 and 2 respectively. The difference between the treatment conditions of the samples is the reduction time at 750° C. Also included are the yield and the sulfur loss for each treatment as well as the reduction efficiency after treatment at 600° C. and 750° C. The reduction efficiency is defined as ##EQU1## The different ion contents were determined by ion chromatography of the solution obtained by leaching the solids or char. The total sulfur content was determined by the Schdniger combustion method and subsequent ion chromatographic analysis of the produced SO -2 4 . The percentages of total sulfur and all the anions are based on the original weight of the black liquor solids.
The results in Tables 1 and 2 show that the reduction efficiencies after pyrolysis at 600° C. are low, 8.6 and 8.3% for samples 1 and 2 respectively. However after treatment at 750° C. the reduction efficiencies increase to 87 and 83.8% respectively. It should be noted that the sulfur in the form of S 2- and SO 2- 4 after pyrolysis at 600° C. accounts for 90.7 and 98.5% of the total sulfur in samples 1 and 2 respectively. Also after further treatment at 750° C., the amount of sulfur as S 2- and SO 2- 4 is relatively unchanged at 88.9 and 97.6% respectively of the total sulfur. Finally the total sulfur loss during pyrolysis and reduction are 24.3 and 6.8% for samples 1 and 2 respectively.
TABLE 1______________________________________Pyrolysis and reduction of oxidized black liquor solids. (Sample 1) Black liquor Black Black liquor char treated liquor solids pyrolyzed at 750° C. solids at 600° C.* for 60 minutes*______________________________________Initial weight (g) -- 0.1817 0.2004Total S (%) 2.80 2.12 2.13SO.sub.4.sup.2- (%) 4.96 4.93 0.43SO.sub.3.sup.2- (%) 0.37 <0.1 <0.1S.sub.2 O.sub.3.sup.2- (%) <0.05 <0.05 <0.05S.sup.2- (%) <0.1 0.28 1.75CO.sub.3.sup.2- (%) 15.4 23.3 21.0yield (%) -- 74.1 89.6Sulfur loss (%) -- 24.3 0.0Reduction <3.2 8.6 87.0efficiency (%)______________________________________ *Total sulfur and anion percentages are based on the weight of the original black liquor solids.
TABLE 2______________________________________Pyrolysis and reduction of oxidized black liquor solids. (Sample 2) Black liquor Black Black liquor char treated liquor solids pyrolyzed at 750° C. solids at 600° C.* for 45 minutes*______________________________________Initial weight (g) -- 0.2241 0.1261Total S (%) 2.76 2.02 1.96SO.sub.4.sup.2- (%) 5.30 5.13 0.55SO.sub.3.sup.2- (%) 0.1 0.1 <0.1S.sub.2 O.sub.3.sup.2- (%) <0.05 <0.05 <0.05S.sup.2- (%) <0.1 0.28 1.73yield (%) -- 74.9 87.0Sulfur loss (%) -- 26.8 3.0Reduction <3.0 8.3 83.8efficiency (%)______________________________________ *Total sulfur and anion percentages are based on the weight of the original black liquor solids.
TABLE 3______________________________________Pyrolysis and reduction of non-oxidized black liquor solids. Black liquor Black Black liquor char treated liquor solids pyrolyzed at 750° C. solids at 600° C.* for 60 minutes*______________________________________Initial weight (g) -- 0.2971 0.1356Total S (%) 2.37 1.30 1.16SO.sub.4.sup.2- (%) 0.27 0.47 0.56SO.sub.3.sup.2- (%) 2.78 <0.1 <0.1S.sub.2 O.sub.3.sup.2- (%) <0.1 <0.16 <0.1S.sup.2- (%) <0.1 0.40 0.46CO.sub.3.sup.2- (%) 12.8 -- 8.6yield (%) -- 74.6 91.3Sulfur loss (%) -- 45.0 11.0Reduction -- 58.0 58.0efficiency (%)______________________________________ *Total sulfur and anion percentages are based on the weight of the original black liquor solids.
EXAMPLE 2
In this example the same black liquor as described in Example 1 was used except that the oxidation in the continuously stirred reactor was deleted. Again the dried black liquor solids were pyrolyzed at 600° C. under helium and 10% carbon monoxide and subsequently exposed at 750° C. to the same gas mixture. The analysis of the black liquor solids, the 600° C. pyrolyzed char and the char treated at 750° C. are shown in Table 3. The analysis shows that the main inorganic sulfur containing species in black liquor solids is SO 2- 3 , contrary to Example 1 where SO 2- 4 is the dominant ion. Subsequent pyrolysis at 600° C. gives a slightly higher sulfide content for the non-oxidized sample compared to the oxidized samples in Example 1. However the 45% sulfur loss is considerably larger than in Example 1. Further treatment of the non-oxidized sample at 750° C. increases the total sulfur-loss to 56%, while the reduction efficiency is unchanged at 58%. Thus from comparison of Examples 1 and 2 it is clear that a strongly oxidized black liquor is preferred in order to minimize the sulfur-loss and maximize the reduction efficiency.
EXAMPLE 3
About 10 mg of oxidized black liquor solids were pyrolyzed in a thermobalance by linearly increasing the temperature from 20° to 750° C. at a rate of 20° C./minute. The gas atmosphere was pure nitrogen up to 550° C. and 88% N 2 plus 12% CO above 550° C. After stabilization of the temperature at 750° C., CO 2 is added to a concentration of 20%, with the remaining gas being 10% CO and 70% N 2 . The addition of CO 2 leads to gasification of the carbon in black liquor char as indicated by the recorded weight-loss and CO production. The composition of black liquor char during gasification is shown in Table 4. The results in Table 4 show a continuous decrease in inorganic sulfur content, while the reduction efficiency is maintained at 80-90%. COS was measured gas chromatographically as the only sulfur gas produced during gasification. The reaction responsible for the sulfur-loss is
Na.sub.2 S+2CO.sub.2 →COS+Na.sub.2 CO.sub.3
The high S 2 O 2- 3 content is due to rapid oxidation of S 2- in aqueous solution before analysis of the water leachate of black liquor char by ion chromatography. The small sample size and the presence of carbon makes it extremely difficult to prevent the oxidation. It should also be noted that Na 2 S 2 O 3 cannot exist at 750° C. Combining this result with the preceding examples, it can be concluded that gasification leads to gaseous sulfur emission due to reaction between Na 2 S and CO 2 (and/or H 2 O vapor).
TABLE 4______________________________________Composition of sulfur speciesin black liquor char during CO.sub.2 gasification.Gasification Carbon Reductiontime burn- S.sup.2- SO.sub.4.sup.2- S.sub.2 O.sub.3.sup.2- efficiency(min) off (%) (% wt)* (% wt)* (% wt)* (%)______________________________________0 0 0.96 0.17 0.7 904 25 0.5 0.13 0.5 86 9.5 50 0.7 0.13 0.4 9016 75 0.3 0.13 0.6 8036 100 0.4 0.10 0.4 87______________________________________ Conditions: 1) Temperature 750° C. 2) CO concentration 10% 3) CO.sub.2 concentration 20% *Based on the weight of dry black liquor solids.
EXAMPLE 4
About 10 mg of oxidized black liquor char solids were pyrolyzed in a thermobalance under an atmosphere of pure helium by linearly increasing the temperature from 20° C. at a rate of 20° C./minute. The sample was kept at a final pyrolysis temperature until no further weight-loss occurred. The composition of the pyrolysis residue for different final pyrolysis temperatures is listed in Table 5. The table shows that no sulfur is lost under an inert atmosphere, and that high reduction efficiencies are achieved. It should also be noticed that a considerable loss of Na 2 CO 3 occurs at higher pyrolysis temperatures in an inert atmosphere.
TABLE 5______________________________________Composition of char after pyrolysis in helium.T S.sub.total S.sup.2- S.sub.4.sup.2- S.sub.3.sup.2- S.sub.2 O.sub.3.sup.2- Na.sup.+ CO.sub.3.sup.2-(°C.) (%) (%) (%) (%) (%) (%) (%)______________________________________b.l. 3.1 -- 1.2 3.6 -- 19.5 10.5solids675 2.3 1.8 0.9 <0.1 <0.05 18.1 17.9775 2.3 2.0 0.3 <0.1 <0.05 5.73 2.96800 2.4 2.2 0.2 0.2 <0.05 -- --______________________________________ 1) Pyrolysis in helium until negligible weightloss. 2) Percentages given are based on original weight of black liquor solids.
TABLE 6______________________________________Composition of char after pyrolysis in 88% Heand 12% CO for 30 minutes at T.sub.final.T.sub.final S.sub.total S.sup.2- S.sub.4.sup.2- S.sub.3.sup.2- S.sub.2 O.sub.3.sup.2- Na.sup.+ CO.sub.3.sup.2-(°C.) (%) (%) (%) (%) (%) (%) (%)______________________________________b.l. 3.1 -- 1.2 3.6 -- 19.5 10.5solids750 2.4 1.7 1.1 0.1 0.2 17.6 15.5800 2.4 2.2 0.1 <0.1 0.1 17.7 10.6______________________________________
EXAMPLE 5
About 10 mg of oxidized black liquor solids were pyrolyzed in a thermobalance under an atmosphere of 88% helium and 12% carbon monoxide. The temperature of the oven was linearly increased from 20° C. to a final temperature at a rate of 20° C./minute. The composition of the pyrolysis residue after being kept at the final pyrolysis temperature for 30 minutes is seen in Table 6. The results listed in Table 6 show that contrary to Table 5, no significant amount of sodium is lost at the higher pyrolysis temperatures when CO is present besides helium. Again no sulfur is lost at the higher pyrolysis temperatures. This shows that sodium emission can be suppressed by the presence of CO in the pyrolysis atmosphere.
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A kraft black liquor recovery system utilizing three separate reactors for liquor pyrolysis, sulfate reduction and carbon plus organics combustion, respectively. Oxidized black liquor is pyrolyzed in a fluid bed reactor. The temperature in the fluid bed reactor is 600° C. or lower. The resulting char, containing Na 2 CO 3 and Na 2 SO 4 and a significant amount of carbon, is separated from the pyrolysis gases and introduced in an indirect heated reactor where reduction of Na 2 SO 4 to Na 2 S takes place in the solid state under an atmosphere generated by the reduction. The reduced char is cooled and leached to produce green liquor. The leached char and gases from the pyrolysis and reduction reactors are burned in a fluid bed combustion unit operating below the melting point of mixtures of Na 2 CO 3 and Na 2 SO 4 . The fluid bed particles, consisting mainly of Na 2 CO 3 and Na 2 SO 4 , serve to remove the volatile oxidized sulfur species formed by combustion of the pyrolysis gas. The overflow of pellets are ground and dissolved in the incoming heavy black liquor feed.
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FIELD OF THE INVENTION
The present invention is directed to an earth-working vehicle, such as a backhoe loader, having an implement, such as a backhoe, in which the implement is capable of being shifted transversely of the vehicle.
BACKGROUND OF THE INVENTION
For many years, it has been common to mount the backhoe support structure or swing tower on a frame and utilize a pair of hydraulic cylinders to pivot the tower with respect to the frame. In such a unit, the hydraulic cylinders are usually connected to the boom support or swing tower on opposite sides of the vertical pivot axis between the swing tower and the frame. For example, in one type disclosed in Long U.S. Pat. No. 3,047,171, the free ends of the piston rods of the hydraulic cylinders are connected to the frame structure at spaced locations while the cylinder barrels are connected at transversely spaced points to the swing tower or mast.
In more recent years, an earth-working vehicle of the type disclosed in the Long patent has also been mounted in a manner that the entire unit can be shifted transversely with respect to the vehicle. The frame supporting the mast or tower is supported on transversely extending rails that are secured to the rear end of the vehicle. This allows the operator to position the frame in any one of an infinite number of positions with respect to the fixed rails and readily lock the unit with respect to the rails.
A side-shaft backhoe incorporates a frame which supports the backhoe mechanism and which is mounted for lateral, transverse movement with respect to the tractor or the like on which the backhoe is mounted. This type of backhoe was developed primarily for trenching in confined spaces, such as in close proximity to a house or other obstruction and enables operation closer to the obstructions than if the backhoe were mounted centrally of the rear of the tractor.
Traditionally, an implement bucket has been repositioned by uncontrolled movement of the backhoe while supporting the backhoe bucket teeth on the ground to one side and pushing the slide carrying the backhoe out on the other side using hydraulic cylinders. Some of the side-shift backhoes required complex components including hydraulically or manually operated clamps or pins.
SUMMARY OF THE INVENTION
In one preferred embodiment, an earth-working vehicle, such as a backhoe loader, has an elongated main frame and an implement support slidingly mounted to the main frame. The implement support is mounted at one end of the main frame and is capable of sliding transversely with respect to the elongated main frame. The vehicle also includes a motive means to slide the implement support with respect to the elongated main frame. The motive means includes a hydraulic motor mounted to one of the main frame and the implement support and either a chain having both ends secured to the other of the main frame and the implement support or the rack of a rack and pinion secured to the other of the main frame and the implement support. The hydraulic motor has a driving sprocket to drive the chain or a pinion to drive the rack and slide the implement support.
Other features and advantages of the present invention will be apparent from the following more detailed description of the preferred embodiment, taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a fragmentary perspective view of a vehicle having an earth-working implement attached to the rear end thereof;
FIG. 2 is an enlarged fragmentary sectional view, as viewed along line 2 - 2 of FIG. 1 ;
FIG. 3 is an enlarged fragmentary sectional view, as viewed along line 3 - 3 of FIG. 2 ; and
FIG. 4 is a schematic illustration, as viewed along line 4 - 4 of FIG. 3 , showing structural support components.
FIG. 5 is a schematic illustration, similar to FIG. 4 , showing a second embodiment of the slidable implement support.
FIG. 6 is a schematic illustration, similar to FIG. 4 , showing a third embodiment of the slidable implement support.
FIG. 7 is a schematic illustration, similar to FIG. 4 , showing a fourth embodiment of the slidable implement support.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 of the drawings generally shows an earth-working vehicle 10 including rear wheels 13 with an earth-working implement 14 secured to the rear end of the vehicle 10 . The vehicle 10 has a pair of horizontally oriented, vertically spaced rails 16 secured to the rear end of the vehicle 10 . Each of the rails 16 is substantially rectangular in cross section (see FIG. 3 ) and includes a rear vertical implement support plate 18 , with the rails releasably connected to vehicle 10 through quick release frame 17 . However, other rail and plate arrangements may be used. As most clearly shown in FIG. 3 , tower frame 20 consists of upper and lower plates 22 and 24 that are interconnected by a pair of vertical beams 26 . The transversely spaced vertical columns or beams 26 each have a pair of lock members or means 28 supported thereon for securely locking the tower frame 20 in any one of a plurality of adjusted positions with respect to rails 16 . These lock members or means may be of the type disclosed in Magee U.S. Pat. No. 3,494,636 or may be hydraulically actuated assemblies well known in the art.
Upper and lower plates 22 and 24 each have a pair of transversely spaced abutments 27 secured thereto by bolts and the abutments engage the forward surfaces of plates 18 while the lower surface of upper plate 22 is supported on the edge of upper plate 18 . Thus, the entire tower frame 20 may be laterally shifted with respect to rails 16 and locked in adjusted positions by lock means 28 .
Mobile tower frame 20 supports a swing tower 40 that has a substantial C-shaped configuration with upper and lower portions 42 and 44 respectively pivotally supported on upper and lower plates 22 and 24 by pivot pins 46 . Pivot pins 46 define a vertical tower pivot axis for supporting swing tower 40 for pivotal movement on tower frame 20 . Swing tower 40 supports an implement, such as backhoe 48 for pivotal movement about a horizontal pivot 49 . The backhoe 48 is well known in the art.
The swing tower 40 is pivoted with respect to the tower frame 20 by a pair of hydraulic cylinders that are mounted in order to allow the tower frame 20 to be moved along the sliding rails 16 while still having the center of gravity for the backhoe 48 as close as possible to the rear axle for the vehicle 10 . As most clearly shown in FIGS. 2 and 3 , the tower frame 20 has a support portion consisting of three plates 50 extending between rails 16 and the plates 50 terminating forwardly of the rails 16 . The two hydraulic cylinders, which define the swing mechanism for swing tower 40 , each include a cylinder barrel 52 and a piston rod 54 that extends from one end of the cylinder barrel 52 . Each of the cylinder barrels 52 has a trunnion mounting bracket 56 secured to the cylinder barrel 52 intermediate opposite ends with a pair of trunnions 58 carried by the bracket 56 . The trunnions 58 are received in openings 60 in the plates 50 so that the two cylinder barrels 52 are mounted in vertically spaced relation to each other and are located between an adjacent pair of plates 50 . Also, the openings 60 are positioned so that both cylinder barrels 52 are supported on a common vertical pivot axis at the forward ends of the plates 50 . It will be noted in FIG. 2 that the common pivot axis defined by openings 60 and trunnions 58 are located on a plane P, which extends through the pivot axis defined by pins 46 and this plane is generally parallel to the longitudinal axis of the vehicle 10 and the pivot axis may be located forward of rails 16 and between the rear edges of wheels 13 .
Piston rods 54 of the hydraulic cylinders are connected to an intermediate portion of the swing tower 40 . This connection consists of brackets 66 extending from the body of the swing tower 40 with pins 68 extending through the apertures in the brackets and apertures in the end of piston rods 54 . As shown in FIGS. 2 and 3 , the piston rods 54 are connected to the intermediate portion of the swing tower 40 at laterally and vertically spaced points, both of which are spaced from the vertical pivot axis defined by pins 46 .
As shown in FIG. 4 , a hydraulic motor 72 is supported on mounting bracket 73 that is securely mounted on the rear end of the vehicle main frame 74 . The hydraulic motor 72 provides the motive power to slide the implement support plate 18 and the attached backhoe 48 transversely of the vehicle 10 . The hydraulic motor 72 may be a low speed high torque hydraulic motor (LSHT motor). A driving sprocket 76 is mounted on the shaft of the hydraulic motor 72 .
The ends of a roller chain 79 are secured to a pair of yoke end connectors 80 that are mounted on the implement support plate 18 . See FIG. 4 . One end of the roller chain 79 is secured to one of the yoke end connectors 80 . The roller chain 79 passes around a chain sprocket 82 mounted to one side of the quick release frame 17 at one end of the rails 16 , around the driving sprocket 76 , around tensioner sprocket 84 mounted to the mounting bracket 73 , around a second chain sprocket 82 mounted to the other side of the quick release frame 17 at the opposite end of the rails 16 , and is secured to the second yoke end connector 80 . The tensioner sprocket 84 deters the roller chain 79 from jumping out from the sprockets.
The LSHT motor 72 rotates under applied hydraulic pressure from the vehicle hydraulic circuit at very low speeds without need for an intermediate speed reducer, and directly moves the roller chain 79 , which moves the backhoe 48 . The mechanism is simple with very few parts. Hence, frictional losses are minimal and the system is easy to maintain. The steel roller chain 79 is designed to operate without an enclosure. Due to the short duration and extent of movement, as well as the low speed of operation, the roller chain 79 runs efficiently without lubrication.
By using the present system, movement of the backhoe 48 is controlled. Safety is improved since the controlled movement is without jerking that is prevalent in the prior systems. The present system is compact and improves vehicle maneuverability.
A second embodiment of the slidable implement support is shown in FIG. 5 . In this embodiment, the mounting bracket 73 , on which the hydraulic motor 72 is secured, is mounted on the implement support plate 18 and the yoke end connectors 80 are secured to the main frame 74 . One end of the roller chain 79 is secured to one of the yoke end connectors 80 and passes around a chain sprocket 82 mounted to one side of the quick release frame 17 at one end of the rails 16 , around the driving sprocket 76 , around tensioner sprocket 84 mounted to the mounting bracket 73 , around a second chain sprocket 82 mounted to the other side of the quick release frame 17 at the opposite end of the rails 16 , and secured to the second yoke end connector 80 . A third chain sprocket may be mounted on the mounting bracket 73 opposite the tensioner sprocket 84 to guide the roller chain 79 more parallel to the movement of the implement support plate 18 .
In FIG. 6 , the mounting bracket 73 and hydraulic motor 72 are mounted on the implement support plate 18 and the roller chain 79 is replaced with a rack 86 . The hydraulic motor 72 drives the pinion 88 moving the implement support plate 18 transversely with respect to the vehicle main frame 74 .
The mounting bracket 73 , hydraulic motor 72 and pinion 88 may be mounted on the rails 16 , as shown in FIG. 7 . In that case, the rack 86 is mounted on the implement support plate 18 .
While the invention has been described with reference to a number of preferred embodiments, 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 scope 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 embodiments 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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An earth-working vehicle, such as a backhoe loader, has an implement, such as a backhoe, mounted in a manner that the implement can be shifted transversely with respect to the vehicle. A hydraulic motor and roller cable or rack are secured to the vehicle main frame and implement supporting plate to position the implement transversely of the vehicle without the jerky movements of prior backhoe loaders.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates generally to a nitrogen oxide reducing system for a diesel engine and a nitrogen gas generating device for reducing a nitrogen oxide in an exhaust gas by adjusting a nitrogen concentration in induction air. More particularly, the present invention relates to a system for preventing oxidation of nitrogen by mounting a nitrogen gas generating device on a mixer for mixing air in the mixer with nitrogen supplied from the nitrogen gas generating device for increasing nitrogen concentration.
[0003] 2. Description of the Related Art
[0004] Currently, as a part of environment protection policy, restriction for discharge of exhaust gas from a diesel engine for suppressing air pollution is becoming more and more strict year by year. Particularly, even in a large size diesel engine to be employed in a special purpose vehicle, such as a construction machine, industrial machine or the like, severe regulation is being about applied.
[0005] Conventionally, as one of causes of air pollution, various proposals have heretofore been made for reducing nitrogen oxide contained in the exhaust gas of the diesel engine.
[0006] As one of the proposals, so-called exhaust gas recirculation (EGR) to recirculate a part of exhaust gas to induction air to lower combustion temperature to restrict generation of nitrogen oxide, has been widely known.
[0007] On the other hand, as disclosed in Japanese Patent Application Laid-open No. 2(1990) -191859, there has been disclosed an air induction system of the diesel engine including a separator having an oxygen selective transmission wall having an oxygen separating function, a device for sucking oxygen rich air via the oxygen selective transmission wall of the separator, and means for sucking air having low oxygen concentration upstream of the oxygen selective transmission wall in a partial load condition to the engine, adjusting oxygen concentration of suction air depending upon driving conditions for restricting combustion in the partial load condition of the engine for reducing generation of nitrogen oxide.
[0008] Furthermore, a system for removing nitrogen oxide by means of a catalyst has also be proposed.
[0009] However, among the prior arts, the exhaust gas recirculation system introduces the exhaust gas per se into the induction air so that particulates, sulfur oxide and so on contained in the exhaust gas are inherently introduced into the engine to degrade a lubricant oil and to accelerate wearing of sliding portions in the engine. Therefore, in view of durability and combustion ability of the engine, it should be a problem to perform exhaust gas recirculation in a sufficient amount for restricting generation of nitrogen oxide. Therefore, in the diesel engine having the exhaust gas recirculation system, non of the system has been successfully adapted to the current regulation.
[0010] On the other hand, in the air induction system for the diesel engine as disclosed in Japanese Patent Application Laid-Open No. 2 (1990)-191859, problems in the exhaust gas recirculation will not be encountered since the oxygen rich air is sucked through the oxygen selective transmission wall of the separator by a suction pump and air having low oxygen concentration as removed oxygen is sucked into the engine, and the exhaust gas per se is not introduced into the induction air.
[0011] However, oxygen molecule transmission hole of the oxygen selective transmission wall formed from oxygen enrichment membrane using high molecular material, is in an order of micron. Therefore, even though oxygen is sucked by means of the suction pump utilizing negative pressure, since transmission resistance of the oxygen molecule is large and sufficient pressure difference cannot be obtained by the suction pump utilizing negative pressure, a sufficient amount of induction air, oxygen concentration of its low enough to restrict generation of nitrogen oxide, is practically impossible to instantly obtain in a distance of short separator forming a part of the suction passage. As a result, it has been practically impossible to introduce a sufficient amount of induction air with low oxygen concentration sufficient for restricting generation of nitrogen oxide without causing lowering of engine output, and thus is impractical. Therefore, it is clear that restriction cannot be satisfied in this system.
[0012] Furthermore, the system employing a catalyst cannot achieve sufficient effects. Therefore, currently, no system can satisfy the current restriction value.
SUMMARY OF THE INVENTION
[0013] It is an object of the present invention to solve the problems in the prior art set forth above and to provide a nitrogen oxide reducing system of a diesel engine which can reduce nitrogen oxide contained in an exhaust gas of the diesel engine, thereby adapting to restrictions.
[0014] Another object of the present invention is to provide a nitrogen gas generating device suitable for use in such nitrogen oxide reducing system for the diesel engine.
[0015] It is almost impossible to remove once nitrogen in the air is introduced into a combustion chamber and is converted into nitrogen oxide.
[0016] Particularly, in accordance with an aspect of the present invention, there is provided a nitrogen oxide reducing system for a diesel engine comprising:
[0017] a mixer provided in an induction passage of the diesel engine; and
[0018] a nitrogen gas generating device supplying a pressurized nitrogen gas of more than or equal to a predetermined concentration in a predetermined amount relative to an intake air flow rate.
[0019] With the construction set forth above, since the pressurized nitrogen gas in a concentration greater than or equal to a predetermined concentration is supplied in a predetermined amount with respect to the intake air flow rate, is supplied to the mixer provided in the air induction passage. Therefore, unlike the conventional system of exhaust gas recirculation or supplying low oxygen concentration air utilizing negative pressure, a sufficient amount of clean nitrogen gas can be supplied to restrict discharge amount of nitrogen oxide in a range less than or equal to a restriction value.
[0020] Here, the nitrogen gas generating device may be a nitrogen gas cylinder filled with nitrogen gas at a predetermined pressure or a psa type nitrogen gas generator.
[0021] In this case, unlike a diesel engine mounted on a vehicle, it is effective for a stationary engine used for power generation or the like.
[0022] With the construction set forth above, utilizing the compressor driven by the engine, the nitrogen gas of the concentration greater than or equal to the predetermined concentration can be obtained. Therefore, it is effective for a diesel engine to be mounted on a vehicle.
[0023] With the construction set forth above, even while the engine or the compressor is in an inoperative state, the predetermined pressure of the compressed air can be accumulated in the first pressure accumulation tank. Therefore, upon re-starting, the compressed air and thus the nitrogen gas can be obtained quickly.
[0024] With the construction set forth above, fluctuation of pressure and flow rate of the discharged nitrogen gas due to individual difference of the engine, compressor or the membrane unit, can be adjusted at a desired value. With the construction set forth above, since the pressure reduction valve is provided downstream of the nitrogen gas generator, the predetermined nitrogen gas flow rate can be obtained with maintaining the pressure in the nitrogen gas generator at the predetermined pressure.
[0025] With the construction set forth above, since the nitrogen gas can be accumulated in the second pressure accumulation tank at the predetermined pressure, the predetermined amount of the nitrogen gas can be stably supplied even upon occurrence of fluctuation of load on the engine.
[0026] With the construction set forth above, even during an inoperative state of the engine or the compressor, the predetermined pressure of the nitrogen gas can be accumulated in the second pressure accumulation tank, nitrogen gas can be quickly supplied to the engine upon re-starting.
[0027] With the construction set forth above, since the nitrogen gas flow rate can be controlled in response to variation of the intake air flow rate of the engine, an appropriate amount of nitrogen gas can be supplied adapting to the operating condition. Also, in comparison with supplying a constant amount, wasting of the nitrogen gas can be successfully prevented.
[0028] With the construction set forth above, special heating devices for the black smoke reducing device become unnecessary and black smoke can be reduced effectively.
[0029] According to another aspect of the present invention, there is provided a nitrogen gas generating device comprising: a compressor for compressing air; a first pressure accumulation tank accumulating compressed air at a predetermined pressure; and a nitrogen gas generator having a membrane unit having a plurality of hollow fiber membranes for selectively transmitting oxygen from the compressed air supplied from the first pressure accumulation tank for separation to discharge a nitrogen gas of greater than or equal to a predetermined concentration.
[0030] With the construction set forth above. by driving the compressor, the nitrogen gas of the concentration greater than or equal to the predetermined concentration can be obtained instantly. Thus, it is effective for mounting on a vehicle.
[0031] With the construction set forth above, even while the compressor is in an inoperative state, the predetermined pressure of the compressed air can be accumulated in the first pressure accumulation tank. Therefore, upon re-starting, the compressed air and thus the nitrogen gas can be obtained quickly.
[0032] With the construction set forth above, fluctuation of pressure and flow rate of the discharged nitrogen gas due to individual differences of the compressor or the membrane unit, can be adjusted at a desired value. This is advantageous in practice.
[0033] With the construction set forth above, the predetermined nitrogen gas flow rate can be obtained with maintaining the pressure in the nitrogen gas generator at the predetermined pressure.
[0034] With the construction set forth above, since the nitrogen gas can be accumulated in the second pressure accumulation tank at the predetermined pressure, the predetermined amount of the nitrogen gas can be stably supplied as required.
[0035] With the construction set forth above, even during an inoperative state of the compressor, the predetermined pressure of the nitrogen gas can be accumulated in the second pressure accumulation tank, nitrogen gas can be quickly supplied to the engine upon re-starting.
[0036] The above and other objects, effects, features and advantages of the present invention will become more apparent from the following description of embodiments thereof taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0037] [0037]FIG. 1 is a block diagram showing a basic construction of a nitrogen oxide reducing system for a diesel engine according to the present invention;
[0038] [0038]FIG. 2 is a block diagram showing more particular construction of the diesel engine including the nitrogen oxide reducing system according to the present invention;
[0039] [0039]FIG. 3 is a section showing one embodiment of the preferred nitrogen gas generator employed in the nitrogen oxide reducing system according to the present invention;
[0040] [0040]FIG. 4 is a graph showing a result of measurement in eight modes as experiment 4 employing the nitrogen oxide reducing system according to the present invention;
[0041] [0041]FIG. 5 is a graph showing a result of measurement in eight modes as experiment 5 employing the nitrogen oxide reducing system according to the present invention; and
[0042] [0042]FIG. 6 is a graph showing a result of measurement in eight modes as experiment 6 employing the nitrogen oxide reducing system according to the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0043] [0043]FIG. 1 is a block diagram showing a basic construction of the present invention. Reference numeral 1 denotes an engine body, 2 denotes an air intake of the engine, 3 denotes a mixer communicated with the air intake 2 of the engine, 4 denotes an air inlet, 5 denotes a nitrogen gas generating device communicated with the mixer 3 and 6 denotes an exhaust passage of the engine.
[0044] [0044]FIG. 2 is a block diagram showing more particular construction of a diesel engine system 100 incorporating a nitrogen oxide reducing system according to the present invention. Reference numeral 110 denotes an engine body, 120 denotes a mixer provided in an air intake passage 112 of the engine, 130 denotes a nitrogen gad generating device connected to the mixer 120 through a passage 151 which will be discussed later.
[0045] In the air intake passage 112 of the engine, an air cleaner 114 is provided in the vicinity of an inlet and is communicated with the engine body 110 via an intake manifold 116 . As shown In FIG. 2, it is convenient for providing the mixer 120 on upstream side of a compressor 118 in the engine provided with a turbocharger, when the present invention is applied to existing engines.
[0046] The shown embodiment of the nitrogen gas generating device 130 is mainly comprised of a compressor 132 generating compressed air as a compressed air generating device, a first pressure accumulation tank 135 accumulating the compressed air compressed by the compressor 132 , a nitrogen gas generator 140 supplied with the compressed air at a predetermined pressure from the first pressure accumulation tank 135 and generating nitrogen gas, and a second pressure accumulating tank 150 accumulating the generated nitrogen gas.
[0047] In greater detail, an air cleaner 131 is provided at an inlet of the compressor 132 . To a passage between the compressor 132 and the first pressure accumulation tank 135 , a check valve 134 for preventing reverse flow from the first pressure accumulation tank 135 is provided. It should be noted that reference numeral 136 is a safety valve provided in the first pressure accumulation tank 135 , which is opened when a pressure of the first pressure accumulation tank 135 exceeds a predetermined pressure Furthermore, in a passage 137 between the first pressure accumulation tank 135 and the nitrogen gas generator 140 , an on-off valve 138 and a water drainage filter 139 are provided. The on-off valve 138 may be constructed as a pressure responsive valve which is opened when the pressure in the first pressure accumulation tank 135 exceeds the predetermined pressure, or as an electromagnetic valve which is opened in response to starting-up of the engine or the like. The water drainage filter 139 is for removing moisture content in the compressed air flowing through the passage 137 and is constructed to be replaced per every predetermined driving period.
[0048] Furthermore, in a passage 148 between the nitrogen gas generator 140 and the second pressure accumulation tank 150 located downstream of the nitrogen gas generator 140 , a check valve 149 preventing reverse flow from the second pressure accumulation tank 150 is provided. The second pressure accumulation tank 150 can be communicated with the mixer 120 via a passage 151 . In the passage 151 , a pressure reduction valve 152 and an on-off valve 153 are provided. The pressure reduction valve 152 reduces a pressure of a pressurized nitrogen gas accumulated in the second pressure accumulation tank 150 The on-off valve 253 is opened only while the engine is in operation for supplying the predetermined pressure of pressurized nitrogen gas to the mixer 120 . For this purpose, the on-off valve 153 is a pressure actuated valve to introduce the pressure of the passage 137 via a passage 154 for receiving a pressure upstream of the nitrogen gas generator 140 as a pilot pressure.
[0049] Furthermore, in the passage 151 , a flow rate control valve 155 is provided downstream of the on-off valve 153 and upstream of the mixer 120 . The flow rate control valve 155 is arranged together with a fuel injection device 111 per an engine cylinder of the engine body 110 and open degree of the valve 155 is controlled depending upon a depression amount of an accelerator pedal 105 . In engines, in which an intake air flow rate is not significantly varied, such as a stationary engine for electric power generation or a kind of engine for a construction machine, a nitrogen gas higher than or equal to a predetermined concentration may be supplied in a predetermined amount. Therefore, a flow rate control valve can be omitted.
[0050] On the other hand, the reference numeral 160 denotes an exhaust passage, which is communicated with the engine body 110 via an exhaust manifold 162 . At intermediate positions, a turbine 164 of the turbocharger, a black smoke removing device 166 and muffler 168 are provided. In the black smoke removing device 166 , separated oxygen separated from the nitrogen gas generator 140 is supplied via a passage 169 .
[0051] The reference numeral 170 denotes a gear box connected to the engine body 100 . In the shown embodiment, the gear box 170 is provided with a power take out (PTO) mechanism and can drive the compressor 132 . The compressor 132 may be driven by another drive source such as an electric motor. Type of the compressor 132 is not limited to a particular type. However, by employing a screw compressor, it becomes possible to obtain the predetermined pressure of compressed air can be obtained in the first pressure accumulation tank 135 instantly after starting up. Therefore, the screw compressor is preferred for capability of supplying the compressed air with stable pressure. Since a track or the like has a sufficient space around the gear box 170 , the compressor 132 may be installed with rigidly securing on the gear box 170 or the like together with the first pressure accumulation tank 135 .
[0052] Next, detailed constrution of the shown embodiment of the nitrogen gas generator, 140 will be described. The nitrogen gas generator 140 includes a body casing 141 having generally quadrangular section of 135 mm in one edge, for example, and about 1000 mm of the main body in entire length, for example, and a membrane unit casing 142 provided within the body casing 141 , being in substantially circular cross section of about 100 mm in diameter in the main body portion, for example, and about 900 mm in overall length, for example.
[0053] In the membrane unit casing 142 , a membrane unit 143 consisted of a flux of a plurality of high polymer hollow fiber membranes is received in a cylindrical main body portion 142 a in such a manner that an inlet space 142 b is defined at an inlet end of the membrane unit 143 and an outlet space 142 c is defined at an outlet end thereof. Furthermore, the membrane unit casing 142 has a cylindrical inlet portion 142 d communicated with the inlet space 142 b and formed in a smaller diameter than the cylindrical main body 142 a. The cylindrical inlet portion 142 d is connected to the passage 137 via an appropriate connecting member through an inlet opening 141 a at an end wall of the body casing 141 . A communication cylinder 142 e connected to a communication opening formed in a peripheral wall of the cylindrical main body portion 142 a of the membrane unit casing 142 , is connected to the passage 169 set forth above through the body casing 141 .
[0054] Furthermore, at the outlet end of the outlet space 142 c of the membrane unit casing 142 , a cylindrical partitioning wall 144 fixed to the end wall of the body casing 141 is connected for preventing leakage of the nitrogen gas into the body casing 141 . The membrane unit casing 142 is thus fixed to the body casing 141 . Then, in the cylindrical partitioning wall 144 , a plate-like adjusting member 145 is provided for adjusting an opening area of an outlet 142 f of the outlet space 142 c of the membrane unit casing 142 .
[0055] The adjusting member 145 is supported by bolts 146 (three in this embodiment) threaded with the end wall of the body casing 141 . By varying a threading amount of the bolts, the position of the adjustment member 145 , namely the open area of the outlet 142 f of the outlet space 142 c can be adjusted. It should be noted that the foregoing passage 148 is connected to the opening 141 b of the end wall of the body casing 141 .
[0056] The nitrogen gas generator 140 in this embodiment is a so-called membrane type and is a system utilizing deferent permeability between molecules in high polymer thin membrane. This type of the nitrogen gas generator 140 has few movable portion, compact and superior in maintenance ability, and thus is suitable for mounting on a vehicle. The high polymer membrane is formed as high polymer hollow fiber membrane for transmitting oxygen externally using a pressure difference between inner surface and outer surface to selectively separating nitrogen therein In the shown embodiment, the membrane unit 143 is consisted of a flux of a plurality of high polymer hollow fiber membranes. Oxygen is transmitted externally through the membrane unit 143 and is supplied to the black smoke removing device 166 through the communication cylinder passage 142 e connected to the connection opening formed in the peripheral wall of the cylindrical main body 142 a and the passage 169 . Then, only nitrogen gas selectively separated Is fed to the second pressure accumulating tank 150 via the outlet 142 f of the outlet space 142 c of the membrane unit casing 142 .
[0057] It should be noted that as the nitrogen gas generating device 130 , in place of the membrane type nitrogen gas generator 140 , a nitrogen gas cylinder including a liquid nitrogen tank or a psa (pressure swing adsorption) may be employed.
[0058] The psa is a system for taking out only a necessary component using adsorbent and utilizing difference of adsorbing ability of molecules or difference of molecular size. Two adsorbent containers are used. Pressurized air is supplied to one of the adsorbent containers so as to switch to the other adsorbent container when an adsorbed amount of the one adsorbent container is in saturated condition. Then, when the saturated adsorbent container is reduced in pressure, the nitrogen gas adsorbed in the adsorbent (normally, molecular sieving carbon is employed) is re-generated for use.
[0059] On the other hand, the foregoing nitrogen gas cylinder or psa have particular problems and thus is restricted in application. Namely, since a usable amount or time is limited in the case of the nitrogen gas cylinder, it is not suitable for a vehicle mounting application, but is useful in the case of stationary type engines. On the other hand, psa can generate high purity nitrogen gas up to 99.99% at the maximum. However, in order to certainly obtain the predetermined flow rate of the nitrogen gas, a large size container is required. Moreover, for insufficiency of durability for vibration, it is not suitable for a vehicular application. However, psa is useful for stationary type engines.
[0060] The black smoke removing device 166 is constructed with a heat resistant container including a plurality of titanium alloy ball formed by rounding to have fine passage network of thin wire-like titanium alloy (e.g. alloy of titanium and aluminum). Into this container, oxygen is supplied through the passage 169 . Since titanium alloy has heat accumulation characteristics, even by passing the exhaust gas through this container, the exhaust gas temperature is elevated. For example, the exhaust gas temperature from the engine during idling condition is about 200° C. When the exhaust gas passes through this container, the temperature of the exhaust gas becomes about 350° C. Here, in the shown embodiment, in the black smoke removing device 166 , oxygen is supplied. Thus, the exhaust gas temperature is elevated up to about 500° C. to burn particulates in the black smoke to significantly reduce the discharge amount of the black smoke.
[0061] Here, operation of the shown embodiment constructed as set forth above will be explained.
[0062] Associating with turning ON of not shown starter switch, air and fuel are supplied to the engine body 110 in a known manner to start engine revolution. At the same time, the compressor 132 is driven and the predetermined pressure (e.g. 784 kPa) of the compressed air is accumulated in the first pressure accumulating tank 135 . It should be noted that, upon re-starting of the engine, compressed air is accumulated in the first pressure accumulating tank 135 .
[0063] The compressed air accumulated in the first pressure accumulation tank 135 is introduced into the nitrogen gas generator 140 through the on-off valve 138 in an open condition. Then, by means of the membrane unit 143 in the nitrogen gas generator 140 , nitrogen and oxygen are separated from each other. The predetermined concentration of nitrogen gas removed oxygen is accumulated at a predetermined pressure (e.g. 686 kPa) in the second pressure accumulation tank 150 via the check valve 149 . Then, the pressure of the nitrogen gas is reduced to the predetermined pressure (e.g. 490 kPa) by the pressure reduction valve 152 to be fed to the mixer 120 through the on-off valve 153 in an open condition and the flow rate control valve 155 .
[0064] Then, in the mixer 120 , the nitrogen gas is mixed with the intake air introduced through the air filter 114 and is compressed by the compressor 118 of the turbocharger to be supplied to the engine body 110 . It should be noted that the oxygen separated in the nitrogen gas generator 140 is supplied to the black smoke removing device 166 via is the passage 169 as set forth above.
[0065] When the engine is stopped, the compressor 132 is also stopped. In this case, since the on-off valve 138 is closed, in cooperation with the function of the check valve 134 , the predetermined pressure of compressed air is accumulated in the first pressure accumulation tank 135 . On the other hand, in the second pressure accumulation tank 150 , associating with closing of the on-off valve 138 , the on-off valve 153 taking the pressure of the passage 137 downstream of the on-off valve 138 as the pilot pressure, is also closed. Then, together with the function of the check valve 149 , the predetermined pressure of the pressurized nitrogen gas is accumulated in the second pressure accumulation tank 150 . Therefore, at subsequent re-starting, the predetermined amount of the nitrogen gas is instantly supplied from the second pressure accumulation tank 150 to be mixed with the intake air.
[0066] Here, a necessary nitrogen gas amount required for adapting the nitrogen oxide reduction regulation, has been found to be preferably in an amount for establishing oxygen versus nitrogen ratio of about 17:83 in the combustion chamber of the engine by supplying the predetermined amount of the nitrogen gas for the normal intake air (atmospheric air) having oxygen versus nitrogen ratio of 21:79, from experiments. The necessary nitrogen gas amount, namely the predetermined nitrogen gas amount is about 100 to 500 liters per minute from the idling condition where the intake air flow rate is minimum to the high speed and high load condition where the intake air flow rate is maximum, while it is variable depending upon engine displacement, engine speed, load and presence or absence of turbocharger and so forth, assuming that the concentration of the nitrogen gas is greater than or equal to 90%, and the engine with a turbocharger has about 5000 cc of displacement. It should be noted that in the engine having smaller displacement, required amount of the nitrogen gas becomes smaller. However, since the engine for the construction machine or the like requires large torque, it generally has large engine size.
[0067] In short, the predetermined nitrogen gas amount is a nitrogen gas amount to establish a ratio of about 0.05 when an intake air flow rate determined by the engine displacement and engine speed is 1 in the case of natural aspiration engines. On the other hand, in the case of the engine with the turbocharger, in a no-load condition, the nitrogen gas may be supplied in substantially the same ratio as the normal aspiration engine. Upon increasing of the load, in consideration of increasing of the intake air flow rate by boosting by the turbocharger, the absolute amount may be increased while ratio becomes smaller. In the case of the engine with the turbocharger having displacement of 5000 cc, the nitrogen gas: amount becomes 500 liters per minute at high speed and high load condition (2200 rpm, 100% load) where the intake air flow rate becomes maximum.
[0068] Then, in order to certainly provide a nitrogen gas amount required by the engine for adapting to the nitrogen oxide reduction regulation, it is important that predetermined concentration of the nitrogen gas can be obtained in the nitrogen gas generating device 130 and the predetermined amount of the obtained predetermined concentration of the nitrogen gas can be supplied in compliance with the operating condition of the engine as set forth above.
[0069] Accordingly, in order to obtain the predetermined concentration of the nitrogen gas, in one embodiment of the present invention, the pressure of the compressed air to be supplied to the nitrogen gas generator 140 is set to be higher at about 784 kPa (8 atm), and by providing the adjusting member 145 for adjusting the opening area of the outlet 142 f of the output space 142 c of the membrane unit casing 142 to maintain the output pressure of the membrane unit casing 142 at about 490 kPa. The adjusting member 145 is a stationary regulator, it has to be adjusted depending upon individual differences per individual engines, required nitrogen gas amount per kind of the engine.
[0070] Therefore, in another embodiment, immediately following the outlet of the membrane unit casing 142 , a pressure reduction valve 152 is provided in place of the adjusting member 145 , for maintaining the outlet pressure of the membrane unit casing 142 at about 490 kPa. However, in the embodiment where the pressure reduction valve 152 is provided in place of the adjusting member 145 , similarly to the embodiment providing the adjusting member 145 , oxygen separation performance in the membrane unit 143 is lowered in the vicinity of the outlet for lowering of pressure due to loss in the vicinity of the outlet of the membrane unit casing 142 . Therefore, it is not preferred to obtain high concentration nitrogen gas since extra flow rate becomes necessary for lower concentration.
[0071] Accordingly, in a further embodiment of the present invention, the second pressure accumulation tank 150 is provided between the outlet of the membrane unit casing 142 and the pressure reduction valve 152 and the pressure in the second pressure accumulation tank 150 is set at about 686 kPa. The pressure of the membrane unit 143 is maintained to have a pressure drop about 0.490 kPa by oxygen separation to improve oxygen separation performance to obtain the nitrogen gas of higher concentration.
[0072] On the other hand, in order to supply thus obtained nitrogen gas of predetermine concentration in the predetermined amount adapting to the driving condition of the engine, the present invention employs the pressurized nitrogen gas. In the shown embodiment, the nitrogen gas of the pressure lowered down to about 490 kPa by the pressure reduction valve 152 , is supplied to the mixer 120 .
(Results of Experiments)
[0073] The cases where the present invention is employed and not employed, comparison experiments were performed. The results are as follows.
[0074] Experiment 1)
[0075] Employing an engine of Mitsubishi Heavy Industries Ltd. (Type: 6D34-TE1, displacement: 5861 cc, with turbocharger), the nitrogen gas of about 89% in concentration is supplied at 100 liters per minute. Reduction ratio of nitrogen oxide is shown in the following table 1.
TABLE 1 Nitrogen Oxide Idling 2000 r.p.m. System Provided 80 vol ppm 153 vol ppm System Not provided 101 vol ppm 172 vol ppm Reduction Ratio 21% 11%
[0076] Experiment 2)
[0077] Employing an engine of Mitsubishi Heavy Industries Ltd. (Type: 6D34-TE1, displacement exhaust amount: 5861 cc, with turbocharger), the nitrogen gas of about 98.5 concentration is supplied at 100 liters per minute. Reduction ratio of nitrogen oxide is shown in the following table 2
TABLE 2 Nitrogen Oxide Idling 2000 r.p.m. System Not Provided 188 vol ppm 219 vol ppm System Provided 126 vol ppm 188 vol ppm Reduction Ratio 32% 14%
[0078] Experiment 3)
[0079] Employing an engine of Isuzu Motor Co. Ltd. (Type: 4BDI, displacement: 4100 cc, with turbocharger), the nitrogen gas of about 93% in concentration is supplied at 220 liters per minute. Reduction ratio of nitrogen oxide is shown in the following table 2.
TABLE 3 Nitrogen Oxide Idling 2000 r.p.m. System Not Provided 172 vol ppm 375 vol ppm System Provided 57 vol ppm 274 vol ppm Reduction Ratio 67% 27%
[0080] It should be noted that the foregoing experiments 1) to 3) were performed by Shikoku Keisoku Kogyo K. K. Experiments 4) to 6).
[0081] Employing an engine of Komatsu Ltd. (Type; SAA6D95L, displacement; 4890 cc, with turbocharger and intercooler), for Experiment 4) the nitrogen gas of about 90% in concentration is supplied at 110 liters per minute, for Experiment 5) the nitrogen gas of about 91.5% in concentration is supplied at 120 liters per minute, and for Experiment 6) the nitrogen gas of about 95% in concentration is supplied at 350 liters per minute. Experiments were performed for measurement in eight modes in Japan Automobile Research Institute. In the experiments 4) to 6), variation of nitrogen oxide discharge amount in the cases where the system of the present invention is employed and not employed are shown in graphs of FIGS. 4 to 6 . In the graphs of FIGS. 4 to 6 , line A shows the case where the system of the present invention is not employed and line B shows the case where the present invention is employed. In the graphs, number in parenthesis is nitrogen oxide reduction ratio in respective mode.
[0082] Average reduction ratio in eight modes in the experiments 4) to 6) are shown in the following table 4.
8 Modes Nitrogen Oxide Total Discharge Amount Experiment 4 Experiment 5 Experiment 6 No System 5608.4 ppm 5537.3 ppm 4982.9 ppm System Present 4755.2 ppm 4643.6 ppm 3173.9 ppm Ave. Reduction 18.68% 18.58% 39.76%
[0083] The present invention has been described in detail with respect to preferred embodiments, and it will now be apparent from the foregoing to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects, and it is the intention, therefore, in the appended claims to cover all such changes and modifications as fall within the true spirit of the invention.
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A nitrogen oxide reducing system of a diesel engine can reduce nitrogen oxide contained in an exhaust gas of the diesel engine and whereby cab adapt to a restriction. At a tip end of a mixer, air holes required by the engine are formed, a nitrogen gas generating device for increasing concentration of nitrogen in the air is mounted to introduce nitrogen into the mixer, the mixer is mounted to the induction opening of the engine at opposite side of the air hole to introduce increased amount of nitrogen to prevent oxidation of nitrogen and discharge nitrogen.
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BACKGROUND OF THE INVENTION
In the art of the manufacturing cable by twisting strands, it is common practice to rotate reels on which strands are coiled about an axis on which the cable is to be formed. In the past, each strand left its reel under substantial tension and passed over guide pulleys on its way to the point at which the strands were gathered into the cable.
While this system is satisfactory for strong materials, it does not work well for fragile strands, such as optical fibre. In order to maintain the structual integrity of the glass fibre, it is necessary that it not be subjected to tension and sharp bending. These and other difficulties experienced with the prior art machines have been obviated in a novel way by the present invention.
It is, therefore, an outstanding object of the invention to provide a cabling machine for fragile strands in which the strand is not subjected to tension and sharp bending.
Another object of this invention is the provision of a cabling machine in which the strands are fed from cans without twist.
A further object of the present invention is the provision of a cabler for optical strands in which the strands are not subjected to air stream interference.
It is another object of the instant invention to provide a cabler for delicate strands, which machine lacks pulley-type guides for the strands.
A still further object of the invention is the provision of a cabler in which the helix angle of the cable strands can be readily adjusted.
With these and other objects in view, as will be apparent to those skilled in the art, the invention resides in the combination of parts set forth in the specification and covered by the claims appended hereto.
SUMMARY OF THE INVENTION
In general, the invention relates to a cabling machine for use with delicate strands, wherein the axis of cable orientation is vertical, the strands are gravity-tensioned, and the strands are fed from reel-less packaging in cylindrical open-top containers. In addition, a conical enclosure is provided for each strand to prevent air stream interference at high rotational speeds.
More specifically, inclined holders are provided for the containers and they are always aimed at the closing point of the strands, despite the fact that each container is rotating about its own axis, while the machine's rotor assembly revolves around its axis, three ball casters being used for this purpose.
Guide sheaves are eliminated and the inclined angle of the strands may be adjusted to suit the desired helix angle of the cable. The planetary motion is achieved by an eccentric ring and cranks.
BRIEF DESCRIPTION OF THE DRAWINGS
The character of the invention, however, may be best understood by reference to one of its structural forms, as illustrated by the accompanying drawings, in which:
FIG. 1 is a perspective view of a cabling machine incorporating the principles of the present invention,
FIG. 2 is a front elevational view of the machine,
FIG. 3 is an enlarged front elevational view of a portion of the machine,
FIG. 4 is an enlarged front elevational view of another portion of the machine,
FIG. 5 is a vertical sectional view of the machine taken on the line V--V of FIG. 6,
FIG. 6 is a horizontal sectional view of the machine taken on the line VI--VI of FIG. 3, and
FIG. 7 is a generally vertical sectional view of the machine taken on the line VII--VII of FIG. 3.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring first to FIG. 1, wherein are best shown the general features of the invention, the cabling machine, indicated generally by the reference numeral 10, is shown as intended to form a number of fine strands 11 into a cable by twisting them together. A vertical main drive spindle 13 is rotatably mounted on a base 12 and driven by an electric motor (not shown) mounted on the base.
As is evident in FIG. 2, a disk-like horizontal table 14 is carried by the spindle and is rotatable therewith. A plurality of vertical shafts 15 are rotatably carried by the table and arranged in a circle which is concentric with the spindle 13, Each shaft including a universal joint 16. A platen 17 is carried on the upper end of each shaft; each platen is adapted to carry an open-mouthed container 18 packaged with strand 11 coiled in the well-known manner to feed from the upper end.
In FIG. 3, it can be seen that a set of three anti-friction pillars 19 are carried by the table under each platen 17 to support and hold the platen at a preselected angle A to the axis of the spindle 13. A differential means 21 joins the spindle 13 to the shafts 15, so that each platen 17 rotates once about the axis of its shaft during each rotation of the spindle.
A cone-shaped funnel 22 extends upwardly from the upper end of each container and elongated tubular guides 23 extend from the upper ends of the funnels to the upper end of the spindle toward a gathering point where the cable is formed and passes onto a large pulley (FIG. 1) mounted at the top of the machine.
FIG. 6 shows the arrangement of the pillars 19 around the shaft 15 and their relationship to the main drive spindle 13. The two outer pillars lie on opposite sides of the radial line joining the axes of the spindle 13, the inner pillar, and the shaft 15.
The differential means 21 is shown in FIGS. 4 and 5 and includes the table 14 which rotates with the spindle 13 and a lower table 25 which also moves with it. The shafts 15 extend through and are rotatable in the two upper tables.
An annular ring 26 is arranged under the table 25, is spaced from, and is parallel to it. The ring is mounted to be independently movable relative to the spindle 13 and the tables 14 and 25. As is best evident in FIG. 5, each shaft 15 extends downwardly through the table 25 and is fixed to one end of a horizontal crank 27. A vertical post 28 extends upwardly from the periphery of the ring 26 and rides in a bearing 29 mounted in the other end of the crank.
The ring floats in a horizontal plane and is restrained by two rollers (not shown). These rollers are mounted on the base 12 and rotate about vertical axes. They are located on diametrically opposite sides of the spindle. The ring, therefore, surrounds the spindle and the rollers; it has an inner cylindrical surface 30 that engages the rollers. They serve to hold the ring in a position in which it is eccentric with the spindle. The cranks 27 connect the ring 26 to the shafts 15 to rotate each shaft and its platen in reverse through 360° during each rotation of the cable.
FIG. 7 makes it evident that the platen 17 and its container 18 not only rotate around the main spindle 13, but that they also rotate about their own axes, as determined by the shaft 15. This differential reverse motion causes the same spot on the container 18 to face the spindle 13 at all times. The net effect is that the strand 11 leaves the container without a twist, which is important in the formation of the cable, particularly when a brittle, delicate strand is being used. The fact that the light-weight strand lies within the funnel 22 means that the air current generated by rotation about the spindle 13 does not act on the strand and cause deleterious effects.
It should be noted that the guide 23 in FIG. 3 is supported at the upper end by a universal ring 31 in the nature of the well-known ball-and-socket arrangement known as a "male rod end" and manufactured by SEALMASTER. The lower end of the guide 23 is supported in a similar universal ring 32; this last ring, however, is mounted on a hub 33 which can be slidably adjusted lengthwise of the spindle 13. This construction, combined with adjustable height of the pillars 19 (LANGLEY castor ball Model 5BT-1), permits selection of the strand angle, while maintaining the strand in a straight line from the container to the gathering die 34.
It is obvious that minor changes may be made in the form and construction of the invention without departing from the material spirit thereof. It is not, however, desired to confine the invention to the exact form herein shown and described, but is is desired to include all such as properly come within the scope claimed.
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Cabling machine for fine strands, in which the strands feed from cans that are arranged in a circle about the axis of a rotary table, each can taking part in one rotation about its axis for each rotation of the table.
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FIELD OF THE INVENTION
[0001] The present invention relates to a system for prevention of and protection against a fire caused by fuse misuse. More particularly, the present invention relates to a system for prevention of and protection against a fire caused by fuse misuse, in which if a user who does not know an electric circuit well uses a high capacity fuse connected to an excessive electrical load, an overcurrent flowing to the wring exceeds a permissible capacity of the wiring, and in order to prevent this from occurring, a slow blow fuse designed to be blown out more slowly than a normal fuse is installed at a rear end of the high capacity fuse so that the machine can be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
BACKGROUND OF THE INVENTION
[0002] A convention general electric power circuit is configured such that electricity from a battery is supplied to a load via a fuse, and the fuse is blown out if an abnormal state such as short-circuit occurs in the load as shown in FIG. 1 .
[0003] However, in the case where a user arbitrarily connects an additional electric device to a normal circuit and thus the capacity of the fuse is increased, if a shot-circuit occurs in the normal circuit, the wiring is not protected but an electric overload is applied due to the fuse with the increased capacity, so that the wiring may be melt, leading to a fire.
[0004] That is, if the user who does not know an electric circuit well uses a high capacity fuse connected to an excessive electrical load, an overcurrent flowing to the wring exceeds a permissible capacity of the wiring, and as a result, a damage and a fire of the wiring may occur.
DETAILED DESCRIPTION OF THE INVENTION
Technical Problems
[0005] Accordingly, the present invention has been made to solve the aforementioned problem occurring in the prior art, and it is an object of the present invention to provide a system for prevention of and protection against a fire caused by fuse misuse, in which the machine can be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
Technical Solution
[0006] To accomplish the above object, a system for prevention of and protection against a fire caused by fuse misuse in accordance with an embodiment of the present invention in accordance with an embodiment of the present invention is configured such that if a user who does not know an electric circuit well uses a high capacity fuse connected to an excessive electrical load, an overcurrent flowing to the wring exceeds a permissible capacity of the wiring, and in order to prevent this from occurring, a slow blow fuse designed to be blown out more slowly than a normal fuse is installed at a rear end of the high capacity fuse so that the machine can be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
[0007] Specifically, the present invention provides a system for prevention of and protection against a fire caused by fuse misuse, comprising a load and a high breaking capacity fuse having a rated capacity higher than that of a normal fuse that is installed to be suit to the capacity of the load, wherein the improvement comprises a slow blow fuse installed between the high breaking capacity fuse and the load and having a melting part that is melted to be broken due to a temperature rise when an overcurrent having passed through the high breaking capacity fuse is applied to the slow blow fuse to interrupt the overcurrent flowing to the load.
[0008] Preferably, the load may be any one selected from among a lamp installed on a boom or an operator's cab, a wiper motor, a fan motor, and a machine controller.
[0009] In addition, the slow blow fuse may include: an element made of a metal to enable electricity to flow therethrough; a housing configured to securely fix the element; a cover made of a transparent material to allow the state of the fuse to be confirmed therethrough; and the melting part positioned on the element inside the housing without being in close contact with the housing and the cover, the melting part being melted to be broken due to a temperature rise when the overcurrent flows therethrough.
Advantageous Effect
[0010] The system for prevention of and protection against a fire caused by fuse misuse in accordance with an embodiment of the present invention as constructed above has the following advantages.
[0011] If a user who does not know an electric circuit well uses a high capacity fuse connected to an excessive electrical load, an overcurrent flowing to the wring exceeds a permissible capacity of the wiring. In order to prevent this from occurring, a slow blow fuse designed to be blown out more slowly than a normal fuse is installed at a rear end of the high capacity fuse so that the machine can be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification
[0012] That is, the present invention enables the machine to be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The above objects, other features and advantages of the present invention will become more apparent by describing the preferred embodiments thereof with reference to the accompanying drawings, in which:
[0014] FIG. 1 is a schematic block diagram showing a fuse system for a general vehicle in accordance with the prior art;
[0015] FIG. 2 is a schematic block diagram showing a system for prevention of and protection against a fire caused by fuse misuse in accordance with an embodiment of the present invention; and
[0016] FIG. 3 is a perspective view showing an example of a slow blow fuse that can be used in the present invention.
EXPLANATION ON REFERENCE NUMERALS OF MAIN ELEMENTS IN THE DRAWINGS
[0017] 101 : high breaking capacity fuse
[0018] 102 : load
[0019] 103 : slow blow fuse
PREFERRED EMBODIMENTS OF THE INVENTION
[0020] Now, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. The matters defined in the description, such as the detailed construction and elements, are nothing but specific details provided to assist those of ordinary skill in the art in a comprehensive understanding of the invention, and the present invention is not limited to the embodiments disclosed hereinafter.
[0021] In order to definitely describe the present invention, a portion having no relevant to the description will be omitted, and throughout the specification, like elements are designated by like reference numerals.
[0022] In the specification and the claims, when a portion includes an element, it is meant to include other elements, but not exclude the other elements unless otherwise specially stated herein.
[0023] FIG. 2 is a schematic block diagram showing a system for prevention of and protection against a fire caused by fuse misuse in accordance with an embodiment of the present invention
[0024] As shown in FIG. 2 , if a user who does not know an electric circuit well uses a high capacity fuse connected to an excessive electrical load, an overcurrent flowing to the wring exceeds a permissible capacity of the wiring. In order to prevent this from occurring, the system according to the present invention is configured such that a slow blow fuse 103 designed to be blown out more slowly than a normal fuse is installed at a rear end of the high capacity fuse so that the machine can be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
[0025] Specifically, in the inventive system for prevention of and protection against a fire caused by fuse misuse, including a load 102 and a high breaking capacity fuse 101 having a rated capacity higher than that of a normal fuse that is installed to be suit to the capacity of the load 102 , a slow blow fuse 103 is installed between the high breaking capacity fuse 101 and the load 102 .
[0026] In other words, in a system for prevention of and protection against a fire caused by fuse misuse, including a load 102 and a high breaking capacity fuse 101 having a rated capacity higher than that of a normal fuse that is installed to be suit to the capacity of the load 102 , a slow blow fuse 103 is installed between the high breaking capacity fuse 101 and the load 102 and has a melting part that is melted to be broken due to a temperature rise when an overcurrent having passed through the high breaking capacity fuse 101 is applied to the slow blow fuse 103 to interrupt the overcurrent flowing to the load 102 .
[0027] Herein, for example, in the case where instead of a normal fuse having a rated capacity of 15 A, a high breaking capacity fuse having a rated capacity of 20 A is used in a state of being connected to a load, when an overcurrent flows to the load, it exceeds a permissible capacity range of the wiring designed to be suited to both the existing normal fuse having the rated capacity of 15 A and the load, so that the high breaking capacity fuse is not blown out but the wiring is burnt. In order to solve this problem, the present invention provides a system in which a slow blow fuse 103 is installed at a rear end of the high breaking capacity fuse so that when an overcurrent exceeding a maximum design capacity flows to the wiring, the slow blow fuse 103 is caused to be blown out, thereby preventing a dangerous situation such a fire or the like that may occurs additionally.
[0028] In a system for prevention of and protection against a fire caused by fuse misuse according to the present invention, including a load 102 and a high breaking capacity fuse 101 having a rated capacity higher than that of a normal fuse that is installed to be suit to the capacity of the load 102 , a slow blow fuse 103 is installed between the high breaking capacity fuse 101 and the load 102 and has a melting part that is melted to be broken due to a temperature rise when an overcurrent having passed through the high breaking capacity fuse 101 is applied to the slow blow fuse 103 to interrupt the overcurrent flowing to the load 102 .
[0029] In a detailed configuration, the system according to the present invention has a structure in which the slow blow fuse 103 is installed between the load 102 and the high breaking capacity fuse 101 having a rated capacity higher than that of a normal fuse that is installed to be suit to the capacity of the load 102 , and a melting part is melted to be broken due to a temperature rise when an overcurrent having passed through the high breaking capacity fuse 101 is applied to the slow blow fuse 103 to interrupt the overcurrent flowing to the load 102 .
[0030] For example, the slow blow fuse 103 may include: an element made of a metal to enable electricity to flow therethrough; a housing configured to securely fix the element; a cover made of a transparent material to allow the state of the fuse to be confirmed therethrough; and the melting part positioned on the element inside the housing without being in close contact with the housing and the cover, the melting part being melted to be broken due to a temperature rise when the overcurrent flows therethrough.
[0031] The load 102 that is connected to a rear end of the flow blow fuse 103 according to the present invention may be any one selected from among a lamp installed on a boom or an operator's cab, a wiper motor, a fan motor, and a machine controller.
[0032] The operation of the a system for prevention of and protection against a fire caused by fuse misuse in accordance with an embodiment of the present invention as shown in FIG. 2 will be described hereinafter.
[0033] The operation of the inventive system is performed in such a manner that the slow blow fuse 103 is installed between the load 102 and the high breaking capacity fuse 101 having a rated capacity higher than that of a normal fuse that is installed to be suit to the capacity of the load 102 , so that the melting part is melted to be broken due to a temperature rise when an overcurrent having passed through the high breaking capacity fuse 101 is applied to the slow blow fuse 103 to interrupt the overcurrent flowing to the load 102 .
[0034] For example, in the case of instead of a normal fuse having a rated capacity of 15 A, a high breaking capacity fuse having a rated capacity of 20 A is used in a state of being connected to a load, when an overcurrent flows to the load, it exceeds a permissible capacity range of the wiring designed to be suited to both the existing normal fuse having the rated capacity of 15 A and the load, so that the high breaking capacity fuse is not blown out but the wiring is burnt.
[0035] In order to solve this problem, the present invention provides a system in which a slow blow fuse 103 is installed at a rear end of the high breaking capacity fuse so that when an overcurrent exceeding a maximum design capacity flows to the wiring, the slow blow fuse 103 is caused to be blown out, thereby preventing a dangerous situation such a fire or the like that may occurs additionally.
[0036] The slow blow fuse 103 , for example, may include: an element made of a metal to enable electricity to flow therethrough; a housing configured to securely fix the element; a cover made of a transparent material to allow the state of the fuse to be confirmed therethrough; and the melting part positioned on the element inside the housing without being in close contact with the housing and the cover, the melting part being melted to be broken due to a temperature rise when the overcurrent flows therethrough.
[0037] As described above, if a user who does not know an electric circuit well uses a high capacity fuse connected to an excessive electrical load, an overcurrent flowing to the wring exceeds a permissible capacity of the wiring. In order to prevent this from occurring, a slow blow fuse designed to be blown out more slowly than a normal fuse is installed at a rear end of the high capacity fuse so that the machine can be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
[0038] Hereinafter, a slow blow fuse of the system for prevention of and protection against a fire caused by fuse misuse in accordance with an embodiment of the present invention as shown in FIG. 2 will be described in more detail with reference to FIG. 3 .
[0039] FIG. 3 is a perspective view showing an example of a slow blow fuse that can be used in the present invention.
[0040] As shown in FIG. 3 , the slow blow fuse that can be used in the present invention is a small-sized fuse developed in the form of a glass or chip. The slow blow fuse designed to be capable of being mounted on a PCB, and thus it is impossible for a user to easily change the slow blow fuse. For this reason, if a user who is not an expert change the slow blow fuse easily, there is a risk of misuse of the slow blow fuse.
[0041] For reference, the slow blow fuse that can be used in the present invention is mounted on an electric circuit for an automobile, an industrial machine, or the like to prevent damage and fire of the machine due to overcurrrent.
[0042] The slow blow fuse must not be melt to be broken for an overcurrent that is less than about 110% of a rated current capacity. If an overcurrent of more than 110% of the rated current capacity is applied to the machine, the slow blow fuse must be melt to be broken within the time conforming to a standard according to a ratio of the overcurrent, and simultaneously a risk of a fire must be eliminated.
[0043] The slow blow fuse may employ two structures, i.e., a structure in which the slow blow fuse is not subject to soldering, and a structure in which a heat-dissipating plate is formed and then the slow blow fuse is subject to soldering.
[0044] The slow blow fuse according to the present invention is installed between a high capacity fuse and a load to protect the machine from a risk of damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
INDUSTRIAL APPLICABILITY
[0045] As described above, according to the system of the present invention as constructed above, if a user who does not know an electric circuit well uses a high capacity fuse connected to an excessive electrical load, an overcurrent flowing to the wring exceeds a permissible capacity of the wiring. In order to prevent this from occurring, a slow blow fuse designed to be blown out more slowly than a normal fuse is installed at a rear end of the high capacity fuse so that the machine can be protected from a risk of a damage and of a fire of the wiring caused by an electrical overload due to fuse misuse and faulty circuit modification.
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The present invention relates to a system including a slow blow fuse interposed between a high-capacity fuse and a load, and which blocks an overcurrent from flowing into the load with a fusing part melted to be cut when the overcurrent having passed through the high-capacity fuse is input. The system protects equipment from damage to wiring and from the danger of fire that occurs due to electric overloads arising from fuse misuse and faulty circuit modification.
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BACKGROUND OF THE INVENTION
This invention relates to the selective gas phase ethylation of xylene to form a highly isomerically-pure dimethylethylbenzene product and to the use of catalyst compositions comprising metal-modified, crystalline borosilicate molecular sieves, incorporated into an inorganic matrix, for carrying out such selective ethylation. More particularly, this invention relates to the selective gas phase conversion of xylene to highly isomerically pure 3,4-dimethylethylbenzene by contacting xylene, pure or in a mixture, with an ethylating agent under hydrocarbon conversion conditions in the presence of a catalyst composition comprising a metal-ion-modified, crystalline borosilicate molecular sieve incorporated in an inorganic matrix in which the metal ion is intimately associated with the silica framework lattice. The process offers a simple route from xylene to a highly isomerically-pure 3,4-dimethylethylbenzene product having reduced isomer purification problems.
Catalyst compositions, generally useful for hydrocarbon conversion, based upon AMS-1B crystalline borosilicate molecular sieves have been described in U.S. Pat. Nos. 4,268,420, 4,269,813, 4,285,919, and published European Application No. 68796, all of which are incorporated herein by reference.
In U.K. Pat. No. 2,024,790B, catalyst compositions containing high specific surface area crystalline silica based materials modified by boron, which have been impregnated by Pt, Pd, Ni, Co, W, Cu, and Zn, are taught, which materials have catalytic usefulness in, inter alia, the alkylation of toluene with methanol. European Pat. No. 38682 teaches methanol-to-synthesis-gas conversion catalysts comprising a crystalline silica modified by inclusion of cobalt in the crystal lattice in place of a proportion of the silicon atoms. The catalyst is prepared by mixing in water or alcohol a source of silicon, a source of cobalt, a nitrogenous base such as a quaternary ammonium compound and, optionally, a mineralizing agent, and/or an inorganic base like sodium hydroxide. Also, European Pat. No. 63436 describes a methanol or olefin conversion catalyst of general formula 0-9 M 2 O:aY 2 O 3 :at least 100XO 2 :0-35H 2 O, where M is a monovalent cation or 1/n of a cation of valency n, a is from 0-9, X is silicon and Y can be one or more of aluminum, iron, chromium, vanadium, molybdenum, arsenic, antimony, manganese, gallium, or boron.
Selective production of 3,4-dimethylethylbenzene by alkylation of xylene over zeolite catalysts having a silica-to-alumina ratio of at least about 12 and a Constraint Index of greater than 2 and up to about 12 is taught in European Patent Application No. 0021600. The class of zeolites is exemplified by ZSM-5, ZSM-11, ZSM-23, and ZSM-35.
Catalyst compositions made using crystalline borosilicate molecular sieves have shown a great utility for hydrocarbon conversion reactions such as aromatic isomerization and alkylation reactions. While excellent for many purposes, it is desirable to fine-tune the borosilicate family of catalysts to perform more selectively in a particular type of hydrocarbon conversion reaction. Now it has been found that by incorporating a small amount of metal ion in the formation of a HAMS-1B molecular sieve, crystalline borosilicate-based molecular sieves, metalloborosilicates, can be produced which are very selective for producing the 3,4-dimethylethylbenzene isomer during the gas phase ethylation of a xylene alone or in a mixture.
SUMMARY OF THE INVENTORY
Described herein is a process comprising contacting xylene and an ethylating agent under hydrocarbon conversion conditions to selectively form 3,4-dimethylethylbenzene with a catalyst composition comprising a crystalline metalloborosilicate molecular sieve containing between about 0.1 weight percent and about 6 weight percent of metal ion selected from the group consisting of manganese, cobalt, nickel, copper, zinc, and ytterbium ions, said sieve made by crystallization from an aqueous solution containing ammonia or an organic base, an organic templating material, a metal ion-affording compound selected from soluble compounds of said metal ion, and sources of an oxide of silicon and boron and providing an X-ray pattern comprising the X-ray diffraction lines and assigned strengths to be found in Table A below.
These metalloborosilicates are made in such a way that the metal ion content of the sieve, while small, is incorporated differently in the crystalline lattice than metal ion-containing sieves made by ion exchange or impregnation processes. It is believed that the metal ion may be incorporated in the silica lattice of the crystalline metalloborosilicate sieve.
DETAILED DESCRIPTION OF THE INVENTION
Ethylation of xylene in the presence of the catalyst compositions according to this invention is effected by contact of xylene with an ethylating agent, preferably in the gas phase, at a temperature between about 200° and about 600° C. and preferably between about 250° and about 400° C. The reaction generally takes place at atmospheric pressure, but the pressure may be within the approximate range of about 1 atmosphere to about 2000 psig. The molar ratio of xylene to ethylating agent employed is within the approximate range of about 0.5 to about 50, more preferably about 2 to about 20. Reaction is suitably accomplished utilizing a weight hourly space velocity of between about 0.1 and about 100 and preferably between about 0.5 and about 50. The reaction product consisting primarily of the 3,4-dimethylethylbenzene isomer together with comparatively smaller amounts of other isomers may be separated from the other isomers and any unconverted feed materials by any suitable means such as fractionation.
Alkylating agents useful in this invention are ethylene and ethanol and more preferably ethylene is the alkylating agent of choice.
The xylene feed to the instant process can be a single isomer such as ortho-, meta-, or paraxylene or a mixture of such isomers. The feed can be either pure xylene or xylenes, or a xylene or xylenes in mixture with other materials such as ethylbenzene. Too much of an impurity which is ethylatable, however, wastes ethylation agent and should be pre-separated.
The crystalline metalloborosilicate molecular sieves of this invention are characterized by the representative X-ray pattern listed in Table A below and by the composition formula:
xM.sub.2/n O:B.sub.2 O.sub.3 :ySiO.sub.2 :zH.sub.2 O
wherein M is hydrogen and one cation selected from the group manganese, cobalt, nickel, copper, zinc, and ytterbium, n is the valence of the cation, x is between about 2 and about 8 except for Yb where it is between about 0.2 and 0.8, y is between about 25 and about 600, and z is between 0 and about 160.
TABLE A______________________________________Interplanar InterplanarSpacing (1) Assigned Spacing (1) Assignedd, Å Strength d, Å Strength______________________________________11.18 ± 0.20 VS 3.84 ± 0.10 MS10.03 ± 0.20 MS 3.81 ± 0.10 M9.75 ± 0.20 W 3.74 ± 0.10 W6.35 ± 0.20 W 3.71 ± 0.10 M5.98 ± 0.15 W 3.63 ± 0.10 W______________________________________ (1) Copper K alpha radiation (2) VW = very weak; W = weak; M = medium; MS = medium strong; VS = very strong
It is believed that the small metal ion content of the sieves is at least in part incorporated in the silica lattice. Various attempts to remove the metal ion from the metalloborosilicate sieves by exhaustive exchange with sodium, ammonium, and hydrogen ions, although in some cases removing a small amount of metal ion, leaves a definite, residual, nonexchangeable metal percentage, maybe incorporated in the silica lattice.
The metalloborosilicate molecular sieve useful in this invention can be prepared by crystallizing an aqueous mixture, at a controlled pH, of a metal ion-affording compound, sources of an oxide of boron and an oxide of silicon, and an organic template compound.
Typically, the mol ratios of the various reactants can be varied to produce the crystalline metalloborosilicates of this invention. Specifically, the mol ratios of the initial reactant concentrations are indicated below:
______________________________________ Most Broad Preferred Preferred______________________________________SiO.sub.2 /B.sub.2 O.sub.3 5-400 10-150 10-80SiO.sub.2 /MO 4-200 10-150 20-100Base/SiO.sub.2 0.5-5 0.05-1 0.1-0.5H.sub.2 O/SiO.sub.2 5-80 10-50 20-40Template/SiO.sub.2 0-1 0.01-0.2 0.02-0.1______________________________________
By regulation of the quantity of metal ion (represented as MO) and the quantity of boron (represented by B 2 O 3 ) in the reaction mixture, it is possible to vary the SiO 2 /MO and the SiO 2 /B 2 O 3 molar ratios in the final product. In general it is desirable to have the metal ion content of the metalloborosilicate sieve of this invention between about 0.1 and about 6 percent by weight of metal ion. More preferably, the amount of metal ion should be between about 0.5 and about 4 weight percent metal ion. Too much metal ion in the reaction mixture can reduce the sieve crystallinity which can reduce the catalytic usefulness of the sieve.
The metal ion is selected from the group consisting of manganese, cobalt, nickel, copper, zinc, and ytterbium ions and more preferably from the group consisting of manganese, cobalt, nickel, and zinc ions. It is conveniently introduced into the molecular sieve synthesis mixture as a soluble metal salt such as the metal nitrate, acetate, chloride, etc.
More specifically, the material useful in the present invention is prepared by mixing a base, a boron oxide source, a metal ion-affording substance, an oxide of silicon, and an organic template compound in water (preferably distilled or deionized). The order of addition usually is not critical although a typical procedure is to dissolve the metal ion-affording substance in an excess of complexing organic or inorganic base such as ethylenediamine or ammonia in water, add the boric acid and then the template compound. Generally, the silicon oxide compound is added with stirring and the resulting slurry is transferred to a closed crystallization vessel for a suitable time. After crystallization, the resulting crystalline product can be filtered, washed with water, dried, and calcined.
During preparation, acidic conditions should be avoided. Advantageously, the pH of the reaction mixture falls within the range of about 8.0 to about 12.0, more preferably between about 9.0 and about 11.0, and most preferably between about 9.5 and 10.5.
Examples of oxides of silicon useful in this invention include silicic acid, sodium silicate, tetraalkyl silicates, and Ludox, a stabilized polymer of silicic acid manufactured by E. I. DuPont de Nemours & Co. Typically, the oxide of boron source is boric acid although equivalent species can be used such as sodium borate and other boron-containing compounds.
Organic templates useful in preparing the crystalline metalloborosilicate include alkylammonium cations or precursors thereof such as tetraalkylammonium compounds, especially tetra-n-propylammonium compounds. A useful organic template is tetra-n-propylammonium bromide. Diamines, such as hexamethylenediamine, can be used.
Organic bases useful in the process described herein are amines and substituted amines, particularly those compounds which are able to keep the metal ion in solution during formation of the sieve without tying up the metal ion so completely so as not to allow some of it to be incorporated in the sieve.
The crystalline metalloborosilicate molecular sieve can be prepared by crystallizing a mixture of sources for an oxide of silicon, an oxide of boron, an oxide of a metal, an alkylammonium compound and an organic base or ammonia such that the initial reactant molar ratios of water to silica range from about 5 to about 80, preferably from about 10 to about 50, and most preferably from about 20 to about 40. The silica-to-boron oxide molar ratio is preferably about 5 to about 400, more preferably about 10 to about 150 and most preferably about 10 to about 80. In addition, preferable molar ratios for initial reactant silica to oxide of metal range from about 4 to about 200, more preferably from about 10 to about 150, and most preferably from about 20 to about 100. The molar ratio of organic base or ammonia to silicon oxide should be about above about 0.05, typically below about 5, preferably between about 0.05 and about 1.0, and most preferably between about 0.1 and about 0.5. The molar ratio of alkylammonium compound, such as tetra-n-propylammonium bromide, to silicon oxide can range from 0 to about 1 or above, typically above about 0.005, preferably about 0.01 to about 0.2, and most preferably about 0.02 to about 0.1.
The resulting slurry is transferred to a closed crystallization vessel and reacted usually at a pressure at least the vapor pressure of water for a time sufficient to permit crystallization which usually is about 0.25 to about 20 days, typically is about one to about ten days, and preferably is about one to about seven days, at a temperature ranging from about 100° to about 250° C., preferably about 125° to about 200° C. The crystallizing material can be stirred or agitated as in a rocker bomb. Preferably, the crystallization temperature is maintained below the decomposition temperature of the organic template compound. Especially preferred conditions are crystallizing at about 150° C. for about three to about seven days. Samples of material can be removed during crystallization to check the degree of crystallization and determine the optimum crystallization time.
The crystalline material formed can be separated and recovered by well-known means such as filtration with aqueous washing. This material can be mildly dried for anywhere from a few hours to a few days at varying temperatures, typically about 50° to about 225° C., to form a dry cake which can then be crushed to a powder or to small particles and extruded, pelletized, or made into forms suitable for its intended use. Typically, materials prepared after mild drying contain the organic template compound and water of hydration within the solid mass and a subsequent activation or calcination prodecure is necessary, if it is desired to remove this material from the final product. Typically, the mildly dried product is calcined at temperatures ranging from about 260° to about 850° C. and preferably from about 420° to about 600° C. Extreme calcination temperatures or prolonged crystallization times may prove detrimental to the crystal structure or may totally destroy it. Generally, there is no need to raise the calcination temperature beyond about 600° C. in order to remove organic material from the originally formed crystalline material. Typically, the molecular sieve material is dried in a forced draft oven at 165° C. for about 4 hours and is then calcined in air in a manner such that the temperature rise does not exceed 125° C. per hour until a temperature of about 540° C. is reached. Calcination at this temperature usually is continued for about 4 to 16 hour. The metalloborosilicate sieves thus made generally have a surface area greater than about 300 sq. meters per gram as measured by the BET procedure.
The metalloborosilicate sieve useful in this invention is admixed with or incorporated within various binders or matrix materials depending upon the intended process use. The crystalline metalloborosilicates are combined with active or inactive materials, synthetic or naturally-occurring zeolites, as well as inorganic or organic materials which would be useful for binding the metalloborosilicate. Well-known materials include silica, silica-alumina, alumina, magnesia, titania, zirconia, alumina sols, hydrated aluminas, clays such as bentonite or kaolin, or other binders well-known in the art. Typically, the metalloborosilicate is incorporated within a matrix material by blending with a sol of the matrix material and gelling the resulting mixture or slurrying the sieve with the matrix material and drying. Also, solid particles of the metalloborosilicate and matrix material can be physically admixed. Typically, such metalloborosilicate compositions can be pelletized or extruded into useful shapes. The crystalline metalloborosilicate content can vary anywhere from a few up to 100 wt.% of the total composition. Catalytic compositions can contain about 0.1 wt.% to about 100 wt.% crystalline metalloborosilicate material and preferably contain about 10 wt.% to about 95 wt.% of such material and most preferably contain about 20 wt.% to about 80 wt.% of such material.
More specifically, catalytic compositions comprising the crystalline metalloborosilicate material of this invention and a suitable matrix material are formed by adding a finely-divided crystalline metalloborosilicate sieve to an aqueous sol or gel of the matrix material, such as PHF Alumina made by American Cyanamid Co. The resulting mixture is thoroughly blended and gelled, typically by adding a material such as ammonium hydroxide. The resulting gel is dried below about 200° C., more preferably between about 100° and about 150° C. and calcined between about 350° and about 700° C. to form a catalyst composition in which the crystalline metalloborosilicate sieve is distributed throughout the matrix material.
Alternatively, the sieve and a suitable matrix material like alpha-alumina monohydrate such as Conoco Catapal SB Alumina can be slurried with a small amount of a dilute weak acid such as acetic acid, dried at a suitable temperature under about 200° C., preferably about 100° to about 150° C., and then calcined at between about 350° and about 700° C., more preferably between about 400° to about 650° C.
The catalyst compositions of this invention appear to be more selective for the ethylation of xylene when matrixed by the gel technique rather than the slurry technique, so the gel technique of making the catalyst compositions of this invention is preferred.
The catalyst compositions of this invention can be impregnated with a magnesium compound or a phosphorus compound or both, which can be accomplished using the catalyst composition in powder form or already in extrudate or pellet form.
To make the impregnated catalyst compositions, a composition comprising the acid form of the crystalline metalloborosilicate molecular sieve in an inorganic matrix is contacted with a phosphorus compound-containing solution. The resulting mass is then dried at temperatures up to about 150° C. removing in this step essentially all of the impregnation solvent. The resulting composition is then activated by calcination for 3 hours to about 24 hours at about 350° to about 650° C., more preferably about 4 hours to about 24 hours at about 400° to about 600° C. Care should be taken to avoid catalyst degradation during calcination.
The amount of phosphorus incorporated with the catalyst composition should be from about 1 to about 15 percent by weight, especially from about 2 to about 10 percent by weight, with the percents calculated as percent of the element.
Representative phosphorus compounds useful in the impregnation step include primary, secondary, or tertiary phosphines; tertiary phosphine oxides; primary and secondary phosphonic acids; esters of phosphonic acids; the dialkyl alkyl phosphonates; alkyl dialkyl phosphonates phosphinous acids, primary, second, and tertiary phosphites and esters thereof; alkyl dialkylphosphinites, dialkyl alkylphosphonites, their esters, phosphoric acid, phosphite esters such as triethylphosphite and ammonium phosphate salt. Preferred phosphorus-containing compounds include phosphoric acid, phosphite esters such as triethylphosphite, ammonium hydrogen phosphate and ammonium dihydrogen phosphate.
Magnesium compounds can be incorporated with the catalyst compositions in a manner similar to that employed with the phosphorus compounds above. Magnesium impregnation should result in about 4% to 20% by weight magnesium, preferably from about 8% to about 15% by weight magnesium, percent calculated as percent of the element. As with phosphorus, magnesium compound incorporation is effected by contacting the catalyst composition with the solution of an appropriate magnesium compound followed by drying and calcining to substantially convert impregnated magnesium compound to its oxide form. Preferred magnesium-containing compounds include most soluble magnesium salts, more preferably magnesium nitrate or acetate. Drying and calcination times and temperatures are generally the same as recited hereinbefore for drying the calcination of phosphorus-containing catalyst compositions.
The solutions of phosphorus or magnesium compounds used in impregnation may be made from polar or nonpolar solvents, including water and organic solvents generally. Solvents that are destructive of either the zeolite or matrix should be avoided. Water and alcohols are preferred solvents.
When both phosphorus and magnesium impregnation is used, the phosphorus compound and the magnesium compound are impregnated in the catalyst composition sequentially with phosphorus impregnation preceding magnesium impregnation.
The following Examples will serve to illustrate certain embodiments of the hereindisclosed invention. These Examples should not, however, be construed as limiting the scope of the novel invention as there are many variations which may be made thereon without departing from the spirit of the disclosed invention, as those of skill in the art will recognize.
EXAMPLES
General
The reactions in the hydrocarbon conversion Examples below were carried out in a stainless steel reactor of plug-flow design. Reactants were mixed and then fed into a preheater packed with inert Denstone packing and passed into a 1/2-inch O.D.×5-inch reactor tube filled with a 3-5 g catalyst composition charge. The entire reactor and preheater assembly was supported in a fluidized sand bath maintained at reaction temperature. Product was collected in a cooled vessel as it dripped from the reactor and analyzed by gas chromatography on a 60-meter fused silica capillary column. All hydrocarbon isomer amounts are given in percents by weight. In the case of use of mixed xylenes as feed, the xylenes contain about 20% ethylbenzene, the reaction products of which are not included in the data for the table below.
All reaction runs were at ambient pressure and 4-6 hours in length and the system was lined out for at least an hour before collecting conversion and selectivity data. These runs wwee made with ethylene by feeding 0.21 ml/min of aromatic compound together with 5.5 ml/min of ethylene (an 8:1 molar aromatic/ethylene ratio), or in the case of the ethanol runs, feeding a 8:1 molar aromatic/ethanol liquid mixture to the preheater from the feed reservoir. Each run used a 3-5 g catalyst charge and, due to variations in catalyst density, the WHSV are not always constant so that the % conversion values are not strictly comparable.
EXAMPLE 1
A 14.76 g portion of manganese acetate and a 29.45 g portion of boric acid were dissolved in 1000 ml of water. A 23.96 g portion of tetrapropylammonium bromide was dissolved in the solution and the pH raised to 9.8 with 35.05 g of ethylenediamine. Ludox AS-40 supplied by E. I. DuPont in the amount of 300.94 g was then added. The resulting mixture was stirred at room temperature for 15 minutes before recording the final pH and charging to a stainless steel autoclave. Digestion in the autoclave was allowed to proceed at 150° C. for a minimum of 3 days. The result was cooled, filtered, washed well with distilled water, and dried at 165° C. for 4 hours. The dried material was then calcined at 500° C. for 12 hours. The resulting solid was exchanged twice with ammonium acetate solutions and dried at 165° C. The product contained 2.09% by weight manganese.
EXAMPLE 2
A 17.77 g portion of nickel nitrate and a 24.73 g portion of boric acid were dissolved in 1000 ml of water. A 23.98 g portion of tetrapropylammonium bromide was dissolved in the solution and the pH raised to 9.5 with 24.74 g of ethylenediamine. Ludox AS-40 supplied by E. I. DuPont in the amount of 300.94 g was then added. The resulting mixture was stirred at room temperature for 15 minutes before recording the final pH and charging to a stainless steel autoclave. Digestion in the autoclave was allowed to proceed at 150° C. for a minimum of 3 days. The result was cooled, filtered, washed well with distilled water, and then dried at 165° C. for 4 hours. The dried material was then calcined at 500° C. for 12 hours. The resulting solid was exchanged twice with ammonium acetate solutions and dried at 165° C. The product contained 0.91% by weight nickel.
EXAMPLE 3
A 15.42 g portion of cobalt nitrate and a 24.55 g portion of boric acid were dissolved in 1000 ml of water. A 40.55 g portion of tetrapropylammonium bromide was dissolved in the solution and the pH raised to 9.9 with 40.41 g of ethylenediamine. Ludox AS-40 supplied by E. I. DuPont in the amount of 300.94 g was then added. The resulting mixture was stirred at room temperature for 15 minutes before recording the final pH and charging to a stainless steel autoclave. Digestion in the autoclave was allowed to proceed at 150° C. for a minimum of 3 days. The result was cooled, filtered, washed well with distilled water, and then dried at 165° C. for 4 hours. The dried material was then calcined at 500° C. for 12 hours. The resulting solid was exchanged twice with ammonium acetate solutions and dried at 165° C. The product contained 1.01% by weight cobalt. Surface analysis of this sieve using XPS indicates that the cobalt is present in the +2 oxidation state and the Co(II) is incorporated in the sieve lattice rather than present as CoO.
The powder diffraction X-ray pattern is shown in the Table below.
TABLE I______________________________________ Interplanar Spacing d, Å I/Io, %______________________________________ 11.18 100 10.03 49 3.84 47 3.81 35 3.71 23 9.75 17 3.63 16 3.74 14 5.98 14 6.35 11 5.56 9 5.70 8 4.25 7 6.70 5 3.43 5 2.98 5 4.97 5 3.04 4 3.30 4 2.96 4 4.35 4 1.98 4 2.00 4 4.60 4 5.01 4 2.93 3 3.99 3 5.35 2 3.34 2 3.47 2 2.48 2 2.72 2 2.60 2 3.13 2 3.23 1 2.39 1 1.86 1 2.50 1 7.42 1 1.45 1 1.90 1 1.94 1 2.40 1 10.68 1 1.44 1 2.58 1 1.66 1 5.12 1 4.44 1 3.39 1 1.65 1 1.65 1 2.85 1 1.39 1______________________________________
EXAMPLE 4
A 7.99 g portion of copper acetate and a 24.76 g portion of boric acid were dissolved in 1000 ml of water. A 23.96 g portion of tetrapropylammonium bromide was dissolved in the solution and the pH raised to 9.5 with 23.90 g of 30% ammonia. Ludox AS-40 supplied by E. I. DuPont in the amount of 300.94 g was then added. The resulting mixture was stirred at room temperature for 15 minutes before recording the final pH and charging to a stainless steel autoclave. Digestion in the autoclave was allowed to proceed at 150° C. for a minimum of 3 days. The result was cooled, filtered, washed well with distilled water, and then dried at 165° C. for 4 hours. The dried material was then calcined at 500° C. for 12 hours. The resulting solid was exchanged twice with ammonium acetate solutions and dried at 165° C. The product contained 0.46% by weight copper.
EXAMPLE 5
A 7.51 g portion of zinc acetate and a 20.80 g portion of boric acid were dissolved in 1000 ml of water. A 23.96 g portion of tetrapropylammonium bromide was dissolved in the solution and the pH raised to 10.2 with 33.98 g of ethylenediamine. Ludox AS-40 supplied by E. I. DuPont in the amount of 300.94 g was then added. The resulting mixture was stirred at room temperature for 15 minutes before recording the final pH and charging to a stainless steel autoclave. Digestion in the autoclave was allowed to proceed at 150° C. for a minimum of 3 days. The result was cooled, filtered, washed well with distilled water, and then dried at 165° C. for 4 hours. The dried material was then calcined at 500° C. for 12 hours. The resulting solid was exchanged twice with ammonium acetate solutions and dried at 165° C. The product contained 0.69% by weight zinc.
EXAMPLE 6
A 10.00 g portion of ytterbium acetate and a 24.80 g portion of boric acid were dissolved in 1000 ml of water. A 23.96 g portion of tetrapropylammonium bromide was dissolved in the solution and the pH raised to 9.8 with 13.2 g of iminodiacetate and 31.0 g of 30% ammonia. Ludox AS-40 supplied by E. I. DuPont in the amount of 300.94 g was then added. The resulting mixture was stirred at room temperature for 15 minutes before recording the final pH and charging to a stainless steel autoclave. Digestion in the autoclave was allowed to proceed at 150° C. for a minimum of 3 days. The result was cooled, filtered, washed well with distilled water, and then dried at 165° C. for 4 hours. The dried material was then calcined at 500° C. for 12 hours. The resulting solid was exchanged twice with ammonium acetate solutions and dried at 165° C. The product contained 1.31% by weight ytterbium.
EXAMPLE 7
The molecular sieves of Examples 1-6 were converted to catalyst compositions containing 40% by weight metalloborosilicate sieve and 60% by weight alumina as follows. A sample of sieve was mixed into a water sample to which was added a weight of PHF alumina, supplied by American Cyanamid, and the result blended for 3 minutes. This mixture was then gelled with concentrated (30%) ammonia and mixed in a mixmaster for 5 minutes. The result was dried at 365° C. for 4 hours, calcined at 500° C. for an additional 4 hours, and ground to 18/40 mesh. The amounts of sieve and reagents used are shown in the Table below.
TABLE II______________________________________Metallo-boro-silicate Sieve (g) Water (g) Alumina (g) NH.sub.4 OH (ml)______________________________________Mn 31.67 105 462.3 45Ni 20.05 40.6 304.7 31Co 30.20 90 468.5 45Cu 42.50 40 607 60Zn 47.10 65.0 625.05 60Yb 20.70 40.5 301.2 30______________________________________
EXAMPLE 8
The copper metalloborosilicate of Example 4 matrixed as in Example 7 was impregnated with a phosphorus compound as follows: In a small beaker containing 30 ml of water and 3.5 g of the copper borosilicate was dissolved 11.7 g of NH 4 H 2 PO 4 . The mixture was placed in a shaker bath at 50° C. overnight. The sample was dried at 130° C. overnight and calcined at 600° C. This impregnated catalyst composition contained approximately 9% phosphorus by weight.
EXAMPLE 9
The metalloborosilicates of Examples 1 through 6, matrixed as in Example 7 or matrixed and impregnated as in Example 8, were used to ethylate xylene or a mixed xylene as set out in General above. The conversion and selectivity results are given in the Table below.
TABLE III__________________________________________________________________________Conversion of Xylene to Dimethylethylbenzenes IsomerExample.sup.1 Alkylating.sup.3 Selectivity (%) Reaction C.sub.8 Conversion.sup.2No. Feed Agent 3,5 2,5 2,4 3,4 2,6 2,3 T(°C.) (%)__________________________________________________________________________1 Mixed C.sub.8 A 0.7 2.5 5.6 89.8 -- 1.4 325 7.61 Mixed C.sub.8 B 1.0 3.8 8.0 86.2 -- 1.0 325 5.81 p-xylene A 0.7 4.0 4.8 88.5 0.9 1.1 350 7.01 o-xylene A 0.9 1.9 4.6 88.2 -- 4.4 350 5.92 Mixed C.sub.8 A 2.0 5.0 9.6 81.0 -- 2.4 300 8.22 Mixed C.sub.8 B 0.9 3.2 6.4 89.5 -- -- 325 7.22 o-xylene A 1.8 3.4 7.1 83.8 -- 3.9 350 8.63 Mixed C.sub.8 A (1) 2.0 5.4 91.6 -- 1.0 325 7.13 Mixed C.sub.8 B -- 3.2 6.8 88.5 -- 1.5 325 5.53 o-xylene A -- 1.6 4.1 89.5 -- 4.8 350 5.34 Mixed C.sub.8 A 1.5 5.0 9.0 83.0 -- 1.5 325 11.64 Mixed C.sub.8 A -- 1.9 4.4 93.7 -- -- 325 7.14 Mixed C.sub.8 B 1.4 3.1 6.5 87.1 -- 1.9 350 5.74 p-xylene A 1.4 6.1 5.6 85.1 -- 1.8 350 4.64 o-xylene A -- 2.0 4.9 87.7 -- 5.45 Mixed C.sub.8 A 1.8 4.4 7.9 83.7 -- 2.2 325 8.95 Mixed C.sub.8 B 1.2 3.1 7.3 86.4 -- 2.0 325 6.25 o-xylene A 2.0 2.3 5.3 84.0 -- 6.4 350 8.16 Mixed C.sub.8 B -- 3.7 8.0 86.8 -- 1.5 325 4.36 p-xylene A 1.5 5.6 5.9 84.9 -- 2.1 350 7.86 o-xylene A 1.3 2.2 5.3. 86.2 -- 5.0 350 5.98 Mixed C.sub.8 A -- 1.9 4.4 93.7 -- -- 350 4.4Comparison.sup.5 Mixed C.sub.8 A 1.3 4.0 9.5 83.4 -- 1.9 300 8.2Comparison.sup.6 Mixed C.sub.8 A 1.8 4.1 8.8 82.0 -- 3.3 300 8.6Comparison.sup.7 Mixed C.sub.8 A 2.9 3.3 7.4 83.0 -- 3.4 325 9.3Comparison.sup.8 Mixed C.sub.8 A 3.0 3.8 7.8 82.0 -- 3.4 325 9.2__________________________________________________________________________ .sup.1 Example No. refers to the molecular sieve used. Catalyst compositions used for the conversions were the sieves of Examples 1-6 matrixed as in Example 7. .sup.2 Out of a maximum of 12.5% based upon an 8:1 feed ratio, xylene to ethylating agent. .sup.3 Alkylating agent A is ethylene and alkylating agent B is ethanol .sup.4 Mixed C.sub.8 is a mixed xylene which was 19% oxylene, 42% mxylene and 19% pxylene. .sup.5 Sieve made according to Eur. Pat. Appl. No. 68796, Exs. 1-8, and supported 40% sieve and 60%Al.sub.2 O.sub.3. .sup.6 Sieve made according to the teachings of Eur. Pat. Appl. No. 68796 and supported 40% sieve and 60%Al.sub.2 O.sub.3. .sup.7 Catalyst composition of footnote 5 impregnated with manganese acetate and containing 2% by weight Mn. .sup.8 Catalyst composition of footnote 6 impregnated with cobalt acetate and containing 2% by weight Co.
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Described is a process for selectively converting xylene in the gas phase with an ethylating agent under hydrocarbon conversion conditions to a highly pure 3,4-dimethylethylbenzene product in the presence of a catalyst composition comprising a metal-ion-modified, crystalline borosilicate molecular sieve in which the metal is intimately associated with the framework silica lattice, composited in an inorganic matrix.
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part application of application Ser. No. 10/375,829, filed Feb. 26, 2003, now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The subject invention generally pertains to loading dock shelters and more specifically to a side or head shield for such a shelter.
2. Description of Related Art
Trucks and other vehicles typically back up against a loading dock or doorway of a building to facilitate loading and unloading of the vehicle's cargo. Often a dock shelter is installed around the doorway to help shelter the area between the perimeter of the doorway and the rear of the vehicle. If left unsheltered, air gaps between the outer wall of the building and the back of the vehicle might allow the outside weather to increase the building's heating or cooling load, allow rain and snow to enter the interior of the building, or simply subject the inside dock workers to an uncomfortable draft while they service the vehicle.
Dock shelters usually include a framework that extends one to three feet outward from the face of the building wall. In some cases, pliable curtains hang from the framework and are situated to drape over the top and either side of a vehicle parked under the shelter. Such curtains are generally not self-supporting and tend to be rather limp, which can create a poor appearance. Although, functionally, such shelters may be adequate in milder climates, additional or alternate sealing may be required where weather conditions are more severe or where tighter control of environmental conditions is required.
Thus, some loading docks are provided with dock seals made of resiliently compressible foam pads. As a truck backs its trailer into the dock and against the seal, the foam pads conform to the contour of the rear edges of the trailer. Although such seals provide a very effective seal, they do have a few drawbacks when compared to dock shelters. Foam dock seals are typically more expensive than dock shelters. Seals also reduce the access opening into the trailer because the foam pads overlap the perimeter of the trailer's opening. Moreover, a foam pad usually needs a tough outer cover to protect the pad from wear and to prevent the pad from absorbing water and dirt. A cover should be tough to resist wear yet pliable to allow compression of the foam. Unfortunately, some of the toughest cover materials are not very pliable, and vise versa. So, a compromise is often needed in selecting a cover with an optimum combination of toughness and pliability.
Consequently, a need exists for a dock shelter that provides a more positive seal than current shelters, yet is more economical than conventional dock seals.
SUMMARY OF THE INVENTION
A dock shelter is provided with a face panel that is relatively lightweight and firm, yet moveable for sealing against vehicles of various size and position. The face panel can be used as a side curtain or a head curtain. To provide the face panel with durability while minimizing its weight, the face panel includes a rather stiff and durable outer shell with a hollow interior. In some embodiments, the face panel is moveable by virtue of an integral living hinge that connects the face panel to a generally stationary support panel.
In some embodiments, the outer shell of the face panel comprises two half-shells that are fused to each other.
In some embodiments, the two half-shells provide both the face panel and the support panel.
In some embodiments, both the face panel and the support panel are hollow.
In some embodiments, the living hinge between the face panel and support panel is corrugated for greater flexibility.
In some embodiments, a torsion spring urges the face panel to an extended position.
In some embodiments, a pliable elongated member limits the pivotal extension of the face panel.
In some embodiments, the face panel includes a flexible extension plate that helps protect the main body of the face panel from wear.
In some embodiments, the hollow face panel includes recessed areas that enhance the face panel's rigidity.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a front view of one embodiment of a dock shelter.
FIG. 2 is a cross-sectional top view taken along line 2 — 2 of FIG. 1 and shows a vehicle backing into the dock shelter.
FIG. 3 is the same as FIG. 2 , but with the vehicle having already backed into the dock shelter.
FIG. 4 is a cross-sectional top view taken along line 4 — 4 of FIG. 1 .
FIG. 5 is a perspective view showing the upper portion of an integrally formed face panel and support panel, wherein some hardware is removed to illustrate various features of the panels.
FIG. 6 is a cross-sectional top view similar to FIG. 4 but of another embodiment.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIGS. 1-3 , a dock shelter 10 installed around a doorway 12 of a loading dock 14 includes two face panels 16 and 18 that help provide a weather seal between the rear sides of a vehicle 20 and a wall 22 of a building. To help seal along a rear upper surface of vehicle 20 , another face panel 24 (similar to panels 16 and 18 or of another design, such as a conventional curtain or a compressible foam pad) can be installed along an upper portion of dock shelter 10 . To seal a gap that might exist between upper face panel 24 and the two lateral panels 16 and 18 , a curtain 26 can be used to overlap adjacent panels.
Face panels 16 and 18 are coupled to wall 22 by way of two support panels 28 and 30 or by way of some other supporting structure. To allow the face panels to move in response to vehicle 20 backing into dock shelter 10 , face panels 16 and 18 are pivotally connected to support panels 28 and 30 , respectively. Vehicle 20 traveling from its position of FIG. 2 to that of FIG. 3 pivots face panels 16 and 18 towards wall 22 . As the face panels pivot, they engage the sides of vehicle 20 to help provide a shelter around vehicle 20 . The actual structure of dock shelter 10 , according to a preferred embodiment, will be described with reference to face panel 16 ; however, the same construction may be applied to face panels 18 and/or 24 .
Referring to FIGS. 4 and 5 , face panel 16 comprises an outside casing member 32 and an inside casing member 34 that are joined, and preferably fused (e.g., melted), to each other along their perimeter 36 . The term, “fused” refers to a joint wherein separation of the joint would involve severing the base material of one or both of the joined items. However, members 32 and 34 can also be joined in a variety of other ways or by using various fasteners including, but not limited to, screws, snaps, adhesive, clips, etc.
To create a face panel that is generally rigid yet lightweight, casing members 32 and 34 are thermoformed to provide a generally stiff outer shell with a hollow interior (a hollow chamber 38 ). A twin-sheet thermoforming process, as well known to those skilled in the art, involves expanding two heat-softened thermoplastic sheets (e.g., ⅛-inch thick polyethylene) into two opposing mold cavities by applying an absolute pressure differential between an interior and exterior of the two sheets. The interior or area between the two sheets can be pressurized and/or the exterior of the sheets can be exposed to a vacuum. In some cases, such a process can be applied separately to face panel 16 and support panel 28 , which are later connected to each other by a hinge. In a preferred embodiment; however, panels 16 and 28 are thermoformed in a single operation with an integral living hinge 40 formed where panels 16 and 28 meet.
More specifically, outside casing member 32 runs continuously as a unitary sheet across a front face of panel 16 and along one side of support panel 28 . Likewise, inside casing member 34 runs continuously as a unitary sheet across a back face of panel 16 and along another side of support panel 28 . The two casing members 32 and 34 are not only joined to each other along their perimeter but are also joined at several other locations to provide various useful features.
For example, to increase the rigidity of panels 16 and 28 , casing members 32 and 34 include several recessed areas 42 and 44 where the inner surfaces of members 32 and 34 come together. Also, recessed areas 46 and 48 facilitate the mounting of various hardware items, such as a torsion spring 50 , leaf spring 52 , and an extension plate 54 , all of which will be explained further.
While living hinge 40 allows face panel 16 to pivot relative to support panel 28 , torsion spring 50 (or some other type of resilient member) interacts with panels 16 and 28 to urge face panel 16 to pivot away from support panel 28 and toward vehicle 20 . To limit the angular travel of face panel 16 and establish a predetermined angle 56 between panels 16 and 28 (e.g., 90-degrees, as shown) when a vehicle is not presently at loading dock 14 , a fabric strap 58 (or some other pliable elongated member, e.g., chain, cable, rope, etc.) attaches between panels 16 and 28 . Spring 50 and strap 58 can be mounted in various ways; however, in some embodiments, opposite ends of spring 50 are held to panels 16 and 28 by way of clamp plates 60 and fasteners 62 (e.g., screws, bolts, rivets, etc.).
Since hollow chamber 38 helps make face panel 16 rather rigid, the more flexible extension plate 54 (e.g., ¼-inch thick polyethylene) can be fastened to it. Extension plate 54 not only provides face panel 16 with a distal edge 64 that is more adapted to seal against vehicle 20 , but plate 54 also helps protect against wear of other portions of face panel 16 from wear. Distal edge 64 is preferably curved about a vertical axis to avoid having edge 64 catch against the side of vehicle 20 as vehicle departs loading dock 14 .
Although edge 64 is shown curved toward the face of wall 22 , in some embodiments, the edge can curve in an opposite direction, away from wall 22 . In FIG. 6 , for example, a dock shelter 10 ′ includes a distal edge 64 ′ that curves away from wall 22 . This allows the rear vertical edge of a truck's trailer to fit inside the inner surface of the curved distal edge, whereby the curved distal edge 64 ′ helps seal a gap along the trailer's rear door hinges.
To provide extension plate 54 with additional resilience or spring-back, one or more leaf springs 52 can be installed between plate 54 and the front face panel 16 . Fasteners 66 (e.g., rivets, screws, bolts, etc.) can be used to attach plate 54 and spring 52 to face panel 16 . Recessed areas 48 that place interior surfaces of casing members 32 and 34 against each other allow fasteners 66 to tightly clamp extension plate 54 and spring 52 against face panel 16 without adversely crushing panel 16 .
To adapt support panel 28 for mounting to wall 22 , panel 28 is provided with several cavities 68 and 70 , which allow fasteners 72 to be inserted through holes 74 and anchored to wall 22 . Cavities 68 and 70 are alternately formed in casing members 32 and 34 , respectively. Such an alternate arrangement provides support panel 28 with greater strength and resistance to forces that may urge panel 28 to bend about its mounting surface 76 .
To enhance the ability of face panel 16 to pivot relative to support panel 28 , casing member 32 and/or 34 are corrugated in the area of hinge 40 . As face panel 16 pivots through it full range of motion, the corrugations reduce localized strain in the base material of members 32 and 34 by distributing the bending action over the circumference of hinge 40 . The reduced strain increases the fatigue life of hinge 40 .
Although the invention is described with reference to a presently preferred embodiment, it should be appreciated by those skilled in the art that various modifications are well within the scope of the invention. Therefore, the scope of the invention is to be determined by reference to the claims that follow.
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In order to provide a durable loading dock shelter with an effective seal, the dock shelter is provided with a face panel that is relatively lightweight and firm, yet moveable for sealing against vehicles of various size and position. The face panel can be used as a side curtain or a head curtain. To provide the face panel with durability while minimizing its weight, the face panel is thermoformed of twin sheets of plastic to provide a durable outer shell with a hollow interior. In some embodiments, the face panel is moveable by virtue of an integral living hinge that connects the face panel to a generally stationary support panel.
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CROSS-REFERENCE TO RELATED APPLICATIONS
N/A
BACKGROUND OF THE INVENTION
1. The Field of the Invention
The present invention is generally related to puzzles, brain teasers, mind bogglers or benders, magic tricks, or the like. In particular, the present invention provides a device configured to give the illusion that a rubber band or other elastic apparatus is hooked or otherwise captured within a housing device, wherein the operation of hooking or catching the rubber band is virtually and/or conceptually impossible.
2. Background and Related Art
While the invention is subject to a wide range of applications, it is especially suited for use as a puzzle, brainteaser, mind boggler or bender, magic trick, or the like, and will be particularly described in these contexts. In the area of entertainment, there is always a need for new devices that the public might find intriguing. For example, magicians are always looking to find new tricks to add to their repertoire and/or people are continually entertained with new puzzles or mind boggling devices. For such novelty items, simple use and inexpensive manufacturing costs are always a concern.
Accordingly, it is an object of the present invention to provide an illusion device that is simple to use. Further, it is an object of the present invention to provide an illusion device that is inexpensive to manufacture.
BRIEF SUMMARY OF THE INVENTION
In order to meet the above-identified objectives, the present invention provides a method and device that give the illusion that a rubber band or other elastic apparatus is hooked from within a base unit using a rod, wherein actually hooking the elastic apparatus within the base unit is virtually and/or conceptually impossible.
For example, in a first example embodiment an opposite end of the rod is inserted at least partway into the hole of a base unit using the handle end of the rod. The base unit gives the appearance that the elastic device is attached to and extending within the hole thereof. The inserted opposite end of the rod is then pulled partially out of the base unit using a handle end of the rod. Next, before the opposite end of the rod is exposed in viewable sight, at least two of a user's fingers are pressed together on substantially opposing sides of the handle end of the rod in order to forcibly snap the rod back into the base unit giving the illusion that the rod slipped from the user's fingers due to an opposing force from the elastic apparatus pulling on the opposite end of the rod from within the base unit.
In another exemplary embodiment, a device for use in creating the illusion as if a rod has hooked an elastic apparatus from within a hole of a base unit is provided, wherein the actual hooking of the elastic apparatus within the base unit is virtually impossible. The device comprises an elongated base unit with a hole therein running substantially parallel to its length. Further, an elastic apparatus having the appearance that it extends at least partway into the hole of the base unit and is attached thereto is provided. Moreover, the device comprises a rod with a handle end and an opposite end. The handle end is used to insert the opposite end at least partway into the hole of the base unit and also used to partially extract the opposite end from the hole, wherein the handle end of the base unit is formed such that when a user's fingers apply pressure on substantially opposite ends thereof, the rod slips from the user's fingers and forcibly snaps into the base unit giving the illusion that the rod slipped from the user's fingers due to an opposing force from the elastic apparatus pulling on the opposite end of the rod from within the base unit.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the invention. The features and advantages of the invention may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features of the present invention will become more fully apparent from the following description and appended claims, or may be learned by the practice of the invention as set forth hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
In order to describe the manner in which the above-recited and other advantages and features of the invention can be obtained, a more particular description of the invention briefly described above will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings. Understanding that these drawings depict only typical embodiments of the invention and are not therefore to be considered to be limiting of its scope, the invention will be described and explained with additional specificity and detail through the use of the accompanying drawings in which:
FIG. 1 illustrates an example illusory snap puzzle or device that can be used in accordance with exemplary embodiments of the present invention;
FIGS. 2A-2D illustrate a method of using the illusory snap puzzle or device in accordance with exemplary embodiments of the present invention; and
FIG. 3 illustrates another example illusory snap puzzle or device in accordance with exemplary embodiments of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention extends to methods and/or devices for creating the illusion as if a rod has hooked an elastic apparatus within the hole of a base unit, even though the hooking of the elastic apparatus is virtually and/or conceptually impossible. FIG. 1 illustrates an example of a puzzle or device 100 that may used to perform the above described illusion in accordance with exemplary embodiments of the present invention. The puzzle or device 100 includes a base unit 125 that has an elongated hole 120 running substantially parallel to the base unit's length. It should be noted, that although the present invention describes the base unit 125 as elongated and the relationship of the hole 120 in accordance therewith, the present invention is not restricted to any shape and/or relative size of the base unit 125 with relationship to the hole 120 . For example, the base 125 , rather than a rectangular block as shown in FIG. 1 , may be a square cube with the hole 120 running substantially parallel along on of the sides. Accordingly, any specific shape and/or relative size of the base unit 125 in relationship to the hole 120 therein is used for illustrative purposes only and is not meant to limit or otherwise narrow the scope of the present invention unless explicitly claimed.
Regardless of the shape and/or relative size of the base unit 125 and the relationship of the hole 120 thereto, an elastic apparatus 130 is also provided that extends at least partway into the hole 120 of the base unit 125 , as shown in FIG. 1 . In this example, the material used to make the base unit is a nontransparent material such as wood, metal, ceramic, stone, fiberglass, or other similar nontransparent material. Accordingly, a portion of the elastic apparatus, e.g., a rubber band, should extending from the hole 120 outside of the base unit 125 in order to give the illusion that the elastic apparatus 130 extends within the hole 120 of base unit 125 . Because in this example embodiment the inside of the hole 120 in the base unit 125 for nontransparent materials cannot be viewed by the naked eye, whether or not the elastic apparatus 130 actually extends fully within the hole 120 of the base unit 125 is not of critical concern. Accordingly, in this embodiment, it is sufficient to give the illusion as if the elastic apparatus 130 extends fully within the hole 120 . In any event, as will be described in greater detail below, if the elastic apparatus 130 actually extends fully within the hole 120 of the base unit 125 , the device 100 should be configured such that the elastic apparatus 130 cannot be hooked using the rod 105 of the puzzle or device 100 described below.
The rod 105 has a handle end 110 and an opposite or insertion end 115 . The handle end 110 is used to insert the rod 105 (and in particular the opposite or insertion end 115 ) into hole 120 of the base unit 125 . The opposing or insertion end 115 of the rod 105 will typically be formed in the shape of a hook. This enhances the illusion that the rod 105 is actually capable of hooking the elastic apparatus 130 within the base unit 125 . Note, however, that the present invention is not limited to any specific shape or form of the opposite or insertion end 115 . For example, the insertion end may be flat, for boggling or intriguing the mind even more as to how such a device could actually hook a rubber band or elastic apparatus 130 . Accordingly, any specific shape of the opposite or insertion end 115 as described herein is used for illustrative purposes only and is not meant to limit or otherwise narrow the scope of the present invention unless explicitly claimed.
It should be noted that typically the diameter of the hole 120 will be just slightly larger than the diameter of the rod 105 . The present invention, however, is not limited to any specific hole 120 diameter relative to shaft 107 and/or opposite end 115 of the rod 105 diameter. Further, the present invention is not limited in the shape of shaft 107 and/or hole 120 (e.g., the shape of the shaft 107 and/or hole 120 may be triangular); however, the shaft 107 , opposite or insertion end 115 , and/or hole 120 should be of such shape and/or relative sizes such that the shaft 107 of the rod 105 can be sufficiently inserted into the hole 120 of the base unit. An important aspect to note, however, is that regardless of the shape and/or sizes of the shaft 107 , opposite or insertion end 115 , and/or hole 120 , any portion of the elastic apparatus 130 that extends within the base unit hole 120 should be virtually impossible to hook with the rod 105 ; otherwise the illusion described below no longer exists.
For example, if the elastic apparatus 130 fully extends into the hole 120 and the shaft 107 of the rod 105 is long enough such that the opposite or insertion end 115 of the rod 105 can come into actual contact with the elastic apparatus 130 , the opposite or insertion end 115 of rod 105 should be large enough in diameter such that when inserted within the hole 120 of the base unit 125 the insertion end 115 pushes the elastic unit 130 down into the base unit 125 . In other words, the diameter of the opposite or insertion end 115 should be sufficiently larger to ensure that the opposite or insertion end 115 is not actually capable of hooking the elastic unit 130 , for this would frustrate the overall illusion.
Alternatively, if only a small or unsubstantial portion of the elastic apparatus 130 extends within the hole 120 of the base unit 125 —and/or if the length of the shaft 107 is short in length—such that the opposite or insertion end 115 never comes into actual contact with the elastic apparatus 130 —then the size of the opposite or insertion end 115 of the rod 105 and/or shaft 107 relative to the hole 120 should not make a significant difference in performing the illusion of the present invention. Accordingly, as one would recognize, there are a wide variety of shapes and/or sizes for the hole 120 , the shaft 107 of the rod 105 , the opposite or insertion end 115 of the rod 105 , relative to each other.
Furthermore, the placement of the hole 120 and shaft 107 of the rod 105 relative to base unit 125 and handle 110 , respectively, may also vary. In accordance with one embodiment, and as shown in FIG. 1 , the hole 120 and shaft 107 of the rod 105 are off center of the base unit 125 and handle end 110 , respectively. Accordingly, this has the added benefit of giving the illusion that a particular way of twisting the handle end 110 , as described in greater detail below with regard to FIGS. 2A-2D , relative to the base unit 125 actually causes the elastic apparatus 130 rubber band to be hooked. Note, however, that any particular placement of the hole 120 and/or shaft 107 relative to the base unit 125 and/or handle 110 , respectively, are used herein for illustrative purposes only and are not meant to limit or otherwise narrow the scope of the present invention unless explicitly claimed.
Regardless of the shapes, sizes, and/or offsets or positions of the handle, shaft 105 , opposite or insertion end, 115 , and/or hole 120 , the handle end 110 should be formed (e.g., the pyramid shape shown in FIG. 1 ) such that when a user's fingers apply pressure on opposing or substantially opposing sides of the handle 110 , the handle 110 slips from the fingers forcing the rod 105 into the hole 120 of the base unit 125 . Note, however, that the present invention is not limited to any specific shape for the handle 110 . For example, rather than the pyramid shape shown in FIG. 1 , the handle end 110 of the rod 105 may be in the form of many shapes such as spherical, conical (e.g., circular cone, frustum circular cone, general cone, etc.), wedge shaped, substantially square, cylindrical, etc. It should be noted, however, for best results the handle should be formed such that (as described in greater detail below) the rod easily slips from the fingers of a user when pressure is applied to opposing ends of the handle.
FIGS. 2A-2D illustrate a method of giving the illusion that an elastic apparatus is hooked using a rod inserted into a base unit as described above. As shown in FIG. 2A , the base unit 225 is retangular in shape and has a hole (not shown) that extends substantially parallel to its length within the base unit 225 . An elastic apparatus (for example, a rubber band) has the appearance of extending within the hole of the base unit 225 (or may actually extend within the hole of the base unit 225 as previously described). The left (or right) hand of a user 225 firmly grips the base unit 225 . The rod 205 has an opposite or insertion end 215 and a handle end 210 . In this example, the handle end is the shape of a pyramid for ease in slipping from the fingers, as described below. A user's right (or left) hand 240 grips the handle end 210 using at least two fingers (shown here as the index and thumb fingers) the user then inserts the rod 205 into the base unit as shown by arrow 235 .
Once the user has inserted the rod 205 at least partway into the hole of the base unit 225 , the user may then make motions with the hands such as a rotation and/or slight up and down movement of the rod 205 or handle end 210 relative to the base unit 225 . This has the added effect of giving the illusion that some manipulation of the rod 205 can be performed to actually hook the elastic apparatus 230 . As previously mentioned, this feature may be enhanced when the hole in the base unit 225 and the shaft of the rod 205 are slightly off center of the base unit 225 and handle end 210 , respectively.
Regardless of whether the above manipulation operation is performed, after inserting the rod 235 at least partway into the base unit 225 using the handle end 210 , the user then begins to extract the rod 205 from the base unit 255 as shown by arrow 255 in FIG. 2B . For optimum illusory results, this extraction motion 255 should slow down the further the rod is extracted from the base unit 225 . Before the opposite or insertion end 215 can be visibly seen, the user then applies pressure, as shown in FIG. 2C , on opposing ends or substantially opposing ends of the handle end 210 of the rod 205 , as indicated by the arrows 250 . The force of the pressure should be sufficient such that, as shown in FIG. 2D , the handle end 210 slips from the fingers forcing the rod into the base unit 225 —as indicated by arrow 265 —snapping 260 the handle end 210 against the base unit 225 . Accordingly, this gives the illusion as if it was the elastic apparatus 230 was hooked to the opposite or insertion end 215 of the rod and the opposing force of the elastic apparatus 230 caused the handle end 110 of the rod 205 to slip from the user's fingers 240 and force the rod 205 into the base unit 225 .
FIG. 3 illustrates an alternative embodiment wherein at least the base unit 325 of illusory snap device 300 is made from a translucent or partially transparent material such as glass, plastic, or other similar transparent or partially transparent material. In this embodiment, the elastic apparatus 330 does not necessarily need to extend beyond the end of the base unit 325 . Instead, because the elastic apparatus 330 can clearly or partially be seen within the hole 320 of the base unit 325 , it is not necessary for the end thereof to extend beyond the base unit 325 . It may be important, however, to give the appearance that the elastic apparatus 330 is securely fastened within the base unit 325 . For example, a portion 335 of the elastic apparatus 330 may be formed beyond the base 340 of the hole 320 , such that the end 335 of the elastic apparatus 330 is formed and secured by the base unit 325 .
Of course, other means for securing the elastic unit within the transparent base unit are also available to the present invention. For example, the hole 320 may be extended all the way through the base unit 325 , as was shown with regards to FIG. 1 . In such instance, a plug or other device may be used to secure the rubber band to the base unit 325 , and a portion of the elastic apparatus 330 may extend beyond the base unit 325 . Accordingly, any method or means for giving the appearance that elastic apparatus 330 is secured to the base unit 325 is used herein for illustrative purposes only and is not meant to limit or otherwise narrow the scope of the present invention unless explicitly claimed.
In this embodiment, as in other embodiments, the handle end 310 , shaft 307 , and/or opposite or insertion end 315 of the rod 305 may or may not be made of a similar transparent or semi translucent material as the base unit 325 . It should be noted, however, that when such transparent or semi translucent base unit 325 is used, that in order for the illusion to appropriately be applied, the user should take special care in covering that portion of the base unit 325 that the rod 305 is inserted into during the above illusion performance. For example, the user may use her/his hand to cover up that portion of the base unit 325 that the opposite or insertion end 315 is inserted into. Alternatively, the user may cover the base unit 325 with a nontransparent sleeve (not shown) or other device to cover the view of the opposite or insertion end 315 such that one cannot see that the elastic apparatus 330 is not actually hooked by the rod 305 as previously described.
The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
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The present invention provides the illusion that an elastic apparatus is hooked from within a base unit, wherein actually hooking the elastic apparatus is virtually impossible. An opposite end of a rod is inserted at least partway into a hole of a base unit using the handle end of the rod. The base unit gives the appearance that the elastic device is attached to and extending within the hole thereof. The inserted opposite end of the rod is then pulled partially out of the base unit. But before the opposite end of the rod is exposed in viewable sight, two of a user's fingers are pressed together on substantially opposing sides of the handle end in order to forcibly snap the rod back into the base unit giving the illusion that the rod slipped from the user's fingers due to an opposing force from the elastic apparatus.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
Embodiments of this invention relate to lubricating compositions including high concentrations of magnesium and boron in the form of nanoparticles and to methods for making and using same.
More particularly, embodiments of this invention relate to lubricating compositions including high concentrations of magnesium and boron in the form of nanoparticles and to methods for making and using same, where the.
2. Description of the Related Art
Overbased magnesium compounds and methods for their production have been known for many years (see for example Hunt; U.S. Pat. No. 3,150,089; Sep. 22, 1964). They have been used in lubricants, as fuel additives in many combustion applications, and in various antifoulant additives used in refineries. These materials have been much sought after for these and many other as yet undiscovered applications.
Similarly, boron containing compositions have been researched from at least the same time period (see for example NACA Research Memorandum RM E55C07; June 1955) for its perceived value as a fuel and fuel additive. The splendid lubricating properties of boron formulations—especially boric acid—have also been widely investigated and are well known to those familiar with the art (see for example the early patent by Chapman; U.S. Pat. No. 905,649).
Attempts to combine the valuable lubricating properties of boron with various magnesium (and/or other alkali or alkaline earth metals) formulations have been ongoing since at least 1967 (see for example U.S. Pat. No. 3,313,727; April 1967; Peeler, R.). Combination products would theoretically combine the benefits imparted by each element. For example there is evidence suggesting that combinations of magnesium with boron would have enhanced properties as improved antifoulants in refinery use and examination of the high temperature region of the phase diagram of both magnesium and boron would suggest the combination of the two could be valuable as high temperature corrosion prevention additives.
Previously, attempts to produce combination compositions were constrained by the relatively low starting magnesium content of products researchers were required to use. This had the dual effect of forcing low magnesium concentrations as well as the amount of boron that could be reacted with the available magnesium compound was then necessarily low. This is a physical reality since the total composition must add up to 100%, the more “space” taken up by the low magnesium content materials; the less “space” is available for the boron containing material. Similar restrictions result from the even lower atomic weight boron. As is well known, boron is a very light element (low atomic weight). Therefore in order to obtain a viable, high boron content, any other element would need to be relatively dilute. This is so because associated molecular constituents of the boron compound would occupy large volumes of the combination product as the boron content is increased. Previous to this invention maximum starting magnesium contents might reach only 9 to 14 percent with concomitantly low resulting boron contents. The compounds of this invention conversely began as 30% magnesium containing liquids—more than double the previous levels—which allowed for a proportional increase in boron concentration.
Previous researchers were also constrained by the fact that most of those other magnesium compounds were comprised of stabilized magnesium carbonate overbases. Thus it was assumed and believed that only magnesium carbonate overbased materials could be boronated. The process of this invention has shown this is not a requirement. In fact it has been discovered there is no difference in reaction of previously carbonated materials and materials that have not been carbonate.
Similarly, nearly all previous patents concerning the combination of magnesium and boron have featured the prominent removal of water either formed during reaction or added as an ingredient at the start of the procedure. This in turn has led to the use of often hazardous, low boiling point liquids required to assist in the removal of the water. The difficult removal of water has in turn required the introduction of many antifoam products to try to assist the often violent distillation of water. The present invention has discovered that the removal of water is not necessary. It has additionally been found the retention of water has an additional benefit of maintaining all boron materials as boric acid. It is boric acid that has been found to have excellent lubricating properties. By the simple and desired retention of water, any boric oxide that forms is retained as boric acid by reconversion back to boric acid with water. Water may additionally be a catalyst to the ultimate reaction. By not needing to use low boiling solvents, there is no possibility they are present in final formulations. This allows for higher flash points which will make transport and use of any resulting materials safer.
By retaining the water in the reaction mass, it has also been found that the reaction can be run very quickly. It is only necessary to heat to about 100° C. which greatly facilitates any manufacturing process contemplated. Since the water is not removed, expensive heat exchangers and cooling facilities may be avoided.
3. Description of Related Art
Examples of the prior art are provided below to demonstrate some of the many methods previously developed. As will be seen nearly all methods require the use of multiple solvents, distillations, and/or multiple steps. They all differ greatly from the present invention due to the increased numbers of raw materials, solvents to be stripped, complex procedures, and in some cases very low alkaline earth and boron metal contents.
In U.S. Pat. No. 3,313,727 Peeler began with a lubricant base oil, a calcium petroleum sulfonate and then added sodium metaborate octahydrate. This mixture was then heated to partially dehydrate. The product was described as a “glass” which would not be equivalent to the flowable liquid product the present invention produces. No description of the metal content of this product was provided, but presumably it was relatively low and the glassy product would have only limited applicability and only for specialized uses.
In U.S. Pat. No. 3,853,772 Adams began with a lubricant oil, an alkali metal borate (previously produced by an undisclosed method and still containing various waters of hydration), added two dispersant materials—one of which contained an alkaline earth metal and sulfur. This was then heated to produce the product. No description of the metal content of this product was provided, but from an approximate mass balance, presumably it was relatively low.
In U.S. Pat. No. 4,683,126 Inoue mixed a neutral calcium sulfonate, a lubricant oil, powdered magnesium hydroxide, boric acid, water, and a cleaning solvent diluent. After processing to remove water and some of the solvent, a product resulted that was 7.7% calcium and 3.8% boron. Other metal contents were not described.
Fisher in U.S. Pat. No. 4,744,920 started with an overbased sodium carbonate sulfonate. To this was added a diluent oil, toluene, boric acid, and an overbased magnesium carbonate sulfonate. After processing to remove water and excess solvent a product containing 7.35% magnesium and 3.94% boron resulted.
In U.S. Pat. No. 4,900,854 Winterton began with rather exotic boron starting materials (bromo metal boranes was one) and worked at dry ice/acetone temperatures to produce a product that met his requirements. The procedure was too involved to be usable for large scale manufacturing procedures.
Erdemir, in U.S. Pat. No. 5,431,830 claimed boron compounds stabilized in solution by various dispersants are useful as lubricant compositions. He further maintained that boric acid possesses the lubricating properties to the extent that he wants to add materials—water—to convert any boric oxide preferentially back to the orthoborate form. He also states that smaller particles of boric acid are more effective as lubricant additives. However, in this patent he does not explain how to achieve these compounds, only that they are useful as lubricants.
In U.S. Pat. No. 5,854,182 Swami worked initially under strictly anhydrous conditions to produce a magnesium alkoxide material to which was subsequently added boric acid and a neutral calcium or magnesium sulfonate material. After heating this mixture, an alcohol byproduct was removed to provide a product (with magnesium sulfonate) containing 4.2% magnesium and 5.1% boron.
In U.S. Pat. No. 6,872,693 Cain describes a material that is produced from a complex mixture of monoalkyl benzene sulfonic acid, xylene, magnesium oxide, acetic acid, polyisobutylene succinic anhydride, methanol, and water. This was then blown with carbon dioxide. Many of these materials, lost during processing, were replaced and the mixture was again blown with carbon dioxide. After stripping solvents and water the final material contained 7.6% magnesium and 4.35% boron.
Robson in U.S. Pat. No. 7,026,273 utilized a lubricant oil already containing a magnesium or calcium material and added boron containing materials to this to produce products of extremely low (less than 0.5%) magnesium (or calcium) and boron (less than 0.2%) content. Presumably these low concentrations were all that was required for his applications.
In patent application 2008/0300426 Duchesne describes a product that begins with a calcium overbased material. To this was added xylene and methanol. This combined mixture was purged with nitrogen to remove all oxygen before adding a boron source. After stripping of solvents a material containing 7.7% calcium and 4.1% boron resulted.
In U.S. Pat. No. 7,479,568 Le Coent produced a material containing 9.4% calcium and 4.1% boron by combining xylene, methanol, calcium hydroxide, a sulfonic acid, boric acid, and a Group I oil. After suitable reaction and stripping of solvents the described material resulted.
In U.S. Pat. No. 7,547,330 Erdemir reveals a boron compound that when added to fuels imparts lubricating properties to engine parts. This composition consisted of a nanometer sized powder of an organic boron compound, e.g., trialkylborates, boroxins, or combinations of these. The thrust of his invention was exclusively to provide a lubricant composition. No mention was made of other applications. Curiously, although the claims of the patent do not encompass the use of boric acid, all of his example formulations illustrate only the use of boric acid. His formulation also relies heavily on mixing his aforementioned boron source material with a suitable lubricating liquid material.
SUMMARY OF THE INVENTION
Many lubricant formulations and boron processes rely on the use of alcohols for added lubrication and water scavenging. Interestingly, we have found that not removing any formed water actually enhances the incorporation of boric acid into the compositions of this invention. Thus, the water theoretically remains in the material or composition to perform this and other functions, for example, insuring any boric oxide formed remains as boric acid when lubricating properties are desired.
Oftentimes borated lubricant compounds possess desired properties of high viscosity indices, good low temperature characteristics, are not corrosive to copper, and possess antiwear properties.
Organometallic boron-containing compounds are another desired class of additives. In low sulfur fuels these organometallic compounds can effect a lowering of the ignition temperature of exhaust particles especially in diesel engines equipped with exhaust system particulate traps. Magnesium is one of the useful metals intended for this purpose.
This invention, in its various aspects, provides a simplified method to produce higher metal content compositions of magnesium and boron. The present invention overcomes certain well-known problems and deficiencies in the prior art, including those outlined above and reiterated below.
Heretofore, many of the proposed methods have been arduous and dangerous to perform. Many have involved highly flammable solvents, inert atmospheres, or the need for extremely long reaction times to achieve “boronation” without excessive foaming. Other methods have employed difficult to work with dispersing aids; some of which require complex reaction schemes to produce in situ the material to be boronated.
By contrast the current invention utilizes a commonly available high magnesium content sulfonate overbase material. The level of boron addition can be easily adjusted to produce any magnesium to boron ratio desired for the needs of the material being produced. Not wishing to be bound by theory, it is believed that either the natural surfactancy of the magnesium sulfonate or carboxylate material is utilized as well as a suspected reaction of boron compounds with the plentiful oxygen of the sulfonic or carboxylate acid chemical group to produce the desired soluble boron compound.
The reaction scheme requires blending completely the various starting materials comprising the previously produced said magnesium sulfonate or carboxylate material, an amount of boric acid to attain the final boron concentration desired, and optionally a minor amount of a low boiling solvent for viscosity control followed by low temperature heating under reflux conditions of the mixture until said boron solid starting material has been completely dissolved into the magnesium compound. Progress of the reaction can be followed by visual inspection of the product to verify all boron materials have been completely dissolved. The resulting material is clear, highly oil soluble, and when desired free of sediment.
We have surprisingly found that when the water formed during boronation is allowed to remain in the materials, there is also less sediment remaining Careful experiments have found that the process of removing water has led to more sediment that subsequently needs to be removed. Conversely, allowing the water to remain in the product has greatly diminished the amount of sediment to levels where removal may no longer be required. It is thus concluded that water actually leads to improved stability of the product and presumably even smaller particles since the boronated material made in this manner has superior clarity.
Products of this invention have also been found to have lower viscosity. This is in contrast to other similar materials that feature increases of viscosity as the incorporated metal contents are increased.
The compositions of the present invention can be any simple boron compound that dissolves in a common solvent to form a solution. Suitable boron compounds include, but are not limited to, boric acid, borax, boron oxide, or combinations of these. With boric oxide in particular, it is very desirable to add additional water to the process to insure boric acid is reformed.
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of this invention provide a simplified process of producing a magnesium/boron combination composition.
Other embodiments of this invention provide a process to produce magnesium/boron compositions including a nanometer sized, free flowing liquid. Nanometer sized materials are produced by methods well known in the art. These magnesium/boron compositions are desired because: (a) they have a very high surface atom to bulk atom ratio, and (b) they can directly be incorporated into fuels and oil products such as base oils and formulated synthetic oils. Most of the atoms in these nanometer sized particles reside on the surface of the particles and are chemically very active. With very high surface energy, they are both physically and chemically attracted to the hydrocarbon molecules in fuels and oils. The high surface energy also causes the boron atoms, in particular, to be attracted to metal surfaces allowing the composition to have improved lubricating properties.
Other embodiments of the present invention provide compositions having high concentrations of boron relative to magnesium. In previous patents, both metals and consequently their ratios remained relatively low.
The process of this invention produces high concentrations of magnesium and relatively high concentrations of the low atomic weight element boron in the same composition. The method of this invention is easier to implement than previous methods. The method of this invention requires only relatively minor manipulations to produce the compositions of this invention. Heretofore, one general problem when working with boron materials has been excessive foaming and the control of same. This problem has been obviated using the low temperature method of the present invention. The need to add hazardous, flammable solvents, alcohols, and water followed by their subsequent arduous stripping have all be eliminated or substantially reduced using the methods of this invention.
The term boronation refers to the process of adding boron in its many forms to an organic material. It should be recognized and understood by those skilled in the art that there are many combinations and possible structures to explain this process. Many of the most likely theories can be found in text books on boron chemistry and will not be reproduced here.
The term overbase relates to that class of compounds that have an excess of base—normally an alkali or alkaline earth element—relative to a stabilizing acid often sulfonic but sometimes carboxylic acid. These products are well known to those skilled in the art. The elements most often useful as overbases are magnesium, calcium, sodium, and zinc.
The term low boiling as used herein means heating below or only slightly above the boiling point of water, i.e., 100° C.
The magnesium source used in this invention is one or more of the standard products available from Liquid Minerals Group, Incorporated (New Waverly, Tex.). The preferred products are LMG-30S® (a 30% magnesium sulfonate) and LMG-30E® (a 30% magnesium carboxylate). These materials are overbases of magnesium reportedly made through a high temperature process with a proprietary blend of sulfonic or carboxylic acids.
Boric acid is widely available. One source that has proven to be reliable is from Rio Tinto, PLC (London, United Kingdom).
Suitable low boiling solvent include, without limitation, any aromatic hydrocarbon with suitable solvency characteristics and minimum flash point to meet transportation needs and requirements of a commercial product.
Envisioned Uses of the Invention
Embodiments of the method of the present invention relate to the production of magnesium and boron compositions having many potential uses. Many of these uses have been known for years and were the impetus for many of the patents previously described. For example, alkaline earth element and boron chemistries have been known for years to provide excellent lubrication properties in lubricating formulations for automobiles and other non-stationary source equipment. Boron and alkaline earth metal formulations have found use as extreme pressure additives.
Combinations of magnesium and boron can be used in refineries as antifoulants. It is believed the boron has interesting properties to coat metal surfaces making them less prone to accumulating deposits. The magnesium continues to provide its neutralization function inhibiting the formation of acidic materials that lead to the materials that actually form deposits. Nano-sized materials are more effective in this application due to their surface activity and greatly increased number of reactive particles.
The magnesium/boron compositions of this invention could be very useful combustion additives. Traditionally, magnesium has been used for this purpose. The addition of boron to an additive could be very useful to inhibit the effects of vanadium especially with respect to high temperature corrosion in gas turbines. There are multiple products of boron and magnesium with vanadium, which could render this widespread contaminant less corrosive in this growing application.
The flexibility of embodiments of the method of this invention in permitting formulations having with relatively high levels of magnesium relative to boron provides many opportunities for additional uses of these compositions in metals. For example, by adjusting the initial charge of boron to magnesium, compounds can be produced for use as an extreme pressure additive, while other compounds can be produced for use as lubricant additives. The method of the invention allows the preparation of magnesium/boron compositions having a wide range of magnesium to boron ratios and having a wide range in magnesium and boron concentrations, such compositions can be tailored to meet the requirements of these varied applications.
These and other benefits of the composition and methods of this invention will be evident to those of ordinary skill in the art.
EXPERIMENTS OF THE INVENTION
The following examples are provided for illustration purposes and should not be construed as limiting the scope of the inventions disclosed herein.
Example 1
A 1000-mL three neck reaction flask was fitted with stirrer, thermometer, and condenser leading to a Dean Stark trap. To the reaction flask were added 466 grams LMG-305®, 240 grams of boric acid, and 93.5 grams of an aromatic solvent, where the solvent improves fluidity of the mixture. The reaction mass was heated to 102° C. and held at that temperature for four hours until the reaction product became visually clear. Minor amounts of solvent and water were removed into the Dean Stark trap during the reaction. The solvent and water were not added back to the mixture. After slight cooling the reaction mass, the reaction mass was filtered through a 20 micron filter. Then the filter was opened flat, only about a 1 cm circle of solids was observed on the filter. The reaction product included 17.5% magnesium and 5.25% boron.
Example 2
To a 500-mL three neck reaction flask fitted with stirrer, thermometer, and condenser leading to a Dean Stark trap was added 201 grams LMG-30S® and 103 grams boric acid. The reaction flask was heated to 104° C. and held at that temperatures for three hours. During this time, the reaction mass clarified. After cooling, the reaction product included 19.8% magnesium and 5.9% boron.
Example 3
To a 4000-mL resin kettle was added 7.0 pounds of LMG-30S® and 2.5 pounds of an aromatic solvent. The resin kettle was assembled and fitted with stirrer, thermometer, and condenser leading to a Dean Stark trap. After heating to about 110° C., about 5 cubic feet of carbon dioxide were passed through the liquid. Solvent removed during this blowing operation was returned to the resin kettle to maintain fluidity. While heating to about 120° C., two pounds of boric acid were added portion wise. Minor foaming was observed with each addition. After all boric acid was added, the reaction mass was allowed to stir at 120° C. During the reaction, the reaction mass was observed to clarify. Filtration of the reaction mass indicated that essentially all of the boron had been incorporated. The reaction product included 18.75% magnesium and 3.3% boron.
All references cited herein are incorporated by reference. Although the invention has been disclosed with reference to its preferred embodiments, from reading this description those of skill in the art may appreciate changes and modification that may be made which do not depart from the scope and spirit of the invention as described above and claimed hereafter.
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The present invention describes a nanoparticle size composition comprising at least one overbase complex of a magnesium salt and an associated organic boron complex. The present compound is an improvement over previous processes due to less complicated processing requirements and the high concentration of both magnesium and boron that results.
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RELATED APPLICATIONS
[0001] This application, pursuant to 37 C.F.R. §1.78(c) claims priority based on provisional application serial No. 60/384,694, filed May 30, 2002.
BACKGROUND OF INVENTION
[0002] Tinted papers have been around for quite some time, especially papers converted to the small format of 8.5×11, 8.5×14 legal, and others up to about 11×17. The advantage of colored or tinted papers are reduced eye strain, varying levels of contrast with different kinds and colors of printing ink or toners, identification of printed matter, i.e. blue for one purpose and pink for another and individual consumer preference.
[0003] Typically, tinted papers are produced at the paper mill, with the colorant or dye added at the wet end of the paper machine directly to the pulp before the formation of the sheet. This process is known as vat dyeing, and these papers are tinted on both sides and throughout the sheet because the fibers themselves are dyed.
[0004] Some of the disadvantages of the mill produced tinted sheets are that the whole sheet itself is tinted. The mill will only make a few specific colors or tints of paper on a few specific types or grades of paper, and only run these specific sheets at certain times or when minimum tonnage is required. Therefore, if a paper converter requires a limited amount of a tinted paper, often it will not be available or the minimum amount the mill will produce is much greater than the converter's requirements necessitating an excessive inventory burden to the converter. These and other disadvantages of the common practice have contributed to the limited use of color-tinted papers into the large format markets, especially in the “A&E” (Architect and Engineering) markets. By large format we mean paper larger than 11″×17″. For instance large format sheets are generally sold in sizes such as 18″×24″, 24″×36″, 30″×42″ and 36″×48″, but other sizes are available and the term “large format sheets” is meant to include all such sizes large format rolls are generally sold in sizes 24″-52″ wide and up to 500 feet in length. The term “large format rolls” is meant to include any width sheet larger than 17″ and any length roll.
[0005] Historically, the A&E field and building trades use a diazo-type copy of an A&E drawing known as a blueprint for use in the field or the job site. Up to the 1960's, blueprints were a diazo coated sheet that when developed produced white line drawings and text on a blue field or background. These are known as traditional blueprint. Then the diazo process evolved into what is known as “whiteprinting”. These are diazo type prints that when exposed and developed, would produce blue line drawing and test into a white field or background. (Black lines, brown lines, and red lines were also achieved with the same process.) And although this process is properly known as “whiteprints”, the term blueprint is generally applied to this process as well. Some of the advantages of “whiteprints” are increased manufacturing speeds, lower costs, and the ability to process and develop the individual prints at a faster speed, thereby achieving maximum line and text densities, while allowing the background to be developed with a blue cast or shade. This practice, known as “pulling a background” was found to be very beneficial especially to those on the construction site, because no text or lines would be lost and the shaded background was easier to read outside, in direct sunlight, reducing eye strain and glare.
[0006] In the 1980's and especially into the late 1990's xerographic type copiers became much more prolific in the wide format market and these copiers became known as large format copiers or plotters. Their popularity continues to increase, as diazo-type usage declines. These LDC (large document copiers) produce black toner developed images and texts on a white sheet of paper known as engineering, laser or xerographic or offset grades of bond papers. These sheets are often referred to as plain paper. These LDC produced plain paper copies are gradually replacing the traditional blueprint copies at every level in the A&E market due to their lower cost commodity paper stock and lower labor costs to print.
[0007] Some uses for vat dyed bonds have been used in the LDC market as stated before for identification or action of the document (blue=plumbing, pink=iron work−green=landscaping.) But the hidden cost of vat dyed sheet, limited uses, and inventory requirements have never made them cost effective to the A&E printer or client.
[0008] Our invention allows multiple uses of existing low cost sheets of bond, economically coated and tinted with the capability of producing limited or extended runs. The ability to produce multiple shades and colors each allowing its own unique features.
SUMMARY OF INVENTION
[0009] An object of this invention is to provide a paper stock having a different color or shade on each side and method for producing same.
[0010] Another object of the present invention is to provide a white base paper stock color or tinted on one side only.
[0011] Yet another object of the invention is to convert the paper stock into a large format of roll or sheet stock, primarily for use in Large Document Copiers (and/or Plotters), particularly for the Architectural and Engineering markets. Still another object of the invention is to produce a large format paper which reduces glare in sunlight, shows changes or erasures and is economically produced.
BRIEF DESCRIPTION OF DRAWING
[0012] [0012]FIG. 1 is a schematic drawing of a machine for producing the inventive paper and method of making same.
DESCRIPTION OF PREFERRED EMBODIMENT
[0013] The invention preferably uses a paper stock of a neutral or alkaline bond (engineering, xerographic, laser, or offset grades are most desirable although other grades and/or an acid based paper is acceptable). An aqueous dye solution consisting of Water; Dye (acid, direct, or otherwise), in a concentration that produces acceptable color or tint; and may or may not include a polyester or olefinic resin up to 5%, for increased dye binding capabilities so as not to contaminate the fuser roll in the LDC during printing.
[0014] Referring to FIG. 1, paper stock in a roll 2 A is loaded onto coating machine 10 and threaded throughout the machine in the typical manner. Paper in wet form 2 traverses a plurality of tensioning/idler rollers 3 , through the precoat station 4 which preferably does not contain any solutions, but assists in web guiding and tensioning. The precoat station 4 is optimal but may include a supply pan 5 and tension or pressure rollers 7 . A drip pan 8 is provided which is useful if an optional liquid coating is applied in precoat station 4 . Also included are the usual air knife doctor 9 and air knife backing roller 10 to remove excess liquid if present. The web 2 then enters the drying oven 30 via the lower-pass 11 a and passes through the lower drying plenum 11 , exits and returns to the oven 30 over three more tensioning/idler rollers 3 , into the lower-middle-pass 11 b traversing across the upper half of the lower drying plenum 11 and exiting to the sensitizing station 12 . The dye solution is pumped from a holding vessel (not shown) in to sensitizing supply pan 13 where the dye solution is picked up by the driven sensitizer applicator roller 14 and deposited onto the moving web 2 . The web 2 is held down onto driven sensitizer applicator roller 14 by two applicator pressure rollers 15 . These rollers 15 are adjustable and maintain an even pick-up of the dye solution. At this point, the web 2 is covered with an excess of dye solution and passes under another tensioning/idler roller 3 to an air knife doctor 17 and air knife backing roller 18 where the excess dye solution is doctored off via a blast of air from the air knife 17 . The excess solution is removed from the web 2 and deposited onto the sensitizer drip-pan 16 gravity fed back into the sensitizer supply pan to recirculated. The web then exits the sensitizer section 12 , traverses two more tensioning/idler rollers 3 and enters the drying oven 30 via the upper-middle-pass 19 a and travels under the middle drying plenum 19 where the web 2 and dye solution are dried. The web 2 then exits the drying oven at 19 b , traverses two more tensioning/idler rollers 3 and enters the back-coat station 20 where a back-coating solution containing water and preferably up to 1% triethlyene glycol preferably but optionally may be applied, depending on the type or weight of the paper stock that is used, to control curl of the web 2 . The back-coat solution is applied in much the same manner as the dye solution in the sensitizer section 12 utilizing a supply pan 21 , an applicator roller 22 , and an air knife doctor 24 and air knife backing roller 25 . The web then exits the back-coat station 20 , passes two more tensioning/idler rollers 3 , enters the drying oven 30 one last time via the upper-pass 26 a , travels under the upper drying plenum 26 to re-dry the dye solution and dry the back-coat (if used) and exits the drying oven 30 . The finished web 2 then traverses seven tensioning/idler rollers 3 , passes over a chilled roller 27 to cool the web 2 , passes two more idler rollers 3 , and is guided to a driven, surface winder roller 29 or 30 , where the finished coated material is wound into a master roll 31 , ready to be taken from the coating machine's wind-up section 28 , and be converted into large format sized finished goods (i.e. large cut sheets or rolls).
[0015] Although described schematically above, it is clear that the system 10 can be used to coat one or both sides of paper stock with tints or dyes in any combination of stations of 4 , 12 and 20 or additional stations if required. Preferably, a white paper stock is coated on one side only with a blue dye; however, both sides of the paper may be individually coated with dyes of the same or different colors provided that the shade of the dyes are different if both sides are the same color. For instance, one side of the paper may be dyed a dark blue and the other side of the paper could be dyed a much lighter blue. In this circumstance, an erasure on the dark blue side would show as a light blue patch, thereby fulfilling an important and primary object of the present invention. Alternatively, one side of the paper could be coated pink and the other side some other color such as green. Again, a principal object of the invention is to individually coat one or both sides in either different shades or different colors so that an erasure on the side carrying the architectural or engineering indicia will be clearly seen. In this manner, drawings which are authorized by a governmental agency cannot be changed subsequent to the authorization without the agency being aware that changes have been made and without having painstakingly to compare an original drawing with a current drawing. This is a major advantage of the prior invention.
[0016] As may be understood from the foregoing, a wide variety of colors may be used: pink, blue, green, yellow or the like. Further, the bond paper normally used in the A&E fields has a felt side and a wire side with the felt side being smoother and on which the indicia normally is placed. In the preferred embodiment of the present invention, the wire side of the bond large format paper is left white (for purposes of this invention white is a color as that word is used herein) and the felt side of the paper is a light blue. In preparing the preferred embodiment of the present invention, a stock solution of direct dye obtained from the Andrews Paper and Chemical Company is made with 320 grams of direct dye per five gallons of very hot water. The water can be boiling or somewhat cooler than that such as about 165° F., but the exact temperature is not critical. A second dye used in the preferred embodiment of the present invention is methyl violet and a solution thereof is made from 113 grams of methyl violet dye and five gallons of hot water. Both of these dyes are preferably water soluble. The two stock dye solutions are then poured into ninety gallons of water and optionally one liter of isopropyl alcohol as a wetting agent may be added. This combination of direct dye and methyl violet is used in the station 12 in order to apply the dye to the felt side of the paper stock. If a deeper shade of blue is required, more dye may be used and if a lighter shade of paper is required, then obviously less dye will be used.
[0017] The back wet solution applied in station 20 is preferably a triethylene glycol in which five gallons of triethylene glycol are added to about 200 gallons of water and this diluted mixture is applied to the wire side of the paper in station 20 . Glycols other than triethylene glycol are useful, as is diethylene glycol, and in general back wetting solutions are well known in the art and any suitable solution may be used although triethylene glycol is preferred. The back wet solution is applied to the reverse side of the dye coated paper to control the curl of the paper and also to control the moisture content to prevent the paper from becoming brittle.
[0018] In the preferred embodiment of the present invention, the paper web 2 is run at about 84 yards per minute and the temperature in the oven 30 is maintained, preferably at about 250° F. in the first pass and about 340° F. in the second pass. The moisture of the paper is also controlled. Preferably the moisture range of the paper should be between about 4% and about 5% by weight and preferably between about 4% and 4.5% by weight. Normally, 40″ diameter rolls 2 A are used and the length of the roll determines the weight.
[0019] Other materials can be added to the various solutions such as binders and other materials, all as is well known in the art, and it is intended to cover in the claims appended hereto all such art recognized additions to the various solutions in the paper making art.
[0020] The inventive paper herein provides much less glare than standard white bond and is particularly advantageous working outside construction jobs in bright sunlight. Moreover, the paper of the subject invention offers security as any erasures will appear as white marks (provided that the wire side of the paper is white) or otherwise identifiable marks notifying the viewer that the original has been changed. In addition, whiteout changes can be detected instantly against the preferred blue background. With the preferred blue coating, the paper may be folded numerous times without toner or paper cracking or feathering as it is known in the field. The blue color of the paper also provides a higher level of contrast and definition to the indicia thereon, preferably on the felt side.
[0021] Finally, the inventive paper shows an engineering seal significantly better than plain white paper allowing the felt side color and the wire side color (preferably white) to mingle together when sealed giving a clean, legible image that is readily apparent.
[0022] While particular embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects. Therefore, the aim in the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of the invention. The matter set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation. The actual scope of the invention is intended to be defined in the following claims when viewed in their proper perspective based on the prior art.
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A paper stock with at least one side dyed or tinted such that each side has a different color or shade to provide an indication of any erasures on the dyed or tinted side of the paper. Machinery and systems are disclosed for practicing the method of making the inventive paper.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of my copending application Ser. No. 302,567, filed Oct. 30, 1972, which was a continuation-in-part of my then copending application Ser. No. 121,572, filed Mar. 5, 1971 and since abandoned.
BACKGROUND OF THE INVENTION
This invention relates to compositions of matter, and to methods and intermediates for producing them. In particular, the several aspects of this invention relate to novel oxa-phenylene analogs of some of the known prostaglandins, for example, prostaglandin E 1 (PGE 1 ), prostaglandin E 2 (PGE 2 ), progstaglandin F 1 (PGF 1 .sub.α and PGF 1 .sub.β), prostaglandin F 2 (PGF 2 .sub.α and PGF 2 .sub.β), prostaglandin A 1 (PGA 1 ), prostaglandin A 2 (PGA 2 ), prostaglandin B 1 (PGB 1 ), prostaglandin B 2 (PGB 2 ), the corresponding PG 3 's, and the dihydro PG 1 derivatives, to novel methods for producing those novel prostaglandin analogs, and to novel chemical intermediates useful in those novel methods.
Each of the above-mentioned known prostaglandins is a derivative of prostanoic acid which has the following structure and atom numbering: ##SPC1##
A systematic name for prostanoic acid is 7-[(2β-octyl)-cyclopent-1α-yl]heptanoic acid.
PGE 1 has the following structure: ##SPC2##
PGF 1 .sub.α has the following structure: ##SPC3##
PGF 1 .sub.β has the following structure: ##SPC4##
PGA 1 has the following structure: ##SPC5##
PGB 1 has the following structure: ##SPC6##
Each of the known prostaglandins PGE 2 , PGF 2 .sub.α, PGF 2 .sub.β, PGA 2 , and PGB 2 has a structure the same as that shown for the corresponding PG 1 compound except that in each, C-5 and C-6 are linked with a cis carbon-carbon double bond. For example, PGE 2 has the following structure: ##SPC7##
Each of the known PG 3 prostaglandins has a structure the same as that of the PG 2 compounds except that in each, C-17 and C-18 are linked with a cis carbon-carbon double bond. For example, PGE 3 has the following structure: ##SPC8##
Each dihydro derivative of PGE 1 , PGF 1 .sub.α, PGF 1 .sub.β, PGA 1 , and PGB 1 has a structure the same as that shown for the corresponding PG 1 compound except that in each, C-13 and C-14 are linked with a carbon-carbon single bond. For example, dihydro-PGE 1 has the following structure: ##SPC9##
The prostaglandin formulas mentioned above each have several centers of asymmetry. As drawn, formulas II to IX each represents the particular optically active form of the prostaglandin obtained from certain mammalian tissues, for example, sheep vesicular glands, swine lung, and human seminal plasma, or by reduction or dehydration of a prostaglandin so obtained. See, for example, Bergstrom et al., Pharmacol. Rev. 20, 1 (1968), and references cited therein. The mirror image of each formula represents a molecule of the enantiomer of that prostaglandin. The racemic form of the prostaglandin consists of equal numbers of two types of molecules, one represented by one of the above formulas and the other represented by the mirror image of that formula. Thus, both formulas are needed to define a racemic prostaglandin. See Nature 212, 38 (1966) for discussion of the stereochemistry of the prostaglandins.
In formulas I-IX, as well as in the formulas given hereinafter, broken line attachments to the cyclopentane ring indicate substituents in alpha configuration, i.e., below the plane of the cyclopentane ring. Heavy solid line attachments to the cyclopentane ring indicate substituents in beta configuration, i.e., above the plane of the cyclopentane ring.
Prostaglandins with carboxyl-terminated side chains attached to the cyclopentane ring in beta configuration are also known. These are derivatives of 8-iso-prostanoic acid which has the following formula: ##SPC10##
A systematic name for 8-iso-prostanoic acid is 7-[(2β-octyl)-cyclopent-1β-yl]heptanoic acid.
The side-chain hydroxy at C-15 in formulas II to IX is in alpha (S) configuration. See Nature 212, 38 (1966) for discussion of the stereochemistry of the prostaglandins.
PGE 1 , PGE 2 , dihydro-PGE 1 , and the corresponding PGF.sub.α, PGF.sub.β, PGA, and PGB compounds, and their esters, acylates, and pharmacologically acceptable salts, are extremely potent in causing various biological responses. For that reason, these compounds are useful for pharmacological purposes. See, for example, Bergstrom et al., Pharmacol. Rev. 20, 1 (1968), and references cited therein. A few of those biological responses are stimulation of smooth muscle as shown, for example, by tests on strips of guinea pig ileum, rabbit duodenum, or gerbil colon; potentiation of other smooth muscle stimulants; antilipolytic activity as shown by antagonism of epinephrine-induced mobilization of free fatty acids or inhibition of the spontaneous release of glycerol from isolated rat fat pads; inhibition of gastric secretion in the case of the PGE and PGA compounds as shown in dogs with secretion stimulated by food or histamine infusion; activity on the central nervous system; controlling spasm and facilitating breathing in asthmatic conditions; decreasing blood platelet adhesiveness as shown by platelet-to-glass adhesiveness, and inhibition of blood platelet aggregation and thrombus formation induced by various physical stimuli, e.g., arterial injury, and various biochemical stimuli, e.g., ADP, ATP, serotonin, thrombin, and collagen; and in the case of the PGE and PGB compounds, stimulation of epidermal proliferation and keratinization as shown when applied in culture to embryonic chick and rat skin segments.
Because of these biological responses; these known prostaglandins are useful to study, prevent, control, or alleviate a wide variety of diseases and undesirable physiological conditions in birds and mammals, including humans, useful domestic animals, pets, and zoological specimens, and in laboratory animals, for example, mice, rats, rabbits, and monkeys.
For example, these compounds, and especially the PGE compounds, are useful in mammals, including man, as nasal decongestants. For this purpose, the compounds are used in a dose range of about 10 μg. to about 10 mg. per ml. of a pharmacologically suitable liquid vehicle or as an aerosol spray, both for topical application.
The PGE, PGF.sub.α, PGF.sub.β, and PGA compounds are useful in the treatment of asthma. For example, these compounds are useful as bronchodilators or as inhibitors of mediators, such as SRS-A, and histamine which are released from cells activated by an antigen-antibody complex. Thus, these compounds control spasm and facilitate breathing in conditions such as bronchial asthma, bronchitis, bronchiectasis, pneumonia and emphysema. For these purposes, these compounds are administered in a variety of dosage forms, e.g., orally in the form of tablets, capsules, or liquids; rectally in the form of suppositories; parenterally, subcutaneously, or intramuscularly, with intravenous administration being preferred in emergency situations; by inhalation in the form of aerosols or solutions for nebulizers; or by insufflation in the form of powder. Doses in the range of about 0.01 to 5 mg. per kg. of body weight are used 1 to 4 times a day, the exact dose depending on the age, weight, and condition of the patient and on the frequency and route of administration. For the above use these prostaglandins can be combined advantageously with other anti-asthmatic agents, such as sympathomimetics (isoproterenol, phenylephrine, ephedrine, etc); xanthine derivatives (theophylline and aminophylline); and corticosteroids (ACTH and predinisolone). Regarding use of these compounds see South African Pat. No. 681,055.
The PGE and PGA compounds are useful in mammals, including man and certain useful animals, e.g., dogs and pigs, to reduce and control excessive gastric secretion, thereby reducing or avoiding gastrointestinal ulcer formation, and accelerating the healing of such ulcers already present in the gastrointestinal tract. For this purpose, the compounds are injected or infused intravenously, subcutaneously, or intramuscularly in an infusion dose range about 0.1 μg. to about 500 μg. per kg. of body weight per minute, or in a total daily dose by injection or infusion in the range about 0.1 to about 20 mg. per kg. of body weight per day, the exact dose depending on the age, weight, and condition of the patient or animal, and on the frequency and route of administration.
The PGE, PGF.sub.α, and PGF.sub.β compounds are useful whenever it is desired to inhibit platelet aggregation, to reduce the adhesive character of platelets, and to remove or prevent the formation of thrombi in mammals, including man, rabbits, and rats. For example, these compounds are useful in the treatment and prevention of myocardial infarcts, to treat and prevent post-operative thrombosis, to promote patency of vascular grafts following surgery, and to treat conditions such as atherosclerosis, arteriosclerosis, blood clotting defects due to lipemia, and other clinical conditions in which the underlying etiology is associated with lipid imbalance or hyperlipidemia. For these purposes, these compounds are administered systemically, e.g., intravenously, subcutaneously, intramuscularly, and in the form of sterile implants for prolonged action. For rapid response, especially in emergency situations, the intravenous route of administration is preferred. Doses in the range about 0.005 to about 20 mg. per kg. of body weight per day are used, the exact dose depending on the age, weight, and condition of the patient or animal, and on the frequency and route of administration.
The PGE, PGF.sub.α, and PGF.sub.β compounds are especially useful as additives to blood, blood products, blood substitutes, and other fluids which are used in artifical extracorporeal circulation and perfusion of isolated body portions, e.g., limbs and organs, whether attached to the original body, detached and being preserved or prepared for transplant, or attached to a new body. During these circulations and perfusions, aggregated platelets tend to block the blood vessels and portions of the circulation apparatus. This blocking is avoided by the presence of these compounds. For this purpose, the compound is added gradually or in single or multiple portions to the circulating blood, to the blood of the donor animal, to the perfused body portion, attached or detached, to the recipient, or to two or all of those at a total steady state dose of about 0.001 to 10 mg. per liter of circulating fluid. It is especially useful to use these compounds in laboratory animals, e.g., cats, dogs, rabbits, monkeys, and rats, for these purposes in order to develop new methods and techniques for organ and limb transplants.
PGE compounds are extremely potent in causing stimulation of smooth muscle, and are also highly active in potentiating other known smooth muscle stimulators, for example, oxytocic agents, e.g., oxytocin, and the various ergot alkaloids including derivatives and analogs thereof. Therefore, PGE 2 , for example, is useful in place of or in combination with less than usual amounts of these known smooth muscle stimulators, for example, to relieve the symptoms of paralytic ileus, or to control or prevent antonic uterine bleeding after abortion or delivery, to aid in expulsion of the placenta, and during the puerperium. For the latter purpose, the PGE compound is administered by intravenous infusion immediately after abortion or delivery at a dose in the range about 0.01 to about 50 μg. per kg. of body weight per minute until the desired effect is obtained. Subsequent doses are given by intravenous, subcutaneous, or intramuscular injection or infusion during puerperium in the range 0.01 to 2 mg. per kg. of body weight per day, the exact dose depending on the age, weight, and condition of the patient or animal.
The PGE, PGF.sub.α, and PGF.sub.β compounds are useful in place of oxytocin to induce labor in pregnant female animals, including man, cows, sheep, and pigs, at or near term, or in pregnant animals with intrauterine death of the fetus from about 20 weeks to term. For this purpose, the compound is infused intravenously at a dose of 0.01 to 50 μg. per kg. of body weight per minute until or near the termination of the second stage of labor, i.e., expulsion of the fetus. These compounds are especially useful when the female is one or more weeks post-mature and natural labor has not started, or 12 or 60 hours after the membranes have ruptured and natural labor has not yet started. An alternative route of administration is oral.
The PGE, PGF.sub.α, and PGF.sub.β compounds are useful for controlling the reproductive cycle in ovulating female mammals, including humans and animals such as monkeys, rats, rabbits, dogs, cattle, and the like. By the term ovulating female mammals is meant animals which are mature enough to ovulate but not so old that regular ovulation has ceased. For that purpose PGF 2 .sub.α, for example, is administered systemically at a dose level in the range 0.01 mg. to about 20 mg. per kg. of body weight of the female mammal, advantageously during a span of time starting approximately at the time of ovulation and ending approximately at the time of menses or just prior to menses. Intravaginal and intrauterine are alternative routes of administration. Additionally, expulsion of an embryo or a fetus is accomplished by similar administration of the compound during the first third of the normal mammalian gestation period.
As mentioned above, the PGE compounds are potent antagonists of epinephrine-induced mobilization of free fatty acids. For this reason, this compound is useful in experimental medicine for both in vitro and in vivo studies in mammals, including man, rabbits, and rats, intended to lead to the understanding, prevention, symptom alleviation, and cure of diseases involving abnormal lipid mobilization and high free fatty acid levels, e.g., diabetes mellitus, vascular diseases, and hyperthyroidism.
The PGA compounds and derivatives and salts thereof increase the flow of blood in the mammalian kidney, thereby increasing volume and electrolyte content of the urine. For that reason, PGA compounds are useful in managing cases of renal dysfunction, especially those involving blockage of the renal vascular bed. Illustratively, the PGA compounds are useful to alleviate and correct cases of edema resulting, for example, from massive surface burns, and in the management of shock. For these purposes, the PGA compounds are preferably first administered by intravenous injection at a dose in the range of 10 to 1000 μg. per kg. of body weight or by intravenous infusion at a dose in the range 0.1 to 20 μg. per kg. of body weight per minute until the desired effect is obtained. Subsequent doses are given by intravenous, intramuscular, or subcutaneous injection or infusion in the range 0.05 to 2 mg. per kg. of body weight per day.
The PGE and PGB compounds promote and accelerate the growth of epidermal cells and keratin in animals, including humans, useful domestic animals, pets, zoological specimens, and laboratory animals. For that reason, these compounds are useful to promote and accelerate healing of skin which has been damaged, for example, by burns, wounds, and abrasions, and after surgery. These compounds are also useful to promote and accelerate adherence and growth of skin autografts, especially small, deep (Davis) grafts which are intended to cover skinless areas by subsequent outward growth rather than initially, and to retard rejection of homografts.
For these purposes, these compounds are preferably administered topically at or near the cite where cell growth and keratin formation is desired, advantageously as an aerosol liquid or micronized powder spray, as an isotonic aqueous solution in the case of wet dressings, or as a lotion, cream, or ointment in combination with the usual pharmaceutically acceptable diluents. In some instances, for example, when there is substantial fluid loss as in the case of extensive burns or skin loss due to other causes, systemic administration is advantageous, for example, by intravenous injection or infusion, separate or in combination with the usual infusions of blood, plasma, or substitutes thereof. Alternative routes of administration are subcutaneous or intramuscular near the site, oral, sublingual, buccal, rectal, or vaginal. The exact dose depends on such factors as the route of administration, and the age, weight, and condition of the subject. To illustrate, a wet dressing for topical application to second and/or third degree burns of skin area 5 to 25 square centimeters would advantageously involve use of an isotonic aqueous solution containing 1 to 500 μg./ml. of the PGB compound or several times that concentration of the PGE compound. Especially for topical use, these prostaglandins are useful in combination with antibiotics, for example, gentamycin, neomycin, polymyxin B, bacitracin, spectinomycin, and oxytetracycline, with other antibacterials, for example, mafenide hydrochloride, sulfadiazine, furazolium chloride, and nitrofurazone, and with corticoid steroids, for example, hydrocortisone, prednisolone, methylprednisolone, and fluprednisolone, each of those being used in the combination at the usual concentration suitable for its use alone.
The PGE and PGF compounds are useful in causing cervical dilation in pregnant and nonpregnant female mammals for purposes of gynecology and obstetrics. In labor induction and in clinical abortion produced by these compounds, cervical dilation is also observed. In cases of infertility, cervical dilation produced by PGE and PGF compounds is useful in assisting sperm movement to the uterus. Cervical dilation by prostaglandins is also useful in operative gynecology such as D and C (Cervical Dilation and Uterine Curettage) where mechanical dilation may cause performation of the uterus, cervical tears, or infections. It is also useful in diagnostic procedures where dilation is necessary for tissue examination. For these purposes, the PGE and PGF compounds are administered locally or systemically. PGE 2 , for example, is administered orally or vaginally at doses of about 5 to 50 mg. per treatment of an adult female human, with from one to five treatments per 24 hour period. PGE 2 is also administered intramuscularly or subcutaneously at doses of about 1 to 25 mg. per treatment. The exact dosages for these purposes depend on the age, weight, and condition of the patient or animal.
The PGE, PGF.sub.α, PGF.sub.β, PGA, and PGB compounds are useful in reducing the undesirable gastrointestinal effects resulting from systemic administration of anti-inflammatory prostaglandin synthetase inhibitors, and are used for that purpose by concomitant administration of the prostaglandin and the anti-inflammatory prostaglandin synthetase inhibitor. See Partridge et al., U.S. Pat. No. 3,781,429, for a disclosure that the ulcerogenic effect induced by certain non-steroidal anti-inflammatory agents in rats is inhibited by concomitant oral administration of certain prostaglandins of the E and A series, including PGE 1 , PGE 2 , PGE 3 , 13,14-dihydro-PGE 1 , and the corresponding 11-deoxy-PGE and PGA compounds.
The anti-inflammatory synthetase inhibitor, for example, indomethacin, aspirin, or phenylbutazone is administered in any of the ways known in the art to alleviate an inflammatory condition, for example, in any dosage regimen and by any of the known routes of systemic administration. The prostaglandin is administered along with the anti-inflammatory prostaglandin synthetase inhibitor either by the same route of administration or by a different route. For example, if the anti-inflammatory substance is being administered orally, the prostaglandin is also administered orally or, alternatively, is administered rectally in the form of a suppository or, in the case of women, vaginally in the form of a suppository or a vaginal device for slow release, for example as described in U.S. Pat. No. 3,545,439. Alternatively, if the anti-inflammatory substance is being administered rectally, the prostaglandin is also administered rectally or, alternatively, orally or, in the case of women vaginally. It is especially convenient when the administration route is to be the same or both anti-inflammatory substance and prostaglandin, to combine both into a single dosage form.
The dosage regimen for the prostaglandin in accord with this treatment will depend upon a variety of factors, including the type, age, weight, sex and medical condition of the mammal, the nature and dosage regimen of the anti-inflammatory synthetase inhibitor being administered to the mammal, the sensitivity of the particular individual mammal to the particular synthetase inhibitor with regard to gastrointestinal effects, and the particular prostaglandin to be administered.
SUMMARY OF THE INVENTION
It is a purpose of this invention to provide novel oxa-phenylene prostaglandin analogs, and process for making them.
The novel prostaglandin analogs of this invention each have an oxa oxygen (--O--) and a divalent phenylene moiety ##SPC11##
in the carboxyl-terminated side chain of the prostanoic acid structure (I) or the 8-iso-prostanoic acid structure (X). These divalent groups are located between the carboxyl group and the cyclopentane ring, and are either in addition to the 6 methylene portions of said chain or in place of 1 to 5 of said methylene portions. Bonding to the phenylene ring is either ortho, meta, or para. The oxa group is between the phenylene moiety and the carboxyl group.
Some of the novel prostaglandin analogs of this invention also have, in addition, a benzene ring as part of the C-13 to C-20 chain of the prostanoic acid structure (I) or 8-iso-prostanoic acid structure (X). That benzene ring is present as a substituted or unsubstituted phenyl moiety attached as a substituent to one of the methylenes between C-15 and the terminal methyl of the prostanoic acid or 8-isoprostanoic acid structure. Alternatively, the substituted or unsubstituted phenyl moiety is attached to the terminal or omega carbon of the C-16 to C-20 portion of the chain, replacing one of the hydrogens of the terminal methyl, the entire terminal methyl, or the terminal methyl plus one to four of the methylenes adjacent to that terminal methyl.
For example, five of the novel prostaglandin analogs of this invention are represented by the formulas: ##SPC12##
Based on its relationship to PGE 1 and prostanoic acid, the compound of formula XI is named 3-oxa-4,5-inter-p-phenylene-PGE 1 . Similarly the compound of formula XII is named 15(R)-3-oxa-3,6-inter-m-phenylene-4,5-dinor-13,14-dihydro-PGF 1 .sub..alpha., the compound of formula XIII is named 8-iso-3-oxa-19-phenyl-4,7-inter-m-phenylene-5,6-dinor-PGA 1 , the compound of formula XIV is named 3-oxa-16-(4-chloro-phenyl)-3,5-inter-o-phenylene-4,17,18,19,20-pentanor-PGF 2 .sub.β, and the compound of formula XV is named 5,6-dehydro-4-oxa-4,5-inter-m-phenylene-PGB 2 .
These names for the compounds of formulas XI to XV are typical of the names used hereinafter for the novel compounds of this invention. These names can better be understood by reference to the structure and numbering system of prostanoic acid (Formula I, above). That formula has 7 carbon atoms in the carboxy-terminated chain and 8 carbon atoms in the hydroxy-containing chain. In these names, "3-oxa" and "4-oxa" indicate an oxa oxygen (--O--) in place of the 3-methylene and 4-methylene, respectively of the PG compound.
The use of "nor", "dinor", "trinor", "tetranor", "pentanor", "hexanor", and the like in the names for the novel compounds of this invention indicates the absence of one or more of the chain carbon atoms and the attached hydrogen atoms. The number or numbers in front of nor, dinor, etc., indicate which of the original prostanoic acid carbon atoms are missing in the named compound.
Each of the names of the novel compounds of this invention contains (inter-p-phenylene), (inter-m-phenylene), or (inter-o-phenylene), preceded by two numbers. That indicates that p-phenylene, m-phenylene, or o-phenylene has been inserted between (inter) the 2 carbon atoms so numbered in the formula of prostanoic acid.
Thus, formula XIII differs from prostanoic acid in that an oxa oxygen replaces carbon 3, carbons 5 and 6 of prostanoic acid are missing, m-phenylene has been inserted between carbons 4 and 7 of prostanoic acid, and a phenyl has been attached to carbon 19 of prostanoic acid. Formula XIII also, of course, is an A type prostaglandin, having a carbonyl oxygen and a 10:11 double bond.
Novel compounds of this invention with the carboxyl-terminated chain attached to the cyclopentane ring in beta configuration are 8-iso compounds (formula X), and are so designated by using "8-iso" in the name. An example is the name given above for the compound of formula XIII. If 8-iso does not appear in the name, attachment of the carboxy-terminated chain in alpha configuration is to be assumed.
Novel compounds of this invention with epi configuration for the hydroxy at C-15 are so designated by using " 15(R)" in the name. See, for example, the name given above for the formula-XII compound. Alternately, "15-beta" is used. See. R. S. Cahn, Journal of Chemical Education Vol. 41, page 116 (1964) for a discussion of S and R configurations. If "15(R)" or "15-beta" does not appear in the name, the natural configuration for the C-15-hydroxy, identified as the "S" configuration for PGE 1 , is to be assumed.
Some of the novel compounds of this invention differ structurally in other ways from the known prostanoic acid derivatives, having for example, more or fewer carbon atoms in either chain, and having one or more alkyl and/or fluoro substituents in the chains.
The following formulas represent the novel oxaphenylene compounds of this invention. ##SPC13## ##SPC14## ##SPC15## ##SPC16##
Formulas XVI-XIX, and XXXII represent oxa-phenylene compounds of the PGE type. Formulas XX-XXIII, and XXXIII represent oxa-phenylene compounds of the PGF type. Formulas XXIV-XXVII, and XXXIV represent oxa-phenylene compounds of the PGA type. Formulas XXVIII-XXXI, and XXXV represent oxa-phenylene compounds of the PGB type.
In formulas XVI to XXXV, the wavy line ˜ indicates attachment of the hydroxyl or the side chain to the cyclopentane ring in alpha or beta configuration;
G is (1) alkyl of 2 to 10 carbon atoms, inclusive, substituted with zero, one, 2, or 3 fluoro or (2) a monovalent moiety of the formula ##SPC17##
wherein C t H 2t represents a valence bond or alkylene of 1 to 10 carbon atoms, inclusive, substituted with 0, 1, or 2 fluoro, with one to 7 carbon atoms, inclusive, between ##EQU1## and the ring, wherein T is alkyl of 1 to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR 6 , wherein R 6 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, and wherein s is 0, 1, 2, or 3, with the proviso that not more than two T's are other than alkyl; R 1 is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, 2, or 3 chloro or alkyl of 1 to 4 carbon atoms, inclusive, or ethyl substituted in the β-position with 3 chloro, 2 or 3 bromo, or 1, 2, or 3 iodo;
Q is ##EQU2## wherein R 2 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive; R 3 and R 4 are hydrogen or methyl; and R 5 is alkyl of 1 to 4 carbon atoms, inclusive, substituted with 0, 1, 2, or 3 fluoro.
Likewise, in formulas XVI to XXXV, C g H 2g represents a valence bond or alkylene of 1 to 4 carbon atoms, inclusive, with 1 or 2 chain carbon atoms between --CH 2 -- and the ring; C j H 2j represents a valence bond or alkylene of 1 or 2 carbon atoms with one chain carbon atom between the chain unsaturation and the ring; C n H 2n is alkylene of 1 to 4 carbon atoms, inclusive; C p H 2p represents a valence bond or alkylene of 1 to 4 carbon atoms, inclusive, with 1 or 2 chain carbon atoms between the ring and --O--, wherein C g H 2g and C p H 2p together represent 0 to 8 carbon atoms, inclusive, with total chain lengths 0 to 3 carbon atoms, inclusive, and wherein C j H 2j and C p H 2p together represent 0 to 6 carbon atoms, inclusive, with total chain lengths 0 to 3 carbon atoms, inclusive.
Regarding the meaning of C g H 2g , C j H 2j , and C p H 2p as defined above, the novel compounds of this invention include compounds wherein a carbon atom of the phenylene moiety is attached directly to the C-7 methylene or the C-5 =CR 4 -- in ortho, meta, or para orientation relative to the oxa-containing portion of the carboxyl chain. When C g H 2g represents alkylene, the chain of carbon atoms which connects the C-7 methylene to a carbon atom of phenylene will be 1 or 2 carbon atoms long. When C j H 2j represents alkylene, the chain of carbon atoms which connects =CR 4 -- to a carbon atom of phenylene will be 1 carbon atom long. C p H 2p represents a valence bond or alkylene of 1 to 6 carbon atoms, inclusive, with one or 2 carbon atoms between the ring and the --O--. Any or all of these alkylene chains are unsubstituted or substituted with alkyl carbons in the form of one or more alkyl groups within the total carbon content of each chain as specified above, i.e., a maximum of 4 carbon atoms of C g H 2g , 2 carbons for C j H 2j , and 4 carbons for C p H 2p . When C g H 2g or C j H 2j is alkylene, it is the same as or different than C p H 2p , 8 carbon atoms being the maximum total carbon content and 3 carbon atoms being the maximum total chain length for the combination of C g H 2g and C p H 2p , and 6 carbon atoms being the maximum total carbon content and 3 carbon atoms being the maximum total chain length for the combination of C j H 2j and C p H 2p . To illustrate these definitions, when C g H 2g is ethylene, C p H 2p is methylene, or one of them is a valence bond and the other is ethylene, but both are not ethylene. In this first illustration, where the total chain length of C g H 2g and C.sub. p H 2p is 3 carbon atoms, up to 5 carbon atoms are in the alkyl substituents.
Formulas XVI through XXXV include the separate isomers wherein Q is either ##EQU3## i.e. where the hydroxyl is in either alpha (natural) or beta configuration. Referring to the prostanoic acid atom numbering (formula I above), the point of attachment corresponds to C-15, and, herein, regardless of the variation in the C-1 to C-7 carboxy chain, these epimers are referred to as "C-15 epimers".
Formulas XX-XXIII, and XXXIII wherein the C-9 hydroxyl (following prostanoic acid atom numbering) is attached to the cyclopentane with a wavy line ˜ include both PGF.sub.α- and PGF.sub.β-type compounds.
Included in Formulas XVII, XXI, XXV, and XXIX, are both the cis and the trans compounds with respect to the C-5 to C-6 double bonds in the carboxyl-terminated side chain. In all of the compounds containing the C 13 to C 14 double bond, that double bond is in trans configuration, and the chain containing that moiety is attached to the cyclopentane ring in beta configuration in compounds encompassed by formulas XVI to XXXV.
The novel oxa-phenylene compounds of this invention include racemic compounds and both optically active enantiomeric forms thereof. As discussed hereinabove, two structural formulas are required to define accurately these racemic compounds. The formulas as drawn herein are intended to represent compounds with the same configuration as the naturally-occurring prostaglandins. However, for convenience in the charts herein only a single structural formula is used, for example in Chart D, to define not only the optically active form but also the racemic compounds which generally undergo the same reactions.
Formula XVI represents 3-oxa-4,5-inter-p-phenylene-PGE 1 (formula XI hereinabove) when C g H 2g is ethylene, C p H 2p is methylene, G is n-pentyl, Q is ##EQU4## R 1 is hydrogen, C g H 2g and C p H 2p are attached to the phenylene in para orientation, and the carboxyl-terminated side chain is attached to the cyclopentane ring in alpha configuration.
With regard to formulas XVI to XXXV, examples of alkyl of 1 to 4 carbon atoms, inclusive, are methyl, ethyl, propyl, butyl, and isomeric forms thereof. Examples of alkyl of 1 to 8 carbon atoms, inclusive, are those given above, and pentyl, hexyl, heptyl, octyl, and isomeric forms thereof. Examples of alkyl of 1 to 12 carbon atoms, inclusive, are those given above, and nonyl, decyl, undecyl, dodecyl, and isomeric forms thereof. Examples of cycloalkyl of 3 to 10 carbon atoms, inclusive, which includes alkyl-substituted cycloalkyl, are cyclopropyl, 2-methylcyclopropyl, 2,2-dimethylcyclopropyl, 2,3-diethylcyclopropyl, 2-butylcyclopropyl, cyclobutyl, 2-methylcyclobutyl, 3-propylcyclobutyl, 2,3,4-triethylcyclobutyl, cyclopentyl, 2,2-dimethylcyclopentyl, 3-pentylcyclopentyl, 3-tert-butylcyclopentyl, cyclohexyl, 4-tert-butylcyclohexyl, 3-isopropylcyclohexyl, 2,2-dimethylcyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, and cyclodecyl. Examples of aralkyl of 7 to 12 carbon atoms, inclusive, are benzyl, phenethyl, 1-phenylethyl, 2-phenylpropyl, 4-phenylbutyl, 3-phenylbutyl, 2-(1-naphthylethyl), and 1-(2-naphthylmethyl). Examples of phenyl substituted by 1 to 3 chloro or alkyl of 1 to 4 carbon atoms, inclusive, are p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, 2,4-dichlorophenyl, 2,4,6-trichlorophenyl, p-tolyl, m-tolyl, o-tolyl, p-ethylphenyl, p-tert-butylphenyl, 2,5-dimethylphenyl, 4-chloro-2-methylphenyl, and 2,4-dichloro-3-methylphenyl.
Examples of alkyl of 2 to 10 carbon atoms, inclusive, substituted with 1 to 3 fluoro, are 2-fluoroethyl, 2-fluorobutyl, 3-fluorobutyl, 4-fluorobutyl, 5-fluoropentyl, 4-fluoro-4-methylpentyl, 3-fluoroisoheptyl, 8-fluorooctyl, 3,4-difluorobutyl, 4,4-difluoropentyl, 5,5-difluoropentyl, 5,5,5-trifluoropentyl, and 10,10,10-trifluorodecyl.
Examples of alkylene within the various scopes of C g H 2g , C j H 2j , C p H 2p , C n H 2n , and C t H 2t , as those are defined above, are methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, and heptamethylene, and those alkylene with one or more alkyl substituents on 1 or more carbon atoms, thereof, e.g., --CH(CH 3 )--, --C(CH 3 ) 2 --, --CH(CH 2 CH 3 )--, --CH 2 --CH(CH 3 )--, --CH(CH 3 )--CH(CH 3 )--, --CH 2 --C(CH 3 ) 2 --, --CH 2 --CH(CH 3 )--CH 2 --, --CH 2 --CH 2 --CH(CH 2 CH 2 CH 3 )--, --CH(CH 3 )--CH(CH 3 )--CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 --C(CH 3 ) 2 --CH 2 --, --CH 2 --CH 2 --CH 2 --CH(CH 3 )--, --CH 2 --CH 2 --CH 2 --CH 2 --CH 2 C(CH 3 ) 2 --, --CH(CH 3 )--CH 2 --CH(CH 3 )--CH 2 --CH 2 --CH(CH 3 )--, and --CH 2 --CH 2 --CH 2 --CH 2 --CH 2 --CH 2 --C(CH 3 2 --.
Examples of alkylene substituted with 1 or 2 fluoro and within the scope of C t H 2t , as defined above, are --CHF--CH 2 --, CHF--CHF--, --CH 2 --CH 2 --CF 2 --, --CH 2 --CHF--CH 2 --, --CH 2 --CH 2 --CF(CH 3 )--, --CH 2 --CH 2 --CH 2 --CF 2 --, and --CHF--CH 2 --CH 2 --CH 2 --CH 2 --CH 2 --CH 2 --.
Examples of ##SPC18##
as defined above are phenyl, p-tolyl, m-tolyl, o-tolyl, p-fluorophenyl, m-fluorophenyl, o-fluorophenyl, p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, p-trifluoromethylphenyl, m-trifluoromethylphenyl, p-trifluoromethylphenyl, p-hydroxyphenyl, m-hydroxyphenyl, o-hydroxyphenyl, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, p-tetrahydropyranyloxyphenyl, m-tetrahydropyranyloxyphenyl, o-tetrahydropyranyloxyphenyl, o-ethylphenyl, m-isopropylphenyl, p-tert-butylphenyl, p-butoxyphenyl, 3,4-dimethylphenyl, 2,4-diethylphenyl, 2,4,6-trimethylphenyl, 3,4,5-trimethylphenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl, 2-chloro-4-methylphenyl, 2-fluoro-4-methoxyphenyl, 3,5-dimethyl-4-fluorophenyl, 2,6-dimethyl-4-hydroxyphenyl, and 2,4-di(trifluoromethyl)phenyl.
The novel formula XVI-XIX, and XXXII PGE-type oxa-phenylene compounds, the novel formula XX-XXIII, and XXXIII PGF.sub.α-type and PGF.sub.β-type oxa-phenylene compounds, the novel formula XXIV-XXVII, and XXXIV PGA-type oxa-phenylene compounds, and the novel formula XXVIII-XXXI and XXXV PGB-type oxa-phenylene compounds each cause the biological responses described above for the PGE, PGF.sub.α, PGF.sub.β, PGA, and PGB compounds, respectively, and each of these novel compounds is accordingly useful for the above-described corresponding purposes, and is used for those purposes in the same manner as described above.
The known PGE, PGF.sub.α, PGF.sub.β, PGA, and PGB compounds uniformly cause multiple biological responses even at low doses. For example, PGE 1 and PGE 2 both cause vasodepression and smooth muscle stimulation at the same time they exert antilipolytic activity. Moreover, for many applications, these known prostaglandins have an inconveniently short duration of biological activity. In striking contrast, the novel prostaglandin analogs of formulas XVI to XXXV are substantially more specific with regard to potency in causing prostaglandin-like biological responses, and have a substantially longer duration of biological activity. Therefore, each of these novel prostaglandin analogs is useful in place of one of the corresponding above-mentioned known prostaglandins for at least one of the pharmacological purposes indicated above for the latter, and is surprisingly and unexpectedly more useful for that purpose because it has a different and narrower spectrum of biological activity than the known prostaglandin, and therefore is more specific in its activity and causes smaller and fewer undesired side effects than the known prostaglandin. Moreover, because of its prolonged activity, fewer and smaller doses of the novel prostaglandin analog can frequently be used to attain the desired result.
To obtain the optimum combination of biological response specificity, potency, and duration of activity, certain compounds within the scope of formulas XVI to XXXV are preferred. For example, in compounds of formulas XVI, XIX, XX, XXIII, XXIV, XXVII, XXVIII, and XXXI, it is preferred that the carboxyl-terminated side chain contain a total of 2 to 4 chain carbon atoms, inclusive, excluding the phenylene and --COOR 1 , and including the C-7 methylene. In other words, preferred compounds of these formulas are those wherein C g H 2g and C p H 2p together represent 0, 1, or 2 chain carbon atoms. Especially preferred compounds of these formulas are those wherein C g H 2g and C p H 2p each represent a valence bond, and those wherein C g H 2g represents a valence bond and C p H 2p represents a single chain carbon atom, especially methylene.
In compounds of formulas XVII, XVIII, XXI, XXII, XXV, XXVI, XXIX, XXX, XXXII, XXXIII, XXXIV, and XXXV, it is preferred that the carboxyl-terminated side chain contain a total of 4 or 5 chain carbon atoms, excluding the phenylene and --COOR 1 , and including --CH 2 --CR 3 =CR 4 -- and --CH 2 --C.tbd.C--. In other words, preferred compounds of these formulas are those wherein C j H 2j and C p H 2p together represent 0 or 1 chain carbon atoms. Included in these compounds are those wherein C j H 2j and C p H 2p each represent a valence bond, and those wherein C j H 2j represents a valence bond, and C p H 2p represents a single chain carbon atom, especially methylene.
As used herein, a chain carbon atom is part of the direct chain of carbon atoms linking the C-7 methylene or =CR 4 -- to the phenylene, the phenylene to the oxa, and the oxa to --COOR 1 . Thus, the chain --CH(CH 3 )--C(CH 3 ) 2 -- contains 5 carbon atoms but only 2 chain atoms.
Another preference for the carboxy-terminated side chain in compounds of formulas XVI to XXXV is that the phenylene be a meta-phenylene.
Another preference for the compounds of formulas XVI to XXXV is that R 2 , R 3 , and R 4 are hydrogen or methyl. All of those R groups can be hydrogen, all can be methyl, or there can be any of the possible combinations of hydrogen and methyl.
Certain variations in the nature of G in the compounds of formulas XVI to XXXV are especially important. In the known PG 1 and PG 2 prostaglandins, e.g., PGE 1 , the portion of the molecule corresponding to G in formulas XVI to XXXI is n-pentyl. When G is unsubstituted alkyl or fluoro-substituted alkyl as defined above, there is a preference which results in compounds with optimum combinations of biological properties: namely that G is straight chain alkyl of 3 to 7 carbon atoms, inclusive, with or without a fluoro substituent at the 1-position, e.g., --CHF--(CH 2 ) a --CH 3 , wherein a is 1, 2, 3, 4, or 5. Especially preferred among these are n-pentyl and 1-fluoropentyl.
When G is substituted alkyl, it is preferred that the 1-position be mono- or di-substituted with one or two alkyl groups containing from one to 4 carbon atoms, inclusive. Especially preferred are formula XVI-to-XXXV compounds wherein G is substituted at the 1-position with methyl and/or ethyl, e.g. --CH(CH 3 )--(CH 2 ) c --CH 3 , --CH(C 2 H 5 )--(CH 2 ) c --CH 3 , --C(CH 3 ) 2 --(CH 2 ) c --CH 3 , --C(C 2 H 5 ) 2 --(CH 2 ) c --CH 3 , or --C(CH 3 )(C 2 H 5 )--(CH 2 ) c --CH 3 , wherein c is 2, 3, or 4.
When G represents ##SPC19##
as defined above, it is preferred for compounds with optimum combination of biological properties that C t H 2t be a valence bond, i.e., t is 0, or alkylene of 1 to 4 carbon atoms, inclusive, i.e., --(CH 2 ) d -- wherein d is 1, 2, 3, or 4, with or without a fluoro or alkyl substituent on the carbon adjacent to the hydroxy-substituted carbon (C-15 in PGE 1 ), e.g., --CHF--(CH 2 ) e --, --CH(CH 3 )--(CH 2 ) e --, or --C(CH 3 ) 2 --(CH 2 ) e --, wherein e is 0, 1, 2, or 3. Further, it is preferred that the phenyl ring when present and substituted, be substituted at least at the para position.
In compounds of formulas XXXII to XXXV, it is preferred that C n H 2n be methylene and that R 5 be ethyl.
Another way of expressing the above preferences for G is that when G is alkyl or fluoro-substituted alkyl it be a group represented by ##EQU5## wherein a is 1, 2, 3, 4, or 5, and wherein R 21 and R 22 are hydrogen, alkyl of 1 to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that R 22 is fluoro only when R 21 is hydrogen or fluoro.
Furthermore, when G is ##SPC20##
it is preferred that when C t H 2t is alkylene or fluoro-substituted alkylene it be a group represented by ##EQU6## wherein e is 0, 1, 2, or 3, and wherein R 21 and R 22 are as defined above.
Still another preference is that Q be ##EQU7## wherein R 2 is as defined hereinabove.
Another advantage of the novel compounds of this invention, especially the preferred compounds defined hereinabove, compared with the known prostaglandins, is that these novel compounds are administered effectively orally, sublingually, intravaginally, buccally, or rectally, in addition to usual intravenous, intramuscular, or subcutaneous injection or infusion methods indicated above for the uses of the known prostaglandins. These qualities are advantageous because they facilitate maintaining uniform levels of these compounds in the body with fewer, shorter, or smaller doses, and make possible self-administration by the patient.
The PGE, PGF.sub.α, PGF.sub.β, PGA, and PGB type oxa-phenylene compounds encompassed by formulas XVI to XXXV including the special classes of compounds described above, are used for the purposes described above in the free acid form, in ester form, or in pharmacologically acceptable salt form. When the ester form is used, the ester is any of those within the above definition of R 1 . However it is preferred that the ester be alkyl of 1 to 12 carbon atoms, inclusive. Of those alkyl, methyl and ethyl are especially preferred for optimum absorption of the compound by the body or experimental animal system; and straight-chain octyl, nonyl,, decyl, undecyl, and dodecyl are especially preferred for prolonged activity in the body or experimental animal.
Pharmacologically acceptable salts of these formula XVI-to-XXXV compounds useful for the purposes described above are those with pharmacologically acceptable metal cations, ammonium, amine cations, or quaternary ammonium cations.
Especially preferred metal cations are those derived from the alkali metals, e.g., lithium, sodium and potassium, and from the alkaline earth metals, e.g., magnesium and calcium, although cationic forms of other metals, e.g., aluminum, zinc, and iron, are within the scope of this invention.
Pharmacologically acceptable amine cations are those derived from primary, secondary, or tertiary amines. Examples of suitable amines are methylamine, dimethylamine, trimethylamine, ethylamine, dibutylamine, triisopropylamine, N-methylhexylamine, decylamine, dodecylamine, allylamine, crotylamine, cyclopentylamine, dicyclohexylamine, benzylamine, dibenzylamine, α-phenylethylamine, β-phenylethylamine, etheylenediamine, diethylenetriamine, and like aliphatic, cycloaliphatic, and araliphatic amines containing up to and including about 18 carbon atoms, as well as heterocyclic amines, e.g., piperidine, morpholine, pyrrolidine, piperazine, and lower-alkyl derivatives thereof, e.g., 1-methylpiperidine, 4-ethylmorpholine, 1-isopropylpyrrolidine, 2-methylpyrrolidine, 1,4-dimethylpiperazine, 2-methylpiperidine, and the like, as well as amines containing water-solubilizing or hydrophilic groups, e.g., mono-, di-, and triethanolamine, ethyldiethanolamine, N-butylethanolamine, 2-amino-1-butanol, 2-amino-2-ethyl-1,3-propanediol, 2-amino-2-methyl-1-propanol, tris-(hydroxymethyl)aminomethane, N-phenylethanolamine, N-(p-tert-amylphenyl)-diethanolamine, galactamine, N-methylglucamine, N-methylglucosamine, ephedrine, phenylephrine, epinephrine, procaine, and the like.
Examples of suitable pharmacologically acceptable quaternary ammonium cations are tetramethylammonium, tetraethylammonium, benzyltrimethylammonium, phenyltriethylammonium, and the like.
The PGE, PGF.sub.α, PGF.sub.β, PGA, and PGB type oxa-phenylene compounds encompassed by formulas XVI to XXXV including the special classes of compounds described above, are also used for the purposes described above in free hydroxy form or in the form wherein the hydroxy moieties are transformed to lower alkanoate moieties, e.g., --OH to --OCOCH 3 . Examples of lower alkanoate moieties are acetoxy, propionyloxy, butyryloxy, valeryloxy, hexanoyloxy, heptanoyloxy, octanoyloxy, and branched chain alkanoyloxy isomers of those moieties. Especially preferred among these alkanoates for the above described purposes are the acetoxy compounds. These free hydroxy and alkanoyloxy compounds are used as free acids, as esters, and in salt form all as described above.
As discussed above, the compounds of formulas XVI to XXXV are administered in various ways for various purposes; e.g., intravenously, intramuscularly, subcutaneously, orally, intravaginally, rectally, buccally, sublingually, topically, and in the form of sterile implants for prolonged action. For intravenous injection or infusion, sterile aqueous isotonic solutions are preferred. For that purpose, it is preferred because of increased water solubility that R 1 in the formula XVI-to-XXXV compound be hydrogen or a pharmacologically acceptable cation. For subcutaneous or intramuscular injection, sterile solutions or suspensions of the acid, salt, or ester form in aqueous or non-aqueous media are used. Tablets, capsules, and liquid preparations such as syrups, elixirs, and simple solutions, with the usual pharmaceutical carriers are used for oral sublingual administration. For rectal or vaginal administration, suppositories prepared as known in the art are used. For tissue implants, a sterile tablet or silicone rubber capsule or other object containing or impregnated with the substance is used.
The PGE, PGF.sub.α, PGF.sub.β, PGA and PGB type oxa-phenylene compounds encompassed by formulas XVI to XXXV are produced by the reactions and procedures described and exemplified hereinafter.
The various PGF.sub.α-type and PGF.sub.β-type oxa-phenylene compounds encompassed by formulas XX-XXIII and XXXIII are prepared by carbonyl reduction of the corresponding PGE type compounds encompassed by formulas XVI-XIX and XXXIII. For example, carbonyl reduction of 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 gives a mixture of 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α and 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.β.
These ring carbonyl reductions are carried out by methods known in the art for ring carbonyl reductions of known prostanoic acid derivatives. See, for example, Bergstrom et al., Arkiv Kemi 19, 563 (1963), Acta Chem. Scand. 16, 969 (1962), and British Patent Specification No. 1,097,533. Any reducing agent is used which does not react with carbon-carbon double bonds or ester groups. Preferred reagents are lithium(tri-tert-butoxy)aluminum hydride, the metal borohydrides, especially sodium, potassium and zinc borohydrides, and metal trialkoxy borohydrides, e.g., sodium trimethoxyborohydride. The mixtures of alpha and beta hydroxy reduction products are separated into the individual alpha and beta isomers by methods known in the art for the separation of analogous pairs of known isomeric prostanoic acid derivatives. See, for example, Bergstrom et al., cited above, Granstrom et al., J. Biol. Chem. 240, 457 (1965), and Green et al., J. Lipid Research 5, 117 (1964). Especially preferred as separation methods are partition chromatographic procedures, both normal and reversed phase, preparative thin layer chromatography, and countercurrent distribution procedures.
The various PGA-type oxa-phenylene compounds encompassed by formulas XXIV-XXVII and XXXIV are prepared by acidic dehydration of the corresponding PGE type compounds encompassed by formulas XVI-XIX and XXXII. For example, acidic dehydration of 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 gives 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 .
These acidic dehydrations are carried out by methods known in the art for acidic dehydrations of known prostanioc acid derivatives. See, for example, Pike et al., Proc. Nobel Symposium II, Stockholm (1966), Interscience Publishers, New York, pp. 162-163 (1967); and British Patent Specification No. 1,097,533. Alkanoic acids of 2 to 6 carbon atoms, inclusive, especially acetic acid, are preferred acids for this acidic dehydration. Dilute aqueous solutions of mineral acids, e.g., hydrochloric acid, especially in the presence of a solubilizing diluent, e.g., tetrahydrofuran, are also useful as reagents for this acidic dehydration, although these reagents may cause partial hydrolysis of an ester reactant.
The various PGB-type oxa-phenylene compounds encompassed by formulas XXVIII-XXXI and XXXV are prepared by basic dehydration of the corresponding PGE type compounds encompassed by formulas XVI-XIX and XXXII, or by contacting the corresponding PGA type compounds encompassed by formulas XXIV-XXVII and XXXIV with base. For example, both 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 and 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 give 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGB 1 on treatment with base.
These basic dehydrations and double bond migrations are carried out by methods known in the art for similar reactions of known prostanoic acid derivatives. See, for example, Bergstrom et al., J. Biol. Chem. 238, 3555 (1963). The base is any whose aqueous solution has pH greater than 10. Preferred bases are the alkali metal hydroxides. A mixture of water and sufficient of a water-miscible alkanol to give a homogeneous reaction mixture is suitable as a reaction medium. The PGE-type or PGA-type compound is maintained in such a reaction medium until no further PGB-type compound is formed, as shown by the characteristic ultraviolet light absorption near 278 mμ for the PGB type compound.
The various transformations of PGE-type oxa-phenylene compounds of formulas XVI-XIX to the corresponding PGF.sub.α, PGF.sub.β, PGA and PGB type oxa-phenylene compounds are shown in Chart A, wherein G, Q, R 1 , and ˜ are as defined above, wherein E' is --CH 2 CHR 9 -- or trans--CH=CR 9 --, wherein R 26 and R 9 are hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, and wherein J' is ##SPC21##
wherein V is C g H 2g , cis or trans ##EQU8## or --C.tbd.C--C j H 2j wherein C g H 2g , C j H 2j , C p H 2p , R 3 , and R 4 are as defined above, and wherein C q H 2q represents alkylene of 1 to 6 carbon atoms, inclusive, with 1, 2, or 3 carbon atoms between --O-- and --COOR 1 .
The various 13,14-dihydro-PGE 1 , --PGF 1 , --PGA 1 , and --PGB 1 , type oxa-phenylene compounds encompassed by formulas XIX, XXIII, XXVII, and XXXI are prepared by carbon-carbon double bond reduction of the corresponding PGE, PGF, PGA, and PGB type compound containing a trans double bond in the hydroxy-containing side chain. A cis or trans double bond or a triple bond can also be present in the carboxy-terminated side chain of the unsaturated reactant, and will be reduced at the same time to --CH 2 CH 2 --. For example, 13,14-dihydro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 is produced by reduction of 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 , 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 2 , or 5,6-dehydro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 2 .
These reductions are carried out by reacting with the unsaturated PGE, PGF.sub.α, PGF.sub.β, PGA, or PGB type oxa-phenylene compound with diimide, following the general procedure described by van Tamelen et al., J. Am. Chem. Soc. 83, 3725 (1961). ##SPC22## See also Fieser et al., "Topics in Organic Chemistry," Reinhold Publishing Corp., New York, pp. 432-434 (1963) and references cited therein. The unsaturated acid or ester reactant is mixed with a salt azodiformic acid, preferably an alkali metal salt such as disodium or dipotassium salt, in the presence of an inert diluent, preferably a lower alkanol such as methanol or ethanol, and preferably in the absence of substantial amounts of water. At least one molecular equivalent of the azodiformic acid salt is used for each multiple bond equivalent of the unsaturated reactant. The resulting suspension is then stirred, preferably with exclusion of oxygen, and the mixture is made acid, advantageously with a carboxylic acid such as acetic acid. When a reactant wherein R 1 is hydrogen is used, the carboxylic acid reactant also serves to acidify an equivalent amount of the azodiformic acid salt. A reaction temperature in the range of about 10° to about 40° C. is usually suitable. Within that temperature range, the reaction is usually complete within less than 24 hours. The desired dihydro production is then isolated by conventional methods, for example, evaporation of the diluent, followed by separation from inorganic materials by solvent extraction.
In the case of the oxa-phenylene unsaturated PGE, PGF.sub.α, and PGF.sub.β type reactants, the reductions to the corresponding dihydro-PGE 1 , dihydro-PGF 1 .sub.α, and dihydro-PGF 1 .sub.α type oxa-phenylene compounds are also carried out by catalytic hydrogenation. For that purpose, palladium catalysts, especially on a carbon carrier, are preferred. It is also preferred that the hydrogenation be carried out in the presence of an inert liquid diluent, for example, methanol, ethanol, dioxane, ethyl acetate, and the like. Hydrogenation pressures ranging from about atmospheric to about 50 p.s.i., and hydrogenation temperatures ranging from about 10° to about 100° C. are preferred. The resulting dihydro product is isolated from the hydrogenation reaction mixture by conventional methods, for example, removal of the catalyst by filtration or centrifugation, followed by evaporation of the solvent.
Diimide reductions and catalytic hydrogenations to produce the various novel formula XIX, XXIII, XXVII, and XXXI 13,14-dihydro compounds of this invention from the corresponding PGE, PGF, PGA and PGB type oxa-phenylene compounds of the PG 1 , PG 2 , trans-5,6-dehydro-PG 1 , and 5,6-dehydro-PG 2 series are shown in Chart B. G, J', Q, R 1 , R 9 , R 26 , and ˜ are as defined above, and L' is ##SPC23##
wherein C g H 2g , C p H 2p , and C q H 2q are as defined above.
The oxa-phenylene compounds of the PGE 2 , PGF 2 , PGA 2 , and PGB 2 type wherein the carbon-carbon double bond in the carboxy-terminated side chain is in cis configuration are prepared by reduction of the corresponding acetylenic oxa-phenylene compounds, i.e., those with a carbon-carbon triple bond in place of said carbon-carbon double bond. For that purpose, there are used any of the known reducing agents which reduce an acetylenic linkage to a cis-ethylenic linkage. Especially preferred for that purpose are diimide, or hydrogen and a catalyst, for example, palladium (5%) on barium sulfate, especially in the presence of pyridine. See Fieser et al., "Reagents for Organic Synthesis," pp. 566-567, John Wiley and Sons, Inc., New York, N.Y. (1967). ##SPC24##
These reductions are shown in Chart C, wherein G, Q, R 1 , R 9 , R 26 and ˜ are as defined above, and M' is ##SPC25##
wherein C j H 2j , C p H 2p , and C q H 2q are defined above. These oxa-phenylene cis compounds of the PGE 2 , PGF 2 .sub.α, PGF 2 .sub.β, PGA 2 , and PGB 2 type are also prepared as described hereinafter.
The oxa-phenylene PGE-type compounds of formulas XVI-XIX except wherein R 1 is hydrogen, and the oxa-phenylene PGA-type compounds of formulas XXIV-XXVII except wherein R 1 is hydrogen are prepared by the series of reactions shown in Chart D, wherein G, J', R 2 , R 9 , and R 26 are as defined above; G' is the same as G except that T is replaced by T', wherein T' is the same as T above except that R 9 is not hydrogen; R 10 is the same as the above definition of R 1 except that R 10 does not include hydrogen; R 11 and R 12 are alkyl of 1 to 4 carbon atoms, inclusive R 13 is alkyl of 1 to 5 carbon atoms inclusive; and ˜ indicates attachment of --CHR 26 --J'--COOR 10 to the cyclopentane ring in alpha or beta configuration, and attachment of the moiety to the cyclopropane ring in exo and endo configuration.
The oxa-phenylene PGE 1 -type compounds of formula XVI, the oxa-phenylene 5,6-dehydro-PGE 2 type compounds of formula XVIII, the oxa-phenylene PGA 1 -type compounds of the formula XXIV and the oxa-phenylene 5,6-dehydro-PGA 2 type compounds of formula XXVI are also prepared by the series of reactions shown in Chart E, wherein G, G', R.sub. 2, R 9 , R 10 , R 13 , and R 26 are as defined above; Z' is L' or --C.tbd.C--M'-- wherein L' and M' are as defined above; and ˜ indicates attachment of --CHR 26 --Z'--COOR 10 to the cyclopentane ring in alpha or beta configuration, and attachment of the moiety to the ##SPC26## ##SPC27## ##SPC28##
cyclopropane ring in exo or endo configuration.
It should be observed regarding the series of reactions shown in Charts D and E, that the reactions starting with glycol XXXVIII in Chart D are similar to the reactions starting with glycol XLV in Chart E. The only differences here are the definitions of the divalent moieties J' (Chart D) and Z' (Chart E). J' includes saturated, cis and trans ethylenic, and acetylenic divalent moieties. Z' is limited to the saturated and acetylenic divalent moieties encompassed by J'. In other words, final oxa-phenylene PGE-type compounds of formula XL (Chart D) encompass compounds of formulas XVI to XVIII. Final oxa-phenylene PGA-type compounds of formula XLI (Chart D) encompass compounds of formulas XXIV to XXVI. On the other hand, final oxa-phenylene PGE-type compounds of formula XLVII (Chart E) encompass only compounds of formulas XVI and XVIII, and final oxa-phenylene PGA-type compounds of formula XLVIII (Chart E) encompass only compounds of formula XXIV and XXVI.
As will subsequently appear, an acetylenic intermediate of formulas XXXVII, XXXVIII, or XLV is transformed by step-wise reduction to the corresponding cis or trans ethylenic intermediates of formulas XXXVII or XXXVIII; and an acetylenic intermediate of formulas XXXVII, XXXVIII or XLV or a cis or trans ethylenic intermediate of formulas XXXVII or XXXVIII is transformed by reduction to the corresponding saturated intermediate of formulas XXVII, XXXVIII, or XLV.
The initial bicyclo-ketone reactant of formula XLIII in Chart E is also used as an initial reactant to produce the initial bicyclo-ketone cyclic ketal reaction of formula XXXVI in Chart D. The following reactions will produce cyclic ketal XXXVI, wherein THP is tetrahydropyranol, and φis phenyl: ##SPC29##
The bicyclo-ketone reactant of formula XLIII exists in four isomeric forms, exo and endo with respect to the attachment of the --CR 9 =CR 2 G moiety, and cis and trans with respect to the double bond in that same moiety. Each of those isomers separately or various mixtures thereof are used as reactants according to this invention to produce substantially the same final oxa-phenylene PGE or PGA type product mixture.
The process for preparing either the exo or endo configuration of the formula-XLIII bicyclo-ketone is known to the art. See. U.S. Pat. No. 3,776,940 and Belgian Pat. No. 702,477, and Derwent Farmdoc No. 30,905.
See West Germany Offenlegungsschrift No. 1,937,912; reprinted in Farmdoc Complete Specifications, Book No. 14, No. 6869 R, Week R 5 , Mar. 18, 1970.
In said U.S. Pat. No. 3,776,940 a reaction sequence capable of forming exo ketone XLIII is as follows: The hydroxy of 3-cyclopentenol is protected, for example, with a tetrahydropyranyl group. Then a diazoacetic acid ester is added to the double bond to give an exo-endo mixture of a bicyclo[3.1.0]hexane substituted at 3 with the protected hydroxy and at 6 with an esterified carboxyl. The exo-endo mixture is treated with a base to isomerize the endo isomer in the mixture to more of the exo isomer. Next, the carboxylate ester group at 6 is transformed to an aldehyde group or ketone group, --CHO or ##EQU9## wherein R 9 is as defined above. Then, said aldehyde group or said keto group is transformed by the Wittig reaction, in this case to a moiety of the formula --CR 9 =CR 2 G which is in exo configuration relative to the bicyclo ring structure. Next, the protective group is removed to regenerate the 3-hydroxy which is then oxidized, for example, by the Jones reagent, i.e., chromic acid (see J. Chem. Soc. 39 (1946)), to give said exo ketone XLIII.
Separation of the cis-exo and trans-exo isomers of XLIII is described in said U.S. Pat. No. 3,776,940. However, as mentioned above, that separation is usually not necessary since the cis-trans mixture is useful as a reactant in the next process step.
The process described in said U.S. Pat. 3,776,940 for producing the exo form of bicyclo-ketone XLIII uses, as an intermediate, the exo form of a bicyclo [3.1.0]hexane substituted at 3 with a protected hydroxy, e.g., tetrahydropranyloxy, and at 6 with an esterified carboxyl. When the corresponding endo compound is substituted for that exo intermediate, the process in said Offenlegungsschrift No. 1,937,912 leads to the endo form of bicyclo-ketone XLIII. That endo compound to be used has the formula ##SPC30##
Compound LII is prepared by reacting endo-bicyclo[3.1.0]-hex-2-ene-6-carboxylic acid methyl ester with diborane in a mixture of tetrahydrofuran and diethyl ether, a reaction generally known in the art, to give endo-bicyclo[3.1.0] -hexane-3-ol-6-carboxylic acid methyl ester which is then reacted with dihydropyran in the presence of a catalytic amount of POCl 3 to give the desired compound. This is then used as described in said German Offenlegungsschrift No. 1,937,912 to produce the endo form of bicyclo-ketone XLIII.
As for exo XLIII, the above process produces a mixture of endo-cis and endo-trans compounds. These are separated as described for the separation of exo-cis and exo-trans XLIII, but this separation is usually not necessary since, as mentioned above, the cis-trans mixture is useful as a reactant in the next process step.
In the process of said U.S. patent and said Offenlegungsschrift, certain organic halides, e.g., chlorides and bromides, are necessary to prepare the Wittig reagents used to generate the generic moiety, --CR 9 =CR 2 G of bicyclo-ketone XLIII. These organic chlorides and bromides ##EQU10## are known in the art or can be prepared by methods known in the art.
To illustrate the availability of these organic chlorides consider first the above-described oxa-phenylene PGE-type compounds of formulas XVI to XIX wherein R 2 is hydrogen and G is either (1) alkyl of 1 to 10 carbon atoms, inclusive, substituted with 0, 1, 2, or 3 fluoro or ##SPC31##
wherein C t H 2t represents a valence bond or alkylene of 1 to 10 carbon atoms, inclusive, substituted with 0, 1, or 2fluoro, with 1 to 7 carbon atoms, inclusive, between ##EQU11## and the ring; wherein T is alkyl of 1 to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR 6 , wherein R 6 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, and s is 0, 1, 2, or 3, with the proviso that not more than two T's are other than alkyl.
For those products wherein G is alkyl of 2 to 10 carbon atoms, substituted with 0-3 fluoro atoms, there are available the monohalo hydrocarbons, e.g., bromo-(or chloro-) -ethane, -propane, -pentane, -octane, and -decane; and the monohalofluorohydrocarbons, e.g., CH 2 FCH 2 BR, CHF 2 CH 2 Cl, CF 3 CH 2 Br, F(CH 2 ) 3 Br, CH 3 CF 2 CH 2 Cl, CF 3 (CH 2 ) 2 Br, F(CH 2 ) 4 Cl, CH 3 CF 2 CH 2 CH 2 Cl, C 4 H 9 CFHCH 2 Br, CF 3 (CH 2 ) 3 Cl, CF 3 (CH 2 ) 2 BrCH 3 , CH 2 F(CH 2 ) 4 Cl, C 2 H 5 CF 2 (CH 2 ) 2 Cl, CF 3 (CH 2 ) 4 Cl, CH 3 (CH 2 ) 4 CF 2 (CH 2 ) 2 CH 2 Cl, and CH 3 (CH 2 ) 3 CF 2 (CH 2 ) 3 CH 2 Cl, as described in "Aliphatic Fluorine Compounds", A. M. Lovelace et al., Am. Chem. Soc. Monograph Series, 1958, Reinhold Publ. Corp. Those halides not available are prepared by methods known in the art by reacting the corresponding primery alcohol G--CH 2 OH with PCl 3 PBr 3 , or any of the other halogenating agents useful for this purpose. Available alcohols include CH 2 CH(CF 3 )CH 2 OH, (CH 3 ) 2 CHCH 2 CH 2 OH, (CH 3 ) 3 CCH 2 OH, CF 3 CH(CH 3 )CH 2 CH 2 OH, for example. For those halides of the formula G--CH 2 --Hal wherein Hal is chloro or bromo, G is R 27 --(CH 2 ) h --, h being 1, 2, 3, or 4, and R 27 being isobutyl, tert-butyl, 3,3-difluorobutyl, 4,4-difluorobutyl, or 4,4,4-trifluorobutyl, the intermediate alcohols are prepared as follows.
In the case of R 27 being isobutyl or tert-butyl, known alcohols are converted to bromides, thence to nitriles with sodium cyanide, thence to the corresponding carboxylic acids by hydrolysis, and thence to the corresponding primary alcohols by reduction, e.g., with lithium aluminum hydride, thus extending the carbon chain one carbon atom at a time until all primary alcohols are prepared.
In the case of R 27 being 3,3-difluorobutyl, the necessary alcohols are prepared from keto carboxylic acids of the formula, CH 3 --CO--(CH 2 ) r --COOH, wherein r is 2, 3, 4, 5, or 6. All of those acids are known. The methyl esters are prepared and reacted with sulfur tetrafluoride to produce the corresponding CH 3 --CF 2 --(CH 2 ) r --COOCH 3 compounds, which are then reduced with lithium aluminum hydride to CH 3 --CF 2 --(CH 2 ) r --CH 2 OH. These alcohols are then transformed to the bromide or chloride by reaction with PBr 3 or PCl 3 .
In the case of R 27 being 4,4-difluorobutyl, the initial reactants are the known dicarboxylic acids, HOOC--(CH 2 ) f --COOH, wherein f is 3, 4, 5, 6, or 7. These dicarboxylic acids are esterified to CH 3 OOC--(CH 2 ) f --COOCH 3 and then half-saponified, for example with barium hydroxide, to give HOOC--(CH 2 ) f --COOCH 3 . The free carboxyl group is transformed first to the acid chloride with thionyl chloride and then to an aldehyde by the Rosenmund reduction. Reaction of the aldehyde with sulfur tetrafluoride then gives CHF 2 --(CH 2 ) f --COOCH 3 which by successive treatment with lithium aluminum hydride and PBr 3 or PCl 3 gives the necessary bromides or chlorides, CHF 2 --(CH 2 ) f --CH 2 Br or CHF 2 --(CH 2 ) f --CH 2 Cl.
In the case of R 27 being 4,4,4-trifluorobutyl, aldehydes of the formula CH 3 OOC--(CH 2 ) f --CHO are prepared as described above. Reduction of the aldehyde with sodium borohydride gives the alcohol CH 3 OOC--(CH 2 ) f --CH 2 OH. Reaction with PBr 3 or PCl 3 then gives CH 3 OOC--(CH 2 ) f CH 2 --Hal. Saponification of that ester gives the carboxylic acid which by reaction with sulfur tetrafluoride gives the necessary CF 3 --(CH 2 ) f --CH 2 --Br or CF 3 --(CH 2 ) f --CH 2 --Cl.
For the above reactions of SF 4 , see U.S. Pat. No. 3,211,723 and J. Org. Chem. 27, 3164 (1962).
For those products wherein R 2 is hydrogen and G is ##SPC32##
the halides necessary to prepare those compounds, if not readily available, are advantageously prepared by reacting the corresponding primary alcohol, ##SPC33##
with PCl 3 , PBr 3 , HBr, or any of the other halogenating agents known in the art to be useful for this purpose. Some of the readily available halides are shown in Table I wherein s, T, and t of the formula for the intermediate halides are as defined above, and Hal is chloro, bromo, or iodo. Thus, compound No. 1 of Table I is represented by the formula wherein s and t are 0, and Hal is chloro, i.e. ##SPC34##
namely α-clorotoluene or benzyl chloride; compound No. 8 of Table I is represented by the formula wherein s is 0,t is 2, and Hal is bromo, i.e. ##SPC35##
namely 1-bromo-3-phenylpropane or 3-bromopropylbenzene; and compound No. 63 of Table I represented by the formula wherein s is 3, T is methyl in the 2-, 4- and 5-positions with respect to the C t H 2t substitution, t is 2, and Hal is bromo, i.e., ##SPC36##
namely 1 -(3-bromopropyl)-2,4,5-trimethylbenzene.
TABLE 1______________________________________Intermediate Halidesrepresented by the formulaNo. s T t Hal______________________________________1 0 -- 0 Cl2 0 -- 0 Br3 0 -- 0 l4 0 -- 1 Cl5 0 -- 1 Br6 0 -- 1 l7 0 -- 2 Cl8 0 -- 2 Br9 0 -- 2 l10 0 -- 3 Cl11 0 -- 3* Cl12 0 -- 3 Br13 0 -- 4 Cl14 1 2-CH.sub.3 0 Cl15 1 2-C.sub.2 H.sub.5 0 Cl16 1 4-C.sub.2 H.sub.5 0 Cl17 1 2-CF.sub.3 0 Cl18 1 4-OCH.sub.3 0 Cl19 1 3-CH.sub.3 0 Br20 1 4-CH.sub.3 0 Br21 1 4-C.sub.5 H.sub.11 0 Br22 1 4-Cl 0 Br23 1 2-CF.sub.3 0 Br24 1 3-CF.sub.3 0 Br25 1 4-CH.sub. 3 0 l26 1 4-F 1 Cl27 1 3-Cl 1 Br28 1 4-Cl 1 Br29 1 4-F 1 Br30 1 2-Cl 2 Br31 1 3-Cl 2 Br32 1 4-Cl 2 Br33 1 4-F 3* Br34 1 2-Cl 4 Br35 1 2-CH.sub.3 0 Cl 4-CH.sub.336 2 2-CH.sub.3 0 Cl 5-CH.sub.337 2 2-CH.sub.3 0 Cl 6-CH.sub.338 2 3-CH.sub.2 0 Cl 4-CH.sub.339 2 2-CH.sub.3 0 Cl 4-Cl40 2 2-CH.sub.3 0 Br 5-CH.sub.341 2 2-CH.sub.3 0 Br 6-CH.sub.342 2 3-CH.sub.3 0 Br 5-t-butyl43 2 3-CH.sub.3 0 Br 4-Cl44 2 2-CH.sub.3 0 Br 3-Br45 2 3-OCH.sub.3 0 Cl 4-OCH.sub.346 2 3-OCH.sub.3 0 Cl 5-OCH.sub.347 2 3-OCH.sub.3 0 Br 5-OCH.sub.348 2 2-CH.sub.3 1 Cl 4-CH.sub.349 2 2-CH.sub.3 1 Br 4-CH.sub.350 2 3-CH.sub.3 1 Br 4-CH.sub.351 2 3-OCH.sub.3 1 Br 4-OCH.sub.352 2 3-OCH.sub.3 1 Br 5-OCH.sub.353 2 3-OCH.sub.3 1 l 4-OCH.sub.354 2 3-OCH.sub.3 2 Br 4-OCH.sub.355 2 3-OCH.sub.3 2 Br 5-OCH.sub.356 2 3-OCH.sub.3 4 Br 5-OCH.sub.357 3 2-CH.sub.3 0 Cl 4-CH.sub.3 5-CH.sub.358 3 2-CH.sub.3 0 Cl 4-CH.sub.3 6-CH.sub.359 3 4-CH.sub.3 0 Cl 2-OCH.sub.3 5-OCH.sub.360 3 2-CH.sub.3 0 Br 3-CH.sub.3 6-CH.sub.361 3 2-CH.sub.3 0 Br 4-CH.sub.3 6-CH.sub.362 3 2-CH.sub.3 0 Br 3-OCH.sub.3 6-OCH.sub.363 3 2-CH.sub.3 2 Br 4-CH.sub.3 5-CH.sub.3______________________________________ --CH--*-branched | Et
Next, considering the intermediate halides for producing oxa-phenylene PGE-type compounds of formulas XIII to XVI wherein R 2 is alkyl of one to 4 carbon atoms, inclusive (A), and G is either of the two types (1) or (2) above, these organic chlorides and bromides, ##EQU12## are known to the art or can be prepared by methods known in the art.
For type A-(1) above, i.e. wherein R 2 is alkyl and G is alkyl of 1 to 10 carbon atoms and 0-3 fluoro atoms, there are available such monohalofluorohydrocarbons as CHF 2 CHClCH 3 , CF 3 CHBrCH 3 , CF 3 CH 2 CHBrCH 3 , CH 3 CF 2 CHClCH 3 , CF 3 CHClC 2 H 5 , and C 2 H 5 CF 2 CHClCH 3 , for example. Those not readily available are prepared from the corresponding secondary alcohol ##EQU13## wherein R 2 is as defined above, with PCl 3 , PBr 3 , or any of the other halogenating agents known in the art to be useful for this purpose. Such alcohols include, for example, CH 2 FCH(OH)CH 2 F, CF 3 (CH 2 ) 2 CH(OH)CH 3 , CF 3 CH(OH)(CH 2 )CH 3 , CF 3 CH(OH)(CH 2 ) 3 CH 3 , CF 3 CH(OH)C(CH 3 ) 3 , and CF 3 CH(OH)(CH 2 ) 5 CH 3 . For those halides of the formula G--CHR 2 --Hal, wherein G is R 27 --(CH 2 ) h --, using the definitions of Hal, h, R 2 , and R 27 above, the intermediate alcohols are prepared as follows.
In the case of R 27 being isobutyl or tert-butyl, lower molecular weight primary alcohols are transformed to the corresponding longer-chain carboxylic acids and thence to the corresponding secondary alcohols by preparing the intermediate ketones, ##EQU14## by known procedures, for example G--COCl + (R 2 ) 2 Cd, thereafter reducing the ketone to the secondary alcohol with sodium borohydride.
In the case of R 27 being 3,3-difluorobutyl, the procedure described above is applicable to converting CH 3 --CF 2 --(CH 2 ) 2 --COOCH 3 described above to ##EQU15## These alcohols are then transformed to the bromide or chloride by reaction with PBr 3 or PCl 3 .
In the case of R 27 being 4,4-difluorobutyl, the corresponding secondary alcohols are prepared as described above, using intermediates prepared for the primary alcohols of this type above.
In the case of R 27 being 4,4,4-trifluorobutyl, corresponding secondary alcohols are prepared by transforming CH 3 OOC--(CH 2 ) f --CHO to CH 3 OOC--(CH 2 ) f --C(R 2 )O by known methods and then proceeding with that ketone as described above for the corresponding aldehyde.
For type A-(2) halides, i.e. R 2 is alkyl and G is ##SPC37##
some of the readily available halides are shown in Table II. Thus, compound No. 1 of Table II is represented by the formula wherein s=0, R 2 =methyl, t=0, and Hal=Cl, i.e. ##SPC38##
namely (1-chloroethyl)benzene; and compound No. 13 of Table II is represented by the formula wherein s=2, T=methyl, R 2 =methyl, t=1, and Hal=Br, i.e. ##SPC39##
namely 4-(2-bromopropyl)-o-xylene or 1-(2-bromopropyl)3-methyl-4-methylbenzene.
TABLE II______________________________________Intermediate Halidesrepresented by the FormulaNo. s T R.sub.2 t Hal______________________________________1 0 -- CH.sub.3 0 Cl2 0 -- C.sub.2 H.sub.5 0 Cl3 0 -- C.sub.2 H.sub.5 0 Br4 0 -- CH.sub.3 0 l5 0 -- CH.sub.3 1 Cl6 0 -- n-C.sub.3 H.sub.7 1 Cl7 0 -- CH.sub.3 1 Br8 0 -- C.sub.2 H.sub.5 2 Cl9 1 4-C.sub.2 H.sub.5 CH.sub.3 0 Cl10 1 4-F CH.sub.3 0 Cl11 1 4-Cl C.sub.2 H.sub.5 0 Br12 1 4-F C.sub.2 H.sub.5 0 Br13 2 3-CH.sub.3 CH.sub.3 1 Br 4-CH.sub.314 2 3-OCH.sub.3 CH.sub.3 1 Br 4-OCH.sub.315 2 2-OCH.sub.3 CH.sub.3 1 Br 6-OCH.sub.3______________________________________
Other intermediate halides of the general formula ##SPC40##
may be obtained from the secondary alcohols as discussed above. The secondary alcohols, wherein R 2 is alkyl, are prepared by transforming the --COOH of the corresponding carboxylic acid, ##SPC41##
to a ketone by known procedures, e.g. by way of the acyl chloride and a dialkylcadmium. Reduction of the ketone with sodium borohydride then yields the secondary alcohol, ##SPC42##
Hydroxyl groups on the aromatic ring are suitably protected during these reactions by first forming the corresponding tetrahydropyranyl ether with dihydropyran; the hydroxyl groups are restored by mild acid hydrolysis as is well known in the art.
In the case of C t H 2t substituted with one or 2 fluoro atoms, there are a number of routes to the intermediate halides. The corresponding alcohols, for example β-fluorophenethyl alcohol, β-fluoro-α-methyl-phenethyl alcohol, β-fluoro-α,β-dimethyl-phenethyl alcohol and the like, are reacted with PCl 3 , PBr 3 or HBr to form the halide. Alternatively, the carboxylic acid having one less carbon atom in the chain than the desired intermediate halide, i.e. ##SPC43##
where g = t-1, is converted by a series of known methods to the 2,2-difluorohalide. Thus, the free carboxyl group is transformed first to the acid chloride with thionyl chloride and thence by way of the nitrile to the α-keto-acid. The carboxyl group is reduced to the alcohol with diborane and then converted to the α-keto halide. Finally, by reaction of the keto group with sulfur tetrafluoride, there is obtained ##SPC44##
As mentioned above, formula XVI-to-XXXI compounds with an alpha-fluoro substituent in a straight chain 3-to-7-carbon G, i.e., G being --CHF--(CH 2 )a --CH 3 wherein a is 1, 2, 3, 4, or 5, represent embodiments among the novel oxa-phenylene compounds of this invention. Among those, for example, is 3-oxa-16-fluoro-3-7-inter-m-phenylene-4,5,6-trinor-PGE 1 . The formula-XLIII bicyclo-ketones necessary to produce those mono-fluoro compounds are advantageously prepared by reacting either of the above-mentioned bicyclo-aldehydes, exo or endo, with a Wittig reagent prepared from CH 3 --(CH 2 )a --CO--CH 2 -Br and triphenylphosphine. The aldehyde group is thereby transformed to ##EQU16## The resulting unsaturated ketone is reduced to the corresponding ##EQU17## compound. The --OH in that group is replaced with fluoro by known methods, for example, directly by reaction with 2-chloro-1,1,2-trifluorotriethylamine or indirectly, for example, by transforming the hydroxy to tosyloxy or mesyloxy, and reacting the resulting compound with anhydrous potassium fluoride in diethylene glycol. Similarly, the oxa-phenylene PG-type compounds wherein G is ##SPC45##
having an alpha-fluoro substituent on the carbon adjacent to the hydroxy-substituted carbon (C-15 in PGE 1 ) represent preferred embodiments of this invention. In preparing the formula-XLIII bicyclo-ketone intermediates, there is used a Wittig reagent prepared from ##SPC46##
and triphenylphosphine. Following the steps above, the resulting unsaturated ketone containing the moiety ##SPC47##
is reduced to the corresponding secondary alcohol. The --OH in that group is replaced by fluoro by known methods.
Another preference mentioned above is that the 1-position of G in the formula XVI-to-XXXI compounds be mono- or di-substituted with alkyl of 1 to 4 carbon atoms, particularly methyl or ethyl. In the steps of the synthesis shown in Charts D and E, G is then G'" --CR 21 R 22 -- wherein R 21 and R 22 are methyl or ethyl and G'" is preferably alkyl of 2 to 6 carbon atoms or ##SPC48##
wherein k is 0, 1, 2, or 3. Thus, preparing the formula-XLIII intermediate olefin, a Wittig reagent is prepared from a halo compound of the general formula G'" --CR 21 R 22 --CR 2 H--Hal wherein Hal is chloro or bromo. These compounds are known in the art or can be prepared by methods known in the art, including those methods described above.
For example, when G'" is CH 3 CH 2 ) 3 --, R 2 and R.sub.(CH.sub. are hydrogen, and R 22 is methyl, there is employed 1-bromo(or -chloro)-2-methylhexane. If the halo compound is not available, the corresponding carboxylic acid is transformed to the alcohol and thence to the halide. Thus, 2,2-diethylvaleric acid yields 1-bromo-2,2-diethylpentane, wherein G'" is CH 3 (CH 2 ) 2 --, R 2 is hydrogen, and R 21 and R 22 are ethyl.
2-Ethylhexanoic acid yields 3-chloromethylheptane, wherein G'" is CH 3 (CH 2 ) 3 --, R 2 and R 21 are hydrogen, and R 22 is ethyl. 2-Ethyl-2-methylhexanoic acid yields 3-bromo-methyl-3-methylheptane, wherein G'" is CH 3 (CH 2 ) 3 --, R 2 is hydrogen, R 21 is methyl, and R 22 is ethyl. 2-Phenylpropionic acid yields 1-bromo-2-phenylpropane, wherein G'" is phenyl, R 2 and R 21 are hydrogen, and R 22 is methyl. 2-Methyl-2-phenylbutyric acid yields 1-bromo-2-methyl-2-phenylbutane, wherein G'" is phenyl, R 2 is hydrogen, R 21 is methyl, and R 22 is ethyl. 2-Methyl-4-(2,4,5-trimethoxyphenyl)butyric acid yields 1-chloro-2-methyl-4-(2,4,5-trimethoxyphenyl)butane, wherein G'" is (2,4,5-trimethoxyphenyl)ethyl, R 2 and R 21 are hydrogen, and R 22 is methyl.
Mono-alkyl substituted alkanoic acids useful for preparing the above halo intermediates are prepared by alkylation of an α-keto acid, G'" --CO--COOH, e.g. ##SPC49##
(prepared via the acid chloride and thence the nitrile) by means of a Grignard reagent, R 22 MgHal for example.
The transformation of bicyclo-ketone-olefin XLIII to glycol LI is carried out by reacting olefin XLIII with a hydroxylation reagent. Hydroxylation reagents and procedures for this purpose are known in the art. See, for example, Gunstone, Advances in Organic Chemistry, Vol. I, pp. 103-147, Interscience Publishers, New York, N.Y. (1960). Especially useful hydroxylation reagents for this purpose are osmium tetroxide and performic acid (formic acid plus hydrogen peroxide). Various isomeric glycols are obtained depending on such factors as whether olefin XLIII is cis or trans and endo or exo, and whether a cis or a trans hydroxylation reagent is used. These various glycol mixtures can be separated into individual isomers by silica gel chromatography. However, this separation is usually not necessary, since all isomers of particularly glycol are equally useful as intermediates according to this invention and the processes outlined in Chart D to produce final products of formulas XL and XLI, and then, according to Chart A, B, and C to produce the other final products of this invention.
The transformation of glycol LI to the cyclic ketal of formula XXXVI (Chart D) is carried out by reacting said glycol with a dialkyl ketone of the formula ##EQU18## wherein R 11 and R 12 are alkyl of 1 to 4 carbon atoms, inclusive, in the presence of an acid catalyst, for example potassium bisulfate or 70% aqueous perchloric acid. A large excess of the ketone and the absence of water is desirable for this reaction. Examples of suitable dialkyl ketones are acetone, methyl ethyl ketone, diethyl ketone, methyl propyl ketone, and the like. Acetone is preferred as a reactant in this process.
Referring again to Chart D, cyclic ketal XXXVI is transformed to cyclic ketal XXXVII by alkylating with an alkylation agent of the formula ##EQU19## wherein R 10 , R 26 , and J' are as defined above, and Hal is chlorine, bromine, or iodine. Similarly, referring to Chart E, olefin XLIII is transformed to olefin XLIV by alkylating with an alkylation agent of the formula ##EQU20## wherein R 10 , R 26 , Z', and Hal are as defined above.
Any of the alkylation procedures known in the art to be useful for alkylating cyclic ketones with alkyl halides and haloalkanoic esters are used for the transformations of XXXVI to XXXVII and of XLIII to XLIV. See, for example, the above-mentioned Belgian Pat. No. 702,477 for procedures useful here and used there to carry out similar alkylations, e.g., employing the bicyclo enamines.
For these alkylations, it is preferred that Hal be bromo or iodo. Any of the usual alkylation bases, e.g., alkali metal alkoxides, alkali metal amides, and alkali metal hydrides, are useful for this alkylation. Alkali metal alkoxides are preferred, especially tert-alkoxides. Sodium and potassium are preferred alkali metals. Especially preferred is potassium tert-butoxide. Preferred diluents for this alkylation are tertrahydrofuran and 1,2-dimethoxyethane. Otherwise, procedures for producing and isolating the desired formula-XXXVII and -XLIV compounds are within the skill of the art.
These alkylation procedures produce mixtures of alpha and beta alkylation products, i.e. a mixture of formula-XXXVII products wherein part has the --CHR 26 --J'--COOR 10 moiety attached in alpha configuration, and wherein part has that moiety attached in beta configuration, or a mixture of the formula-XLIV products with the --CHR 26 --Z'--COOR 10 moiety in both alpha and beta configurations. When about one equivalent of base per equivalent of formula-XXXVI or -XLIII ketone is used, the alpha configuration usually predominates. Use of an excess of base and longer reaction times usually result in production of larger amounts of beta products. These alpha-beta isomer mixtures are separated at this stage or at any subsequent stage in the multi-step processes shown in Charts D and E. Silica gel chromatography is preferred for this separation.
The necessary alkylating agents for the above-described alkylations, e.g. compounds of the formulas ##EQU21## are prepared by methods known in the art. There are four groups of compounds encompassed by these two genera of alkylating agents.
Alkylating agents of the formula ##EQU22## include compounds of the formulas: ##SPC50##
Alkylating agents of the formula ##EQU23## include the above-listed compounds of formuls LIII and LIV, and also compounds of the following formulas ##SPC51##
These alkylating agents of formulas LIII to LVI are accessible to those of ordinary skill in the art. In one route, the ##EQU24## compounds are obtained from aldehyde or ketone reactants by a series of transformations as follows: ##EQU25## For example, methyl m-formylphenoxyacetate on reduction with sodium borohydride yields methyl m-(hydroxymethyl)-phenoxyacetate, which in turn is transformed to the formula-LIX compound, methyl m-(chloromethyl)phenoxyacetate, with thionyl chloride.
Those formula-LVII or formula-LVIII reactants which are not commercially available are advantageously prepared by adaptation of the Williamson ether syntheses, e.g. employing a hydroxy reactant and a halo-substituted acid or ester. Thus, the reaction ##SPC52##
wherein Hal is chloro, bromo, or iodo, preferably iodo, proceeds in the presence of strong base, for example sodium hydride when R 1 is a carbon-containing group, and lithium diisopropyl amide when R 1 is hydrogen. Within definitions of C g H 2g , C p H 2p , and C q H 2q , suitable reactants are readily available or are prepared by methods known to those skilled in the art.
Thus, when R 26 is hydrogen, and considering the variations of C g H 2g and C p H 2p , the aldehyde reactants include (o, m, or p)-hydroxybenzaldehyde, (o, m, or p-hydroxyphenyl)acetaldehyde, (o or p)-hydroxyhydrocinnamaldehyde, 4-(o or p-hydroxyphenyl)butyraldehyde, o-(2-hydroxyethyl)benzaldehyde, and the like. Other aldehyde reactants are also accessible by methods known to those skilled in the art. For example, (o, m, or p-hydroxyethyl)benzaldehydes are obtained from (o, m, or p)-bromostyrene by the series of reactions: ##SPC53##
The reaction with ethylene oxide is carried out on a Grignard reagent prepared from the bromostyrene and magnesium. Substituted ethylene oxides are used to obtain substituted C p H 2p chains, e.g. propylene oxide, 1,2-epoxy-2-methylpropane, 1,2-epoxybutane, 1,2-epoxy-2,3-dimethylbutane, and the like. Instead of using ozone to form the aldehyde, hydroxylation and oxidation with osmium tetroxide and periodic acid are optional (see J. Org. Chem. 21, 478, 1956).
Compounds with C g H 2g chains are obtained by replacing ##SPC54##
e.g. 1-allyl-4-bromobenzene 1-allyl-2-chlorobenzene, 4-(o, m, or p-chlorophenyl)-1-butene, and the like. Compounds with C p H 2p chains are obtained by replacing ethylene oxide with suitable alkylating agents, e.g. trimethylene oxide, 1,3-epoxybutane, 1,3-epoxy-3-methylbutane and the like, or suitable reactions steps.
Other variations of the above reactions and reactants will be apparent to those skilled in the art. Thus, an alkene-substituted phenol is condensed with a halo-substituted acid or ester and thereafter transformed as an aldehyde to the halo alkylating agent within the scope of formula LIX by the following steps: ##SPC55##
Available for this series of reactions are (o, m, or p)-vinylphenol, p-allylphenol, 4-(o, m, or p-hydroxyphenyl)-1-butene, and the like.
Alternatively, a haloalkylphenol is condensed with a halo-substituted acid or ester by the reaction: ##SPC56##
Available are p-(2-bromoethyl)phenol, p-(3-bromobutyl)-phenol, and the like.
Considering the halo-substituted acid or ester reactants in the above ether syntheses and the variations of C q H 2q , there are a wide variety of reactants available, which will lead to the desired formula-LIX alkylating agent. For example: ##EQU26## wherein R 23 is hydrogen or alkyl of 1 to 5 carbon atoms, inclusive; Br--(CH 2 ) 2 --COOH, Br--C(CH 3 ) 2 --COOH, Br--C(C 2 H 5 ) 2 --COOH, BrC(CH 3 )(C 2 H 5 )--COOH, Br--CH(CH 3 )--CH 2 --COOH, Br--(CH 2 ) 3 )--COOCH 3 , Cl--CH(C 2 H 5 )--CH 2 --COOCH 3 , Cl--CH(n--C 3 H 7 )--CH 2 --COOCH 3 , Br--CH(CH 3 )--(CH 2 ) 2 --COOC 2 H 5 , Br--CH(CH 3 )--CH 2 --CH(CH 3 )--COOC 2 H 5 , Br--CH(CH 3 )--CH(CH 3 )--CH 2 --COOC 2 H 5 , Br--C(CH 3 ) 2 --CH(CH 3 )--COOC 2 H 5 , Cl--CH(n--C 4 H 9 )--CH 2 --COOC 2 H 5 , Cl--C(CH 3 ) 2 --CH 2 --COOC 2 H 5 , Br--CH(n--C 2 H 7 )--(CH 2 ) 2 --COOH, and Cl--CH(C 2 H 5 )--(CH.sub. 2) 2 --COOH are available. The preferred iodo reactants are obtained by methods known to those skilled in the art.
When C q H 2q has two alkyl groups attached to the ω or ω-1 carbon atom of the halo-substituted acid or ester reactants, it is preferred that halo be replaced with mesyloxy or tosyloxy prior to the ether synthesis, and that relative mild bases and reaction conditions be used, for example, potassium tert-butoxide in dimethyl sulfoxide.
In another route to the formula-LIX alkylating agents, the Williamson ether synthesis employs hydroxy-esters or acids of the formula HO--C q H 2q --COOR 1 for condensation with halo-substituted reactants as follows: ##SPC57##
For example, α,α'-dibromo-o-xylene is contacted with ethyl glycolate in the presence of sodium hydride to yield ethyl O-(bromomethyl)-benzyloxyacetate.
Typical halo reactants which are useful for this reaction are α-bromo-(o, m, or p)-chlorotoluene, 1-bromo-(2 or 3)-(2-bromoethyl)benzene, 1-(3-bromopropyl)-(1 or 2)-chlorobenzene, and 1-(4-bromobutyl)-1-chlorobenzene.
When C p H 2p has two alkyl groups attached to the carbon atom to which Hal is attached, it is preferred that this Hal be replaced with mesyloxy or tosyloxy prior to the ether synthesis and that relatively mild bases and reaction conditions be used.
Considering the hydroxy acid or ester reactants, there are available a wide range of suitable compounds within the scope of HO--C q H 2q --COOR 1 which will lead to the desired formula-LIX alkylating agent. For example: HOCH(CH 3 )--COOCH 3 , HOC(CH 3 ) 2 --COOH, HOCH(C 2 H 5 )--COOH, HOC(CH 3 )(C 2 H 5 )--COOH, HO(CH 2 ) 2 --COOC 2 H 5 , HOCH(CH 3 )--CH 2 --COOH, HOCH(n--C 3 H 7 )--COOH, HOC(n--C 3 H 7 )(CH 3 )--COOH, HOCH(C 2 H 5 )--CH 2 --COOH, HOCH(CH 3 )--(CH 2 ) 2 --COOH, HOCH(n-C 4 H 9 )--COOH, HOC(n--C 4 H 9 )(CH 3 )--COOH, HOCH(n--C 3 H 7 )--CH 2 --COOCH 3 , HOCH(C 2 H 5 )--(CH 2 ) 2 --COOH, HOCH(n--C 5 H 11 )--COOH, HOCH(n--C 4 H 9 )--CH 2 --COOH, HOCH(n--C 3 H 7 )--(CH 2 ) 2 --COOH are available.
When a formula-LIX alkylating agent is desired in which there are two alkyl substituents on both carbon atoms attached to the oxa --O--, it is preferred that, if the halo-acid route be used, the halo atom on the acid be chloro and that freshly precipitated wet magnesium hydroxide in an inert solvent suspension be used as the base; and if the hydroxy-acid route be used, the --C p H 2p --Hal group is preferrably --C p H 2p --Cl. If the hydroxy-acid route is used with --C p H 2p --I, silver oxide is used as the base.
The alkylating agents of formulas LIII to LVI are esters. Any of the above acid forms are readily converted to esters. Variations in R 10 within the definition of R 10 herein, are readily made by methods known in the art. The ester moiety is chosen according to the desired type of final oxa-phenylene PG-type product.
Formula-LVII aldehyde reactants which lead to the formula LIX alkylating agents are also obtained by reaction of halo-substituted aldehydes with hydroxy acids or ester reactants. Thus, there are employed o-(bromoethyl)benzaldehyde, p-chlorohydratropaldehyde, and the like.
When R 26 is alkyl, the formula-LIX ##EQU27## alkylating agents are prepared from the corresponding reactants wherein R 26 is methyl, ethyl, propyl, or butyl, or their isomers. For example m-bromo-α-methylstyrene reacts as follows: ##SPC58##
Typical halo-substituted ketones available for this purpose include (2', 3', or 4')-(bromo, chloro, or iodo)-acetophenone, (3' or 4')-bromopropiophenone, (3' or 4')-chlorobutyrophenone, and 4'-(bromo or chloro)-valerophenone. Other reactants leading to the R 26 (alkyl)-substituted formula-LIX alkylating agents are accessible to those skilled in the art.
Although the above methods are generally useful for preparing alkylating agents within the scope of formulas ##EQU28## above, there are preferred methods for preparing the formula-LIV compounds containing --C.tbd.C--C j H 2j -- moiety.
Considering compounds of the formula ##SPC59##
there is employed as starting material (o, m, or p-)vinylanisole in the following series of transformations: ##SPC60##
Herein, THP represents tetrahydropyranyl and R 28 represents ##SPC61##
The reagents and conditions for bringing about these transformations are known to those skilled in the art. Thus, in step a, reacting first with bromine and then with sodium amide in liquid ammonia yields the acetylenic derivative (see J. Am. Chem. Soc. 56, 2064, 1934). Step b utilizes boron tribromide for example. Step c proceeds either with ethylene chlorohydrin and a strong base, e.g., NaOH or KOH, followed by dihydropyran in the presence of an acid catalyst, or with the tetrahydropyranyl ether of the chlorohydrin and a strong base. Step d utilizes R 26 COCl in the presence of a strong base, e.g., sodium amide, phenyllithium, or sodium triphenylmethane. Alternatively, if R 26 is desirably hydrogen, paraformaldehyde is employed (see J. Am. Chem. Soc. 92, 6314 (1970). The reaction in step e is done with a metal hydride, e.g., sodium borohydride. In step f thionyl chloride yields the formula-LX chloro compounds. Finally, in step g the THP moiety is selectively removed by mild hydrolysis in acid medium and the terminal --CH 2 OH moiety is oxidized to --COOH, e.g. with the Jones reagent. The alkylating agent is converted by known means to an ester, as defined by R 10 , to yield the desired compounds.
Considering the compounds of the formula ##SPC62##
the above series of transformations are used, except that in c ClCH 2 CH 2 OH is replaced by Cl--C q H 2q --CH 2 OH. There are obtained in step f compounds of the formula ##SPC63##
wherein C q H 2q , Hal, R 26 and THP are as defined above. Thereafter these formula-LXI compounds are transformed as in step g above to the desired compounds.
Considering the compounds of the formula ##SPC64##
there are employed as starting materials the ar-halostyrenes. These are transformed by the following steps: ##SPC65##
Thereafter, these formula-LXII compounds are transformed as in step g above to the desired compounds. In step a, the halo compounds are converted to a Grignard reagent with magnesium and thence reacted with ethylene oxide. In step b, the hydroxy group is converted to --OTHP with dihydropyran, the acetylenic moiety is formed as in step a leading to the formula-LX compounds above, and the THP moiety removed by mild acid hydrolysis. In step c, the chain is extended by reaction with Hal--CH 2 CH 2 OH, preferably the bromo or iodo derivatives, in the presence of strong base, e.g., phenyl lithium, sodium triphenylmethane, or sodium hydride. Thereafter, in step d the transformations follow the general scheme of steps d-f leading to the formula-LX compound to yield the formula-LXII compounds. Transformation as in step g above yields the desired compounds.
Considering the compounds of the formula ##SPC66##
the series of transformations in the paragraph immediately preceeding are used, except that in step c Hal--CH 2 CH 2 OH is replaced by Hal--C q H 2q --CH 2 OH. There are obtained in step d compounds of the formula ##SPC67##
These formula-LXIII compounds are transformed as in step g above to the desired esters.
Considering the compounds of the formula ##SPC68##
there are employed as starting materials anisolyl aliphatic acids, e.g., anisolylacetic acid, in the following steps: ##SPC69##
In step a, the carboxyl group is reduced with a metal hydride, e.g. lithium aluminum hydride. In step b, where Ts represents the toluenesulfonyl ("tosyl") moiety, the reaction is carried out with toluenesulfonyl chloride and pyridine. In step c, the acetylenic moiety is introduced with lithium acetylide (see J. Am. Chem. Soc. 80, 6626, 1958) to yield the formula-LXIV intermediates. Subsequent steps in d to form the formula-LXV compounds follow from steps b-f for the formula-LX compounds above. Finally, the formula-LXV compounds are transformed as in step g above to the desired esters.
Considering the compounds of the formula ##SPC70##
there are employed as starting materials benzenedialiphatic acids, e.g., benzenediacetic acid, in the following steps: ##SPC71##
In step a, the carboxyl groups are reduced with a metal hydride, e.g. lithium aluminum hydride. In step b, reaction with toluenesulfonyl halide yields the bistosyl derivative. In step c one tosyloxy group is replaced by reaction with HO--C q H 2q --CH 2 OTHP in the presence of sodium hydride in an inert solvent, e.g. dimethyl formamide. In step d, the acetylenic moiety is introduced as in forming the formula-LXIV compounds above. Subsequent steps in e to form the formula-LXVI compounds follow from steps b-f for the formula-LX compounds above. Finally, the formula-LXVI compounds are transformed as in step g above to the desired esters.
Variations in the above formula LX-to-LXVI compounds and their corresponding ester alkylating agents as to chain length or branching in the C g H 2g , C j H 2j , C p H 2p , and C q H 2q moieties and as to the identity of R 1 or R 26 , within the scope of these terms as herein defined, are available to those skilled in the art making use of the principles disclosed herein.
Other modifications which are encompassed within this disclosure include the use of alkylating agents wherein Hal is replaced by hydrocarbonsulfonyl, e.g. tosyl or mesyl (methanesulfonyl) groups. Furthermore, the formula-LX, -LXI, -LXII, -LXIII, -LXV, and -LXVI compounds are alternatively employed as alkylating agents, instead of the corresponding esters, and the alkylated formula-XXXVI and -XLIII compounds subsequently converted to the desired formula-XXXVII and -XLIV compounds by mild hydrolysis to remove the THP moiety, oxidation to convert the --CH 2 OH moiety to --COOH, and, optionally, esterification to the desired R 1 identity.
The cis and trans ethylenic alkylating agents of formulas LV and LVI above are preferably prepared by cis or trans reduction of the corresponding formula-LIV acetylenic compounds prepared as above, or by cis or trans reduction of any earlier acetylenic intermediate in which both ends of the acetylenic bond are substituted, i.e., not hydrogen as in the moiety HC.tbd.C--. Alternatively, this cis or trans reduction is carried out on any subsequent acetylenic reaction product leading up to and including the final acetylenic alkylating agent of formula LIV.
For these cis reductions of acetylenic bonds, it is advantageous to use hydrogen plus a catalyst which catalyzes hydrogenation of --C.tbd.C-- only to cis --CH=CH--. Such catalysts and procedures are well known to the art. See, for example, Fieser et al., "Reagents for Organic Syntheses", pp. 566-567; John Wiley and Sons, Inc., New York, N.Y. (1967). Palladium (5%) on barium sulfate, especially in the presence of pyridine as a diluent, is a suitable catalyst for this purpose. Alternative reagents useful to transform these acetylenic compounds to cis-ethylenic compounds are bis(3-methyl-2-butyl)borane ("disiamylborane") and diisobutyl-aluminum hydride.
For trans reductions of the acetylenic bond, except for those compounds containing halogen, it is advantageous to use sodium or lithium in liquid ammonia or a liquid alkylamine, e.g., ethylamine. When the moiety HO--CH 2 --C.tbd.C-- is present in the acetylenic compound being reduced, the use of lithium aluminum hydride gives trans reduction of the triple bond. Procedures for these trans reductions are known in the art. See, for example, Fieser et al., above cited, pp. 577, 592-594, and 603, and J. Am. Chem. Soc. 85, 622 (1963).
The alkylating agents of the formulas ##SPC72## are available by methods known to those skilled in the art.
Thus, the above-described intermediates within the scope of ##SPC73##
are transformed to the phosphoranes and condensed with halo-substituted ketones of the formula ##EQU29## wherein THP is tetrahydropyranyl, by the Wittig reaction (Organic Reactions, Vol. 14, p. 270, Wiley, 1965). Mixtures of the cis and trans isomers of formulas LXVII and LXVIII are usually obtained, which are separable by methods known in the art. Higher proportions of the cis isomers are obtained in the presence of Lewis bases; higher proportions of the trans isomers result by employing the phosphonate modification (D. H. Wadsworth et al., J. Org. Chem. 30, 680 (1965)). Thereafter, hydrogen on the terminal carboxyl group is replaced with R 10 , THP is replaced with hydrogen, and the terminal hydroxyl group replaced with Hal, for example with PBr 3 or PCl 3 .
Alternatively, an intermediate of the formula ##SPC74##
is condensed by the Wittig reaction with a phosphorane or phosphonate derived from ##EQU30## Subsequently, the terminal hydroxy group is replaced with Hal by suitable reagents, for example PBr 3 or PCl 3 .
Concerning the alkylation of the cyclopentane ring, another useful alkylation procedure utilizes an intermediate enamine. That enamine is prepared by mixing either the formula-XXXVI ketal or the formula-XLIII olefin ketone with a secondary amine of the formula ##EQU31## wherein R 24 and R 25 are alkyl or alkylene linke together through carbon or oxygen to form together with a nitrogen a 5 to 7-numbered heterocyclic ring. Examples of suitable amines are diethylamine, dipropylamine, dibutylamine, dihexylamine, dioctylamine, dicyclohexylamine, methylcyclohexylamine, pyrrolidine, 2-methylpyrrolidine, piperidine, 4-methylpiperidine, morpholine, hexamethylenimine, and the like.
The enamine is prepared by heating a mixture of the formula-XXXVI ketal or the formula-XLIII olefin ketone with an excess of the amine preferably in the presence of a strong acid catalyst such as an organic sulfonic acid, e.g., p-toluenesulfonic acid, or an inorganic acid, e.g., sulfuric acid. It is also advantageous to carry out this reaction in the presence of a water-immiscible diluent, e.g., benzene or toluene, and to remove water by azeotropic distillation as it is formed during the reaction. Then, after water formation ceases, the enamine is isolated by conventional methods.
The enamine is then reacted with a haloester, ##EQU32## to give the desired formula-XXXVII or -XLIV product. This reaction of the enamine is carried out by the usual procedures. See "Advances in Organic Chemistry," Interscience Publishers, New York, N.Y., Vol. 4, pp. 25-47 (1963) and references cited therein. In addition to halogen, R 29 in ##EQU33## can also be tosylate, mesylate, and the like. It is especially preferred that R 29 be bromine or iodine. Dimethylsulfoxide is especially useful as a diluent in the reaction of the enamine with the haloester.
Referring again to Chart D, after alkylation as discussed above, cyclic ketal XXXVII is transformed to glycol XXXVIII by reacting the cyclic ketal with an acid with pK less than 5. Suitable acids and procedures for hydrolyzing cyclic ketals to glycols are known in the art. Suitable acids are formic acid, hydrochloric acid, and boric acid. Especially preferred as diluents for this reaction are tetrahydrofuran and β-methoxyethanol.
Referring again to Chart E, after alkylation as discussed above, olefin XLIV is hydroxylated to glycol XLV. As discussed above, the divalent moiety --Z'-- includes the moieties ##SPC75##
wherein C g H 2g , C j H 2j , and C q H 2q are as defined above. When Z' is ##SPC76##
this hydroxylation of XLIV is carried out as described above for the hydroxylation of olefin XLIII to glycol LI, i.e., with any of the known reagents and procedures described in Gunstone, above cited. When Z' is ##SPC77##
some of the reagents and procedures described by Gunstone tend to attack the acetylenic linkage as well as the ethylenic linkage of the formula-XLIV olefin. Therefore it is preferred to use a hydroxylation reagent and procedure which attacks the ethylenic linkage preferentially. For this, it is preferred to carry out hydroxylation of these acetylenic formula-XLIV olefins with organic peracids, e.g., performic acid, peracetic acid, perbenzoic acid, and m-chloro-perbenzoic acid, as described by Gunstone, above cited, pp. 124-130.
As discussed above regarding the hydroxylation of unalkylated olefin XLIII to unalkylated glycol LI, various isomeric glycols are obtained by hydroxylation of the formula-XLIV alkylated olefin. The particular formula-XLV glycol or glycol mixture obtained depends on such factors as whether the olefin XLIV is cis or trans and endo or exo, and whether a cis or trans hydroxylation takes place. However, all of the isomeric formula-XLIV glycols and the various glycol mixtures are equally useful as intermediates according to this invention and the processes of Chart E to produce final products of formulas XLVII and XLVIII, and then according to Charts A, B, and C, to produce the other final products of this invention. Therefore, it is usually not necessary to separate individual formula-XLV glycol isomers before proceeding further in the synthesis, although that separation can be accomplished by silica gel chromatography.
It is preferred that glycols XXXVIII and XLV of Charts D and E, respectively, be free of phenolic hydroxyl substituents before the alkanesulfonation step. If any of the intermediate formula-XXXVIII or formual XLV compounds have phenolic hydroxyls, these hydroxyls are readily converted to tetrahydropyranyloxy (OTHP) by reaction with dihydropyran, e.g. in the presence of a catalytic amount of POCl 3 . The --OTHP group is subsequently replaced by OH under mildly acidic conditions.
Referring again to Charts D and E, bis(alkanesulfonic acid) esters XXXIX and XLVI are prepared by reacting glycols XXXVIII and XLV, respectively, with an alkanesulfonyl chloride or bromide, or with an alkanesulfonic acid anhydride, the alkyl in each containing 1 to 5 carbon atoms, inclusive. Alkanesulfonic chlorides are preferred for this reaction. The reaction is carried out in the presence of a base to neutralize the byproduct acid. Especially suitable bases are tertiary amines, e.g., dimethylaniline or pyridine. It is usually sufficient merely to mix the two reactants and the base, and maintain the mixture in the range 0° to 25° C. for several hours. The formula-XXXIX and XLVI bis(sulfonic acid) esters are then isolated by procedures known to the art.
Referring now to Chart D, bis(sulfonic acid) esters XXXIX are transformed either to oxa-phenylene PGE-type compounds XL, or to oxa-phenylene PGA-type compoupnds XLI. Referring to Chart E, bis(sulfonic acid) esters XLVI are transformed either to oxa-phenylene PGE-type compounds XLVII, or to oxa-phenylene PGA-type compounds XLVIII.
The transformations of XXXIX and XLVI to the PGE-type compounds XL and XLVII, respectively, are carried out by reacting bis-esters XXXIX and LXVI with water in the range about 0° to about 60°C. In making the oxa-phenylene PGE 1 compounds, 25° C. is a suitable reaction temperature, the reaction then proceeding to completion in about 5 to 20 hours. It is advantageous to have a homogenous reaction mixture. This is accomplished by adding sufficient of a water-soluble organic diluent which does not enter into the reaction. Acetone is a suitable diluent. The desired product is isolated by evaporation of excess water and diluent if one is used. The residue contains a mixture of formula-XL or formula-XLVII C-15 epimers which differ in the configuration of the side chain hydroxy, that being either "natural" or "epi", i.e. α or β. These are separated from by-products and from each other by silica gel chromatography. A usual by-product is the mono-sulfonic acid ester of formula XLII (Chart D) or formula XLIX (Chart E). These mono-sulfonic acid esters are esterified to the formula-XXXIX or -XLVI bis(sulfonic acid) esters, respectively, in the same manner described above for the transformation of glycol XXXVIII or XLV to bis-ester XXXIX or XLVI and thus are recycled back to additional formula-XL or -XLVII final product.
The transformations of XXXIX and XLVI to the PGA type compounds XLI and XLVIII, respectively, are carried out by heating bis-esters XXXIX and XLVI in the range 40° to 100° C. with a combination of water, a base characterized by its water solution having a pH 8 to 12, and sufficient inert water-soluble organic diluent to form a basic and substantially homogenous reaction mixture. A reaction time of one to 10 hours is usually used. Preferred bases are the water-soluble salts of carbonic acid, especially alkali metal bicarbonates, e.g., sodium bicarbonate. A suitable diluent is acetone. The products are isolated and separated as described above for the transformation of bis-esters XXXIX and XLVI to PGE-type products XL and XLVII. The same mono-sulfonic acid esters XLII and XLIX observed as by-products in those transformations are also observed during preparation of PGA-type products XLI and XLVIII.
For the transformations of bis(sulfonic acid) esters XXXIX and XLVI to final products XL, XLI, XLVII, and XLVIII, it is preferred to use the bis-mesyl esters, i.e., compounds XXXIX and XLVI wherein R 13 is methyl.
Referring again to Charts D and E, the configuration of the ##EQU34## moiety in the formula-XXXIX bis-esters or the configuration of the ##EQU35## moiety in the formula-XLVI bis-esters does not change during these transformations of XXXIX to XL, XLI, and XLII, and of XLVI to XLVII, XLVIII, and XLIX. Therefore, when in formula XXXIX for example, J' is ##SPC78##
G' is --(CH 2 ) 4 --CH 3 , and R 2 , R 9 and R 26 are hydrogen, natural- and epi-configuration 3-oxa-4,5-inter-o-phenylene-PGE 1 esters (XL) are obtained when ##EQU36## is attached initially (XXXIX) in alpha configuration, and natural- and epi-configuration 8-iso-3-oxa-4,5-inter-o-phenylene-PGE 1 esters (XL) are obtained when that moiety is attached in beta configuration. Similarly, when in formula XXXIX, J' is ##SPC79##
G' is --(CH 2 ) 4 --CH 3 , and R 2 , R 9 , and R 26 are hydrogen, natural- and epi-configuration 5,6-dehydro-3-oxa-4,5-inter-p-phenylene-PGE 2 esters are obtained when ##EQU37## is attached initially in alpha configuration, and the corresponding 8-iso compounds are obtained when that moiety is attached in beta configuration. The same retention of ##EQU38## configuration occurs when formula-XLI and XLII compounds are produced, and a similar retention of ##EQU39## configuration occurs when formula-XLVII, XLVIII, and XLIX compounds are produced from formula-XLVI bis-esters
The PGE 3 -type oxa-phenylene compounds encompassed by formula XXXII are prepared by the transformations shown in Chart F, wherein C n H 2n , M', Q, R 2 , R 5 , R 9 , R 10 R 13 , THP, and ˜ are as defined above. ##SPC80##
Starting material L, previously discussed, is converted to the formula-LXIX compound by several steps known in the art, employing first a Wittig reaction of a phosphonium salt of a haloalkyne of the formula BR--CHR 2 --C n H 2n --C.tbd.C--R 5 wherein C n H 2n , R 2 , and R 5 are as defined above. See, for example, U. Axen et al., Chem. Comm. 1969, 303, and ibid. 1970, 602.
Compound LXIX is then alkylated with an alkylation agent of the formula Hal--CH 2 --C.tbd.C--M'--COOR 10 wherein M', R 10 , and Hal are as defined above, i.e. M' is ##SPC81##
wherein C j H 2j , C p H 2p , and C q H 2q are as defined above, R 10 is the same as the definition of R 1 except that R 10 does not include hydrogen, and Hal is chloro, bromo, or iodo. These alkylating agents have been discussed above in connection with Charts D and E and the procedures for alkylation are similar to those employed in preparing the acetylenic compounds above. See also Axen et al., referenses cited.
Accordingly, for the preparation of 3-oxa-3,5-inter-m-phenylene-4-nor-PGE 3 compounds of formula XXXII wherein C j H 2j and C p H 2p are valence bonds, there is used an alkylating agent of the formula ##SPC82##
prepared, for example, from compound LX as discussed above.
Referring again to Chart F, after alkylation, compound LXX is hydroxylated to glycol LXXI. Hydroxylation reagents and procedures for this purpose are known in the art. See also Axen et al., references cited.
Bis(alkanesulfonic acid) esters LXXII are prepared by reacting glycol LXXI with an alkanesulfonyl chloride or bromide, for example methanesulfonyl chloride in the presence of a tertiary amine, by methods known in the art.
Referring again to Chart F, bis(sulfonic acid) esters LXXII are transformed to oxa-phenylene bisdehydro PGE 3 -type compounds LXXIII by reaction with water in the range about 0° to about 60° C., preferably in an acetone-water mixture, as known in the art and discussed hereinabove. See also Axen, references cited.
Transformation of LXXIII to the PGE 3 -type compounds LXXIV is accomplished by hydrogenation of LXXIII using a catalyst which catalyzes hydrogenation of --C.tbd.C-- only to cis--CH=CH--, as known in the art and discussed hereinabove. Preferred is Lindlar catalyst in the presence of quinoline, see Axen, references cited.
The product is a mixture of formula-LXXIV C-15 epimers which are separated from by-products and from each other by silica gel chromatography.
The transformations of the formula-LXXIV PGE 3 -type products to the corresponding PGF 3 , PGA 3 , and PGB 3 products are carried out by the steps shown in Chart A, discussed hereinabove.
The formula-LX and XLVII oxa-phenylene PGE-type compounds and the formula-XLI and XLVIII oxa-phenylene PGA-type compounds shown in Charts D and E and the formula-LXXIV oxa-phenylene PGE 3 -type compounds shown in Chart F are all R 10 carboxylic acid esters, wherein R 10 is as defined above. Moreover when those PGE-type and PGA-type R 10 esters are used to prepare the other oxa-phenylene prostaglandin-like compounds according to Charts A, B, and C, corresponding R 10 esters are likely to be produced, especially in the case of the oxa-phenylene PGF-type compounds. For some of the uses described above, it is preferred that the novel formula XVI-to-XXXV oxa-phenylene prostaglandin-like compounds of this invention be in free acid form, or in salt form which requires the free acid as a starting material. Likewise, when a formula XVI-to-XXXV oxa-phenylene prostaglandin-like compound is available as an ester, say the methyl ester, and another ester is desired, it is usually necessary to convert the available ester to the free acid form and from it prepare the desired ester. Esters are prepared by methods known in the art or described herein, for example by reaction with diazohydrocarbons.
The PGF-type esters of formulas XX-XXIII and XXXIII and the PGB-type compounds of formulas XXVIII-XXXI and XXXV are easily hydrolyzed or saponified to the free acids by the usual known procedures, especially when R 1 (R 10 ) is alkyl of 1 to 4 carbons, inclusive, preferably methyl or ethyl.
On the other hand, the PGE type esters of formulas XVI-XIX and XXXII and the PGA type esters of formulas XXIV-XXVII and XXXIV are difficult to hydrolyze or saponify without causing unwanted structural changes in the desired acids. There are two other procedures to make the free acid forms of these PGE- and PGA-type compounds.
One of those procedures is applicable mainly in preparing the free acids by subjecting their alkyl esters to the acylase enzyme system of a microorganism species of Subphylum 2 of Phylum III, and thereafter isolating the acid. See West Germany Offenlegungsschrift No. 1,937,678; Derwent Farmdoc No. 6863R. This enzymatic hydrolysis is also applicable to the above PGF- and PGB-type alkyl esters. Another method using an esterase enzyme composition from P. homomalla is described in U.S. Pat. No. 3,761,356.
Another procedure for making the free acids of the above PGE- and PGA-type compounds involves treatment of certain haloethyl esters of those acids with zinc metal and an alkanoic acid of 2 to 6 carbon atoms, preferably acetic acid. Those haloethyl esters are the esters wherein R 10 is ethyl substituted in the β-position with 3 chloro, 2 or 3 bromo, or one, 2, or 3 iodo. Of those haloethyl moieties, β,β,β-trichloroethyl is preferred. Zinc dust is preferred as the physical form of the zinc. Mixing the haloethyl ester with the zinc dust at about 25° C. for several hours usually causes substantially complete replacement of the haloethyl moiety of the formula XVI-XIX, XXXII, XXIV-XXVII, and XXXIV ester with hydrogen. The free acid is then isolated from the reaction mixture by procedures known to the art. This procedure is also applicable to the production of PGF- and PGB-type free acids.
Formula-XXXVII cyclic ketals and formula XLIV olefins wherein R 10 is haloethyl as above defined are necessary as intermediates for this route to the final PGE, PGF, PGA, and PGB type free acids. These formula-XXXVII and -XLIV haloethyl ester intermediates can be prepared by alkylation of cyclic ketal XXXVI (Chart D) or olefin XLIII (Chart E), respectively, with the appropriate formula LIII-to-LVI or LXVII-LXVIII alkylating agent wherein R 10 is haloethyl as above defined. However, preferred routes of the formula-XXXVII and -XLIV haloethyl ester intermediates are shown in Charts G and H.
In Charts G and H, G, J', R 2 , R 9 , R 26 , R 11 , R 12 , Z', and ˜ are as defined above. Haloethyl represents ethyl substituted in the β-position with 3 chloro, or 2 or 3 bromo, or 1, 2, or 3 iodo, preferably --CH 2 CCl 3 . R 15 represents alkyl of 1 to 4 carbon atoms, inclusive, preferably methyl or ethyl. ##SPC83## ##SPC84##
Compound LXXVI in Chart G is within the scope of compound XXXVII in Chart D. Compound LXXXII in Chart H is within the scope of compound XLIV in Chart E. These ketones LXXVI and LXXXII are reduced to corresponding hydroxy compounds LXXVII and LXXXIII, respectively, with a carbonyl reducing agent, e.g., sodium borohydride, as described above in discussion of Chart A. Then, hydroxy esters LXXVII and LXXXII are saponified by known procedures to hydroxy acids LXXVIII and LXXXIV, respectively. These two hydroxy acids are transformed to keto haloethyl esters LXXXI and LXXXVI, respectively, by oxidation of the hydroxy group to keto and esterification of the carboxyl group to --COO-haloethyl. As shown in Charts G and H, these two reactions are carried out in either order. However, it is preferred to oxidize first and then esterify.
Hydroxy acids LXXVIII and LXXXIV are oxidized to keto acids LXXX and LXXXVI, respectively, and hydroxy haloesters LXXIX and LXXXV are oxidized to keto haloesters LXXXI and LXXXVII, respectively, by reaction with an oxidizing agent which does not attack other parts of these molecules, especially the cyclic ketal group of compounds LXXVIII and LXXIX or ethylenic linkage of compounds LXXXIV and LXXXV. An especially useful reagent for this purpose is the Jones reagent, i.e., acidic chromic acid. Acetone is a suitable diluent for this purpose, and a slight excess of oxidant and temperatures at least as low as about 0° C., preferably about -10° to about -20° C. should be used. The oxidation proceeds rapidly and is usually complete in about 5 to about 30 minutes. Excess oxidant is destroyed, for example, by addition of a lower alkanol, advantageously isopropyl alcohol, and the aldehyde is isolated by conventional methods, for example, by extraction with a suitable solvent, e.g., diethyl ether. Other oxidizing agents can also be used. Examples are mixtures of chromium trioxide and pyridine or mixtures of dicyclohexylcarbodiimide and dimethyl sulfoxide. See, for example, J. Am. Chem. Soc. 87, 5661 (1965).
Haloethyl esters LXXIX, LXXXI, LXXXV, and LXXXVII are prepared by reacting agents LXXVIII, LXXX, LXXXIV, and LXXXVI respectively, with the appropriate haloethanol, e.g., β,β,β-trichloroethanol, in the presence of a carbodiimide, e.g., dicyclohexylcarbodiimide, and a base, e.g., pyridine, preferably in the presence of an inert liquid diluent, e.g., dichloromethane, for several hours at about 25° C.
As described above, the alkylations of cyclic ketal XXXVI to XXXVII (Chart D) and olefin XLIII and XLIV (Chart E) usually produce mixtures of alpha and beta alkylation products with respect to the ##EQU40## moieites. Also as described above, those two isomers lead to different final products, alpha leading to the PG-type series and beta leading to the 8-iso-PG-type series. If a compound in one or the other of those two series is preferred, there are two methods for favoring production of the preferred final product.
One of those methods involves isomerization of the final product of formulas XVI to XXXV. Either the alpha isomers of a formula XVI-to-XXXV compound, ester or free acid, or the corresponding beta isomer is maintained in an inert liquid diluent in the range 0° to 80° C. and in the presence of a base characterized by its water solution having a pH below about 10 until a substantial amount of the isomer has been isomerized to the other isomer, i.e., alpha to beta or beta to alpha. Preferred bases for this purpose are the alkali metal salts of carboxylic acids, especially alkanoic acids of 2 to 4 carbon atoms, e.g., sodium acetate. Examples of useful inert liquid diluents are alkanols of one to 4 carbon atoms, e.g., ethanol. This reaction at about 25° takes about one to about 20 days. Apparently an equilibrium is established. The mixtures of the two isomers, alpha and beta, are separated from the reaction mixture by known procedures, and then the two isomers are separated from each other by known procedures, for example, chromatography, recrystallization, or a combination of those. The less preferred isomer is then subjected to the same isomerization to produce more of the preferred isomer. In this manner by repeated isomerizations and separations, substantially all of the less preferred isomer of the formula XVI-to-XXXV compound is transformed to more preferred isomer.
The second method for favoring production of a preferred formula XVI-to-XXXV isomer involves any one of the keto intermediates of formulas XXXVII, XXXVIII, XLIV, XLV, LXX, or LXXI (Charts D, E, and F). Either the alpha form or the beta form of one of those intermediates is transformed to a mixture of both isomers by maintaining one or the other isomer, alpha or beta, in an inert liquid diluent in the presence of a base and in range 0°to 100° C, until a substantial amount of the starting isomer has been isomerized to the other isomer. Preferred bases for this isomerization are alkali metal amides, alkali metal alkoxides, alkali metal hydrides, and triarylmethyl alkali metals. Especially preferred are alkali metal tert-alkoxides of 4 to 8 carbon atoms, e.g., potassium tert-butoxide. This reaction at about 25° C. proceeds rapidly (1 minute to several hours). Apparently an equilibrium mixture of both isomers is formed, starting with either isomer. The isomer mixtures in the equilibrium mixture thus obtained are isolated by known procedures, and then the two isomers are separated from each other by known procedures, for example, chromatogaphy. The less preferred isomer is then subjected to the same isomerization to produce more of the preferred isomer. In this manner, by repeated isomerizations and separations, substantially all of the less preferred isomer of any of these intermediates in transformed to the more preferred isomer. Cyclic ketalketone intermediates of formula XXXVII are preferred over the other intermediates for this isomerization procedure.
The novel oxa-phenylene PGE, PGF, PGA and PGB type compounds of formula XVI to XXXV wherein R 2 is alkyl of 1 to 4 carbon atoms, inclusive, preferably methyl or ethyl, are preferred over the corresponding oxa-phenylene PGE, PGF, PGA, and PGB type compounds in which R 2 is hydrogen for the above-described pharmacological purposes.
These 15-alkyl prostaglandin analogs are suprisingly and unexpectedly more useful than the corresponding 15-hydrogen compounds for the reason that they are substantially more specific with regard to potency in causing prostaglandin-like biological responses, and have substantially longer duration of biological activity. For that reason, fewer and smaller doses of these 15-alkyl prostaglandin analogs are needed to attain the desired pharmacological results.
Although the above-mentioned 15-alkyl compounds are produced by the methods outlined above in Charts A-F, the preferred methods are set forth in Chart I and J as follows.
In Chart I is shown the transformation of 15-alkyl PGF-type acids and alkyl esters to the corresponding PGE-type acids and alkyl esters by oxidation. For this purpose, an oxidizing agent is used which selectively oxidizes secondary hydroxy groups to carbonyl groups in the presence of carbon-carbon double bonds. Formula LXXXVIII in Chart I includes optically active compounds as shown and racemic compounds of that formula and the mirror images thereof, and also the 15-epimers of both of those, i.e., wherein the configuration at C-15 is β rather than α as shown. Also in Chart I, E', G, J', R 1 , and R 26 are as defined above, and R 16 is alkyl of 1 to 4 carbon atoms.
For the transformations of Chart I, the β-hydroxy isomers of reactant LXXXVIII are preferred starting materials when the carboxyl side chain is alpha, although the corresponding α-hydroxy isomers are also useful for this purpose.
Oxidation reagents useful for the transformation set forth in Chart I are known to the art. An especially useful reagent for this purpose is the Jones reagent, i.e., acidified chromic acid. See J. Chem. Soc. 39 (1946). A slight excess beyond the amount necessary to oxidize one of the secondary hydroxy groups of the formula-LXXXVIII reactant is used. Acetone is a suitable diluent for this purpose. Reaction temperatures at least as low as about 0° C. should be used. ##SPC85## ##SPC86##
Preferred reaction temperatures are in the range -10° to -50° C. The oxidation proceeds rapidly and is usually complete in about 5 to 20 minutes. The excess oxidant is destroyed, for example by addition of a lower alkanol, advantageously, isopropyl alcohol, and the formula-LXXXIX PGE-type product is isolated by conventional methods.
Examples of other oxidation reagents useful for the Chart H transformations are silver carbonate on Celite (Chem. Commun. 1102 (1969)), mixtures of chromium trioxide and pyridine (Tetrahedron Letters 3363 (1968), J. Am. Chem. Soc. 75, 422 (1953), and Tetrahedron, 18, 1351 (1962)), mixtures of sulfur trioxide in pyridine and dimethyl sulfoxide (J. Am. Chem. Soc. 89, 5505 (1967)), and mixtures of dicyclohexylcarbodiimide and dimethyl sulfoxide (J. Am. Chem. Soc. 87, 5661 (1965)).
The novel 15-alkyl oxa-phenylene PGF.sub.α- and PGF.sub.β-type acids and esters of formulas XX-XXIII and XXXIII wherein R 2 is 1 to 4 carbon atoms, inclusive, are preferably prepared from the corresponding 15-hydrogen compounds by the sequence of transformations shown in Chart J, wherein formulas XC through XCIV, inclusive, include optically active and racemic natural- and epi-configuration compounds of those formulas and the mirror images thereof. Also in Chart J, R 16 is alkyl of 1 to 4 carbon atoms, inclusive, and E', G, Hal, J', R 1 , R 26 , and ˜ are as heretofore defined; G" in formula XCII is the same as G except that T is replaced by T", wherein T" is the same as T above except that, in R 6 , --Si(R 8 ) 3 replaces hydrogen. Also in Chart J, R 8 is alkyl of 1 to 4 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, or phenyl substituted with one or 2 fluoro, chloro, or alkyl of 1 to 4 carbon atoms inclusive, and R 17 is R 1 as defined above or silyl of the formula-Si--(R 8 ) 3 wherein R 8 is as defined above. The various R 8 's of a --Si(R 8 ) 3 moiety are alike or different. For example, a --Si(R 8 ) 3 can be trimethylsilyl, dimethylphenylsilyl, or methylphenylbenzylsilyl. Examples of alkyl of 1 to 4 carbon atoms, inclusive, are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, and tert-butyl. Examples of aralkyl of 7 to 12 carbon atoms, inclusive, are benzyl, phenethyl, α-phenylethyl, 3-phenylpropyl, α-naphthylmethyl, and 2-(β-naphthyl)ethyl. Examples of phenyl substituted with one or 2 fluoro, chloro, or alkyl of 1 to 4 carbon atoms, inclusive, are p-chlorophenyl, m-fluorophenyl, o-tolyl, 2,4-dichlorophenyl, p-tert-butylphenyl, 4-chloro-2-methyl-phenyl, and 2,4-dichloro-3 -methylphenyl.
In Chart J, the final PGF.sub.α and PGF.sub.β-type products are those encompassed by formulas XCIII and XCIV, respectively.
The initial optically active or racemic reactants of formula XC in Chart J i.e., the oxa-phenylene PGF 1 -, PGF 2 -, 5,6-dehydro-PGF 2 -, and dihydro-PGF 1 -type compounds in their α and β forms, and their esters, are prepared by methods described herein. Thus, racemic oxa-phenylene dihydro-PGF 1 .sub.α- and -PGF 1 .sub.β-type compounds, and their esters are prepared by catalytic hydrogenation of the corresponding racemic oxa-phenylene PGF 1 .sub.α or PGF 2 .sub.β, and PGF 1 .sub.β or PGF 2 .sub.βtype compounds, respectively, e.g. in the presence of 5% palladium-on-charcoal catalyst in ethyl acetate solution at 25° C. and 1 atmosphere pressure of hydrogen.
The heretofore-described acids and esters of formula XC are transformed to the corresponding intermediate 15-dehydro acids and esters of formula XCI, by oxidation with reagents such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, activated manganese dioxide, or nickel peroxide (see Fieser et al., "Reagents for Organic Syntheses," John Wiley & Sons, Inc., New York, N.Y. pp. 215, 637, and 731). Alternatively, and especially for the formula-XC reactants wherein E' is --CH 2 CH 2 and J' is L as defined above, these oxidations are carried out by oxygenation in the presence of the 15-hydroxyprostaglandin dehydrogenase of swing lung (see Arkiv for Kemi 25, 293 (1966)). These reagents are used according to procedures known in the art. See, for example, J. Biol. Chem. 239, 4097 (1964).
Referring again to Chart J, intermediate compounds of formula XCI are transformed to silyl derivatives formula XCII by procedures known in the art. See, for example, Pierce, "Silylation of Organic Compounds," Pierce Chemical Co., Rockford, Ill. (1968). Both hydroxy groups of the formula-XCI reactants are thereby transformed to --O--Si(R 8 ) 3 moieties wherein R 8 is as defined above, and sufficient of the silylating agent is used for that purpose according to known procedures. When R 1 in the formula-XCI intermediate is hydrogen, the --COOH moiety thereby defined is simultaneously transformed to --COO--Si(R 8 ) 3 , additional silylating agent being used for this purpose. This latter transformation is aided by excess silylating agent and prolonged treatment. Likewise, when R 6 in T of the formula-XCI intermediate is hydrogen, the phenolic hydroxyl thereby defined is simultaneously transformed to --O--Si(R 8 ) 3 in the silylation step. G" in formula XCII, as defined above, therefore is the same as G except that T is replaced by T", wherein T" is the same as T above except that, in R 6 , --Si(R 8 ) 3 replaces hydrogen. When R 1 in formula XCI is alkyl, then R 17 in formula XCII will also be alkyl. The necessary silylating agents for these transformations are known in the art or are prepared by methods known in the art. See, for example, Post, "Silicones and Other Organic Silicon Compounds," Reinhold Publishing Corp., New York, N.Y. (1949).
Referring again to Chart J the intermediate silyl compounds of formula XCII are transformed to the final compounds of formulas XCIII and XCIV by first reacting the silyl compound with a Grignard reagent of the formula R 16 MgHal wherein R 16 is as defined above, and Hal is chloro, bromo, or iodo. For this purpose, it is preferred that Hal be bromo. This reaction is carried out by the usual procedure for Grignard reactions, using diethyl ether as a reaction solvent and saturated aqueous ammonium chloride solution to hydrolyze the Grignard complex. The resulting disilyl trisily, or tetrasilyl tertiary alcohol is then hydrolyzed with water to remove the silyl groups. For this purpose, it is advantageous to use a mixture of water and sufficient of a water-miscible solvent, e.g., ethanol to give a homogeneous reaction mixture. The hydrolysis is usually complete in 2 to 6 hours at 25° C., and is preferably carried out in an atmosphere of an inert gas, e.g., nitrogen or argon.
The mixture of 15-α and 15-β isomers obtained by this Grignard reaction and hydrolysis is separated by procedures known in the art for separating mixtures of prostanoic acid derivatives, for examle, by chromatography on neutral silica gel. In some instances, the lower alkyl esters, especially the methyl esters of a pair of 15-α and 15-β isomers are more readily separated by silica gel chromatography than are the corresponding acids. In those cases, it is advantageous to esterify the mixture of acids as described below, separate the two esters, and then, if desired, saponify the esters by procedures known in the art for saponification of prostaglandins F.
Although fromula-XCIII and -XCIV compounds wherein E' is --CH 2 CHR 9 --and J' is L' as defined above may be produced according to the processes of Chart J, it is preferred to produce those novel dihydro-PGF 1 analogs by hydrogenation of one of the corresponding unsaturated compounds, i.e., a compound of formula XCIII or XCIV wherein E is trans --CH=CR 9 --and J' is either L', --CH=CH--M'--, --C.tbd.C--M'-, M' being defined above. This hydrogenation is advantageously carried out catalytically, for example, in the presence of a 5% palladium-on-charcoal catalyst in ethyl acetate solution at 25° C. and one atmosphere pressure of hydrogen.
The novel 15-alkyl oxa-phenylene PGA-type and PGB-type acids and esters of formula XXIV-XXXI and XXXIV-XXXV are prepared from the 15-alkyl oxa-phenylene PGE compounds, heretofore described, by dehydrations and double bond migrations previously described, as shown in Chart A. Likewise the 15-alkyl PGB-type compounds are prepared by contacting the 15-alkyl PGA-type compounds with base. For the transformation of the 15-alkyl PGE-type compounds to the 15-alkyl PGA-type compounds of this invention (Chart K), it is preferred that a dehydrating agent be used which removes ##SPC87## the hydroxy group from the alicyclic ring in the presence of a hydroxy group on a tertiary carbon atom. In Chart K, E', G, J', R 1 , R 2 , R 26 , and ˜ are as defined above. Formula XCV as shown includes optically active compounds and racemic compounds of that formula and the mirror images thereof, and also the 15-epimers of both of those. Any of the known substantially neutral dehydrating agents is used for these reactions. See Fieser et al., cited above. Preferred dehydrating agents are mixtures of at least an equivalent amount of a carbodiimide and a catalytic amount of a copper (II) salt. Especially preferred are mixtures of at least an equivalent amount of dicyclohexyl carbodiimide and a catalytic amount of copper (II) chloride. An equivalent amount of a carbodiimide means one mole of the carbodiimide for each mole of the formula-XCV reactant. To ensure completeness of the reaction, it is advantageous to use an excess of carbodiimide, i.e., 1.5 to 5 or even more equivalents of the carbodiimide.
The dehydration is advantageously carried out in the presence of an inert organic diluent which gives a homogeneous reaction mixture with respect to the formula-XCV reactant and the carbodiimide. Diethyl ether is a suitable diluent. It is advantageous to carry out the dehydration in an atmosphere of an inert gas, e.g., nitrogen, helium, or argon. The time required for the dehydration will depend in part on the reaction temperature. With the reaction temperature in the range 20° to 30°C., the dehydration usually takes place in about 40 to 60 hours.
The formula-XCVI product is isolated by methods known in the art, e.g., filtration of the reaction mixture and evaporation of the filtrate. The product is then purified by methods known in the art, advantageously by chromatography on silica gel.
The final formula XVI-to-XXXV compounds prepared by the processes of this invention, in free acid form, are transformed to pharmacologically acceptable salts by neutralization with appropriate amounts of the corresponding inorganic or organic base, examples of which correspond to the cations and amines listed above. These transformations are carried out by a variety of procedures known in the art to be generally useful for the preparation of inorganic, i.e., metal or ammonium, salts, amine acid addition salts, and quaternary ammonium salts. The choice of procedure depends in part upon the solubility characteristics of the particular salt to be prepared. In the case of the inorganic salts, it is usually suitable to dissolve the formula XVI-to-XXXV acid in water containing the stoichiometric amount of a hydroxide, carbonate, or bicarbonate corresponding to the inorganic salt desired. For example, such use of sodium hydroxide, sodium carbonate, or sodium bicarbonate gives a solution of the sodium salt. Evaporation of the water or addition of a water-miscible solvent of moderate polarity, for example, a lower alkanol or a lower alkanone, gives the solid inorganic salt if that form is desired.
To produce an amine salt, the formula XVI-to-XXXV acid is dissolved in a suitable solvent of either moderate or low polarity. Examples of the former are ethanol, acetone, and ethyl acetate. Examples of the latter are diethyl ether and benzene. At least a stoichiometric amount of the amine corresponding to the desired cation is then added to that solution. If the resulting salt does not precipitate, it is usually obtained in solid form by addition of a miscible diluent of low polarity or by evaporation. If the amine is relatively volatile, any excess can easily be removed by evaporation. It is preferred to use stoichiometric amounts of the less volatile amines.
Salts wherein the cation is quaternary ammonium are produced by mixing the formula XVI-to-XXXV acid with the stoichiometric amount of the corresponding quaternary ammonium hydroxide in water solution, followed by evaporation of the water.
The final formula XVI-to-XXXV acids or esters prepared by the processes of this invention are transformed to lower alkanoates by interaction of the formula XVI-to-XXXV hydroxy compound with a carboxyacylating agent, preferably the anhydride of a lower alkanoic acid, i.e., an alkanoic acid of one to 8 carbon atoms, inclusive. For example, use of acetic anhydride gives the corresponding diacetate. Similar use of propionic anhydride, isobutyric anhydride, and hexanoic acid anhydride gives the corresponding carboxyacylates.
The carboxyacylation is advantageously carried out by mixing the hydroxy compound and the acid anhydride, preferably in the presence of a tertiary amine such as pyridine or triethylamine. A substantial excess of the anhydride is used, preferably about 10 to about 10,000 moles of anhydride per mole of the hydroxy compound reactant. The excess anhydride serves as a reaction diluent and solvent. An invert inorganic diluent, for example, dioxane, can also be added. It is preferred to use enough of the tertiary amine to neutralize the carboxylic acid produced by the reaction, as well as any free carboxyl groups present in the hydroxy compound reactant.
The carboxyacylation reaction is preferably carried out in the range about 0° to about 100° C. The necessary reaction time will depend on such factors as the reaction temperature, and the nature of the anhydride and tertiary amine reactants. With acetic anhydride, pyridine, and a 25° C. reaction temperature, a 12 to 24-hour reaction time is used.
The carboxyacylated product is isolated from the reaction mixture by conventional methods. For example, the excess anhydride is decomposed with water, and the resulting mixture acidified and then extracted with a solvent such as diethyl ether. The desired carboxyacylate is recovered from the diethyl ether extract by evaporation. The carboxyacylate is then purified by conventional methods, advantageously by chromatography.
By this procedure, the formula XVI-XIX and XXXII PGE-type compounds are transformed to dialkanoates, the formula XX-XXIII and XXXIII PGF-type compounds are transformed to trialkanoates, and the formula XXIV-XXXI and XXXIV-XXXV PGA-type and PGB-type compounds are transformed to monoalkanoates.
When a PGE-type dialkanoate is transformed to a PGF-type compound by carbonyl reduction as shown in Chart A, a PGF-type dialkanoate is formed and is used for the above-described purposes as such or is transformed to a trialkanoate by the above-described procedure. In the latter case, the third alkanoyloxy group can be the same as or different from the two alkanoyloxy groups present before the carbonyl reduction.
Molecules of each of the compounds encompassed by formulas XVI to XXXV and, except for XLIII and L, of each intermediate formula each have at least one center of asymmetry, and each can exist in racemic form and in either enantiomeric form, i.e., d and l. A formula accurately defining the d form would be the mirror image of the formula which defined the l form. Both formulas are necessary to define accurately the corresponding racemic form. The various formulas XVI-to-XXXV as drawn each represents the optically active form with the same configuration as the naturally-occurring prostaglandins.
When an optically active (d or l ) final compound is desired, that is made by resolution of the racemic compound or by resolution of one of the asymmetric racemic intermediates. These resolutions are carried out by procedures known in the art. For example, when final compound XVI to XXXV is a free acid, the dl form thereof is resolved into the d and l forms by reacting said free acid by known general procedures with an optically active base, e.g., brucine or strychnine, to give a mixture of two diastereoisomers which are separated by known general procedures, e.g., fractional crystallization, to give the separate diastereisomeric salts. The optically active acid of formula XVI to XXXV is then obtained by treatment of the salt with an acid by known general procedures. Alternatively, the free acid form of cyclic ketal XXXVII, olefins XLIV or LXX, or glycols XXXVIII, XLV, or LXXI is resolved into separate d and l forms and then esterified and transformed further to the corresponding optically active form of the final product XVI to XXXV as described above.
In another method, bicyclo ketone reactants XXXVIII, XLV, or LXXI in exo or endo form, are transformed to ketals with an optically active 1,2-glycol, e.g., D-(--)-2,3-butanediol, by reaction of said 1,2-glycol with the formula-XXXVIII, XLV, or LXXI compound in the presence of a strong acid, e.g., p-toluenesulfonic acid. The resulting ketal is a mixture of diastereoisomers which is separated into the d and l diastereoisomers, each of which is then hydrolyzed with an acid, e.g., oxalic acid, to the original keto compound, now in optically active form. These reactions involving optically active glycols and ketals for resolution purposes are generally known in the art. See, for example, Chem. Ind. 1664 (1961) and J. Am. Chem. Soc. 84, 2938 (1962). Dithiols may be used instead of glycols.
Still another procedure for obtaining optically active oxa-phenylene PGF-type compounds is by stereoselective microbiological reduction of the racemic oxa-phenylene PGE compounds. For this purpose actively fermenting baker's yeast is employed. The PGE compound is contacted with a yeast-sugar-water mixture at about 25° C. for 24-48 hours. There is produced by reduction a mixture of the PGF.sub.α compound and the enantiomeric PGF.sub.β compound, which are separable by silica gel chromatography for example. Accompanying this transformation, carboxylic ester groups are removed by hydrolysis. Accordingly, from dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 methyl ester, there are obtained natural configuration 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α and enantiomeric 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.β.
An alternate method of synthesis is provided hereinafter for a group of oxa-phenylene analogs within the scope of formulas XVI and XX above, represented by the following formulas XCVII-CIV: ##SPC88## ##SPC89## ##SPC90##
and the racemic mixtures of those compounds and their respective enantiomers represented by the mirror images of the above formulas. The terms C p H 2p , C t H 2t , R 1 , R 2 , T, and s are as defined above; R 30 is alkyl of 2 to 10 carbon atoms, inclusive, substituted with zero, one, 2, or 3 fluoro.
The alternate method of synthesis disclosed hereinafter is also useful for preparing oxa-phenylene 17,18-didehydro prostaglandin analogs within the scope of formulas CV-CVIII: ##SPC91## ##SPC92##
wherein C n H 2n , C p H 2p , R 1 , R 2 and R 5 are as defined and used above.
These 17,18-didehydro analogs of formulas CV-CVIII together with compounds of formulas XXXII and XXXIII above are within the scope of 17,18-didehydro PGE- and PGF-type compounds represented by the formulas: ##SPC93##
and ##SPC94##
wherein ˜ indicates attachment of the hydroxyl or the side chain to the cyclopentane ring in alpha or beta configuration; wherein V is (1) C g H 2g or (2) --CH=CH-- C j H 2j --, wherein C g H 2g represents a valence bond or alkylene of one to 4 carbon atoms, inclusive, with one or 2 chain carbon atoms between --CH 2 -- and the phenylene ring, and wherein C j H 2j represents a valence bond or alkylene of one or 2 carbon atoms with one chain carbon atom between --CH=CH-- and the phenylene ring; wherein C n H 2n is alkylene of one to 4 carbon atoms, inclusive; wherein C p H 2p represents a valence bond or alkylene of one to 4 carbon atoms, inclusive, with one or 2 chain carbon atoms between the ring and --O--; wherein C g H 2g and C p H 2p together represent zero to 8 carbon atoms, inclusive, with total chain lengths zero to 3 carbon atoms, inclusive; wherein Q is ##EQU41## wherein R 2 is hydrogen or alkyl of one to 4 carbon atoms, inclusive; wherein R 1 is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, 2, or 3 chloro or alkyl of one to 4 carbon atoms, inclusive; and wherein R 5 is alkyl of one to 4 carbon atoms, inclusive, substituted with zero, one, 2, or 3 fluoro.
The corresponding 17,18-didehydro PGA- and PGB-type compounds are available by methods disclosed herein or known in the art, for example by acid or base dehydration of the formula-CXXXVII PGE-type compounds.
The alternate method of synthesis utilizes oxetane intermediates having the grouping ##SPC95##
prepared from bicyclo hexene starting materials.
Reference to Chart L will make clear the steps by which starting material CIX is transformed to product CXVIII. The formula-CIX compound wherein R 31 and R 32 together are --CH 2 --C(CH 3 ) 2 --CH 2 -- and ˜ is endo, i.e. bicyclo[3.1.0]hex-2-ene-6-endo-carboxaldehyde neopentyl glycol acetal, is available either in racemic or optically active form. See U.S. Pat. No. 3,711,515.
In Chart L the symbols used therein have the same meanings as defined above, as to C p H 2p , G, Q, R 1 , R 2 , R 31 , R 32 , R 39 , R 42 , and ˜. R 43 represents hydrogen, carboxyacyl R 39 , benzoyl, substituted benzoyl, mono-esterified phthaloyl, and substituted naphthoyl. Furthermore, in Chart L and likewise in the other charts of this specification, the formulas as drawn represent specific optical isomers following the conventions applied herein to the end products. However, for purposes of convenience and brevity it is intended that such representations of the process steps for the optically active intermediates are applicable to those same process steps as used for the corresponding racemic intermediates.
Both the endo and exo forms of bicyclo hexene CIX are available or are made by methods known in the art, in either their racemic or optically active forms. See. U.S. Pat. ##SPC96## ##SPC97## No. 3,711,515. Either the endo or exo starting material will yield the ultimate analogs of formula CXVIII by the processes of Chart L.
In step (a) oretane CX is obtained by reaction of the formula-CIX bicyclo hexene with an aldehyde of the formula ##SPC98##
wherein C p H 2p represents a valence bond or alkylene of one to 4 carbon atoms, inclusive, with one or 2 carbon atoms in the chain between the phenylene ring and --O--, and wherein R 39 is carboxyacyl of the formula ##EQU42## wherein R 40 is hydrogen, alkyl of one to 19 carbon atoms, inclusive, or aralkyl of 7 to 12 carbon atoms, inclusive, wherein alkyl or aralkyl are substituted with zero to 3 halo atoms.
The formula-CXIX aldehydes are available or readily prepared by methods known in the art. Examples of such compounds within the scope of formula CXIX are: ##SPC99## ##SPC100##
The formation of oxetane CX is accomplished by photolysis of a mixture of the bicyclo hexene and the aldehyde in a solvent. The bicyclo hexene is preferably used in excess over the molar equivalent, for example 2 to 4 times the theoretical equivalent amount. The solvent is a photochemically inert organic liquid, for example liquid hydrocarbons, including benzene or hexane, 1,4-dioxane, and diethyl ether. The reaction is conveniently done at ambient conditions, for example 25° C., but may be done over a wide range of temperature, from about -78° C. to the boiling point of the solvent. The irradiation is done with mercury vapor lamps of the low or medium pressure type, for example those peaking at 3,500 A. Such sources are available from The Southern New England Ultraviolet Co., Middletown, Conn. Alternatively, those lamps which emit a broad spectrum of wavelengths and which may be filtered to transmit only light of λ˜3000-3700 A may also be used. For a review of photolysis see D. R. Arnold in "Advances in Photochemistry," Vol. 6, W. A. Noyes et al., Wiley-Interescience, New York, 1968, pp. 301-423.
In step (b) the cleavage of the oxetane ring to yield the formula-CXI compounds is accomplished with an alkali metal in the presence of a primary amine or alcohol. Preferred is lithium in ethylamine, or sodium in ethyl alcohol. See L. J. Altman et al., Synthesis 129 (1974). The cleavage transformation may also be accomplished by catalytic hydrogenation over an inert metal catalyst, e.g. Pd on carbon, in ethyl acetate or ethanol.
In step (c) the formula CXI diol is prepared for step (d) by preferably blocking the two hydroxyl groups with carboxyacyl groups within the scope of R 39 , i.e. ##EQU43## as defined above. For example, the diol is treated with an acid anhydride such as acetic anhydride, or with an acyl halide in a tertiary amine. Expecially preferred is pivaloyl chloride in pyridine.
Other carboxyacylating agents useful for this transformation are known in the art or readily obtainable by methods known in the art, and include carboxyacyl halides, preferably chlorides, bromides, or fluorides, i.e. R 40 C(O)Cl, R 40 C(O)Br, or R 40 C(O)F, and carboxyacid anhydrides, (R 40 C-) 2 O, wherein R 40 is as defined above. The preferred reagent is an acid anhydride. Examples of acid anhydrides useful for this purpose are acetic anhydride, propionic anhydride, butyric anhydride, pentanoic anhydride, nonanoic anhydride, trideconoic anhydride, steric anhydride, (mono, di, or tri) chloroacetic anhydride, 3-chlorovaleric anhydride, 3-(2-bromoethyl)-4,8-dimethylnonanoic anhydride, cyclopropaneacetic anhydride, 3-cycloheptanepropionic anhydride, 13-cyclopentanetridecanoic anhydride, phenylacetic anhydride, (2 or 3)-phenylpropionic anhydride, 13-phenyltridecanoic anhydride, phenoxyacetic anhydride, benzoic anhydride, (o, m, or p)-bromobenzoic anhydride, 2,4 (or 3,4)-dichlorobenzoic anhydride, p-trifluoromethylbenzoic anhydride, 2-chloro-3-nitrobenzoic anhydride, (o, m, or p)-nitrobenzoic anhydride, (o, m, or p)-toluic anhydride, 4-methyl-3-nitrobenzoic anhydride, 4-octylbenzoic anhydride, (2,3, or 4)-biphenylcarboxylic anhydride, 3-chloro-4-biphenylcarboxylic anhydride, 5-isopropyl-6-nitro-3-biphenylcarboxylic anhydride, and (1 or 2)-naphthoic anhydride. The choice of anhydride depends upon the identity of R 40 in the final acylated product, for example when R 40 is to be methyl, acetic anhydride is used; when R 40 is to be 2-chlorobutyl, 3-chlorovaleric anhydride is used.
When R 40 is hydrogen, ##EQU44## is formyl. Formylation is carried out by procedures known in the art, for example, by reaction of the hydroxy compound with the mixed anhydride of acetic and formic acids or with formylimidazole. See, for example, Fieser et al., Reagents for Organic Synthesis, John Wiley and Sons, Inc., pp. 4 and 407 (1967) and references cited therein. Alternatively, the formula CXI diol is reacted with two equivalents of sodium hydride and then with excess ethyl formate.
In formula CXII, R 43 may also represent a blocking group including benzoyl, substituted benzoyl, monoesterified phthaloyl and substituted naphthoyl. For introducing those blocking groups, methods known in the ary are used. Thus, an aromatic acid of the formula R 39 OH, wherein R 39 is as defined above, for example benzoic acid, is reacted with the formula-CXI compound in the presence of a dehydrating agent, e.g. sulfuric acid, zinc chloride, or phosphoryl chloride; or an anhydride of the aromatic acid of the formula (R 39 ) 2 O, for example benzoic anhydride, is used.
Preferably, however, an acyl halide, e.g. R 39 Cl, for example benzoyl chloride, is reacted with the formula-CXI compound in the presence of a tertiary amine such as pyridine, triethylamine, and the like. The reaction is carried out under a variety of conditions using procedures generally known in the art. Generally, mild conditions are employed, e.g. 20°-60° C., contacting the reactants in a liquid medium, e.g. excess pyridine or an inert solvent such as benzene, toluene or chloroform. The acylating agent is used either in stoichiometric amount or in excess.
As examples of reagents providing R 39 for the purposes of this invention, the following are available as acids (R 39 OH), anhydrides ((R 39 ) 2 O), or acyl chlorides (R 39 Cl): benzoyl; substituted benzoyl, e.g. (2-, 3-, or 4-)methylbenzoyl, (2-, 3-, or 4-)ethylbenzoyl, (2-, 3-, or 4-)isopropylbenzoyl, (2-, 3-, or 4-)tert-butylbenzoyl, 2,4-dimethylbenzoyl, 3,5-dimethylbenzoyl, 2-isopropyltoluyl, 2,4,6-trimethylbenzoyl, pentamethylbenzoyl, α-phenyl-(2-, 3-, or 4-(toluyl, 2-, 3-, or 4-phenethylbenzoyl, 2-, 3-, or 4-nitrobenzoyl, (2,4-, 2,5-, or 3,5-)dinitrobenzoyl, 4,5-dimethyl-2-nitrobenzoyl, 2-nitro-6-phenethylbenzoyl, 3-nitro-2-phenethylbenzoyl; mono-esterified phthaloyl, e.g. ##SPC101##
isophthaloyl, e.g. ##SPC102##
or terephthaloyl, e.g. ##SPC103##
(1- or 2-)naphthoyl; and substituted naphthoyl, e.g. (2-, 3-, 4-, 5-, 6-, or 7-)-methyl-1-naphthoyl, (2- or 4-)ethyl-1-naphthoyl, 2-isopropyl-1-naphthoyl, 4,5-dimethyl-1-naphthoyl, 6-isopropyl-4-methyl-1-naphthoyl, 8-benzyl-1-naphthoyl, 8-benzyl-1-naphthoyl, (3-, 4-, 5-, or 8-)-nitro-1-naphthoyl, 4,5-dinitro-1-naphthoyl, (3-, 4-, 6-, 7- or -)-methyl-8)-methyl-1-naphthoyl, 4-ethyl-2-naphthoyl, and (5- or 8-)-nitro-2-naphthoyl. There may be employed, therefore, benzoyl chloride, 4-nitrobenzoyl chloride, 3,5-dinitrobenzoyl chloride, and the like, i.e. R 39 Cl compounds corresonding to the above R 39 groups. If the acyl chloride is not available, it is made from the corresponding acid and phosphorus pentachloride as is known in the art.
In step (d), the formula -CXII acetal is converted to aldehyde CXIII by acid hydrolysis, known in the art, using dilute mineral acids, acetic or formic acids, and the like. Solvents such as acetone, dioxane, and tetrahydrofuran are used.
For steps (e) through (h) it is optional whether R 42 be hydrogen or a "blocking group" as defined below. For efficient utilization of the Wittig reagent it is preferred that R 42 be a blocking group. If the formula-CXII compound is used wherein R 43 is hydrogen, the formula-CXIII intermediate will have hydrogen at R 42 . If R 42 is to be a blocking group, that may be readily provided prior to step (e) by reaction with suitable reagents as discussed below.
The blocking group, R 41 , is any group which replaces hydrogen of the hydroxyl groups, which is not attacked by nor is reactive to the reagents used in the respective transformations to the extent that the hydroxyl group is, and which is subsequently replaceable by hydrogen at a later stage in the preparation of the prostaglandin-like products.
Several blocking groups are known in the art, e.g. tetrahydropyranyl, acetyl, and p-phenylbenzoyl (see Corey et al., J. Am. Chem. Soc. 93, 1491 (1971)).
Those which have been found useful include (a) carboxyacyl within the scope of R 39 above, i.e. acetyl, and also benzoyl, naphthoyl, and the like; (b) tetrahydropyranyl; (c) tetrahydrofuranyl; (d) a group of the formula ##EQU45## wherein R 48 is alkyl of 1 to 18 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, or phenyl substituted with 1, 2, or 3 alkyl of 1 to 4 carbon atoms, inclusive, wherein R 49 and R 50 are the same or different, being hydrogen, alkyl of 1 to 4 carbon atoms, inclusive, phenyl or phenyl substituted with 1, 2, or 3 alkyl of 1 to 4 carbon atoms, inclusive, or, when R 49 and R 30 are taken together, --(CH 2 ) u -- or --(CH 2 ) v --O--(CH 2 ) w -- wherein u is 3, 4, or 5, v is 1, 2, or 3, and w is 1, 2, or 3 with the proviso that v plus w is 2, 3, or 4, and wherein R 51 is hydrogen or phenyl; or (e) --Si(A) 3 wherein A is alkyl of 1 to 4 carbon atoms, inclusive, phenyl, phenyl substituted with 1 or 2 fluoro, chloro, or alkyl of 1 to 4 carbon atoms, inclusive, or aralkyl of 7 to 12 carbon atoms, inclusive.
In replacing the hydrogen atoms of the hydroxyl groups with a carboxyacyl blocking group, methods known in the art are used. The reagents and conditions are discussed above for R 43 on compound CXII.
When the blocking group is tetrahydropyranyl or tetrahydrofuranyl, the appropriate reagent, e.g. 2,3-dihydropyran or 2,3-dihydrofuran, is used in an inert solvent such as dichloromethane, in the presence of an acid condensing agent such as p-toluenesulfonic acid or pyridine hydrochloride. The reagent is used in slight excess, preferably 1.0 to 1.2 times theory. The reaction is carried out at about 20°-50° C.
When the blocking group is of the formula ##EQU46## as defined above, the appropriate reagent is a vinyl ether, e.g. isobutyl vinyl ether or any vinyl ether of the formula R 48 --O--C(R 49 )=CR 50 R 51 wherein R 48 , R 49 , R 50 , and R 51 are as defined above; or an unsaturated cyclic or heterocyclic compound, e.g. 1-cyclohex-1-yl-methyl ether ##SPC104##
or 5,6-dihydro-4-methoxy-2H-pyran ##SPC105##
See C. B. Reese et al., J. Am. Chem. Soc. 89, 3366 (1967). The reaction conditions for such vinyl ethers and unsaturates are similar to those for dihydropyran above.
When the blocking group is silyl of the formula --Si(A) 3 , the formula-CXIII compound is transformed to a silyl derivative of formula CXIII by procedures known in the art. See, for example, Pierce, "Silylation of Organic Compounds," Pierce Chemical Co., Rockford, Ill. (1968). The necessary silylating agents for these transformations are known in the art or are prepared by methods known in the art. See, for example, Post "Silicones and Other Organic Silicon Compounds," Reinhold Publishing Corp., New York, N.Y. (1949). These reagents are used in the presence of a tertiary base such as pyridine at temperatures in the range of about 0° to +50° C. Examples of trisubstituted mono-chlorosilanes suitable for this purpose include chlorotrimethylsilane, chlorotriisobutylsilane, chlorotriphenylsilane, chlorotris(p-chlorophenyl)silane, chlorotri-m-tolylsilane, and tribenzylchlorosilane. Alternately, a chlorosilane is used with a corresponding disilazane. Examples of other silylating agents suitable for forming the formula-CXIII intermediates include pentamethylsilylamine, pentaethylsilylamine, N-trimethylsilydiethylamine, 1,1,1-triethyl-N,N-dimethylsilylamine, N,N-diisopropyl-1,1,1,-trimethylsilylamine, 1,1,1-tributyl-N,N-dimethylsilylamine N,N-dibutyl-1,1,1-trimethylsilylamine, 1-isobutyl-N,N,1,1-tetramethylsilylamine, N-benzyl-N-ethyl-1,1,1-trimethylsilylamine, N,N,1,1-tetramethyl-1-phenylsilylamine, N,N-diethyl-1,1-dimethyl-1-phenylsilylamine, N,N-diethyl-1-methyl-1,1-diphenylsilylamine, N,N-dibutyl-1,1,1-triphenylsilylamine, and 1-methyl-N,N,1,1-tetraphenylsilylamine.
In step (e) the aldehyde group is transformed by the Wittig reaction to a moiety of the formula --CH=CR 2 G. For this purpose a phosphonium salt prepared from an organic chloride or bromide of the formula ##EQU47## is employed, wherein G and R 2 are as defined above. These organic chlorides or bromides are known in the art or are readily prepared by methods known in the art. See for example the above-identified German Offenlegungsschrift No. 2,209,990. As to the Wittig reaction, see, for example, U.S. Pat. No. 3,776,941 and references cited therein.
In step (f) compound CXV is obtained by deblocking if necessary. When C p H 2p is a valence bond, and R 42 is a hindered carboxyacyl, e.g. ##EQU48## R 41 on the phenolic hydroxy is selectively replaced with hydrogen by hydrolysis with sodium or potassium hydroxide in ethanol-water. Instead of ethanol, other water-miscible solvents may be substituted, for example 1,4-dioxane, tetrahydrofuran, or 1,2-dimethoxyethane. The selective hydrolysis is preferably carried out at -15° to 25° C. Higher temperatures may be used but with some decrease in selectivity.
Total hydrolysis of R 42 blocking groups on compound CXIV is accomplished, when R 42 is carboxyacyl, with an alkali alkoxide in an alcoholic solvent, preferably sodium methoxide in methanol at a temperature from 25° C. to reflux. When R 42 is tetrahydropyranyl, aqueous acid, e.g. dilute acetic acid, is used at 25° to 50° C. When R 42 is trialkylsilyl, either aqueous acid or base are used at 25° to 50° C.
Continuing with Chart L, in step (g) a Williamson synthesis is employed to obtain compound CXVI. The formula-CXV alcohol or phenol is condensed with a haloacetate within the scope of Hal--CH 2 --COOR 1 wherein Hal is chloro, bromo, or iodo and R 1 is as defined above. Normally the reaction is done in the presence of a base such as n-butyllithium, phenyllithium, triphenylmethyllithium, sodium hydride, potassium t-butoxide, sodium hydroxide, or potassium hydroxide.
The transformation from compound CXVI to product CXVIII may be accomplished by any of several routes known in the art. See U.S. Pat. No. 3,711,515. Thus, by step (h), the alkenene CXVI is hydroxylated to glycol CXVII. For this purposes osmium tetroxide is a suitable reagent, for example in conjunction with N-methylmorpholine oxide-hydrogen peroxide complex (see Fieser et al., "Reagents for Organic Synthesis," p. 690, John Wiley and Sons, Inc., New York (1967)). Thereafter, several methods are available for obtaining the formula-CXVIII product. In one method the glycol is converted to a bis(alkanesulfonic acid) ester and subsequently hydrolyzed to CXVIII by methods known in the art (see, for example German Offenlegungsschrift No. 1,937,676, Derwent Farmdoc No. 6862R). Another method is by way of a diformate by formolysis of the glycol (see U.S. Pat. No. 3,711,515).
Still another method is by way of a cyclic ortho ester. For this purpose, glycol CXVII is reacted with an ortho ester of the formula ##EQU49## wherein R 46 is hydrogen, alkyl of 1 to 19 carbon atoms, inclusive, or aralkyl of 7 to 12 carbon atoms, inclusive, substituted with zero to 3 halo atoms; and R 47 is methyl or ethyl. There is then formed a cyclic ortho ester of the formula ##SPC106##
wherein C p H 2p , G, R 1 , R 2 R 42 , R 46 , R 47 , and ˜ are as defined above. The reaction goes smoothly in a temperature range of -50° C. to +100° C., although for convenience 0° C. to +50° C. is generally preferred. From 1.5 to 10 molar equivalents of the ortho ester are employed, together with an acid catalyst. The amount of the catalyst is usually a small fraction of the weight of the glycol, say 1%, and typical catalysts include pyridine hydrochloride, formic acid, hydrogen chloride, p-toluenesulfonic acid, trichloroacetic acid, or trifluoroacetic acid. The reaction is preferably run in a solvent, for example benzene, dichloromethane, ethyl acetate, or diethyl ether. It is generally completed within a few minutes and is conveniently followed by TLC (thin layer chromatography on basic silica gel plates).
The ortho ester reagents are known in the art or readily available by methods known in the art. See for example S. M. McElvain et al., J. Am. Chem. Soc. 64, 1925 (1942), starting with an appropriate nitrile. Examples of useful ortho esters include:
trimethyl orthoformate,
triethyl orthoacetate,
triethyl orthopropionate,
trimethyl orthobutyrate,
triethyl orthovalerate,
trimethyl orthooctanoate,
trimethyl orthophenylacetate, and
trimethyl ortho (2,4-dichlorophenyl)acetate.
Preferred are those ortho esters wherein R 46 is alkyl of 1 to 7 carbon atoms; especially preferred are those wherein R 46 is alkyl of 1 to 4.
Next, the cyclic orthoester CXX is reacted with anhydrous formic acid to yield a diol diester of the formula ##SPC107##
wherein C p H 2p , G, R 1 R 2 , R 42 , R 46 , and ˜ are as defined above.
By "anhydrous formic acid" is meant that it contains not more than 0.5% water. The reaction is run with an excess of formic acid, which may itself serve as the solvent for the reaction. Solvents may be present, for example dichloromethane, benzene, or diethyl ether, usually not over 20% by volume of the formic acid. There may also be present organic acid anhydrides, for example acetic anhydride, or alkyl orthoesters, for example trimethyl orthoformate, which are useful as drying agents for the formic acid. Although the reaction proceeds over a wide range of temperatures, it is conveniently run at about 20°-30° C. and is usually completed within about 10 minutes.
Finally, the diol diester CXXI is converted to product CXVIII by methods known in the art, for example by hydrolysis in the presence of a base in an alcoholic medium. Examples of the base are sodium or potassium carbonate or sodium or potassium alkoxides including methoxides or ethoxides. The reaction is convenienty run in an excess of the solvolysis reagent, for example methanol or ethanol. The temperature range is from -50° C. to 100° C. The time for completion of the reaction varies with the nature of R 46 and the base, proceeding in the case of alkali carbonates in a few minutes when R 46 is hydrogen but taking up to several hours when R 46 is ethyl, for example.
When the solvolysis proceeds too long or when conditions are too severe, ester groups at R 1 may be removed. They are, however, readily replaced by methods known in the art. For example, the alkyl, cycloalkyl, and aralkyl esters are prepared by interaction of the formula-CXVIII acids with the appropriate diazohydrocarbon. For example, when diazomethane is used, the methyl esters are produced. Similar use of diazoethane, diazobutane, 1-diazo-2-ethylhexane, diazocyclohexane, and phenyldiazomethane, for example, gives the ethyl, butyl, 2-ethylhexyl, cyclohexyl, and benzyl esters, respectively.
Esterification with diazohydrocarbons is carried out by mixing a solution of the diazohydrocarbon in a suitable inert solvent, preferably diethyl ether, with the acid reactant, advantageously in the same or a different inert diluent. After the esterification reaction is complete, the solvent is removed by evaporation, and the ester purified if desired by conventional methods, preferably by chromatography. It is preferred that contact of the acid reactants with the diazohydrocarbon be no longer than necessary to effect the desired esterification, preferably about one to about ten minutes, to avoid undesired molecular changes. Diazohydrocarbons are known in the art or can be prepared by methods known in the art. See, for example Organic Reactions, John Wiley & Sons, Inc., New York, N. Y., Vol. 8, pp. 389-394 (1954).
An alternative method for esterification of the carboxyl moiety comprises transformation of the free acid to the corresponding silver salt, followed by interaction of that salt with an alkyl iodide. Examples of suitable iodides are methyl iodide, ethyl iodide, butyl iodide, isobutyl iodide, tere-butyl iodide, cyclopropyl iodide, cyclopentyl iodide, benzyl iodide, phenethyl iodide, and the like. The silver salts are prepared by conventional methods, for example, by dissolving the acid in cold dilute aqueous ammonia, evaporating the excess ammonia at reduced pressure, and then adding the stoichiometric amount of silver nitrate.
The phenyl and substituted phenyl esters are prepared by silylating the acid to protect the hydroxy groups, for example, replacing each --OH with --O--Si--(CH 3 ) 3 . Doing that may also change --COOH to --COO--Si--(CH 3 ) 3 . A brief treatment of the silylated compound with water will change --COO--Si--(CH 3 ) 3 back to --COOH. Procedures for this silylation are known in the art. Then, treatment of the silylated compound with oxalyl chloride gives the acid chloride which is reacted with phenol or the appropriate substituted phenol to give a silylated phenyl or substituted phenyl ester. Then the silyl groups, e.g., --O--Si--(CH 3 ) 3 are changed back to --OH by treatment with dilute acetic acid. Procedures for these transformations are known in the art.
Referring to Chart M, there are shown process steps by which the formula-CIX bicyclo hexene is transformed first to an oxetane CXXII with a fully developed side chain. ##SPC108## ##SPC109## ##SPC110##
and ultimately to a PGE analog. In Chart M, R 44 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, and R 45 is hydrogen, alkyl of 1 to 4 carbon atoms, inclusive, or silyl of the formula (A) 3 Si-- wherein A is as defined herein above.
In step (a) of Chart M, there is employed an aldehyde of the formula ##SPC111##
wherein C p H 2p and R 44 are as defined above. Such aldehydes are available or readily prepared by methods known in the art. Examples of such compounds include: ##SPC112## ##SPC113##
The conditions for step (a) of Chart M are essentially the same as for step (a) of Chart L. Thereafter, step (b) for cleavage of the oxetane ring, steps (c) and (d) leading to the formula-CXXV aldehyde, and the Wittig reaction of step (e) are similar to and employ the same conditions as the corresponding steps of Chart L discussed above.
Refering to step (g) of Chart M, the hydroxyl on the cyclopentane ring at the C-9 position is oxidized to an oxo group.
Oxidation reagents useful for this transformation are known in the art. A useful reagent for this purpose is the Jones reagent, i.e., acidified chromic acid. See J. Chem. Soc. 39 (1946). A slight excess beyond the amount necessary to oxidize the C-9 secondary hydroxy groups of the formula -CXXVII reactant is used. Acetone is a suitable diluent for this purpose. Reaction temperatures at least as low as about 0° C. should be used. Preferred reaction temperatures are in the range 0° to -50° C. An especially useful reagent for this purpose is the Collins reagent, i.e. chromium trioxide in pyridine. See J. C. Collins et al., Tetrahedron Lett., 3363 (1968). Dichloromethane is a suitable diluent for this purpose. Reaction temperatures of below 30° C. should be used. Preferred reaction temperatures are in the range 0° to +30° C. The oxidation proceeds rapidly and is usually complete in about 5 to 20 minutes.
Examples of other oxidation reagents useful for this transformation are silver carbonate on Celite (Chem. Commun. 1102 (1969)), mixtures of chromium trioxide and pyridine (J. Am. Chem. Soc. 75, 422 (1953), and Tetrahedron, 18, 1351 (1962)), t-butylchromate in pyridine (Biochem. J. 84, 195 (1962)), mixtures of sulfur trioxide in pyridine and dimethylsulfoxide (J. Am. Chem. Soc. 89, 5505 (1967)), and mixtures of dicyclohexylcarbodiimide and dimethyl sulfoxide (J. Am. Chem. Soc. 87, 5661 (1965)).
Step (h) of Chart M and subsequent steps by which the product CXXX is obtained are similar to and employ the same conditions as the corresponding steps of Chart L discussed above.
Referring next to Chart N the process steps are shown whereby aldehyde CXIII of Chart L is transformed to a 17,18-tetradehydro-PG analog CXXXVI and a 17,18-didehydro-PG analog CXXXVII.
In step (a) of Chart N, a Wittig reagent is employed which is prepared from a phosphonium salt of a haloalkyne of the formula
Cl--CHR.sub.2 --C.sub.n H.sub.2n --C.tbd.C--R.sub.5
or
Br--CHR.sub.2 --C.sub.n H.sub.2n --C.tbd.C--R.sub.5
wherein C n H 2n , R 2 , and R 5 are as defined above. See, for example, U. Axen et al., Chem. Comm. 1969, 303, and ibid. 1970, 602.
Thereafter, in steps (b) to (d) and subsequent steps yielding the 17,18-tetradehydro compound CXXXVI the reagents ##SPC114## ##SPC115##
and conditions are similar to those employed for the corresponding reactions shown in Chart L.
Transformation of CXXXVI to the formula-CXXXVII compounds is accomplished by hydrogenation of CXXXVI using a catalyst which catalyzes hydrogenation of --C.tbd.C-- only to cis--CH=CH--, as known in the art. See, for example, Fieser et al., "Reagents for Organic Syntheses," pp. 566-567, John Wiley and Sons, Inc., New York (1967). Preferred is Lindlar catalyst in the presence of quinoline, see Axen, references cited.
The intermediates of Charts L, M, and N, including those compounds represented by formulas CX, CXI, CXII, CXIII, CXIV, CXV, CXVI, CXVII, CXXII, CXXIII, CXXIV, CXXV, CXXVI, CXXVII, CXXVIII, CXXIX, CXXXII, CXXXIII, CXXXIV, CXXXV, and CXXXVI are frequently not isolated but used directly for a subsequent process step. When they are isolated, they are purified by methods known in the art, for example partition extraction, fractional crystallization, and, preferably, silica gel column chromatography.
The products represented by formulas CXVIII, CXXX, and CXXXVII obtained from these intermediates are often a mixture of 15-α and 15-β isomers. These are separated by methods known in the art, for example, by chromatography on neutral silica gel. In some instances, particularly where R 2 is alkyl, the lower alkyl esters are more readily separated than are the corresponding acids. In those cases wherein R 1 is hydrogen, it is advantageous to esterify the mixture of acids, as with diazomethane, to form the methyl esters, separate the two epimers, and then, if desired, replace the carboxyl methyl with hydrogen by methods known in the art.
When an optically active intermediate or starting material is employed, subsequent steps yield optically active intermediates or products. That optical isomer of bicyclo hexene CIX is used which will yield product CXVIII for example, in the configuration corresponding to that of the naturally occurring prostaglandins. When the racemic form of the intermediate or starting material is employed, the subsequent intermediates or products are obtained in their racemic form.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The invention can be more fully understood by the following examples and preparations:
All temperatures are in degrees centigrade.
Infrared absorption spectra are recorded on a Perkin-Elmer Model 421 infrared spectrophotometer. Except when specified otherwise, undiluted (neat) samples are used.
Ultraviolet spectra are recorded on a Cary Model 15 spectrophotometer.
NMR spectra are recorded on a Varian A-60, A-60D, or T-60 spectrophotometer using deuterochloroform solutions with tetramethylsilane as an internal standard (downfield).
Mass spectra are recorded on a CEC Model 110B Double Focusing High Resolution Mass Spectrometer or an LKB Model 9,000 Gas Chromatograph-Mass Spectrometer (ionization voltage 70 ev).
Circular dichroism curves are recorded on a Cary 60 recording spectropolarimeter.
Specific rotations are determined for solutions of a compound in the specified solvent with a Perkin-Elmer Model 141 Automatic Polarimeter.
The collection of chromatographic eluate fractions starts when the eluant front reaches the bottom of the column.
"Brine," herein, refers to an aqueous saturated sodium chloride solution.
The A-IX solvent system used in thin layer chromatography is made up from ethyl acetate-acetic acid-2,2,4-trimethylpentane-water (90:20:50:100) according to M. Hamberg and B. Samuelsson, J. Biol. Chem. 241, 257 (1966).
"Skellysolve-B" refers to mixed isomeric hexanes.
Silica gel chromatography, as used herein, is understood to include elution, collection of fractions, and combination of those fractions shown by TLC (thin layer chromatography) to contain the desired product free of starting material and impurities.
PREPARATION 1
dl-Endo-6-(1-heptenyl)-3-(1-pyrrolidyl)-bicyclo[3.1.0]hex-2-ene.
A solution of formula-XLIII endo-6-(cis- and trans-1-heptenyl)bicyclo[3.1.0]hexan-3-one (see Example 29 of West Germany Offenlegungsschrift No. 1,937,912, cited above) (15 g.), 25 ml. of pyrrolidine, and 200 ml. of benzene is heated under reflux while removing the water formed by distillation. After 2 hrs. the benzene is replaced by 50 ml. of toluene which is then removed in vacuo to give the title compound. This material gives an infrared spectrum having absorption attributable to the enamine double bond at 1610 cm - 1 and free of carbonyl absorption.
PREPARATION 2
Methyl m-(Chloromethyl)phenoxyacetate (Formula LIII: C g H 2g and C p H 2p are valence bonds in meta relationship, C q H 2q is methylene, Hal is chloro, R 26 is hydrogen, and R 10 is methyl).
a. m-Formylphenoxyacetic Acid. To a solution of m-hydroxybenzaldehyde (48.8 g.) and sodium hydroxide (16.16 g.) in 500 ml. of water is added a solution prepared from chloroacetic acid (75 g.) and sodium hydroxide (32 g.) in 100 ml. of water. The mixture is heated under reflux for 2 hrs., cooled, and the pH is adjusted to pH 1 or 2. The mixture is extracted with dichloromethane-ether and the extract is dried and concentrated. The solid is taken up in saturated aqueous sodium bicarbonate, extracted with ether and the aqueous phase is made acidic. The aqueous phase is extracted with dichloromethane. The organic layer is concentrated and the residue is recrystallized from water to give m-formylphenoxyacetic acid (34.0 g.) m.p. 114°-117°.
b. Methyl M-Formylphenoxyacetate. A solution of the product of step a (30.0 g.) in 400 ml. of diethyl ether-tetrahydrofuran is treated with an excess of ethereal diazomethane generated from N-methyl-N'-nitro-N-nitro-soguanidine (32.5 g.) and 200 ml. of 30% potassium hydroxide. The organic extract is washed with 5% sodium hydroxide, dried and concentrated to give methyl m-formylphenoxyacetate (17 g.), as a light yellow oil.
c. Methyl m-(Hydroxymethyl)phenoxyacetate. A solution of the product of step b (30.0 g.) in 200 ml. of methanol, cooled in an ice bath to 0°, is treated with sodium borohydride (1.55 g.) in 30 ml. of cold water. After the addition, stirring is continued for 20 min., the methanol is removed, and 60 ml. of brine is added. The aqueous phase is extracted with ether and the ether solution is washed, first with 5% aqueous hydrochloric acid, then brine, and dried. Removal of the solvent yields methyl m-(hydroxymethyl)phenoxyacetate(27.0 g.).
d. Methyl m-(Chloromethyl)phenoxyacetate. To the product of step c (27.0 g.) is added 20 ml. of thionyl chloride with stirring. Following the addition, the reaction mixture is stirred at 25° for 30 min. and at reflux for 30 min. After cooling the reaction mixture, it is dissolved in ether and washed carefully with water, saturated aqueous sodium bicarbonate and brine. The organic layer is dried, concentrated and distilled to give the title compound (11.0 g.) b.p. 98°-110°/0.03 mm.
Following the procedures of Preparation 2, but replacing chloroacetic acid with 3-chloropropionic acid, there is obtained, successively, 3-(m-formylphenoxy)propionic acid and its methyl ester, methyl 3-[m-(hydroxymethyl)phenoxy]-propionate, and the formula-LIII compound, methyl 3-[m-(chloromethyl)phenoxy]propionate.
Alternatively, Michael addition of m-hydroxy benzaldehyde to methyl acrylate, with base catalysis, and reduction of the product with sodium borohydride gives methyl 3-[m-(hydroxymethyl)phenoxy]propionate.
PREPARATION 3
Ethyl o-(Bromomethyl)benzyloxyacetate (Formula LIII: C g H 2g is a valence bond, C p H 2p and C q H 2q are methylene, C g H 2g and C p H 2p are in ortho relationship, Hal is bromo, R 26 is hydrogen, and R 10 is ethyl).
To a mixture of α,α'-dibromo-o-xylene (100 g.), ethyl glycolate (47 g.), and dimethylformamide (500 ml.) is added with stirring over a 1-hour period at 0°-5° C., 18 g. of 57% sodium hydride. The mixture is stirred for 16 hrs. at about 25° C. and is then concentrated on a rotating evaporator at 40°-50° C. under vacuum. The residue is diluted with 1 liter of a mixture of isomeric hexanes (Skellysolve B) and diethyl ether (1:2 by volume) and the organic solution is washed successively with dilute hydrochloric acid, dilute potassium hydroxide solution, water, and brine, and is finally dried and concentrated. The residue is chromatographed on a column prepared by wet-packing 3 kg. of silica gel (Brinkman) with 6 l. of 15% ethyl acetate in Skellysolve B and 30 ml. of absolute ethanol. Gradient elution of the column with 16 l. of 15-35% ethyl acetate in Skellysolve B gives fractions of 400 ml. each of which are combined on the basis of thin layer chromatography (TLC). From fractions 18-27 there is obtained 35 g. of the title compound. This material has λ max . in ethanol at 231 mμ (ε 7550) with shoulders at 272 (ε 700) and 278 mμ (ε 462). It has key absorptions in its NMR spectrum at about 7.3 (apparent singlet), 4.7 (singlet), 4.64 (singlet), 4.06 (singlet), 4.0-4.35 (quartet), and 1.1-1.34 (triplet) δ. It has mass spectral peaks at 206, 199, 201, 185, and 183.
PREPARATION 4
Endo-6-(cis-4-phenyl-1-butenyl)-bicyclo[3.1.0]hexan-3-one (Formula XLIII: G is ##SPC116##
R 3 and R 4 are hydrogen; and ˜ is endo).
a. There is first prepared (3-phenylpropyl)triphenylphosphonium bromide. A solution of 597.3 g. of 1-bromo-3-phenylpropane and 786 g. of triphenylphosphine in 1500 ml. of toluene is heated at reflux under nitrogen for 16 hrs., then the mixture is cooled and the solid product is separated by filtration. The solid is then slurried with toluene in a Waring blender, separated by filtration, and dried for 18 hrs. at 70° C. under reduced pressure to give 1068 g. of (3-phenylpropyl)triphenylphosphonium bromide; m.p. 210.5°-211.5° C.
b. A suspension of 314 g. of the product of step a in 3 l. of benzene is stirred at room temperature (25° C.) under nitrogen, and 400 ml. of 1.6 M butyllithium in hexane is added over a 20 min. period. The mixture is heated at 35° C. for 30 minutes, then is cooled to -15° C. and a solution of 100 g. of endo-bicyclo[3.1.0]hexan-3-ol-6-carboxaldehyde 3-tetrahydropyranyl ether in 200 ml. of benzene is added over a 30-min. period. This mixture is heated at 70° C. for 2.5 hrs., cooled, and filtered. The filtrate is washed three times with water, dried over sodium sulfate, and concentrated to 170 g. of crude endo-6-(cis-4-phenyl-1-butenyl)-bicyclo[3.1.0]hexan-3-ol 3-tetrahydropyranyl ether.
A solution of 340 g. (two runs) of this crude endo-6-(cis-4-phenyl-1-butenyl)-bicyclo[3.1.0]hexan-3-ol 3-tetrahydropyranyl ether and 20 g. of oxalic acid in 3600 ml. of methanol is heated at reflux for 3.5 hrs. The mixture is cooled and the methanol is evaporated under reduced pressure. The residue is mixed with dichloromethane, and the dichloromethane solution is washed with aqueous sodium bicarbonate, dried over sodium sulfate, and concentrated to 272 g. of the endo-6-(cis-4-phenyl-1-butenyl)bicyclo[3.1.0]hexan-3-ol.
A solution of 93 g. of the above endo-6-(cis-4-phenyl-1-butenyl)bicyclo[3.1.0]hexan-3-ol in 2570 ml. of acetone is cooled to -5° C. and 160 ml. of Jones reagent (in the proportions 42 g. of chromic anhydride, 120 ml. of water, and 34 ml. of concentrated sulfuric acid) is added over a period of 30 min. while cooling to maintain a temperature of -5° C. The mixture is allowed to stand for 10 min. longer; then 100 ml. of isopropyl alcohol is added and the mixture is swirled for 5 min. The mixture is then diluted with 6 l. of water and extracted several times with dichloromethane. The organic layers are separated, washed with dilute hydrochloric acid, water, dilute aqueous sodium bicarbonate, and brine, then are dried over sodium sulfate, combined and concentrated to 83 g. of crude endo-6-(cis-4-phenyl-1-butenyl)-bicyclo[3.1.0]hexan-3-one.
Crude endo-6-(cis-4-phenyl-1-butenyl)-bicyclo[3.1.0]hexan-3-one (162 g., two runs) is dissolved in isomeric hexanes (Skellysolve B) and chromatographed over 5 kg. of silica gel wet-packed with Skellysolve B, eluting successively with 11 l. of Skellysolve B, 62 l. of 2.5% ethyl acetate in Skellysolve B, and 32 l. of 5% ethyl acetate in Skellysolve B. The last 8 l. of the 2.5% ethyl acetate in Skellysolve B eluates and the 32 l. of 5% ethyl acetate in Skellysolve B eluates are combined and concentrated to 75.8 g. of the title compound; infrared absorption at 3000, 1750, 1610, 1500, 1455, 1405, 1265, 1150, 778, 750 and 702 cm - 1 ., N.M.R. peaks at 7.18 (singlet) and 4.75-6.0 (broad multiplet) δ.
PREPARATION 5
Endo-6-(cis-5-phenyl-1-pentenyl)-bicyclo[3.1.0]hexan-3-one. (Formula XLIII: G is ##SPC117##
R 2 and R 9 are hydrogen; and ˜ is endo).
a. There is first prepared (4-phenylbutyl)triphenylphosphonium bromide. A solution of 145 g. of 4-phenyl-1-bromobutane and 179 g. of triphenylphosphine in 350 ml. of toluene is heated at reflux under nitrogen for 16 hrs. The mixture is then cooled slowly and ether is added giving a precipitate of (4-phenylbutyl)triphenylphosphonium bromide which is washed thoroughly with benzene/ether and dried 18 hrs. at 50° C. under reduced pressure, 268 g., m.p. 139°-140° C.
b. A suspension of 242 g. of the product of step a in 2.3 l. of dry benzene at 25° C. is stirred and 300 ml. of 1.6 M butyllithium in hexane is added over a 15-min. period. The mixture is stirred at 30° C. for 1 hour, then is cooled to 10° C. and a solution of 75 g. of endobicyclo[3.1.0]hexan-3-ol-6-carboxaldehyde 3-tetrahydropyranyl ether in 200 ml. of benzene is added over a 15-min. period. The mixture is heated at 65°-70° C. for 3 hours, cooled and filtered. The filtrate is washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure to give 117 g. of crude endo-6-(cis-5-phenyl-1-pentenyl)-bicyclo[3.1.0]hexan-3-ol tetrahydropyranyl ether showing a single spot, R f 0.75, on thin layer chromatography with silica gel plates developed with 20% ethyl acetate in cyclohexane.
A solution of 117 g. of the above crude endo-6-(cis-5-phenyl-1-pentenyl)-bicyclo[3.1.0]hexan-3-ol tetrahydropyranyl ether and 6 g. of oxalic acid in 2500 ml. of methanol is heated under reflux for 2.5 hrs. The methanol is then removed by distillation under reduced pressure and the residue is diluted with water and extracted with dichloromethane. The dichloromethane extracts are combined, washed with aqueous sodium bicarbonate and brine, dried over sodium sulfate and concentrated under reduced pressure to give 95.7 g. of crude endo-6-(cis-5-phenyl-1-pentenyl)-bicyclo[3.1.0]hexan-3-ol. The entire crude product is chromatographed over 1.5 kg. of silica gel wet-packed with Skellysolve B, eluting successively with 5 l. of Skellysolve B, 4 l. of 2.5%, 6 l. of 5%, 9 l. of 7.5%, 12 l. of 10%, 8 l. of 15%, 10 l. of 20% and 10 l. of 30% ethyl acetate in Skellysolve B, taking 600 ml. fractions. The last fraction of 10% ethyl acetate in Skellysolve B, all the 15% and 20% ethyl acetate in Skellysolve B eluates, and the first 3 fractions of 30% ethyl acetate in Skellysolve B are concentrated to 60.5 g. of purified endo-6-(cis-5-phenyl-1-pentenyl)bicyclo[3.1.0]hexan-3-ol.
A solution of 60.5 g. of the above purified alcohol in 1600 ml. of acetone is cooled to -10° C. and 103 ml. of Jones reagent is added dropwise. After addition is complete the mixture is stirred for 10 min. at 0° C. and 65 ml. of isopropyl alcohol is added. The mixture is poured into 8 l. of water and extracted several times with dichloromethane. The dichloromethane extracts are combined, washed with dilute hydrochloric acid, aqueous sodium bicarbonate and brine, dried over sodium sulfate and concentrated under reduced pressure to give 56 g. of crude endo-6-(cis-5-phenyl-1-pentenyl)bicyclo[3.1.0]hexan-3-one. The crude ketone is slurried in Skellysolve B and chromatographed over 2300 g. of silica gel wet packed in Skellysolve B, eluting successively with 6 l. of Skellysolve B, 16 l. of 2.5% ethyl acetate in Skellysolve B, then gradient elution with 5 l. of 2.5% and 5 l. of 5% ethyl acetate in Skellysolve B and finally 16 l. of 5% ethyl acetate in Skellysolve B, taking 625 ml. fractions. The last fraction of the gradient eluates and the first 19 fractions of 5% ethyl acetate in Skellysolve B are concentrated to give 23.6 of the title compound; infrared absorption at 2980, 1745, 1600, 1490, 1450, 1260, 1145, 770, 750 and 702 cm - 1 ., N.M.R. peaks at 7.17 (singlet), 6.0-5.4 (multiplet), and 5.2-4.7 (broad multiplet) δ.
PREPARATION 6
Endo-6-(1,2-dihydroxy-4-phenylbutyl)-bicyclo[3.1.0]hexan-3-one Acetonide
(Formula XXXVI wherein G is ##SPC118##
R 2 and R 9 are hydrogen, R 11 and R 12 are methyl, and ˜ is endo).
a. There is first prepared the formula-LI dihydroxy compound. To a solution of endo-6-(cis-4-phenyl-1-butenyl)-bicyclo[3.1.0]hexan-3-one (10.0 g., Preparation 4) in about 100 ml. of tetrahydrofuran is added, with stirring, a solution of potassium chlorate (10.0 g.) and osmium tetroxide (0.65 g.) in 250 ml. of water. The mixture is stirred vigorously for 5 hrs. at 50° C. Then, the cooled mixture is concentrated under reduced pressure. The residue is extracted repeatedly with dichloromethane, and the combined extracts are dried and concentrated to an oil. This oil is chromatographed on about 1000 g. of silica gel, and eluted successively with 3 l. of 10% ethyl acetate in a mixture of isomeric hexanes (Skellysolve B), with 5 l. of 25% ethyl acetate in Skellysolve B, and then with 50% ethyl acetate in Skellysolve B, collecting 500 ml. eluate fractions. Fractions 13-19 (50% ethyl acetate) are combined and evaporated to dryness to give dl-endo-6 (1,2-dihydroxy-4-phenylbutyl)-bicyclo[3.1.0]hexane-3-one (Formula LI).
b. A solution of the product of step a (about 8.0 g.) and 700 mg. of potassium bisulfate in 140 ml. of acetone is stirred at 25° C. for 64 hrs. Then, sodium carbonate monohydrate (710 mg.) is added, and the mixture is stirred 10 minutes. The acetone is evaporated at reduced pressure, and water is added. The aqueous solution is extracted repeatedly with dichloromethane, and the extracts are combined, washed with water, dried, and concentrated to about 9.3 g. of an oil. The oil is chromatographed on 400 g. of silica gel, being eluted with 2 l. of 10% ethyl acetate in Skellysolve B, and then with 4 l. of 15% ethyl acetate in Skellysolve B. The 15% ethyl acetate eluates are concentrated to about 7.4 g. of the formula-XXXVI compound, endo-6-(1,2-dihydroxy-4-phenylbutyl)-bicyclo[3.1.0]hexan-3-one acetonide.
PREPARATION 7
Methyl 9-Bromo-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate. (Formula LIV: C j H 2j and C p H 2p are valence bonds in meta relationship C q H 2q is methylene, Hal is bromo, R 26 is hydrogen and R 10 is methyl).
a. To a cold, stirred solution of m-vinylanisole (13.4 g.) in 40 ml. of diethyl ether is slowly added a solution of bromine (15.9 g.) in 60 ml. of diethyl ether. The ether solution is used directly in converting the product, m-(1,2-dibromoethyl)anisole to m-methoxyphenylacetylene by dehydrohalogenation (see T. H. Vaughn, J. Am. Chem. Soc. 56, 2064, 1934). The ether solution above is slowly added, with vigorous stirring, to a mixture of sodium amide prepared from sodium (4.6 g.) in about 200 ml. of liquid ammonia. When the reaction is complete, the volume is reduced about one-half, and an equal volume of water is cautiously added. A layer containing the product is separated, washed with dilute hydrochloric acid, dried, and distilled.
b. To a solution of the product of step a above in 250 ml. of dichloromethane, maintained at 0° C. under nitrogen, is added dropwise over about a 1-hour period with vigorous stirring a solution of about 15 ml. of boron tribromide in 200 ml. of dichloromethane. Cooling and stirring continue for 1 hour. When the reaction is complete as shown by TLC, there is added cautiously a solution of sodium carbonate in water to neutralize the mixture. Thereafter, the solution is saturated with sodium chloride (added as a solid), and the organic phase is separated and combined with additional ethyl acetate washings of the aqueous phase. The organic solutions are washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to yield the acetylenic phenol.
c. To the product of step b (11.8 g.), is added gradually a solution of sodium ethoxide (prepared from sodium and absolute ethanol). Thereafter, ethylene chlorohydrin (8.0 g.) is added in small portions. When all has been added, the mixture is heated at reflux for about 1 hour or until completion, then filtered hot. The combined filtrate and ethanol washings are concentrated to remove alcohol, and the product distilled under reduced pressure.
To the hydroxyethyl ether (16.2 g.) as obtained above, cooled to 15°-20° C., is added 20 ml. of dihydropyran and 100 ml. of diethylether, and, with stirring, 1 ml. of anhydrous diethyl ether saturated with hydrogen chloride. After the exothermic reaction hs diminished, the mixture is kept at 25° C. for 15 hours. The mixture is washed with aqueous sodium bicarbonate, water, and dried, then concentrated under reduced pressure to yield the tetrahydropyranyl ether.
d and e. To a solution of the product of step c (10 g.) in anhydrous tetrahydrofuran (180 ml.) at -78° C. under argon is added the equivalent molecular amount of n-butyllithium in hexane. The resulting solution is stirred at -78° C. for an additional 30 minutes. A suspension of dry paraformaldehyde (two equivalents) in anhydrous tetrahydrofuran is added and the mixture warmed to room temperature over a 30-min. period. It is stirred an additional 1 hour and poured into brine, then extracted with ether, dried, and concentrated to yield the hydroxy compound.
f. The hydroxy compound of step e is converted to the bromo compound by first forming the mesyl derivative by reaction with methanesulfonyl chloride (4 ml.) in pyridine (80 ml.) at -20° C. The mixture is stirred 1 hour at -20° C., and then is poured into a stirred mixture of 3 normal hydrochloric acid (300 ml.) and ice water (500 ml.). This mixture is extracted with diethyl ether, the extract is washed with cold 1 N hydrochloric acid and brine, then dried and concentrated. To a solution of the residue (mesyl derivative) in dry acetone (100 ml.) is added lithium bromide (5 g.) and the mixture stirred and heated at reflux 1 hour, then kept at 25° C. for 15 hours. The acetone is evaporated under reduced pressure, and the residue is extracted with diethyl ether. The extract is washed with water and brine, then dried and concentrated. The residue is chromatographed on silica gel, eluting with 10% ethyl acetate in Skellysolve B. Fractions shown by TLC to contain the product are combined and concentrated to give the formula-LX intermediate.
g. The product of step f above is converted to the corresponding carboxylic acid and its methyl ester as follows. The tetrahydropyranyloxy group is replaced by hydroxyl by contacting the product of f with a mixture of acetic acid/water/tetrahydrofuran (20/10/3) at 40° C. for 2 hours, thereafter removing solvents under reduced pressure.
The substituted glycol from above is oxidized to the acid in acetone solution, using a slight excess of Jones reagent (21 g. chromic anhydride/60 ml. water/17 ml. conc. sulfuric acid) while cooling to maintain a temperature of -5° to 0° C. After about 60 min., isopropyl alcohol is added, the mixture is stirred for 10 min., and then poured into ice water. The acid product is isolated by extraction with chloroform, drying over sodium sulfate, and concentration under reduced pressure.
The acid from above is converted to the methyl ester by reaction with diazomethane in diethyl ether at about 10°-25° C., followed by concentration to yield the desired title compound.
Following the procedures of Preparation 7, but replacing m-vinylanisole with methyl (o, m, or p-)vinylbenzyl ether, there are obtained, respectively, methyl 9-bromo-3-oxa-4,7-inter-o-phenylene-5,6-dinor-7-nonynoate, methyl 10-bromo-3-oxa-4,8-inter-m-phenylene-5,6,7-trinor-8-decynoate, and methyl 11-bromo-3-oxa-4,9-inter-p-phenylene-5,6,7,8-tetranor-9-undecynoate.
PREPARATION 8
Methyl 9-Bromo-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoate (Formula LV: C j H 2j and C p H 2p are valence bonds in meta relationships. C q H 2q is methylene, Hal is bromo, R 26 is hydrogen and R 10 is methyl).
A solution of methyl 9-bromo-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (2.0 g., Preparation 7) in 10 ml. of pyridine is hydrogenated in the presence of a 5% palladium on barium sulfate catalyst (150 mg.) at 25° C. and 1 atmosphere. the resulting mixture is filtered and evaporated to about one-third the original volume. Four volumes of ethyl acetate is added, and the remaining pyridine is removed by addition of ice and 1 N hydrochloric acid. The ethyl acetate layer is separated, washed successively with 1 N hydrochloric acid and brine, dried, and evaporated. The residue is chromatographed on 250 g. of silica gel which has previously been acid-washed to pH 4 (Silicar CC 4 , 100-200 mesh, Mallincrodt Co.), eluting with 3 l. of 25-75% ethyl acetate-Skellysolve B gradient, collecting 100-ml. fractions. The fractions shown to have the desired product free of starting material by TLC are combined and concentrated under reduced pressure to give the title compound containing the cis --CH=CH moiety.
Following the procedures of Preparation 8, but replacing methyl 9-bromo-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate with methyl 9-bromo-3-oxa-4,7-inter-o-phenylene-5,6-dinor-7-nonynoate, methyl 10-bromo-3-oxa-4,8-inter-m-phenylene-5,6,7-trinor-8-decynoate, or methyl 11-bromo-3-oxa-4,9-inter-p-phenylene-5,6,7,8-tetra-nor-9-undecynoate (from the paragraphs following Preparation 7), there is obtained the corresponding formula-LV enoate compounds in which cis--CH=CH-- has replaced --C.tbd.C--.
PREPARATION 9
Methyl 9-Bromo-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-trans-7-nonenoate. (Formula LVI: C j H 2j and C p H 2p are valence bonds in meta relationship, C q H 2q is methylene, Hal is bromo, R 26 is hydrogen and R 10 is methyl).
A solution of the compound represented by the formula ##SPC119##
(1.0 g., Preparation 7, step e) in 20 ml. of tetrahydrofuran is cooled to -10° C. This solution is added to a fresh solution of lithium aluminum hydride (110% of theory) in tetrahydrofuran. The reaction mixture is stirred for 16 hours at 25° C. ambient temperature. Then, water (20 ml.) is added, and the resulting solution is acidified with 1 N hydrochloric acid, and then extracted with ethyl acetate. The extract is washed successively with aqueous sodium bicarbonate solution and brine, dried, and evaporated under reduced pressure. The residue is chromatographed on silica gel, eluting with a 25-75% ethyl acetate-Skellysolve B gradient, combining fractions shown to have the desired product by TLC, and removing solvent from those combined fractions under reduced pressure to yield a compound represented by the formula ##SPC120##
Thereafter, following the procedures of Preparation 7, steps f through g, there is obtained the title compound containing the trans--CH=CH-- moiety.
Following the procedures of Preparation 9, but replacing thst nonynoate with the compound having the formula ##SPC121##
wherein the THP-terminated moiety is attached to the ring in ortho, meta, or para configuration, there is obtained the corresponding formula LVI compound in which trans --CH=CH-- has replaced -C.tbd.C--.
PREPARATION 10
Optically Active Bicyclo[3.1.0]hex-2-ene-6-endo-carboxaldehyde
Following the procedure of Preparation 1 of U.S. Pat. No. 3,711,515, racemic bicyclo[3.1.0]hex-2-ene-6-endo-carboxaldehyde is prepared from bicyclo[2.2.1]hepta-2,5-diene and peracetic acid.
The racemic compound is resolved by the procedure of Example 13 of U.S. Pat. No. 3,711,515, forming an oxazolidine as follows.
Racemic bicyclo[3.1.0]hex-2-ene-6-endo-carboxaldehyde (12.3 g.) and l-ephedrine (16.5 g.) are dissolved in about 150 ml. of benzene. The benzene is removed under vacuum and the residue taken up in about 150 ml. of isopropyl ether. The solution is filtered, then cooled to -13° C. to yield crystals of 2-endo-bicyclo-[3.1.0]hex-2-en-6-yl3,4-dimethyl-5-phenyl-oxazolidine, 11.1 g., m.p. 90°-92° C. Three recrystallizations from isopropyl ether, cooling each time to about -2° C., yield crystals of the oxazolidine, 2.2 g., m.p. 100°-103° C., now substantially a single isomeric form as shown by NMR.
The above re-crystallized oxazolidine (1.0 g.) is dissolved in a few ml. of dichloromethane, charged to a 20 g. silica gel column and eluted with dichloromethane. The silica gel is chromatography-grade (Merck), 0.05-0.2 mm. particle size, with about 4-4 5 g. of water per 100 g. Fractions of the eluate are collected, and those shown by thin layer chromatography (TLC) to contain the desired compound are combined and evaporated to an oil (360 mg.). This oil is shown by NMR to be the desired title compound, substantially free of the ephedrine, in substantially a single optically-active isomeric form. points on the circular dichroism curve are (λ in nm.,θ): 350, 0; 322.5, -4,854; 312, -5,683; 302.5, -4,854; 269, 0; 250, 2,368; 240, 0; and 210, -34,600.
EXAMPLE 1
dl -Methyl 7-[Endo-6-(1-heptenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-heptanoate (Formula XLIV, Chart E: G is n-pentyl; R 2 , R 9 , and R 26 are hydrogen; R 10 is methyl; Z' is ##SPC122##
and ˜ is alpha and endo).
A. A solution prepared from endo-6-(1-heptenyl)-3-(1-pyrrolidyl)-bicyclo[3.1.0]hex-2-ene (Preparation b 1, 5.0 g.) and methyl m-(chloromethyl)-phenoxyacetate (Preparation 2, 4.4 g.) in 60 ml. of dioxane is stirred under a nitrogen atmosphere at about 25° C for 2 days and then heated under reflux for 7 hrs. To the reaction mixture is added water. The solution is heated on a steam bath, cooled and extracted with ether. The extract is washed, first with dilute (about 5% hydrochloric acid, then brine, and dried and concentrated. The residue is chromatographed on 700 g. of silica gel prepared with 20% ether-isomeric hexane mixture (Skellysolve B) and eluted with 1.5 l. of 20% ether-Skellysolve B, 1.5 l. of 25% ether-Skellysolve B, and 1.5 l. of 30% ether-Skellysolve B, collecting 100-ml. fractions. Fractions 25-31 give the title compound (1.7 g.).
B. Alternate synthesis. - A solution of potassium tert-butoxide (9.0 g.) in 500 ml. of nitrogen-purged tetrahydrofuran is added dropwise during 45 min. to a stirred solution of the formula-XLIII bicyclo olefin, endo-6-(1-heptenyl)bicyclo[3.1.0]hexan-3-one (see Example 9 of West Germany Offenlegungsschrift No. 1,937,912, cited above) (10.0 g.), and methyl m-(chloromethyl)phenoxyacetate (Preparation 2, 13 g.) in 250 ml. of tetrahydrofuran under nitrogen at 25° C. The resulting mixture is acidified at once with 120 ml. of 5% hydrochloric acid, and then is concentrated under reduced pressure below 40° C. to remove most of the tetrahydrofuran. Water (400 ml.) is added to the residue, and the mixture is extracted with three 400-ml. portions of ethyl acetate. The combined extracts are washed successively with aqueous sodium thiosulfate solution and brine, dried, and concentrated under reduced pressure. The residue is chromatographed over 4 kg. of silica gel wet-packed with 20% ether-isomeric hexane mixture (Skellysolve B) and eluted with ether-Skellysolve B mixtures having 20-30% ether. Fractions shown by TLC to contain the desired alkylation product are combined to yield the formula-XLIV (Chart E) alkylated olefin title compound.
Following the procedure of Example 1-B but replacing the formula-XLIII (Chart E) endo-6-(1-heptenyl)bicyclo[3.1.0]hexan-3-one with the corresponding bicyclo olefins prepared by reaction of the -tetrahydropyranyl ether of endo-bicyclo[3.1.0]hexan-3-ol-6-carboxaldehyde with intermediate quaternary phosphonium halides (see above-cited West Germany Offenlegungsschrift No. 1,937,912) prepared from 1-bromobutane, 1-chloropentane, 1-bromoheptane, and 1-chlorooctane, there are obtained the corresponding formula-XLIV alkylated olefin compounds wherein G is straight chain alkyl of 3, 4, 6, and 7 carbon atoms, respectively.
Also following the procedure of Example 1-B but employing instead formula-XLIII bicyclo olefins prepared from 1-bromo-2-fluorobutane, 1-chloro-2-fluoro-pentane, 1-bromo-2-fluorohexane, 1-bromo-2-fluoroheptane, and 1-chloro-2-fluorooctane, there are obtained the corresponding formula-XLIV aklyated olefin compounds wherein G is straight chain alkyl of 3 to 7 carbon atoms, inclusive, with a fluoro substituent at the 1-position.
Also following the procedure of Example 1-B but employing, instead, formula-XLIII bicyclo olefins prepared from primary bromides of the formula R 27 --(CH 2 ) b --CH 2 Br, wherein b is 1, 2, 3, or 4, and R 27 is isobutyl, tert-butyl, 3,3-difluorobutyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl, and 3,3,4,4,4-pentafluorobutyl, there are obtained compounds corresponding to the formula-XLIV product of Example 1-B with R 27 --(CH 2 ) b --CH=CH-- in place of the 1-heptenyl moiety.
Also following the procedure of Example 1-B but employing, instead, formula-XLIII bicyclo olefins prepared from primary bromides of the formula:
Ch 3 --(ch 2 ) c --CR 21 R 22 --CH 2 Br wherein c is 2, 3, or 4, and R 21 and R 22 are methyl or ethyl, e.g. CH 3 --(CH 2 ) 2 --C(C 2 H 5 ) 2 --CH 2 --Br, CH 3 --(CH 2 ) 3 --CH(CH 3 )--CH 2 --Br, CH 3 --(CH 2 ) 3 --CH(C 2 H 5 )--CH 2 --Cl, CH 3 --(CH 2 ) 3 --C(CH 3 ) 2 --CH 2 --Br, and CH 3 --(CH 2 ) 3 --C(CH 3 )(C 2 H 5 )--CH 2 --Br, there are obtained the corresponding formula-XLIV alkylated olefin compounds wherein G is mono- or di-substituted at the 1-position with methyl or ethyl.
Also following the procedure with Example 1-B but employing, instead, formula-XLIII bicyclo olefins prepared from α-bromotoluene, (2-bromoethyl)benzene, (5-chloropentyl)benzene, (6-bromohexyl)benzene, and (7-iodoheptyl)benzene; from (1-chloroethyl)benzene, (1-bromopropyl)benzene, (2-bromopropyl)benzene, (3-chloropentyl)benzene, (4-bromopentyl)benzene, (6-bromononyl)benzene and (7-bromononyl)benzene; from 1-bromo-2-phenylpropane, 1-bromo-2-methyl-2-phenylpropane, 1-chloro-2-ethyl-3-phenylpropane, 1-bromo-2-methyl-4-phenylbutane, and 1-bromo-2,2-dimethyl-5-phenylpentane; from α-bromo-m-xylene, α-chloro-p-ethyltoluene, α-bromo-p-chlorotoluene, α'-chloro-α,α,α-trifluoro-m-xylene, 1-(2-bromoethyl)-4-fluorobenzene, 1-(5-bromopentyl)-2-chlorobenzene, 4-(3-iodopropyl)-1,2-dimethoxybenzene, and 1-(3-bromohexyl)-2,4,6-trimethylbenzene; and from (2-bromo-1-fluoroethyl)benzene, (2-bromo-1-fluoropropyl)benzene, (2-chloro-1-fluoro-1-methylpropyl)benzene, (5-bromo-4-fluoropentyl)benzene, (7-iodo-6-fluoropentyl)benzene, (4-bromo-3,3-difluorobutyl)benzene, and (6-bromo-5,5-difluorohexyl)benzene, there are obtained the corresponding formula-XLIV alkylated olefin compounds wherein G is ##SPC123##
including compounds wherein C t H 2t is substituted with 1 or 2 fluoro atoms.
Also following the procedure of Example 1-B, but using formula-XLIII bicyclo olefins obtained from the secondary bromides of the formula ##EQU50## wherein G and R 2 are as defined above, R 2 being alkyl, there are obtained formula-XLIV alkylated olefins corresponding to the product of Example 1-B with ##EQU51## in place of the 1-heptenyl moiety.
Also following the procedure of Example 1-B, but using formula-XLIII bicyclo olefins obtained from bicyclo[3.1.0]-hexane reactants with ##EQU52## in place of ##EQU53## wherein R 9 is as defined above, there are obtained formula-XLIII alkylated olefins corresponding to the product of Example 1-B with ##EQU54## in place of the 1-heptenyl moiety.
Also following the procedure of Example 1-B, but using formula-XLIII bicyclo olefins obtained from bicyclo[3.1.0]hexane reactants with ##EQU55## in place of ##EQU56## and primary and secondary bromides of the formula ##EQU57## (as above defined), there are obtained formula-LIV alkylated olefins corresponding to the product of Example 1-B with ##EQU58## in place of the 1-heptenyl moiety.
Also following the procedure of Example 1-B but using a larger amount of potassium tert-butoxide (16 g.) and maintaining the reaction mixture for 8 hrs. at 25° C. before addition of hydrochloric acid, a product is obtained which contains substantial amounts of both the above-described 2α-yl isomer and the corresponding 2β-yl isomer. These isomers are separated by the above-described silica gel chromatography.
Also following the procedure of Example 1-B but using exo formula-XLIII bicyclo olefins in place of the endo reactant of Example 1-B, there are obtained the corresponding exo formula-XLIV alkylated olefins.
Also following the procedure of Example 1-B but replacing the methyl m-(chloromethyl)phenoxyacetate alkylating agent with the formula-LIII and -LIV compounds, methyl 3-[m-(Chloromethyl)phenoxy]propionate, methyl 9-bromo-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate, and methyl 10-bromo-3 -oxa-4,8-inter-m-phenylene-5,6,7-trinor-8-decynoate, there are obtained alpha and beta, exo and endo, formula-XLIV alkylated olefins corresponding to the product of Example 1-B with ##SPC124##
replaced with ##SPC125##
respectively. In the same manner, but using, according to Example 1-B, other esters of the above-described formula-LIII and -LIV alkylating agnets within the scope of R 10 as above-defined, e.g., the isopropyl, tert-butyl, octyl, cyclohexyl, benzyl, and phenyl esters, there are obtained the corresponding formula-XLIV esters.
Also following the procedure of Example 1-B but using in combination each of the above-described alternative formula-XLIII bicyclo olefins and each of the above-described alternative formula-LIII or -LIV omega-halo alkylation agents, there are obtained formula-XLIV alkylated olefins corresponding to the product of Example 1-B but different therefrom with respect to both the carboxylate-terminated side chain and the side chain attached to the cyclopropane ring in the product.
Also following the procedure of Example 1-B, but using in place of the formula-LIII halo alkylating agent of that Example, each of the other alkylating agents within the scope of ##EQU59## as above defined, i.e., alkylating agents of formulas LIII and LIV as above-described, there are obtained alpha and beta exo and endo formula-XLIV compounds corresponding to the product of Example 1-B with each of the other ##EQU60## side chains in place of the ##SPC126##
side chain of the Example 1-B product. For example, using as formula-LIII alkylating agents in the Example 1-B procedure, the following compounds wherein Et is ethyl; ##SPC127## ##SPC128##
there are obtained exo and endo, alpha and beta, formula-XLIV alkylated bicyclo[3.1.0]hexanes each having a carboxylate-terminated side chain corresponding to one of the specific omega-halo alkylating agents. For example, the side chain will be alpha or beta ##SPC129##
when the alkylating agent is ##SPC130##
Also following the procedure of Example 1-B, but using in combination each of the alternative alkylating formula-LIII and -LIV agents within the scope of ##EQU61## including the specific examples of those just mentioned, and each of the above-described formula-XLIII alternative bicyclo[3.1.0]hexane olefin reactants, there are obtained formula-XLIV exo and endo, alpha and beta, compounds corresponding to the products of Example 1-B, but different therefrom with respect to both the carboxylate-terminated side chain and the side chain attached to the cyclopropane ring of the product. In the same manner, alternative alkylating agents within the scope of ##EQU62## wherein R 10 is other than ethyl, e.g., methyl, isopropyl, tert-butyl, octyl, cyclohexyl, benzyl, phenyl, and β,β,β-trichloroethyl are used.
EXAMPLE 2
dl-Methyl 7-[Endo-6-(1,2-dihydroxyheptyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-heptanoate (Formula XLV, Chart E: G' is n-pentyl; R 2 , R 9 , and R 26 are hydrogen; R 10 is methyl; Z' is ##SPC131##
and ˜ is alpha and endo).
Refer to Chart E. To a solution of dl-methyl 7-[endo-6-(1-heptenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-heptanoate (Example 1, 1.7 g.) in 30 ml. of tetrahydrofuran at 50° is added with stirring osmium tetroxide (200 mg.) followed by potassium chlorate (1.2 g.) and 15 ml. of water. The reaction mixture is maintained at 50° for 2 hrs., cooled, the tetrahydrofuran is removed, and the aqueous phase is extracted with dichloromethane. The organic layer is dried and concentrated and the residue is chromatographed on 200 g. of silica gel. The column is eluted with 1 l. of 35% ethyl acetate-benzene and 1 l. of 40% ethyl acetate-benzene, collecting 30-ml. fractions. Fractions 26-30 contain one isomer (faster moving, less polar) of the title compound (350 mg.). Fractions 32-37 contain the other slower-moving (more polar) isomer (450 mg.). These materials show infrared spectral absorption at 330 cm - 1 .
Following the procedure of Example 2 but using the hex-2β-yl isomer in place of the hex-2α-yl isomer of the bicyclo reactant, dl-methyl 7-[endo-6-(1,2-dihydroxyheptyl)-3-oxobicyclo[3.1.0]hex-2β-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-heptanoate is obtained.
Also following the procedure of Example 2, each of the formula-XLIV exo and endo, alpha and beta, saturated and acetylenic bicyclo[3.1.0]hexane esters defined above after Example 1 is oxidized to mixtures of the corresponding isomeric formula-XLV dihydroxy compounds.
EXAMPLE 3
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 Methyl Ester (Formula XVI: C g H 2g and C p H 2p are valence bonds in metal relationship, G is n-pentyl, Q is ##EQU63## R 1 is methyl, and ˜ is alpha) and dl-15-Beta-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 Methyl Ester ##EQU64##
Refer to Chart E. To a solution of the formula-XLV dihydroxy compound, dl-methyl 7-[endo-6-(1,2-dihydroxyheptyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-heptanoate (800 mg. of a mixture of the slower and faster moving isomers of Example 2) in 10 ml. of pyridine, cooled to 0°, is added 1.2 ml. of methane-sulfonyl chloride. The reaction mixture is stirred for 2 hrs. and 20 g. of ice is added. The mixture is extracted with ether-dichloromethane (1:1) and the organic layer is washed successively with dilute hydrochloride acid, water, saturated aqueous sodium bicarabonate, and brine, dried, and concentrated. The residue, containing the bismesylate, is treated with 15 ml. of acetone and 10 ml. of water and stirred for 8-16 hrs. at 25°. The acetone is removed in vacuo and the remaining solution is extracted with dichloromethane. The extract is dried and concentrated and the residue is chromatographed on 150 g. of silica gel using 500 ml. ethyl acetate followed by 3% methanol ethyl acetate as eluting solvent while collecting 30-ml. fractions. Fractions 15-24 are combined and concentrated to yield the 15-β PGE 1 title compound (50 mg.); mass spectral peak at 404; ultraviolet absorption at 216 (ε = 8100), 264 (ε = 1100), 272 (ε = 1600) and 278 (ε = 1500mμ. Fractions 26-35 are combined and concentrated to yield a residue which is re-chromatographed on 10 g. of silica gel using the same solvent system and collecting 1.5 ml. fractions. Fractions 22-29 are combined and concentrated to give the PGE 1 title compound (75 mg.); mass spectral peak at 404; ultraviolet absorption at 216 (ε = 7700), 264, 272 (ε = 1500), and 278 (ε = 1400) mμ.
Following the procedures of Example 3, each of the formula-XLV dl-endo-1,2-dihydroxy oxa-phenylene esters following Example 2 is transformed to the corresponding dl-endo-1,2-dimesyloxy oxa-phenylene ester, and thence to the corresponding PGE type compound or its isomers.
Also following the procedures of Example 3, each of the formula-XLV and dl-exo-1,2-dihydroxy oxa-phenylene esters corresponding to the above dl-endo-1,2-dihydroxy esters is transformed to the corresponding dl-exo-1,2-dimesyloxy ester, and thence to the corresponding PGE type compound or its isomers.
By the above-outlined procedures, following the steps of Chart E, there are obtained the specific PGE-type esters represented by figures XVI and XVIII, e.g. the esters of the dl-oxa-phenylene PGE 1 compounds and 5,6-dehydro-PGE 2 compounds, including their 8-iso and 15-epi (β) forms. For example, dl-5,6-dehydro-3-oxa-3,7-inter-m-phenylene-18-phenyl-4,19,20-trinor-PGE.sub.2 methyl ester and its 15-epimer are obtained from dl-methyl 7-[endo-6-(cis-4-phenyl-1-butenyl)-3-oxobicyclo[3.1.0]hex-2α-yl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (Example 10 hereinafter) by way of the dihydroxy and bis(mesylate) intermediates of Chart E, following Example 3, as represented by the following formulas: ##SPC132##
Also following the procedure of Example 3, but replacing methanesulfonyl chloride with an alkanesulfonyl chloride or bromide or with an alkanesulfonic acid anhydride, wherein the alkane moiety contains 2 to 5 atoms, inclusive, there is obtained from each dihydroxy compound the corresponding bis(sulfonic acid) esters encompassed by formula XLVI.
In each of the above transformations in Example 3, the monosulfonic acid ester is also obtained as a by-product, which is reacted with additional alkanesulfonyl halide or alkanesulfonic acid anhydride to give the corresponding bis(sulfonic acid) ester and thence recycled back to additional formula-XLVII product.
For satisfactory yields of the bis-sulfonic acid ester, R 10 is not hydrogen. Those intermediate compounds in which R 10 is haloethyl, e.g., β,β,β-trichloroethyl, are especially useful in the sequence of reactions leading to the acid form of the prostaglandin-like products. Each of the exo and endo, alpha and beta, saturated and unsaturated oxa-phenylene bis(alkanesulfonic acid) esters is transformed to the corresponding oxa-phenylene PGE type compound encompassed by formula-XLVII.
EXAMPLE 4
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α Methyl Ester and dl-3-Oxa-3,7-inter-m-phenylene-4,5,6,-trinor-PGF 1 .sub.β Methyl Ester (Formula XX: C g H 2g and C p H 2p are valence bonds in relationship, G is n-pentyl, Q is ##EQU65## R 1 is methyl, and ˜ is alpha for the carboxyl-containing moiety and either alpha or beta for the ring hydroxyl).
Refer to Chart A. A solution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 methyl ester (Example 3, 300 mg.), 20 ml. of tetrahydrofuran, 2.0 ml. of hexamethyldisilazane, and 0.15 ml. of trimethylsilyl chloride is stirred at 25° for 20 hrs. The reaction mixture is concentrated in vacuo, benzene is added, the solution concentrated and this procedure is repeated. The residue is dissolved in 10 ml. of methanol, cooled in an ice-methanol bath, and sodium borohydride (60 mg.) in 20 ml. of cold water is added dropwise. The methanol is removed and the aqueous phase is extracted with dichloromethane, and the resulting dichloromethane solution is dried and concentrated in vacuo. The residue is chromatographed on 45 g. of silica gel using 70 ml. of ethyl acetate and then a gradient of 0-8% methanol ethyl acetate as eluting solvent, collecting 10-ml. fractions. Fractions 22-36 are combined and concentrated to yield the PGF 1 .sub.α -type title compound (100 mg.); mass spectral peak for tris-trimethylsilyl derivative at 622. Fractions 37-42 are combined and concentrated to yield a residue which is chromatographed on a preparative silica gel plate using 5% methanol-methylene chloride as eluting solvent. From the plate is obtained the PGF 1 .sub.β -type title compound (25 mg.); mass spectral peak for tris-trimethylsilyl derivative at 622.
Following the procedure of Example 4, dl-3-oxa-4,7inter-o-phenylene-5,6-dinor-PGE 1 ethyl ester (Example 8 hereinafter) is transformed to dl-3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGF 1 .sub.α and -PGF 1 .sub.β ethyl esters.
Also following the procedure of Example 4, dl-5,6-dehydro-3-oxa-3,7-inter-m-phenylene-18-phenyl-4,19-20-trinor-PGE.sub.2 methyl ester (following Example 3) is transformed to the corresponding PGF 2 .sub.α and PGF 2 .sub.β type compounds.
Also following the procedure of Example 4, the alkyl ester and free acid forms of formula-XX to -XXIII oxa-phenylene PGF compounds in their various spatial configurations, e.g., the PGF 1 .sub.α, PGF 1 .sub.β, PGF 2 .sub.α, PGF 2 .sub.β, trans-5,6-dehydro-PGF 1 .sub.α and -PGF 1 .sub.β type compounds and their 8-iso and 15-beta isomers, are prepared by reduction of the corresponding formula XVI-to -XIX PGE-type alkyl ester or free acid, including those described above after Example 3.
EXAMPLE 5
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 (Formula-XXIV: C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-C 5 H 11 , Q is ##EQU66## R 1 is hydrogen; and ˜ is alpha).
Refer to Chart A. A solution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 methyl ester (Example 3, 300 mg.), 4 ml. of tetrahydrofuran and 4 ml. of 0.5 N hydrochloric acid is left standing at 25° for five days. Brine solution and dichloromethane-ether (1:3) are added and the mixture is stirred. The organic layer is separated, dried and concentrated. The residue is dissolved in either which is washed with saturated aqueous sodium bicarbonate, dried and concentrated. The aqueous phase is quickly acidified with hydrochloric acid and extracted with dichloromethane which in turn is dried and concentrated. The residue is again dissolved in ether, extracted with aqueous sodium bicarbonate, and the aqueous phase is worked up as reported above. This procedure is repeated one additional time to yield the title compound (120 mg.). This material has mass spectral peaks at 372, 354, 189, and 185; and λ max., in ethanol, 215 mμ (ε 12,400), 272 (ε 2250) and 278 (ε 2150).
Following the procedure of Example 5, the formula XIV-to -XIX PGE compounds in their various spatial configurations described after Example 3 are transformed to the corresponding formula XXIV-to -XXVII PGA compounds, either as esters or as free acids.
EXAMPLE 6
dl-Ethyl 7-[Endo-6-(1-heptenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor-heptanoate (Formula-XLIV: G is n-pentyl; R 2 , R 9 , and R 26 are hydrogen; R 10 is ethyl; Z' is ##SPC133##
and ˜ is alpha and endo).
The enamine of the formula-XLIII bicyclo-olefin is first prepared as follows. A mixture of endo-6-(cis- and trans-1-heptenyl)-bicyclo[3.1.0]hexan-3-one (10 g.), benzene (200 ml.), and pyrrolidine (15 ml.) is heated at reflux under a Dean-Stark water trap for 2 hrs. Thereafter about 140 ml. of distillate is taken off over a period of about 30 min. To the remaining liquid is added 100 ml. of toluene and the mixture is concentrated on a rotating evaporator under vacuum. A second portion of toluene (50 ml.) is added, and the mixture concentrated to give the enamine residue.
The above enamine, together with ethyl o-(bromomethyl)-benzyloxyacetate (Preparation 3 above, 15 g.), and dry tetrahydrofuran (200 ml.) is heated at reflux for 4 hrs. and thereafter stirred at about 25° C. for 16 hrs. Water (25 ml.) is added and the mixture heated for 20 min. on a steam bath. Thereafter, the volatiles are moved under vacuum, the residue is diluted with ether, and the organic solution is washed successively with dilute acid, water, dilute base, water, and brine, and finally dried and concentrated under vacuum. The residue is chromatographed on a column prepared by wet-packing 1300 g. of silica gel (E. Merck) with 2.5 l. of 25% diethyl ether in Skellysolve B and 13 ml. of absolute ethanol. The column is eluted with 2 l. of 25% ether in Skellysolve B and then gradient-eluted with 8 l. of 25-50% ether-Skellysolve B. Fractions of about 200 ml. are combined on the basis of TLC data. From fractions 24-31 there is obtained 2.9 g. of the desired formula-XLIV title compound as a mixture of cis and trans forms. This material has key absorptions in its NMR spectrum at about 7.21 (apparent singlet), 5.38-5.8 (multiplet), 4.62 (singlet), 4.06 (singlet), and 4.0 4.35 (quartet) δ. It has mass spectral lines at 398 and 294.
EXAMPLE 7
dl-Ethyl 7-[endo-6-(1,2-dihydroxyheptyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor heptanoate (Formula-XLV: G' is n-pentyl; R 2 , R 9 , and R 26 are hydrogen; R 10 is ethyl; Z' is ##SPC134##
and ˜ is alpha and endo).
Refer to Chart E. To a solution of dl-ethyl 7-[endo-6-(1-heptenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor-heptanoate, as a mixture of its isomers (Example 6, 2.8 g.) in dry tetrahydrofuran (150 ml.) at 50° C. is added 0.15 g. of osmium tetroxide followed by 2.8 g. of potassium chlorate in 60 ml. of water. The mixture is stirred vigorously at 50° C. for about 1.5 hrs. and is then concentrated under vacuum. The residue is extracted with dichloromethane. The extract is washed with water and brine, and then finally dried and concentrated under vacuum. The residue is chromatographed on a column prepared by wet-packing 500 g. of silica gel (E. Merck) with 1 liter of 50% ethyl acetate in Skellysolve B and 5 ml. of absolute ethanol. The column is eluted with 1 l. of 50% ethyl acetate in Skellysolve B and then gradient eluted with 4 l. of 50-75% ethyl acetate in Skellysolve B. Fractions of 100 ml. each are combined on the basis of TLC data. From fractions 12-29 there is obtained 2.6 g. of the title compound.
EXAMPLE 8
dl-3-Oxa-4,7-inter-o-phenylen-5,6-dinor-PGE 1 Ethyl Ester (Formula-XIV: C g H 2g is a valence bond, C p H 2p are in ortho relationship, G is n-pentyl, Q is ##EQU67## R 1 is ethyl, and ˜ is alpha) and dl-15-Beta-3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGE 1 Ethyl ester (Q is ##EQU68##
Refer to Chart E. The formula-XLVI bismesylate is first prepared as follows. To a mixture of dl-ethyl 7-[endo-6-(1,2-dihydroxyhepthyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor-heptanoate (Example 7, 2.6 g.) and 30 ml. of dry pyridine at 0° C. is added, with stirring, 2.7 ml. of methanesulfonyl chloride over a one-minute period. The mixture is stirred at 0° C. for 2.5 hrs., then cooled to about -10° C. and diluted with 2 ml. of water added dropwise over a 5-minute period. Ice (20 g.) is added, and, after stirring the mixture for 5 min., about 150 ml. of ether-dichloromethane (3:1) is added. The organic solution was washed successively with dilute hydrochloric acid, water, dilute sodium bicarbonate solution, and brine, and finally dried and concentrated under vacuum to yield a mixture of the mesylates.
The residue of mesylates is converted to the PGE-type product by contacting with a mixture of acetone (100 ml.) and water (50 ml.) at about 25° C. for 16 hrs. Additional water (100 ml.) is added and the mixture concentrated under vacuum to remove acetone. The residue is extracted with a mixture of ether-dichloromethane (3:1) and the organic extract is washed with dilute sodium bicarbonate solution and brine, then dried and concentrated under vacuum. The residue (2.5 g.) is chromatographed on a column prepared by wet-packing 500 g. of silica gel (E. Merck) with one liter of ethyl acetate and 5 ml. of absolute ethanol. The column is eluted with 2.6 liters of ethyl acetate, then 400 ml. of 2% ethanol in ethyl acetate, then 500 ml. of 4% ethanol in ethyl acetate and finally with 2 liters of 10% ethanol in ethyl acetate, collecting fractions of 100 ml. Fractions are combined on the basis of TLC data.
From fractions 8-14 is obtained 350 mg. of the 15-βPGE 1 title compound. This material has λ max . 279 mμ (ε 19,400) in alcoholic potassium hydroxide; key absorptions in the NMR spectrum at about 7.2 (apparent singlet), 5.25-5.48 (multiplet), 4.58 (singlet), 4.06 singlet, and 4.0-4.35 (quartet) δ; and mass spectral peaks at 414, 396, 310, and 292.
From fractions 18-37 is obtained 496 mg. of the PGE 1 title compound. This material has λ max . 279 mμ (ε 21,750) in alcoholic potassium hydroxide; key absorptions in the NMR spectrum at about 7.18 (apparent singlet), 5.25-5.41 (multiplet), 4.58 (singlet), 4.02 (singlet), and 3.99-4.34 (quartet) δ; and mass spectral peaks at 414, 396, 310, and 292.
EXAMPLE 9
dl-methyl 9-[Endo-6-(1,2-dihydroxy-2-methyl-heptyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoate Acetonide (Formula-XXXVII, Chart D: G is n-pentyl; J' is ##SPC135##
R 9 and R 26 are hydrogen; R 2 , R 10 , R 11 , and R 12 are methyl; and ˜ is endo and alpha).
Refer to the sequence of reactions from formula-L to formula XXVI, and to Chart D.
a. There is first prepared the formula-XLIII olefin. Following the procedure for the Wittig synthesis in Examples 27, 28, and 29 of West Germany Offlegungsschrift No. 1,937,912, cited above, but employing the tetrahydropyranyloxy ether of endo-bicyclo[3.1.0]hexan-3-ol-6-carboxaldehyde and the Wittig ylide of 2-chloroheptane, there is obtained dl-endo-6-(2-methyl-1-heptenyl)-3-oxobicyclo-[3.1.0]-hexan-3-one.
b. To a solution of the product of step a above (approximately 10.0 g.) in water is added a solution of potassium chlorate (10.0 g.) and osmium tetroxide (0.65 g.) in 250 ml. of water. The mixture is stirred vigorously for 5 hrs. at 50° C. Then, the cooled mixture is concentrated under reduced pressure, the residue is extracted repeatedly with dichloromethane, and the combined extracts are dried and evaporated. The residue is chromatographed on about 1000 g. of silica gel, and eluted successively with 3 l, of 10% ethyl acetate in a mixture of isomeric hexanes (Skellysolve B), with 5 l. of 25% ethyl acetate in Skellysolve B, and then with 50% ethyl acetate in Skellysolve B, collecting 500 ml. eluate fractions. Fractions shown by TLC to contain the desired product are combined and evaporated to dryness to give the formula-L1 product, dl-endo-6-(1,2-dihydroxy-2-methylheptyl)bicyclo[3.1.0]hexan-3-one.
c. A solution of the product of step b above (about 8,0 g.) and 700 mg. of potassium bisulfate in 140 ml. of acetone is stirred at 25° C. for 64 hrs. Then, sodium carbonate monohydrate (710 mg.) is added, and the mixture is stirred 10 min. The acetone is evaporated at reduced pressure, and water is added. The aqueous solution is extracted respectedly with dichloromethane, and the extracts are combined, washed with water, dried, and evaporated. The residue is chromatographed on 400 g. of silica gel, being eluted with 2 l. of 10% ethyl acetate in Skellysolve B, and then with 4 l. of 15% ethyl acetate in Skellysolve B. The 15% ethyl acetate eluates are evaporated to give the formula-XXXVI ketal, dl-endo-6-(1,2-dihydroxy-2-methylheptyl)bicyclo[3.1.0]hexan-3-one acetonide.
d. To prepare the formula-XXXVII compound (Chart D), the ketal above is alkylated following the procedure of Example 1-B, but using the formula-XXXVI ketal above instead of the formula-XLIII bicyclo olefin, and, replacing methyl m-(chloromethyl)phenoxyacetate with methyl 9-chloro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoate (Preparation 8, above), thereby yielding the desired formula-XXXVII title compound.
As shown in Chart D, the formula-XXXVII alkylated ketal is transformed via the formula-XXXVIII glycol, thence the mesylate, to a PGE-type compound. Concentrated hydrochloric acid (2.5 ml.) is added to a solution of the formula-XXXVII product above (about 2.0 g.) in a mixture of 50 ml. of tetrahydofuran and 2.5 ml. of water. The mixture is stirred at 25° C. under nitrogen for 6 hrs. The resulting mixture is then concentrated under reduced pressure, and the residue is extracted with ethyl acetate. The extract is washed with brine, dried, and concentrated to dl-methyl-9[endo-6-(1,2-dihydroxy-2-methylheptyl)-3-oxobicyclo[3.1.0.]hex-2α-yl]-3-oxa-3,7- inter-m-phenylene-4,5,6-trinor-cis-7-nonenoate (formula-XXXVIII). Thereafter, following the procedure of Example 3, there is obtained dl-15-methyl-3-oxa-3,5-inter-m-phenylene-4-nor-PGE 2 methyl ester.
Following the procedure of Example 9, but using formula-XLIII exo reactants in place of the endo reactant, there are obtained exo products in each corresponding intermediate of Example 9.
With excess base (e.g., 26 g.) and a longer reaction time (e.g., 24 hrs. at 25° C.) during the alkylation step, the production of a substantial amount of the beta isomer is assured.
Following the procedures of Examples 9-d, but using the trans-7-nonenoate of Preparation 9, above, instead of the cis-7-nonenoate, there is obtained the corresponding formula-XXXVII alkylated ketal wherein the carboxy side chain is in trans configuration instead of cis.
Also following the procedures of Example 9, but replacing the formula-XLIII olefin with each of the endo and exo forms of the formula-XLIII bicyclo olefins described in the paragraphs following Example 1, there are obtained the corresponding alpha and beta, exo and endo, alkylated ketals within the scope of formula XXXVII.
Also following the procedures of Example 9-d, but replacing methyl 9-chloro-3-oxa-3,7-inter-m-phenylene-4,5,6,-trinor-cis-7-nonenoate with the formula-LV compounds of the paragraphs following Preparations 8 and 9, viz. cis or trans methyl 9-bromo-3 -oxa-4,7-inter-o-phenylene-5,6-dinor-7-nonenoate, methyl 10-bromo-3-oxa-4,8-inter-m-phenylene-5,6,7-trinor-8-decenoate, and methyl 11-bromo-3-oxa-4,9-inter-p-phenylene-5,6,7,8-tetranor-9-undecenoate, there are obtained the corresponding formula-XXXVII compounds. Thereafter, these alkylated ketals are transformed following the steps of Chart D as described in Example 9 to the corresponding PGE 2 type compounds.
Also following the procedure of Example 9-d, but using in place of the nonenoate alkylating agent, methyl m-(chloromethyl)phenoxyacetate(Preparation 2), ethyl o-(bromoethyl)benzyloxyacetate (Preparation 3), methyl 9-bromo-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (Preparation 7), and methyl 11-bromo-3-oxa-4,9-inter-p-phenylene-5,6,7,8-tetranor-9-undecynoate (following Preparation 7), there are obtained alpha and beta, exo and endo, compounds corresponding to the product of Example 9 with ##SPC136##
in place of the ##SPC137##
moiety of the Example-9 formula-XXXVII product. In the same manner, but using formula LIII-to -LVI alkylating agents within the scope of the formula ##EQU69## there are obtained the corresponding formula-XXXVII products.
Also following Example 9-d, other esters of the nonenoate alkylating agent and of the other above-mentioned alkylating agents within the scope of R 10 as above-defined, e.g., the methyl, isopropyl, tert-butyl, octyl, β,β,β-trichloroethyl, cyclohexyl, benzyl, and phenyl esters, there are obtained the corresponding esters of these alpha and beta, exo and endo, formula-XXXVII bicyclo[3.1.0]hexane cyclic ketal alkylation products.
Also following the procedure of Example 9 but using in combination each of the above-described alternative formula-XLIII bicyclo[3.1.0]hexane olefin reactants (e.g. following Example 1) and each of the above-described omega-halo alkylation reactants within the scope of ##EQU70## (e.g. following Example 1) there are obtained formula-XXXVII compounds corresponding to the product of Example 9 but different therefrom with respect to both the carboxylate-terminated side chain and the side chain attached to the cyclopropane ring of the product, and in their respective alpha or beta and exo or endo configuration.
Following the procedure of Example 9 but using in place of the acetonide each of the specific formula-XXXVII exo and endo, alpha and beta, saturated, cis and trans ethylenic, and acetylenic bicyclo[3.1.0]hexane cyclic ketal esters defined above, there are obtained the corresponding formula-XXXVIII dihydroxy compounds, and thence the corresponding PGE type compounds.
EXAMPLE 10
dl-Methyl 7-[Endo-6-(cis-4-phenyl-1-butenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (Formula-XLIV, Chart E; G is ##SPC138##
R 2 , r 9 , and R 26 are hydrogen; R 10 is methyl; Z' is ##SPC139##
and ˜ is endo and alpha).
Refer to Chart E. Following the procedures of Example 1-B, but replacing endo-6-(1-heptenyl)bicyclo[3.1.0]hexan-3-one with endo-6-(cis-4-phenyl-1-butenyl)-bicyclo[3.1.0]hexan-3-one (Preparation 4), and replacing methyl m-(chloromethyl)phenoxyacetate with methyl 9-chloro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (Preparation 7), there is obtained the title compound.
EXAMPLE 11
dl-Methyl 7-[Endo-6-(6-(4-phenyl-1,2-dimesyloxybutyl)-3-oxobicyclo[3.1.0.]hex-2.alpha.-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (Formula-XLVI, Chart E; G' is ##SPC140##
R 2 , r 9 , and R 26 are hydrogen; R 10 and R 13 are methyl; Z' is ##SPC141##
and ˜ is alpha and endo).
a. There is first prepared the formula-XLV dihydroxy compound. Following the procedures of Example 2, but replacing dl-methyl 7 -endo-6-(1-heptenyl)-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-heptanoate with dl-methyl 7-[endo-6-(cis-4-phenyl-1-butenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (Example 10), there are obtained isomers of the desired formula-XLV compound, dl-methyl 7-[endo-6-(4-phenyl-1,2-dihydroxybutyl)-3 -oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7nonynoate.
b. Following the procedures of Example 3, but replacing that formula-XLV dihydroxy heptanoate compound with the formula-XLV nonynoate compound of A above, there is obtained the desired formula-XLVI dimesyloxy title compound.
EXAMPLE 12
dl-Methyl 9-[Endo-6-(1,2-dihydroxy-4-phenylbutyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-trans-7-nonenoate Acetonide (Formula-XXXVII, Chart D: G is ##SPC142##
J' is ##SPC143##
R 2 , r 9 , and R 26 are hydrogen; R 10 , R 11 , and R 12 are methyl; and ˜ is endo and alpha).
Refer to the sequence of reactions from formula L to formula XXXVI, and to Chart D.
a. There is first prepared the formula-Ll dihydroxy compound. To a solution of the formula-XLIII olefin (Preparation 4, above, approximately 10.0 g.) in water is added a solution of potassium chlorate (10.0 g.) and osmium tetroxide (0.65 g.) in 250 ml. of water. The mixture is stirred vigorously for 5 hrs. at 50° C. Then, the cooled mixture is concentrated under reduced pressure, the residue is extracted repeatedly with dichloromethane, and the combined extracts are dried and concentrated. The residue is chromatographed on about 1000 g. of silica gel, and eluted successively with 3 l. of 10% ethyl acetate in a mixture of isomeric hexanes (Skellysolve B), with 5 l. of 25% ethyl acetate in Skellysolve B, and then with 50% ethyl acetate in Skellysolve B, collecting 500 ml. eluate fractions. Fractions shown by TLC to contain the desired product are combined and evaporated to dryness to give dl-endo-6-(1,2-dihydroxy-4-phenylbutyl)-bicyclo[3.1.0]hexan-3-one (formula-Ll).
b. A solution of the product of step a above (about 8.0 g.) and 700 mg. of potassium bisulfate in 140 ml. of acetone is stirred at 25° C. for 64 hrs. Then, sodium carbonate monohydrate (710 mg.) is added, and the mixture is stirred 10 min. The acetone is concentrated at reduced pressure, and water is added. The aqueous solution is extracted repeatedly with dichloromethane, and the extracts are combined, washed with water, dried, and concentrated. The residue is chromatographed on 400 g. of silica gel, being eluted with 2 l. of 10% ethyl acetate in Skellysolve B, and then with 4 l. of 15% ethyl acetate in Skellysolve B. The 15% ethyl acetate eluates are concentrated to the formula-XXXVI ketal, dl-endo-6-(1,2-dihydroxy-4-phenylbutyl)-bicyclo[3.1.0]hexan-3-one acetonide.
c. To prepare the formula-XXXVII compound, the ketal above is alkylated following the procedure of Example 1-B, but replacing methyl m-(chloromethyl)phenoxyacetate with methyl 9-chloro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-trans-7-nonenoate (Preparation 9, above), thereby yielding the title compound.
Following the procedures of Example 9, the formula-XXXVII compound is transferred via the formula-XXXVIII and -XXXIX compounds to the corresponding formula-XL PGE-type compound.
EXAMPLE 13
9-[Endo-6-(1,2-dihydroxy-2-methylheptyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoic Acid Acetonide (Formula-LXXX, Chart G: G is n-pentyl; J' is ##SPC144##
R 9 and R 26 are hydrogen; R 2 , R 11 , and R 12 are methyl; and ˜ is alpha and endo.
Refer to Chart G. A solution of sodium borohydride (1.5 g.) in 10 ml. of water is added with stirring to a solution of formula-LXXVI dl-methyl 9-[endo-6-(1,2-dihydroxy-2-methylheptyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoate acetonide (5.0 g.) in 110 ml. of absolute ethanol at 0° C. The mixture is stirred for 2.5 hrs. at 0° to 5° C. Then, 40 ml. of acetone is added, and, after 5 min., the mixture is evaporated under reduced pressure. The residue is extracted with dichloromethane, and the extract is washed successively with dilute hydrochloric acid and brine, dried, and concentrated to the formula -LXXVII compound, dl-methyl 9-[endo-6-(1,2-dihydroxy-2-methylheptyl)-3-hydroxybicyclo[3.1.0]hex-2.alpha.-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoate acetonide.
This formula-LXXVII cyclic ketal hydroxy ester is dissolved in a mixture of methanol (100 ml.) and 45% aqueous potassium hydroxide solution (30 ml.), and the solution is stirred under nitrogen at 25° C. for 15 hrs. Two volumes of water are then added, and the mixture is acidified with cold hydrochloric acid and then extracted with a mixture of dichloromethane and diethyl ether (1:3). The extract is washed with brine, dried, and concentrated to the formula-LXXVIII compound.
EXAMPLE 14
dl-7-[Endo-6-(1-heptenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor-heptanoic Acid (Formula-LXXXVI, Chart H: G is n-pentyl; Z' is ##SPC145##
R 2 , r 9 , and R 26 are hydrogen; and ˜ is alpha and endo).
Refer to Chart H. Following the procedure of Example 13, the formula-LXXXII compound, dl-ethyl 7-[endo-6-(1-heptenty)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor-heptanoate is reduced with sodium borohydride to the formula-LXXXIII compound, dl-ethyl 7-[endo-6-(1-heptenyl)-3-hydroxybicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor-heptanoate. That hydroxy ester is then saponified as described in Example 13 to the formula-LXXXIV compound, dl-7-[endo-6-(1-heptenyl)-3-hydroxybicyclo[3.1.0]hex-2α-yl]-3-oxa-4,7-inter-o-phenylene-5,6-dinor-heptanoic acid. That hydroxy acid is then oxidized as described in Example 13 to the title compound.
Following the procedure of Example 14 but substituting for that formula-LXXXII compound, the formula-LXXXII compound of Example 10, viz. dl-methyl 7-[endo-6-(cis-4-phenyl-1-butenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate, there is obtained on reduction the corresponding formula-LXXXIII compound, dl-methyl-7-[endo-6-(cis-4-phenyl-1-butenyl)-3-hydroxybicyclo[ 3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate; there is likewise obtained on saponification the corresponding formula-LXXXIV compound, dl-7-[endo-6-(cis-4-phenyl-1-butenyl)-3-hydroxybicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoic acid; and there is likewise obtained on oxidation the corresponding formula-LXXXVI compound, dl-7-[endo-6-(cis-4-phenyl-1-butenyl)-3-oxabicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoic acid.
Following the procedure of Example 14, but using in place of the formula-LXXXII 3-oxobicyclo[3.1.0]hexane ester, each of the specific formula-LXXXII endo and exo, alpha and beta, saturated and acetylenic esters described in and following the Examples 1, 6, and 10 is reduced with sodium borohydride to give the corresponding formula-LXXXIII 3-hydroxy-bicyclo[3.1.0]hexane ester. That hydroxy ester is then saponified as described in Example 13 to the corresponding formula-LXXXIV 3-hydroxybicyclo[3.1.0]hexane acid. That hydroxy acid is then oxidized as described in Example 13 to the corresponding formula-LXXXVI 3-oxobicyclo[3.1.0]hexane acid.
EXAMPLE 15
dl-15-Dehydro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α Methyl Ester (Formula-XCI, Chart J: E' is trans --CH=CH--, G is n-pentyl, J' is ##SPC146##
R 1 is methyl, R 26 is hydrogen, and ˜ is alpha).
Refer to Chart J. A solution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α methyl ester (Example 4, about 0.5 g.) in 24 ml. of dioxane is stirred at 50° C. under nitrogen and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.37 g.) is added. The mixture is stirred at 50° C. for 24 hrs., cooled to room temperature, and filtered. The filter cake is washed with tetrahydrofuran, and the filtrate and wash are combined and concentrated under reduced pressure. The residue is taken up in dichloromethane and washed with brine, then dried over sodium sulfate and concentrated under reduced pressure. The residue is chromatographed over 90 g. of silica gel wet-packed in 8% ethanol in dichloromethane, eluting with 300 ml. of 2%, 300 ml. of 3%, 225 ml. of 7.5% and 245 ml. of 10% ethanol in dichloromethane, taking 15-ml. fractions. Fractions shown by TLC to contain the desired product are combined and concentrated to the title compound.
EXAMPLE 16
dl-15-Methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α Methyl Ester (Formula-XX: C g H 2g and C p H 2p are valence bond in meta relationship, G is n-pentyl, Q is ##EQU71## R 1 is methyl, and ˜ is alpha).
Refer to Chart J. A solution of 0.413 g. of dl-15-dehydro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α methyl ester (Example 15, about 0.4 g.), hexamethyldisilazane (3 ml.) and trimethylchlorosilane (0.5 ml.) in 20 ml. of tetrahydrofuran is allowed to stand at about 25° C. for 20 hrs. The mixture is filtered and the filtrate is concentrated under reduced pressure. Xylene (10 ml.) is added to the residue and removed by concentration under reduced pressure. The residue is dissolved in anhydrous ether and 110% of the theoretical amount of 3 M methyl magnesium bromide in ether is added. The mixture is allowed to stand 20 min. at about 25° C. and poured into 100 ml. of saturated aqueous ammonium chloride. The ether layer is separated, the aqueous layer is extracted with ether, and the ether extracts are combined and washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue is dissolved in 300 ml. of ethanol and 30 ml. of water containing 3 drops of glacial acetic acid, and the mixture is stirred for 2 hrs. at about 25° C. The mixture is concentrated under reduced pressure to an aqueous residue and the residue is extracted with dichloromethane. The dichloromethane extract is concentrated under reduced pressure to give a residue which is chromatographed over 60 g. of silica gel wet-packed in 8% ethanol in dichloromethane, eluting with 200 ml. of 5% and 800 ml. of 10% ethanol in dichloromethane and taking 10-ml. fractions. Fractions shown by TLC to contain the desired product are combined and concentrated to yield the title compound. Other fractions yield the 15-epimer.
Likewise, using the corresponding 3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGF 1 .sub.α or PGF 1 .sub.β compound instead of the above oxa-phenylene compounds, there are obtained the corresponding 15-dehydro PGF 1 .sub.α or PGF 1 .sub.β-type compounds, and finally the dl-15-methyl-3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGF 1 .sub.α or -PGF 1 .sub.β ethyl esters and their 15-epimers.
EXAMPLE 17
dl-13,14-Dihydro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 Methyl Ester (Formula XIX C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU72## R 1 is methyl, and ˜ is alpha).
Refer to Chart B. A solution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 methyl ester (Example 3, 100 mg.) in 10 mg. of ethyl acetate is shaken with hydrogen at about 1 atmosphere pressure at 25° C. in the presence of 5% rhodium on charcoal (15 mg.). After approximately 1 equivalent of hydrogen is absorbed, the hydrogenation is stopped, and the catalyst is removed by filtration. The filtrate is concentrated, and the residue is chromatographed on 25 g. of silica gel, eluting with 50-100% ethyl acetate gradient in Skellysolve B. Those fractions shown by TLC to contain the desired product free of the starting product and hydrogenolysis products are combined and concentrated to the title compound.
Following the procedure of Example 17, dl-3-oxa-3,7-m-phenylene-4,5,6-trinor-PGE 1 methyl ester is reduced to dl-13,14-dihydro-3-oxa-3,7-m-phenylene-4,5,6-trinor-PGE 1 ethyl ester. Likewise, dl-3-oxa-4,7-o-phenylene-5,6-dinor-PGE 1 methyl ester is reduced to dl-13,14-dihydro-3-oxa-4,7-o-phenylene-5,6-dinor-PGE 1 methyl ester.
Also following the procedure of Example 17, dl-3-oxa-3,7-m-phenylene-4,5,6-trinor-PGE 2 , -trans-5,6-dehydro-PGE 1 , and -5,6-dehydro-PGE 2 are each reduced to dl-13,14-dihydro-3-oxa-3,7-m-phenylene-4,5,6-trinor-PGE 1 , using 2 equivalents of hydrogen for the first two reactions, and 3 equivalents of hydrogen for the third. Likewise, the corresponding dl-3-oxa-4,7-o-phenylene-5,6-dinor- compounds are reduced to dl-13,14, -dihydro-3-oxa-4,7-o-phenylene-5,6-dinor-PGE 1 .
Also following the procedure of Example 17, the ethyl ester and the free acid form of the formula XVI-to -XVIII PGE compounds in their various spatial configurations are transformed to the corresponding 13,14-dihydro PGE 1 compound by catalytic hydrogenation, using equivalents of hydrogen appropriate to the degree of unsaturation of the reactant, i.e., one equivalent for the PGE 1 type, two equivalents for the PGE 2 type and trans-5,6-dehydro-PGE 1 type, and three equivalents for the 5,6-dehydro-PGE 2 type.
Also following the procedure of Example 17, dl-3-oxa-3,7-m-phenylene-4,5,6-trinor-PGF 1 .sub.α and its ethyl ester are reduced to dl-13,14-dihydro-3-oxa-3,7-m-phenylene-4,5,6-PGF 1 .sub.α and its ethyl ester, respectively.
Also following the procedure of Example 17, the ethyl ester and the free acid form of the formula-XX to -XXII PGF compounds in their various spatial configurations are transformed to the corresponding 13,14-dihydro PGF 1 .sub.α or PGF 1 .sub.β compound by catalytic hydrogenation, using equivalents of hydrogen appropriate to the degree of unsaturation of the reactant.
EXAMPLE 18
dl-13,14-Dihydro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 (Formula-XXVII: C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU73## R 1 is hydrogen, and ˜ is alpha).
Refer to Chart B. A suspension of disodium azodiformate (50 mg.) in 5 ml. of absolute ethanol is added to a stirred solution of 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 (Example 5, 50 mg.) in 10 ml. of absolute ethanol under nitrogen at 25° C. The mixture is made acid with glacial acetic acid, and then is stirred under nitrogen at 25° C. for 8 hrs. The resulting mixture is concentrated under reduced pressure, and the residue is mixed with a mixture of diethyl ether and water (1:1). The diethyl ether layer is separated, dried, and concentrated to the title product.
Following the procedure of Example 18, dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 methyl ester is reduced to dl-13,14-dihydro-3-oxa-3,7-inter-m-phenylene4,5,6-trinor-PGA 1 methyl ester.
Also following the procedure of Example 18, dl-3-oxa-3,7-inter-m-phenylene-PGA 2 , -trans-5,6-dehydro-PGA 1 , and 5,6-dehydro-PGA 2 are each reduced to dl-13,14-dihydro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 , using amounts of the disodium azodiformate reactant appropriate to the degree of unsaturation of the reactant.
Also following the procedure of Example 18, the methyl ester and the free acid form of the formula-XVI to -XVIII PGE type compounds, the formula-XX to -XXII PGF type compounds, the formula-XXIV to -XXVI PGA type compounds, and the formula-XXVIII to -XXX PGB type compounds are transformed to the corresponding 13,14-dihydro PGE 1 , PGF 1 , PGA 1 , or PGB 1 type compound by diimide reduction, using amounts of disodium azodiformate reactant appropriate to the degree of unsaturation of the PGE, PGF, PGA, or PGB type reactant.
EXAMPLE 19
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 Methyl Ester (Formula-XXIV: C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU74## R 1 is methyl, and ˜ is alpha).
Refer to Chart D. A solution of the formula-XXXIX bismesylate, dl-methyl 7-[endo-6-(1,2-dimesyloxyheptyl)-3-oxobicyclo 3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene4,5,6-trinor-heptanoate (Example 3, about 10 g.) in 75 ml. of acetone is mixed with 10 ml. of water and 20 ml. of saturated aqueous sodium bicarbonate solution. The mixture is refluxed under nitrogen for 4 hrs. Then, the mixture is cooled, acidified with 5% hydrochloric acid, and extracted with ethyl acetate. The extract is washed with brine, dried, and concentrated to give the title product.
Following the procedure of Example 19, each of the bismesylates defined in Example 3 is transformed to the corresponding PGA-type ester, including the β,β,β-trichloroethyl esters. Thereafter, each of the β,β,β-trichloroethyl esters is transformed to the corresponding PGA-type free acid by the procedure of Example 23, below.
EXAMPLE 20
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGB 1 (Formula-XXVIII: C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU75## R 1 is hydrogen, and ˜ is alpha).
Refer to Chart A. A solution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 (200 mg.) in 100 ml. of 50% aqueous ethanol containing about one gram of potassium hydroxide is kept at 25° C. for 10 hrs. under nitrogen. Then, the solution is cooled to 10° C. and neutralized by addition of 3 N. hydrochloric acid at 10° C. The resulting solution extracted repeatedly with ethyl acetate, and the combined ethyl acetate extracts are washed with water and then with brine, dried, and concentrated to give the title compound.
Following the procedure of Example 20, dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 is also transformed to the PGB 1 -type title compound.
Following the procedure of Example 20, each of the formula XVI-to -XIX PGE compounds and formula XXIV-to -XXVII PGA compounds are transformed to the corresponding PGB compounds.
EXAMPLE 21
dl-15-Methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 Methyl Ester (Formula XVI: C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-pentyl; Q is ##EQU76## R 1 is methyl, and ˜ is alpha).
Refer to Chart I. A solution of dl-15-methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α methyl ester (95 mg.) in 40 ml. of acetone is cooled to -10° C. To it is added 110% of the theoretical amount of Jones reagent (in the proportions of 21 g. of chromic anhydride, 60 ml. of water, and 17 ml. of concentrated sulfuric acid), precooled to 0° C., with vigorous stirring. After about 10 min., isopropyl alcohol (1 ml.) is added to the cold reaction mixture. After 5 min., the mixture is filtered and the filtrate is concentrated at reduced pressure, and the residue is mixed with 5 ml. of brine. The mixture is extracted repeatedly with ethyl acetate, and the combined extracts are washed with brine, dried with anhydrous sodium sulfate, and concentrated at reduced pressure. The residue is chromatographed on 20 g. of neutral silica gel, eluting with 50% ethyl acetate in Skellysolve B. Concentration of the eluates gives the title product.
Following the procedure of Example 21, there is substituted for the dl-15-methyl-3-oxa-3,7-inter-m-phenylene4,5,6-trinor-PGF 1 .sub.α methyl ester, the free acid, the propyl ester, the octyl ester, the cyclopentyl ester, the benzyl ester, the phenyl ester, the 2,4-dichlorophenyl ester, the 2-tolyl ester, of the β,β,β-trichloroethyl ester, there is obtained the corresponding dl-15-methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 compound.
Following the procedure of Example 21, but substituting for the 15-methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α methyl ester, the methyl ester of each of the 15-methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.β, -PGF 2 .sub.α, -PGF 2 .sub.β, -5,6-dehydro-PGF 2 .sub.α, -5,6-dehydro-PGF 2 .sub.β, -dihydro-PGF 1 .sub.α, and -dihydro-PGF 1 .sub.β compounds in their various natural or 15-epi configurations and optical isomers is transformed to the corresponding PGE-type compound.
Following the procedure of Example 21, each of the various 15-alkyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α methyl ester compounds, including the 15-ethyl, 15-propyl, 15-butyl, and 15-substituted isomeric forms of propyl and butyl, is transformed to the corresponding PGE type compound.
Also following the procedure of Example 21, each of the 15-alkyl PGF-type acids and esters within the scope of formula-LXXXVIII (Chart I) is transformed to a 15-alkyl PGE-type acid or ester encompassed by formula-LXXXIX.
EXAMPLE 22
dl-15-Methyl-3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGA 1 Methyl Ester (Formula XXIV: C g H 2g is a valence bond, C p H 2p is methylene, C g H 2g and C p H 2p are in ortho relationship, G is n-pentyl, Q is ##EQU77## R 1 is methyl, and ˜ is alpha).
Refer to Chart K. A mixture of the formula-XCV 15-methyl-3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGE 1 methyl ester (Example 21, 6 mg.), dicyclohexylcarbodiimide (20 mg.), copper (II) chloride dihydrate (2 mg.), and diethyl ether (2 ml.) is stirred under nitrogen at 25° C. for 16 hrs. Then, additional dicyclohexylcarbodiimide (20 mg.) is added, and the mixture is stirred an additional 32 hrs. at 25° C. under nitrogen. The resulting mixture is filtered, and the filtrate is concentrated under reduced pressure. The residue is chromatographed by preparative thin layer chromatography with the A-IX system to give the title compound.
Following the procedure of Example 22, but substituting for the oxa-phenylene PGE 1 compound, the methyl esters of dl-15-methyl-3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGE 2 , -5,6-dehydro-PGE 2 , and -dihydro-PGE 1 , there are obtained the corresponding formula-XCVI compounds, viz., the methyl esters of dl-15-methyl 3-oxa-4,7-inter-o-phenylene-5,6-dinor-PGA 2 , -5,6-dehydro-PGA 2 , and -dihydro-PGA 1 .
Also following the procedure of Example 22, but substituting for the phenyl-substituted PGE 1 compound, the methyl esters of dl-15-methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 , -PGE 2 , -5,6-dehydro-PGE 2 , and -dihydro-PGE 1 , there are obtained the corresponding formula-XCVI compounds, viz., the methyl esters of dl-15-methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 , -PGA 2 , -5,6-dehydro-PGA 2 , and -dihydro-PGA 1 .
Also following the procedure of Example 22, each of the formula-XCV (Chart K) compounds defined above in Example 21 is transformed to the corresponding formula-XCVI compound.
EXAMPLE 23
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 (Formula XVI: C g H 2p and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU78## R 1 is hydrogen, and ˜ is alpha).
Zinc dust (420 mg.) is added to a solution containing dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 β,β,β-trichloroethyl ester (100 mg.) in 5 ml. of a mixture of acetic acid and water (9:1 v/v). This mixture is under nitrogen 2 hrs. at 25°C. Ethyl acetate (4 volumes) is then added, followed by addition of 1 N. hydrochloric acid (one volume). The ethyl acetate later is separated, washed with water and then with brine, dried, and evaporated. The residue is chromatographed on 15 g. of acidwashed silica gel (Silicar CC4), being eluted with 100 ml. of 50%, 100 ml. of 80%, and 200 ml. of 100% ethyl acetate in Skellysolve B, collecting 20-ml. fractions. The fractions containing the desired product and no starting material or dehydration products as shown by TLC are combined and concentrated to the title compound.
Following the procedure of Example 23, each of the β,β,β-tribromoethyl, -triiodoethyl, β,β-dibromoethyl, -diiodoethyl, and the β-iodoethyl esters of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 is converted to the free acid of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 by reaction with zinc dust and acetic acid.
Following the procedure of Example 23, the β,β,βtrichloroethyl ester of dl-15-methyl-3-oxa-3,5-inter-m-phenylene-4-nor-PGE 2 following Example 9 above is converted to the respective free acid compound using zinc dust with either propionic, butyric, pentanoic, or hexanoic acid instead of acetic acid.
Following the procedure of Example 23, the β,β,β-trichloroethyl ester of each of the PGE, PGF, PGA, and PGF type compounds represented by formulas XVI-XXXV in their various structural configurations and optical isomers is treated with zinc dust and acetic acid to obtain the corresponding free acid form of the compound. The esters are prepared by the procedures disclosed herein, using as intermediates formula-XXXVII cyclic ketals or formula-XLIV or -LXX olefins wherein R 10 is haloethyl, e.g., β,β,β-trichloroethyl. These intermediates are prepared either by alkylation of the respective formula-XXXVI cyclic ketal (Chart D) or formula-XLIII or -LXIX olefin (Charts E and F) with the appropriate alkylating agent wherein R 10 is haloethyl, or by the transformation of the alkylated cyclic ketal or olefin by the steps shown in Charts G and H using procedures disclosed herein, yielding intermediates LXXIX, LXXXI, LXXXV, or LXXXVII.
EXAMPLE 24
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α and -PGF 1 .sub.β (Formula XX; C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU79## R 1 is hydrogen, and ˜ is alpha or beta).
A solution of 146 mg. of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α ethyl ester in a mixture of 4.5 ml. of methanol and 1.5 ml. of water is cooled to 5° C. and 0.6 ml. of 45% aqueous potassium hydroxide is added. The mixture is allowed to stand 3.5 hrs. at 25° C., then is diluted with 75 ml. of water and extracted once with ethyl acetate to remove any neutral material. The aqueous layer is separated, made acid with dilute hydrochloric acid and extracted 4 times with ethyl acetate. The extracts are combined and washed 3 times with water, once with brine, dried over sodium sulfate, and concentrated to give the PGF 1 .sub.α -type title compound.
Following the procedure of Example 24, the methyl ester of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.β is transformed to the free acid, i.e. the formula-XX pGF 1 .sub.β -type title compound.
Following the procedure of Example 24, the methyl or ethyl esters of the various oxa-phenylene PGF-type compounds and their isomers are transformed to the corresponding free-acid oxa-phenylene PGF-type compounds.
EXAMPLE 25
dl-3-Oxa-3,5-inter-m-phenylene-4-nor-PGF 2 .sub.α Methyl Ester (Formula XXI: C j H 2j and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU80## R 1 is methyl, R 3 and R 4 are hydrogen, and ˜ is alpha).
Refer to Chart C. dl-5,6-Dehydro-3-oxa-3,5-inter-m-phenylene-4-nor-PGF 2 .sub.α methyl ester (200 mg.) in pyridine (4 ml.) and methanol (10 ml.) is hydrogenated in the presence of a 5%-palladium-on-barium sulfate catalyst (200 mg.) at 25° and atmospheric pressure. The reaction is terminated when slightly more than one equivalent of hydrogen is absorbed. The mixture is filtered and evaporated. Ethyl acetate is added and residual pyridine is removed by addition of ice and 3 N. hydrochloric acid. The ethyl acetate layer is washed with 1 N. hydrochloric acid and then with brine, dried, and concentrated to yield the title product.
Following the procedure of Example 25, the 5,6-dehydro oxa-phenylene PGF 2 compounds following Example 4 are reduced to the corresponding PGF 2 compounds. Likewise, the 5,6-dehydro oxa-phenylene PGE, PGA, and PGB compounds disclosed herein are reduced to the corresponding PGE 2 , PGA 2 , and PGB 2 compounds.
EXAMPLE 26
dl-β,β,β-Trichloroethyl 9-[endo-6-(1,2-dihydroxy-2-methylheptyl)-3-hydroxybicyclo[3.1.0]hex-2.alpha.-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoate Acetonide (Formula LXXIX, Chart G: G is n-pentyl, J' is cis ##SPC147##
haloethyl is β,β,β-trichloroethyl, R 2 , R 11 , and R 12 are methyl, R 9 and R 26 are hydrogen, and ˜ is alpha and endo).
Refer to chart G. Successively, β,β,β-trichloroethanol (25 ml.), pyridine (15 ml.), and dicyclohexylcarbodiimide (4.0 g.) are added to a solution of formula-LXXVIII compound dl-9-[endo-6-(1,2-dihydroxy-2-methylheptyl)-3-hydroxybicyclo[3.1.0]hex-2.alpha.-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-cis-7-nonenoic acid acetonide (Example 13, 2.0 g.) in 100 ml. of dichloromethane. This mixture is stirred 3 hrs. under nitrogen at 25° C. Water (50 ml.) is then added, and the mixture is stirred 10 min. The dichloromethane is concentrated under reduced pressure, and the residue is extracted repeatedly with ethyl acetate. The combined extracts are washed with ice-cold 3 N. hydrochloric acid. Then, the extracts are washed successively with aqueous sodium bicarbonate solution and brine, dried, and concentrated under reduced pressure. The residue is chromatographed on 600 g. of silica gel, eluting with 10 l. of a 20-100% ethyl acetate-Skellysolve B gradient, collecting 50ml. fractions. The middle fractions which show a product free of starting materials on TLC are combined and concentrated under reduced pressure to give the title compound.
Following the procedure of Example 26, but using in place of the formula-LXXVIII 3-hydroxybicyclo[3.1.0]hexane acid acetonide, each of the specific endo and exo, alpha and beta, saturated and unsaturated formula-LXXVIII hydroxy acid ketals defined after Example 13, there are obtained the corresponding β,β,β-trichloroethyl esters of those 3-hydroxybicyclo[3.1.0]hexane acids.
Following the procedure of Example 26, but using in place of the formula-LXXVIII 3-hydroxybicyclo[3.1.0]hexane acid ketal, each of the specific formula-LXXX 3-oxo-acid ketals defined after Example 13, there are obtained the corresponding formula-LXXXI β,β,β-trichloroethyl esters of those 3-oxo-acid ketals.
Following the procedure of Example 26 but using in place of the formula-LXXVIII 3-hydroxy-acid ketal, each of the specific formula-LXXXIV (Chart H) 3-hydroxy and formula-LXXXVI 3-oxo acids defined after Example 14, there are obtained the corresponding formula-LXXXV and formula-LXXXVII β,β,β-trichloroethyl esters of those acids, respectively.
Following the procedures of Examples 3 and 9, each of the formula-LXXXI cyclic ketal haloethyl esters of Example 26 is transformed to the corresponding formula-XL (Chart D) 3-oxa or 4-oxa phenyl-substituted PGE 1 β,β,βtrichloroethyl ester. Thence, following the procedure of Example 23, each of the esters is transformed to the oxa-phenylene phenylene PGE 1 acid compound wherein R 10 of formula-XL is replaced with hydrogen.
Following the procedure of Examples 2 and 3 each of the formula-LXXXVII olefin haloethyl esters of Example 26 is transformed to the corresponding formula-XLVII (Chart E) oxa-phenylene PGE 1 β,β,β-trichloroethyl ester. Thence, following the procedure of Example 23, each of the esters is transformed to the corresponding PGE 1 -type acid compound wherein R 10 of formula-XL is replaced with hydrogen.
EXAMPLE 27
dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trino-PGA 1 Methyl Ester (Formula XXIV: C g H 2g and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU81## R 1 is methyl, and ˜ is alpha).
A solution of diazomethane (about 50% excess) in diethyl ether (25 ml.) is added to a solution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-pGA 1 (Example 5, 50 mg.) in 25 ml. of a mixture of methanol and diethyl ether (1:1). The mixture is allowed to stand at 25° C. for 5 min. Then the mixture is concentrated to give the title compound.
Following the procedure of Example 27, each of the other specific phenyl-substituted PGB type, PGA type, PGE type, and PGF type free acids defined above is converted to the corresponding methyl ester.
Also following the procedure of Example 27, but using in place of the diazomethane, diazoethane, diazobutane, 1-diazo-2-ethylhexane, and diazocyclohexane, there are obtained the corresponding ethyl, butyl, 2-ethylhexyl, and cyclohexyl esters of 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 . In the same manner, each of the other specific phenyl-substituted PGB type, PGA type, PGE type, and PGF type free acids defined above is converted to the corresponding ethyl, butyl, 2-ethylhexyl, and cyclohexyl esters.
EXAMPLE 28
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 Methyl Ester Diacetate.
Acetic anhydride (5 ml.) and pyridine (5 ml.) are mixed with dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 methyl ester (Example 3, 20 mg.), and the mixture is allowed to stand at 25° C. for 18 hrs. The mixture is then cooled to 0° C., diluted with 50 ml. of water, and acidified with 5% hydrochloric acid to pH 1. That mixture is extracted with ethyl acetate. The extract is washed successively with 5% hydrochloric acid, 5% aqueous sodium bicarbonate solution, water, and brine, dried and concentrated to give the title compound.
Following the procedure of Example 28 but replacing the acetic anhydride with propionic anhydride, isobutyric anhydride, and hexanoic acid anhydride, there are obtained the corresponding dipropionate, diisobutyrate and dihexanoate derivatives of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 methyl ester.
Also following the procedure of Example 28, but replacing the 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 compound with dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α and -PGF 1 .sub.β, and dl-15-methyl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub..alpha. and -PGF 1 .sub.β, there are obtained the corresponding triacetate derivatives of the 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF compounds.
Also following the procedure of Example 28, each of the phenyl-substituted PGE type, PGF type, PGA type, and PGB type esters and free acids defined above is transformed to the corresponding acetates, propionates, isobutyrates, and hexanoates, the PGE-type derivatives being dicarboxyacylates, the PGF-type derivatives being tricarboxyacylates, and the PGA-type and PGB-type derivatives being monocarboxyacylates.
EXAMPLE 29
dl-3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 Sodium Salt.
A solution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 (Example 23, 100 mg.) in 50 ml. of a water-ethanol mixture (1:1) is cooled to 5° C. and neutralized with an equivalent amount of 0.1 N, aqueous sodium hydroxide solution. The neutral solution is concentrated to give the title compound.
Following the procedure of Example 29 but using potassium hydroxide, calcium hydroxide, tetramethylammonium hydroxide, and benzyltrimethylammonium hydroxide in place of sodium hydroxide, there are obtained the corresponding salts of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 .
Also following the procedure of Example 29 each of the phenyl-substituted PGE type, PGF type, PGA type, and PGB type acids defined above is transformed to the sodium, potassium, calcium, tetramethylammonium, and benzyltrimethylammonium salts.
The various Preparations and Examples given above describe the preparation of racemic intermediates and final products. Each of the intermediates and final products named and defined above is also obtained in each of the enantiomeric forms, d and l, by resolution of that compound or by resolution of that intermediate used to prepare that compound. For example, natural configuration 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 free acid is prepared by resolution of dl-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGA 1 free acid (Example 5) or by dehydration as in Example 5 of optically active 3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 free acid with the same absolute configuration. These resolutions are carried out by procedures known in the art, and may be used to obtain prostaglandin-like materials having the spatial configuration of the natural prostaglandins, as typified by the following Examples 30-32.
EXAMPLE 30
Natural Configuration 3-oxa-3,5-inter-m-phenylene-4-nor-PGE 2 and PGF 2 .sub.α Methyl Esters (Formula-XVII and -XXI: wherein C j H 2j and C p H 2p are valence bonds in meta relationship, G is n-pentyl, Q is ##EQU82## R 1 is methyl; R 3 and R 4 are hydrogen; and ˜ is alpha).
The process shown in Chart D is used to prepare the PGE 2 -type compound first. The formula-XXXVII cyclic ketal intermediate wherein G is n-pentyl; J' is ##SPC148##
R 2 , r 9 , and R 26 are hydrogen; R 10 , R 11 , and R 12 are methyl; and ˜ is endo and alpha is prepared following the procedures of Example 9.
The formula-XXXVII compound is resolved as its optical isomers by the method of Corey et al., J. Am. Chem. Soc. 84, 2938 (1962), by reacting this keto compound with optically active L(+)-2,3-butanedithiol in the presence of p-toluene-sulfonic acid. The diastereomeric ketals are completely resolved on a preparative chromatographic column, and are then hydrolyzed separately, following the procedure of Example 9, to the formula-XXXVIII dihydroxy compounds. Transformation to the formula-XVII PGE 2 -type compounds is accomplished by the procedures of Example 3. Of the separate diastereoisomers, one corresponds to the configuration of natural PGE 2 and the other to its enantiomer. Conversion of the PGE 2 -type compound having the configuration of the natural product to the PGE 2 .sub.α -type methyl ester is done by borohydride reduction following the procedure of Example 4. The natural configuration-PGF 2 .sub.α -type free acid is formed from the methyl ester by saponification, following the procedure of Example 24.
EXAMPLE 31
Natural Configuration 3-Oxa-3,5-inter-o-phenylene-4-nor-PGE 1 Methyl Ester (Formula XVI: C g H 2g is ethylene; C p H 2p is a valence bond in ortho relationship to C g H 2g , G is n-pentyl, Q is ##EQU83## R 1 is methyl, and ˜ is alpha).
Refer to Chart E.
A. Methyl 7-[endo-6-(1-heptenyl)-3-oxobicyclo-[3.1.0]hex-2α-yl]-3-oxa-3,5-inter-o-phenylene-4-nor-heptanoate (Formula-XLIV, Chart E: G is n-pentyl; R 2 , R 9 , and R 26 are hydrogen; R 10 is methyl; Z' is ##SPC149##
and ˜ is alpha and endo).
1. Methyl 2-(3-hydroxypropyl)phenoxyacetate. To a solution of potassium t-butoxide (11.2 g.) in 150 ml. of dry tetrahydrofuran at 0°-5° C. is added with stirring 3-(o-hydroxyphenyl)propanol (15.2 g.) followed in a few minutes by methyl bromoacetate (20 g.). The cooling bath is removed and the mixture is stirred at ambient temperature until the reaction mixture becomes essentially neutral. The mixture is concentrated in vacuo at 30° C. and the residue is shaken with ether and water. The organic layer is washed with dilute potassium hydroxide solution, water, brine, and is dried over sodium sulfate and then concentrated in vacuo. The residue is distilled in a high vacuum to afford methyl 2-(3-hydroxypropyl)phenoxyacetate.
2. Methyl 2-(3-chloropropyl)phenoxyacetate. A mixture of methyl 2-(3-hydroxypropyl)phenoxyacetate (step A-1, 25 g.) and thionyl chloride (20 ml.) is heated to reflux for 1-2 hrs. The excess thionyl chloride is removed in vacuo and the residue is distilled in a high vacuum to afford methyl 2-(3-chloropropyl)phenoxyacetate.
3. Methyl 2-(3-iodopropyl)phenoxyacetate. A mixture of methyl 2-(3-chloropropyl)phenoxyacetate (step A-2, 24.3 g.), acetone (250 ml.) and sodium iodide (30 g.) is heated to reflux with stirring for about 40 hrs. The mixture is cooled, filtered and the filtrate is concentrated in vacuo at about 30° C. The residue is diluted with ether and the solution is washed with water, dilute sodium thiosulfate solution, brine and is dried over magnesium sulfate and then concentrated in vacuo. The product, methyl 2-(3-iodopropyl)phenoxyacetate, is used directly in the next step.
4. Following the procedure of Example 1-B, but replacing the methyl m-(chloromethyl)phenoxyacetate with methyl 2-(3-iodopropyl)phenoxyacetate (step A-3, 18 g.) and allowing the alkylation reaction to proceed for about 5 min. before acidification with hydrochloric acid, there is obtained the desired formula-XLIV methyl 7-[endo-6-(1-heptenyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,5-inter-o-phenylene-4-nor-heptanoate.
Following the procedure of Example 30, the above racemic formula-XLIV compound is resolved as two optically active isomers. These are both transformed by the subseqeunt steps of this example to the formula-XVI PGE 1 -type compounds, one of which corresponds to the configuration of natural PGE 1 and the other to its enantiomer.
B. Methyl 7-[endo-6-(1,2-dihydroxyheptyl)-3-oxo-bicyclo[3.1.0]hex-2α-yl]-3-oxa-3,5-inter-o-phenylene-4-nor-heptanoate (Formula-XLV, Chart E: G' is n-pentyl; R 2 , R 9 , and R 26 are hydrogen; R 10 is methyl; Z' is ##SPC150##
and ˜ is alpha and endo). To a solution of methyl 7-[endo-6-(1-heptenyl)-3-oxobicyclo[3.1.0]-hex-2α-yl]-3-oxa-3,5-inter-o-phenylene-4-nor-heptanoate (step A, above, 1,8 g.) in 30 ml. of tetrahydrofuran at 50° is added, with stirring, osmium tetroxide (200 mg.) followed by potassium chlorate (1.2g.) and 15 ml. of water. The reaction mixture is maintained at 50° for 2 hrs., cooled, the tetrahydrofuran is removed, and the aqueous phase is extracted with dichloromethane. The organic layer is dried and concentrated and the residue is chromatographed on 200 g. of silica gel. The column is eluted with 1 l. of 35% ethyl acetate-benzene and 1 l. of 40% ethyl acetate-benzene, collecting 30-ml. fractions. Those fractions containing the formula-XLV compound, in its isomeric erythro and threo forms free of starting material and impurities, are combined and concentrated.
C. Title compound. To a solution of the formula-XLV dihydroxy compound (step B, above, 0.8 g.) in 10 ml. of pyridine, cooled to 0°, is added 1.2 ml. of methane-sulfonyl chloride. The reaction mixture is stirred for 2 hrs. and 20 g. of ice is added. The mixture is extracted with ether-dichloromethane (1:1) and the organic layer is washed successively with dilute hydrochloride acid, water, saturated aqueous sodium bicarbonate, and brine, dried, and concentrated. The residue, containing the bis-mesylate is treated with 15 ml. of acetone and 10 ml. of water and stirred for 8- 16 hrs. at 25°. The acetone is removed in vacuo and the remaining solution is extracted with dichloromethane. The extract is dried and concentrated and the residue is chromatographed on 150 g. of silica gel using 500 ml. ethyl acetate followed by 3% methanol ethyl acetate as eluting solvent while collecting 30-ml. fractions. Those fractions containing the formula-XLVII product, free of starting material and impurities, are combined and concentrated to give the title compound; principle NMR spectral peaks at 6.57-7.3 (multiplet); 5.42-5.65 (multiplet); 4.60 (singlet) and 3.76 (singlet) δ.
EXAMPLE 32
Natural Configuration 3-Oxa-3,5-inter-o-phenylene-4-nor-PGF 1 .sub.α Methyl Ester (Formula-XX: C g H 2g is ethylene, C p H 2p is a valence bond in ortho relationship to C g H 2g , G is n-pentyl, Q is ##EQU84## R 1 is methyl, and ˜ is alpha for the carboxyl-containing moiety and for the ring hydroxyl).
Refer to Chart A. Following the procedure of Example 4, the formula-XVI PGE 1 -type compound of Example 31 is transformed to the title compound; principle NMR spectral peaks at 6.57-7.3 (multiplet); 5.33-5.56 (multiplet); 4.62 (singlet) and 3.75 (singlet) δ.
EXAMPLE 33
dl-3-Oxa-3,5-inter-m-phenylene-4-nor-PGE 3 Methyl Ester (Formula-XXXII; C j H 2j and C p H 2p are valence bonds in meta relationship, C n H 2n is methylene, Q is ##EQU85## R 1 is methyl, R 5 is ethyl, and ˜ is alpha) and dl-15-Beta-3-oxa-3,5-inter-m-phenylene-4-nor-PGE 3 Methyl ester Q is ##EQU86##
a. Refer to Chart F. Following the procedure of Preparation 4b, a solution of 100 g. of endo-bicyclo-[3.1.0]hexan-3-ol-6-carboxaldehyde 3-tetrahydropyranyl ether in 200 ml. of benzene is reacted with 250 g. of (hex-3-ynyl)triphenylphosphonium bromide (Axen et al., Chem. Comm. 1970, 602) in 3 l. of benzene at about -15° C. The mixture is warmed to 70° C. for 2.5 hours., cooled and filtered. The crude product is hydrolyzed to the 3-hydroxy compound and then oxidized to the 3-oxo ketone with Jones reagent. The desired formula-LXIX intermediate is isolated after silica gel chromatography.
b. There is next prepared the formula-LXX compound by alkylation. Following the procedures of Example 1-B, the product of step a above is reacted with methyl 9-chloro-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate (Preparation 7) to yield 7-[endo-6-(cis-1-hepten-4-ynyl)-3-oxobicyclo[3.1.0]hex-2α-yl]-3-oxa-3,7-inter-m-phenylene-4,5,6-trinor-7-nonynoate.
c. Glycol LXXI is next prepared, employing the product of step b and following the procedures of Example 2. Without separating the isomeric glycols, the bismesylate corresponding to formula-LXXII is then prepared following the procedures of Example 3. Thereafter, following hydrolysis of the bismesylate by the procedures of Example 3, the bisdehydro E 3 type compound corresponding to formula-LXXIII is recovered. Silica gel chromatography yields the respective C-15 epimers.
d. Following the procedures of Preparation 8, each of the C-15 epimers of step C above is hydrogenated to yield the corresponding title compounds.
EXAMPLE 34
1-Bicyclo[3.1.0.]hex-2-ene-6-endo-carboxaldehyde Neopentyl Glycol Acetal (Formula CIX: R 31 and R 32 taken together are --CH 2 --C(CH 3 ) 2 --CH 2 -- and ˜ is endo).
A mixture of 2,2-dimethyl-1,3-propanediol (900 g.), 5 l. of benzene and 3 ml. of 85% phosphoric acid is heated at reflux. To it is added, in 1.5 hr., a solution of optically active bicyclo[3.1.0]hex-2-ene-6-endo-carboxaldehyde (Prep.10, 500 g.) in 1 liter of benzene. Provision is made to take off azeotropically distilled water with a Dean-Stark trap. After 3 hr. the mixture is cooled and extracted with 2 liters of 5% sodium bicarbonate. The organic phase is dried over sodium sulfate and concentrated under reduced pressure. The resulting semisolid residue is taken up in methanol and recrystallized, using a total of 1200 ml. of methanol to which 600 ml. of water is added, then chilled to -13° C. to yield 300 g. of the title compound, m.p. 52°-55° C., and having NMR peaks at 0.66, 1.20, 0.83-2.65, 3.17-3.8, 3.96, and 5.47-5.88 δ, [α] D - 227° (C=0.8976 in methanol), and R f 0.60 (TLC on silica gel in 25% ethyl acetate in mixed isomeric hexanes). Further work-up of the mother liquors yields 50-100 g. of additional product.
Following the procedures of Example 34 but replacing the aldehyde with optically active bicyclo[3.1.0]hex-2-ene-6-exo-carboxaldehyde (see U.S. Pat. No. 3,711,515), there is obtained the corresponding formula-CIX acetal.
Following the procedures of Example 34 but using either the endo or exo form of the aldehyde and substituting for 2,2-dimethyl-1,3-propanediol one of the following glycols: ethylene glycol, 1,2-propanediol, 1,2-hexanediol, 1,3-butanediol, 2,3-pentanediol, 2,4-hexanediol, 2,4-octanediol, 3,5-nonanediol, 3,3-dimethyl-2,4-heptanediol, 4-ethyl-4-methyl-3,5-heptanediol, phenyl-1,2-ethanediol and 1-pentyl-1,2-propanediol, there are obtained the corresponding formula-CIX acetals.
EXAMPLE 35
d-8-(m-Acetoxyphenyl)-7-oxa-tricyclo-[4.2.0.0 2 ,4 ]octane-6-endo-carboxaldehyde Neopentyl Glycol Acetal (Formual CX: C p H 2p is a valence bond with attachment in the meta position, R 31 and R 32 taken together are --CH 2 --C(CH 3 ) 2 --CH 2 , R 39 is ##EQU87##
and ˜ is endo).
Refer to Chart L, step (a). A solution of the formula-CIX l-bicyclo[3.1.0]hex-2-ene-6-endo-carboxaldehyde neopentyl glycol acetal (Example 34, 5.82 g.) and m-acetoxybenzaldehyde (1.64 g.) in 25 ml. of benzene is charged to a Pyrex photolysis vessel equipped with an immersible water-cooled cold-finger and a fritted gas inlet tube. Dissolved oxygen is removed by bubbling nitrogen through the solution. The mixture is then irradiated at 350 nm. with a Rayonet Type RS Preparative Photochemical Reacter (The Southern New England Ultraviolet Co., Middletown, Conn.) equipped with 6 RUL 3500 A lamps. After 24 hr. the photolysate is concentrated under reduced pressure to a pale yellow oil, 10 g., which is subjected to silica gel chromatography. Elution with 10-70% ethyl acetate in Skellysolve B (mixture of isomeric hexanes) yields separate fractions of the recovered starting materials and the formula-CX title compound, a pale yellow oil, 0.86 g., having NMR peaks at 0.68. 1.20, 0.8-2.5, 2.28, 2.99, 3.12-3.88, 3.48, 4.97-5.52, and 6.78-7.60 δ; infrared absorption bands at 3040, 2950, 2860, 2840, 1765, 1610, 1590, 1485, 1470, 1370, 1205, 1115, 1020, 1005, 990, 90, 790, and 700 cm - 1 ; mass spectral peaks at 358, 357, 116, 115, 108, 107, 79, 70, 69, 45, 43, and 41; [α] D + 55° (C=0.7505 in 95% ethanol); and R f 0.18 (TLC on silica gel in 25% ethyl acetate in mixed isomeric hexanes).
Following the procedures of Example 35 but replacing the formula-CIX acetal with the formula-CIX compounds disclosed following Example 34, there are obtained the corresponding formula-CX compounds in their endo or exo forms and with corresponding exemplification of R 31 and R 32 .
Likewise following the procedures of Example 35 but replacing m-acetoxybenzaldehyde with aldehydes within the scope of formula CXIX above, as to C p H 2p , the attachment position on the phenyl ring, and the carboxyacyl group R 39 , or defined above, the corresponding formula-CX oxetanes are obtained wherein ˜ is endo or exo, and R 31 and R 32 correspond to the glycols employed after Example 34 above. Specifically, the following formula-CXIX aldehydes are employed: ##SPC151## ##SPC152##
EXAMPLE 36
d-2-Exo-[m-(pivaloyloxy)benzyl]-3-exo-bicyclo[3.1.0]-hexane-6-endo-carboxaldehyde Neopentyl Glycol Acetal (Formula CXII : C p H 2p is a valence bond with attachment in the meta position, R 31 and R 32 taken together are --CH 2 --C(CH 3 ) 2 --CH 2 --, R 43 is ##EQU88## and ˜ is endo).
(I). Refer to Chart L, steps (b) and (c). A mixture of lithium (0.25 g.) in 70 ml. of ethylamine is prepared at 0° C. and cooled to -78° C. A solution of the formula-CX d-8-(m-acetoxyphenyl)-7-oxa-tricyclo[4.2.0.0 2 ,4 ]-octane-6-endo-carboxaldehyde neopentyl glycol acetal (Example 35, 1.83 g.) in 10 ml. of tetrahydrofuran is added dropwise in about 5 min. After stirring at -78° C. for about 3.5 hr. the reaction is quenched with solid ammonium chloride and water-tetrahydrofuran. Unreacted lithium is removed, the mixture is warmed slowly to about 25° C., and ethylamine is removed. The residue is neutralized with dilute acetic acid, mixed with 200 ml. of brine, and extracted with ethyl acetate. The organic phase is washed with brine and a mixture of brine and saturated aqueous sodium bicarbonate (1:1), and dried over sodium sulfate. Concentration under reduced pressure yields the formula-CXI diol as a pale tan foamed oil, 1.64 g., having R f 0.03 (TLC on silica gel in 25% ethyl acetate in mixed isomeric hexanes).
(II). The product of part (I) is dissolved in 30 ml. of pyridine and treated with 1.5 ml. of pivaloyl chloride over a period of 22 hr. at about 25° C. The reaction mixture is mixed with water, then brine and extracted with ethyl acetate. The organic phase is washed successively with brine, water, saturated aqueous copper (II) sulfate, saturated aqueous sodium bicarbonate, and brine, and dried over sodium sulfate. Concentration under reduced pressure yields a residue, 2.53 g., which is subjected to silica gel chromatography to yield the formula-CXII title compound, 1.87 g., having NMR peaks at 0.71, 1.20, 1.33, 0.9-3.1, 3.28-4.00, 4.17, 4.7-5.2, and 6.77-7.53 δ; mass spectral peaks at 486, 485, 115, 73, 72, 57, 44, 43, 42, 41, 30, 29, 15; [α] D +10° (C=0.8385 in ethanol); and R f 0.50 (TLC on silica gel in 25% ethyl acetate in mixed isomeric hexanes).
EXAMPLE 37
d-2-Exo-(m-acetoxybenzyl)-3-exo-acetoxybicyclo]3.1.0]hexane-6-endo-carboxaldehyde Neopentyl Glycol Acetal (Formula CXII : C p H 2p is a valence bond with attachement in the meta position, R 31 and R 32 taken together are --CH 2 C(CH 3 ) 2 --CH 2 --, R 43 is ##EQU89## and ˜ is endo).
Following the precedures of Example 36-(II) but replacing pivaloyl chloride with acetic anhydride, and using 1.01 g. of the formula-CXI diol, there is obtained the title compound, 0.75 g., having NMR peaks at 0.72, 1.22, 1.98, 2.27, 0.8-3.0, 3.28-3.85, 4.17, 4.75-5.22, and 6.8-7.47 δ; mass spectral peaks at 402, 401, 115, 107, 73, 69, 45, 44, 43, 42, 41, 30;[α] D +7° (C=0.7060 in ethanol); and R f 0.66 (TLC on silica gel in 50% ethyl acetate in mixed isomeric hexanes).
EXAMPLE 38
2-Exo-[m-(pivaloyloxy)benzyl[-3-exo-(pivaloyloxy)bicyclo[3.1.0]hexane-6-endo-carboxaldehyde (Formula CXIII: C p H 2p is a valence bond with attachment in the meta position, R 42 is ##EQU90## and ˜ is endo).
Refer to Chart L step (d). The formula --CXII acetal, i.e. d-2-exo-[m-pivaloyloxy)benzyl]-3-exo-(pivaloyloxy)-bicyclo[3.1.0]hexane-6-endo-carboxaldehyde neopentyl glycol acetal (Example 36, 0.48 g.) is treated at 0° C. with 25 ml. of 88% formic acid for 4 hr. The mixture is diluted with 200 ml. of brine and extracted with ethyl acetate. The organic phase is washed with brine and saturated aqueous sodium bicarbonate, and dried over magnesium sulfate. Concentration under reduced pressure yields an oil, 0.55 g., which is subjected to silica gel chromatography. Elution with 5-15% ethyl acetate in Skellysolve B yields the formula-CXIII title compound as an oil, 0.37 g., having NMR peaks at 1.20, 1.33, 0.6-3.2, 5.1-5.5, 6.6-7.5, and 9.73 δ; and R f 0.50 (TLC on silica gel in 25% ethyl acetate in mixed isomeric hexanes).
EXAMPLE 39
2-Exo-[m-(pivaloyloxy)benzyl]-3-exo-(pivaloyloxy)-6-endo-(cis-1-heptenyl)-bicyclo[3.1.0]hexane (Formula CXIV: C p H 2p is a valence bond with attachment in the meta position, G is n-pentyl, R 42 is ##EQU91## R 2 is hydrogen, and ˜ is endo); and 2-Exo-(m-hydroxybenzyl)-3-exo-hydroxy-6-endo-(cis-1-heptenyl)bicyclo[3.1.0]hexane (Formula CXV : C p H 2p is a valence bond in the meta position, G is n-pentyl, R 2 and R 42 are hydrogen, and ˜ is endo).
(I). Refer to Chart L, steps (e) and (f). The Wittig ylid reagent is prepared in 10 ml. of benzene from n-hexyltriphenylphosphonium bromide (0.79 g.) and n-butyllithium (0.6 ml. of 2.32 M. solution in hexane) at about 25° C. for 0.5 hr. After the precipitated lithium bromide has settled, the solution is removed and added to a cold (0° C.) slurry of the formula-CXIII aldehyde (Examples 38, 0.37 g.). After 15 min. there is added 1.0 ml. of acetone and the mixture is heated to 60° C. for 10 min. The mixture is concentrated under reduced pressure. The residue is washed with 10% ethyl acetate in Skellysolve B and these washings are concentrated to the formula-CXIV title compound, an oil, 0.33 g. having NMR peaks at 1.18, 1.33, 0.6-3.2, 4.5-6.0 and 6.67-7.62 δ; and R f 0.78 (TLC on silica gel in 25% ethyl acetate in Skellysolve B).
(II.) The above product of part (I) is transformed to the formula-CXV diol by treatment with sodium methoxide (2.5 ml. of a 25% solution in methanol) for 4 hr., followed by addition of 0.5 g. of solid sodium methoxide and further stirring for 15 hr. at 25° C., then at reflux for 6 hr. The mixture is cooled, mixed with 300 ml. of brine, and extracted with ethyl acetate. The organic phase is washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to a residue, 0.27 g. The residue is subjected to silica gel chromatography, eluting with 25-35% ethyl acetate in Skellysolve B, to yield the formula-CXV title compound an an oil, 0.21 g., having NMR peaks at 0.87, 0.6-3.25, 3.88-4.35, 4.82-5.92, and 6.47-7.33 δ; and R f 0.13 (TLC on silica gel in 25% ethyl acetate in Skellysolve B).
Following the procedures of Examples 36, 38, and 39 but replacing the formula CX oxetane with each of those obtained following Example 35, there are obtained successively the corresponding formula-CXI, -CXII, -CXIII, and -CXIV compounds wherein C p H 2p and its attachment position on the phenyl ring correspond to the specific aldehydes employed following Example 35. These are obtained in both their endo and exo forms.
Further following the procedures of Example 39, but replacing the Wittig ylid reagent with one prepared from a compound of the formula
Br--P(C.sub.6 H.sub.5).sub.3 --CHR.sub.2 --G
wherein --CHR 2 --G is each of the following:
--(CH 2 ) 3 --CH 3
--(ch 2 ) 4 --ch 3
--(ch 2 ) 6 --ch 3
--(ch 2 ) 7 --ch 3
--ch(ch 3 )--(ch 2 ) 5 --ch 3
--ch 2 --ch(ch 3 )--(ch 2 ) 3 --ch 3
--ch 2 --c(ch 3 ) 2 --(ch 2 ) 3 --ch 3
--ch(ch 3 )--c(c 2 h 5 ) 2 --(ch 2 ) 3 --ch 3
--ch 2 --chf--(ch 2 ) 3 --ch 3
--ch 2 --cf 2 --(ch 2 ) 3 --ch 3
--ch(ch 3 )--cf 2 --(ch 2 ) 3 --ch 3 ##SPC153## ##SPC154##
--(ch 2 ) 2 --c.tbd.c--c 2 h 5
--ch 2 --ch(ch 3 )--c.tbd.c--c 2 h 5
--ch 2 --c(ch 3 ) 2 --c.tbd.c--c 2 h 5
or
--CH(CH 3 )--CH 2 --C.tbd.C--C 2 H 5
there are obtained the corresponding compounds within the scope of formula CXIV wherein C p H 2p and its attachment to the phenyl ring correspond to the specific compounds of Example 39 and those illustrated in the paragraph immediately thereafter, in both their endo and exo forms.
EXAMPLE 40
2-Exo-{m-[(carboxy)methoxy]{-3-exo-hydroxy-6-endo-(cis-1-heptenyl)bicyclo[3.1.0]hexane (Formula CXVI : C p H 2p is a valence bond with attachment in the meta position, G is n-pentyl, R 1 , R 2 , and R 42 are hydrogen, and ˜ is endo).
Refer to Chart L, step (g). The formula-CXV diol, i.e. 2-exo-(m-hydroxybenzyl)-3-exo-hydroxy-6-endo-(cis-1-hepentyl)bicyclo[3.1.0]hexane (Example 39, 0.19 g.) is treated in 8 ml. of dioxane with bromoacetic acid (0.61 g.) and 6 ml. of 1N. aqueous sodium hydroxide. After the mixture has been heated at reflux for 3 hr., with sodium hydroxide solution added when necessary to maintain a pH of about 10, the mixture is cooled, diluted with 100 ml. of water, and extracted with diethyl ether. The aqueous phase is acidified to pH 1-2 and extracted with ethyl acetate to yield the formula-CXVI title compound, a pale yellow oil, 0.20 g. Recovered formula- CXV diol is obtained from the diethyl ether organic phase on drying and concentrating, 0.025 g.
Following the procedures of Examples 40 but replacing bromoacetic acid with a haloacetate within the scope of Hal--CH 2 --COOR 1 as defined herein and specifically illustrated as follows
Cl--CH 2 --COOCH 3
Br--CH 2 --COOC 2 H 5
Cl--CH 2 --COOC 8 H 17 (n)
I--ch 2 --cooch 2 c 6 h 5
cl--CH 2 --COO(m--Cl--C 6 H 4 )
there are obtained the corresponding formula-CXVI compounds wherein R 1 is respectively methyl, ethyl, n-octyl, benzyl, and m-chlorophenyl.
Likewise following the procedures of Example 40 with each of the formula-CXIV compounds disclosed following Example 39 and using each of the haloacetates specifically identified above, there are obtained the corresponding formula-CXVI compounds.
EXAMPLE 41
3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGF 1 .sub.α (Formula CI : C p H 2p is a valence bond with attachment in the meta position, R 30 is n-pentyl, and R 1 and R 2 are hydrogen).
(I). Refer to Chart L. The formula-CXVI alkene is transformed to the title compound applying the procedures disclosed in U.S. Pat. No. 3,711,515. Thus, compound CXVI (Example 40) is hydroxylated by the procedures of Example 39 of that patent to the formula-CXVII glycol of Chart L, using osmium tetroxide either alone or in combination with N-methylmorpholine oxide-hydrogen peroxide complex.
The glycol is then either (1) sulfonated, for example to yield the bismesylate, and then hydroyzed to a mixture of the title compound and its 15-epimer, applying the procedures of Example 7 of that patent, or (2) treated with substantially 100% formic acid to form the diformate of CI and thereafter hydroyzed to a mixture of the title compound and its 15 epimer, applying the procedures of Examples 20 and 21 of that patent. The epimers are separated by silica gel chromatography to yield the title compound and its 15-epimer.
(II). A third route from glycol CXVII to the title compound is by way of a formula-CXX cyclic ortho ester ##SPC155##
wherein C p H 2p , R 46 , R 47 and ˜ are as defined above. The glycol CXVII is treated as a 1-20% solution in benzene with trimethyl orthoformate (1.5-10 molar equivalents) and a catalytic amount (1% of the weight of the glycol) of pyridine hydrochloride at about 25° C. The reaction is followed by TLC (thin layer chromatography) and is complete in a few minutes. There is thus obtained the formula-CXX cyclic ortho ester in 100% yield.
The cyclic ortho ester is then treated with 20 volumes of 100% formic acid at about 25° C. In about 10 min. the reaction mixture is quenched in water or aqueous alkaline bicarbonate solution and extracted with dichloromethane. The organic phase is shaken with 5% aqueous sodium bicarbonate, dried over sodium sulfate, and concentrated to yield the formula CXXI diester, in this example identical with the diformate of compound CI. The diformate is contacted with 10-50 volumes of anhydrous methanol and 10-20% of its weight of potassium carbonate at about 25° C. until the formyl groups are removed. The mixture of 15-epimers thus obtained is then separated to yield the formula-CI title compound and its 15-epimer.
Following the procedures of Example 41, each of the formula-CXVI alkenes disclosed following Example 40 is converted into the corresponding oxa-phenylene PGF.sub.α analog and its 15-epimer. There are likewise formed the corresponding oxa-phenylene 17,18-didehydro-PGF.sub.α analogs as shown in Chart N.
EXAMPLE 42
2-Exo-[m-(carboxymethoxy)benzyl]-3-exo-hydroxy-6-endo-(cis-1-heptenyl)bicyclo[3.1.0]hexane (Formula CXXVII: C p H 2p is a valence bond with attachment in the meta position, G is n-pentyl, R 1 and R 2 are hydrogen, and ˜ is endo).
Refer to Chart M, steps (a)-(f). There is first prepared the formula-CXXII oxetane. Following the procedures of Examples 34 and 35 but replacing the m-acetoxybenzaldehyde of Example 35 with an aldehyde within the scope of ##SPC156##
as to C p H 2p , the attachment position on the phenyl ring, and the carboxyl group R 44 , as defined above, the corresponding formula-CXXII oxetanes are obtained with a fully developed side chain. Specifically, the following formula-CXXXI aldehydes are employed: ##SPC157##
Thereafter, following the procedures of Examples 36, 38, and 39, but replacing the formula-XX ocetane of Example 36 with those obtained by the procedure disclosed in the above paragraph of this example, there are obtained the corresponding formula-CXXVI products. Likewise following those procedures of Examples 36, 38, and 39, but replacing the Wittig ylid reagent of Example 39 with each one disclosed after Example 39, and applying it to each of the above formula-CX compounds of this example, there are obtained the corresponding formula-CXXVI compounds with those specific side-chains.
Finally, the blocking groups on each CXXVI compound are removed by methods disclosed herein or known in the art to yield the formula-CXXVII title compound and the corresponding formula-CXXVII compounds from those formula-CXXVI compounds above.
EXAMPLE 43
2-Exo-{m-[(methoxycarbonyl)methoxy]benzyl}3-exo hydroxy-6-endo-(cis-1-heptenyl)bicyclo[3.1.0]hexane (Formula CXXVII: C p H 2p is a valence bond with attachment in the meta position, G is n-pentyl, R 1 is methyl, R 2 is hydrogen, and ˜ is endo).
Refer to Chart M. The formula-CXXVII acid (Example 40, 0.20 g.) is treated in methanol solution at 0° C. with a solution of diazomethane in diethyl ether (prepared from N-methyl-N-nitroso-N'-nitroguanidine (2.0 g.) and potassium hydroxide (6 ml. of 40% aqueous solution)) until a permanent yellow color is produced, and the mixture is concentrated to yield the title compound, a pale tan oil.
EXAMPLE 44
l-6-Endo-(cis-1-heptenyl)-2-exo-{m-[(methoxycarbonyl)methoxy]benzyl}bicyclo[3.1.0]-hexan 3-one (Formula CXXVIII: C p H 2p is a valence bond with attachment in the meta position, G is n-pentyl, R 1 is methyl, R 2 is hydrogen, and ˜ is endo).
Refer to Chart M, step (g). The formula-CXXVII methyl ester is oxidized to the bicyclic hexanone as follows. The formula-CXXVII methyl ester (Example 41, 0.21 g.) is added in 2 ml. of dichloromethane to a solution of Collins reagent (prepared from pyridine (0.53 g.) and chromium trioxide (0.34 g.) in 10 ml. of dichloromethane) at about 25° C. for 15 min. The mixture is then shaken with a mixture of 60 ml. of diethyl ether, ice, and 25 ml. of 1 N. aqueous sodium hydroxide, and the organic phase is separated. The organic phase is washed with 1 N. aqueous sodium hydroxide, 1.2 N. aqueous hydrochloric acid, and brine, dried, and concentrated under reduced pressure. The residue, a colorless oil, 0.19 g., is subjected to silica gel chromatography, eluting with 5- 20% ethyl acetate in Skellysolve B. There is thus obtained the formula-CXXVIII title compound, a colorless oil, 0.13 g., having NMR peaks at 0.87, 0.6-3.3, 3.77, 4.60, 4.5-5.1, 5.37-5.95, and 6.58-7.40 δ; [α] D -39° (C=0.8380 in 95% ethanol); and R f 0.42 (TLC on silica gel in 25% ethyl acetate in Skellysolve B).
Following the procedures of Examples 43 and 44, each of the above-identified formula-CXXVII compounds following Example 42 is oxidized to the corresponding formula-CXXVIII compound.
EXAMPLE 45
3-Oxa-3,7-inter-m-phenylene-4,5,6-trinor-PGE 1 , Methyl Ester (Formula XCVII: C p H 2p is a valence bond with attachment in the meta position, R 1 is methyl, R 30 is n-pentyl, and R 2 is hydrogen).
Following the procedures of Example 41, the formula-CXXVIII alkene is transformed in several steps to the title compound.
Likewise, following the same procedures, each of the formula-CXXVIII alkenes disclosed following Example 44 is converted into the corresponding oxa-phenylene PGE analog and its 15 -epimer.
Following the procedures of Examples 34-45, each of the endo intermediates is replaced by the corresponding exo intermediate to yield the corresponding exo intermediate or the ultimate oxa-phenylene PG analog.
Likewise following the procedures of Examples 34-45, each of the optically active isomers is replaced by the corresponding racemic mixture to yield the corresponding racemic intermediate or ultimate oxa-phenylene PG analog.
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This invention is a group of PGF 1 .sub.α -type oxaphenylene compounds, and processes for making them. These compounds are useful for a variety of pharamcological purposes, including inhibition of platelet aggregation, treatment of asthma, labor inducement at term, and cervical dilation.
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FIELD OF THE INVENTION
The present invention generally relates to continuous separation and reaction of chemical fluids (liquids, solutions and gases) using supercritical fluids, and more particularly to the separation of industrial fluids into sub-components based on the different solubility of the components in supercritical fluids.
BACKGROUND OF THE INVENTION
There are a number of applications in which chemical components in a mixture need to be separated. The fields of application include many industries such as chemical, environmental, food, medical, enzymatic, pharmaceutical and recycling. The problems to be overcome by the present invention will now be discussed with reference to the recycling industry, but it should be understood this discussion is representative of the problems faced by the other industries.
Used lubricating and hydraulic oils are generated by a number of industries, including automotive and commercial shops, large industrial manufacturing facilities, marine facilities and airline and railroad maintenance departments. Used oils are considered hazardous wastes and are heavily regulated. It is the contamination of these oils with water and waste products that prevent their continued use. Generators of used oils are responsible for cradle to grave management of these waste streams and, in most cases, contract with used oil recyclers to remediate or dispose of the waste under the laws that regulate the transport, processing and destruction of the various components that make up these particular waste streams.
Currently, on-site remediation of these waste streams proves to be quite costly. The generators must contract with firms that have special expertise in reclaiming these waste streams as an on-site service. As an alternative, used oil recyclers can pick up oil from generators for transportation back to a plant for processing. After the oil is processed it can be resold as industrial burning fuel. This process of treating used oils is complex, costly and time consuming and produces waste components that require further remediation. Further, these used oils that are burned as fuel oils result in the original value of the oil being greatly reduced. Thorough purification to achieve a state as close to original quality and value as possible, much of the value of these recycled materials can be recovered. It has been the lack of an economical purification process of sufficient quality that has prevented the direct reuse or higher value use of these materials.
The use of supercritical fluids for separation and purification is known. A supercritical fluid is named based on the physical properties exploited. When a gas is compressed and maintained below its critical temperature, it becomes liquid. If during the compression the liquid gas is allowed to exceed its critical temperature, it will result into a dense gas called as supercritical fluid, whose pressure and temperature are above its critical states.
Supercritical fluids have solvation power similar to liquids, but also possess higher diffusion coefficients and lower viscosities at the same temperature. Supercritical fluids have the potential to extract components from a mixture at a more rapid extraction rate than possible with liquid extraction. The “gas like” low viscosities of supercritical fluids are 10-100 times lower than for liquids, and high diffusivities are 10-100 times higher than for liquids. The densities of supercritical fluids are 10 2 to 10 3 times greater than that of a gas at room temperature. Consequently the molecular interactions are greater due to shorter inter-molecular distances; hence the solvation power of supercritical fluids.
There are two general types of supercritical fluid systems typically employed for separation and purification. Both are fundamentally limited due to the specific technology and design approach. The first general type is a “batch” system, in which a batch is processed, the equipment is cleaned or serviced, another batch is processed, and the cycle is repeated as necessary. Batch systems operate at very high pressure and employ vessels of large volume; these systems are extremely expensive and inefficient. The second general type is a “continuous” system, in which the fluid to be processed is processed continuously, and not in “batches”. Existing continuous supercritical fluid systems utilize counter flow technology, in which feed material flows from top to bottom of a very complex long vertical column and a supercritical fluid flows from bottom to top of the column selectively dissolving specific components from the feed liquid. Systems of this type are very inefficient and rely on a large surface area on a wire mesh inside the column to strip off lighter components from the feed liquid. It requires many temperature sensors and complex controls, and it has very limited flow efficiency. Consequently, the liquid is usually required to be recycled several times to sufficiently extract desired components.
Various supercritical fluids have been used to facilitate the separation of emulsions. U.S. Pat. No. 5,435,920 to Penth discloses a process for cleaving spent emulsions such as cooling lubricants by means of carbon dioxide under pressure, and if necessary, heat in an economic and environmentally friendly manner. The emulsion of cooling lubricant is saturated under pressure with carbon dioxide and is heated and/or cooled until cleavage is achieved. Above the cleavage temperature, a floating water-poor oil phase quickly forms above an oil-poor aqueous phase. The process is not very efficient economically due to the relatively low solubility of lubricant in carbon dioxide.
Yamaguchi et al., Volumetric Behavior of Ethyl Esters Related to Fish Oil in the Presence of Supercritical CO 2 , the 4 th International Symposium on Supercritical Fluids, May 11-14, Sendai Japan (1997), pp. 485-488, discloses using supercritical CO 2 for the separation and fractionation of certain components of fish oil. The experimental apparatus included a static mixer in a water bath, and was a batch process. The batch process lowers the competitiveness of the process.
Another example of the use of supercritical CO 2 is Nagase et al., Development of New Process of Purification and Concentration of Ethanol Solution using Supercritical Carbon Dioxide, Id. at pp. 617-619. The experimental apparatus included a pre-heater and a static mixer in an air bath.
Subramanian, M, Supercritical fluid extraction of oil sand bitumen from Uinta Basin, (Utah, Ph.D. dissertation, University of Utah, Salt lake city, Utah, 1996) discloses the use of propane to fractionate oil sand bitumen into different fractions. The process was not continuous in nature. U.S. Pat. No. 2,196,989 to Henry et al. discloses the use of propane in a batch process to purify used engine oil. U.S. Pat. No. 3,870,625 to Wielezynski discloses mixing propane and used oil in a column and letting gravity settle unwanted material in the bottom of the tank. A series of columns allows for multiple repetitions until propane is finally separated from the oil. U.S. Pat. No. 5,556,548 discloses a method by which liquid propane is mixed with used oil and propane/soluble oil is separated from sludge and heavy metal using a settling tank and gravity.
Notwithstanding advances in the art, the need still exists for a process for treating chemical fluids, particularly the recycling of oil, which can be used on-site, which utilizes a continuous flow system and that proves to be cost effective and environmentally friendly.
SUMMARY OF THE INVENTION
This invention broadly contemplates continuous separation and reaction of chemical fluids (liquids, solutions and gases) using supercritical fluids, including the separation of industrial fluids into sub-components based on the different solubility of the components in supercritical fluids. The process focuses on the difference of the solubility of the desired and undesired components of the processed fluid in the supercritical fluid.
The first aspect of the invention is a continuous dynamic mixing of the chemical fluids with supercritical fluid. To achieve this goal the processed fluid is atomized into supercritical fluid using jet-spray micro orifices, additional means to achieve maximum thermodynamic equilibrium during resident time, is using magneto drive and Ultrasonication device.
Another aspect of the invention is using thermal energy to reach desired temperatures for both the process fluid and the supercritical fluid. Another aspect of the invention is the ability to have two modes of continuous operations as required, co-flow and counter-flow modes of operations.
Another aspect of the invention is the need for at least one separation vessel to separate soluble and un-dissolved components and another separation vessel to separate soluble components from the recyclable supercritical fluid. The fractionation of dissolved components, can be done according to their different solubilities in the supercritical fluid at different densities, by using several separation vessels.
Another aspect of the present invention is that it minimizes waste components that require further remediation. For example, when the present invention is used to process a petroleum product, the amount of water and other residues in the starting material does not alter the quality of the final product or its fundamental process procedure. The present invention minimizes the production of the rag layer, that is, un-dissolved oil residue and water layer. This reduces or eliminates another cost element, that is, disposing of the rag layer. The separated components (still under high pressure) can be made harmless to the environment by additional reactions, such as breaking down PCB's into harmless chemicals using on line supercritical water oxidation.
Another aspect of the present invention is that this system can be easily scaled or adapted to both volume and flow. Energy is conserved in the process as part of the fundamental design. The present invention can be scaled down to be dedicated for some specific applications. For example, it can be used on a small scale to recycle well-defined used oil, such as on merchant or navy ships, military engines and other such applications. The clean product can be used as clean engine oil after making up some of the depleted additives.
The present invention is also so compact that it can be used as a mobile processing system making it possible to take the present invention to the source. This is a strategic advantage and one that may introduce a new paradigm in this field. Because of this compact nature it is also possible to integrate the purification into other mechanical systems to continuously purify oil and solvent components.
The fundamental nature of the present invention is more amenable to real time application in conjunction with other process. The continuous operation and the fewer requirements for a holding tank, allow the process to be applied in other than tank or tanker batches and permit a new flexibility. By adding one module to the existing system it can also be used as a dedicated application for cleaning of oil contaminated solids such as metal parts, machinery or rags with the oil directed to the oil purification process.
Those and other advantages and benefits of the present invention will become apparent from the tailed Description of the Preferred Embodiment herein below
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 depicts a block diagram of the major elements of a system capable of practicing the method of the present invention.
FIG. 2 is a block diagram of sub-system in co-flow operation.
FIG. 3 is a block diagram of preferred action within the high-pressure reactor.
FIG. 4 is a block diagram of a sub-system in counter-flow operation.
FIG. 5 is a block diagram showing the preferred action with a reactor.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 depicts a block diagram of the major elements of a system capable of practicing the method of the present invention. The fluid to be processed is transferred from the chemical reservoir ( 1 ) by chemical fluid pump ( 2 ) into a heat exchanger ( 3 ), then into the sub-system ( 100 ). The sub-system ( 100 ) may be either co-flow or counter-flow, and the operation of each is discussed in detail below. Supercritical fluid is transferred from solvent liquid reservoir ( 4 ) by solvent pump ( 5 ) into high-pressure heat exchanger ( 6 ) to achieve supercritical conditions of temperature and pressure, then the supercritical fluid enters reactor ( 100 ). The high-pressure reactor is maid of metal alloy, which is not compatible with using another form of heating such as microwave. In addition using microwave compatible material such as peek will limit the maximum pressure and reduce the efficiency and the safety of the process. The dissolved components in the supercritical fluid are phased out from the supercritical fluid by lowering the pressure at cyclone separator ( 10 ) using backpressure regulators ( 11 , 15 ) and heat exchanger ( 16 ). The supercritical fluid can be changed into liquid or gas by decreasing the pressure, this will result in the loss of the solvation power and hence, the phasing out of the dissolved components. The fractionation of dissolved components can be done according to their different solubilities in the supercritical fluid at different densities. The dissolved components can be phased out when the new conditions the supercritical fluid becomes liquid or gas. The previously dissolved components are no longer soluble and phase separation takes place, which results in the separation of these components to the bottom of cyclone separator ( 10 ). The gas may be condensed and cooled down into liquid with heat exchanger ( 12 ), or alternatively the liquid could be cooled. The resulting liquid is pressurized and heated into supercritical, subcritical or liquid before recycling back to solvent pump ( 5 ) for continuous operation. The dissolved components ( 18 ) are preferably periodically drawn off cyclone separator ( 10 ) in a controlled manner.
Referring now to FIG. 2 , a block diagram of sub-system ( 100 ) in co-flow operation is shown. In this embodiment, sub-system ( 100 ) includes a high-pressure reactor ( 13 ), and cyclone separator ( 14 ). The pre-filtered fluid is injected into the high-pressure reactor ( 13 ) as described below. Cyclone separator ( 14 ) is used for the separation of dissolved and un-dissolved components from the supercritical fluid. The un-dissolved components in the supercritical fluid are allowed to precipitate and settle out in cyclone separator ( 14 ) and these un-dissolved components ( 17 ) are preferably periodically drawn off in a controlled manner. Backpressure regulator ( 15 ) and heat exchanger ( 16 ) are used in conjunction with cyclone separator ( 10 ) and backpressure regulator ( 11 ) to phase out the dissolved components in the supercritical fluid as discussed above.
Referring now to FIG. 3 , the preferred action within high-pressure reactor ( 13 ) is shown. The supercritical fluid enters from one end of the reactor. The jet spray of the chemical fluid is done perpendicular to the flow of the supercritical fluid. High-pressure jet spray micro-orifices ( 20 ) atomize the fluid to micro droplets inside the supercritical fluid reactor ( 13 ) resulting in a mixing of the two fluids and the solubilization of some components into supercritical fluid. The solubility depends on the type and conditions of the supercritical fluid, and polarity and the chemical structure of the molecules in the processed fluid. To ensure complete mixing of the processed fluid and the supercritical fluid without creating backpressure, a magneto driven impeller shaft ( 19 ) is preferably employed along the axis of the reactor ( 13 ). This active mixing tool ensures complete mixing and consequently achieving thermodynamic equilibrium during the contact time between the supercritical fluid and the fluid being processed. An ultrasonic gun ( 21 ) made of titanium is preferably inserted on the other side of the reactor to add micro-mixing agitation. Ultrasonication in supercritical conditions can create sinusoidal compression/decompression waves inside the supercritical reactor. The advantage of this technology is to increase mixing strength to a maximum level extending to the molecular level. This tool is additional factor to achieving thermodynamic equilibrium in the reactor ( 13 ). Because the fluid to be processed and the supercritical fluid, collectively the fluids, travel together through the system from this point on, the process is referred to as a co-flow process.
The present invention combines two fluids (the fluid being processed and a supercritical fluid) at high pressure and achieves active mixing by a device employing jet spray micro-orifices, impeller shaft, and ultrasonic gun. Using passive mixing such as static mixing elements may be simpler, however, problems such as excessive back-pressure and incomplete mixing may be created in the due process. The purpose of this is to vigorously atomize the processed fluid and mix two components into essentially one homogenous suspension phase and achieve full thermodynamic equilibrium during the resident time in the reactor. This attribute is derived from the turbulence and the fluids' high linear flow velocity. When the fluids are no longer subjected to the turbulent mixing, the fluids will separate into individual components according to density and molecular weight and according to their solubility in the supercritical fluid. The insoluble and heavy material will settle out collecting in the bottom of the cyclone separator ( 14 ). The solution of supercritical fluid, which includes dissolved components, will flow from the top of the first cyclone separator ( 14 ) to the second cyclone separator ( 10 ). One aspect of the present invention is that a series of cyclone separators precisely calibrated for temperature and pressure create unique environments and will phase out higher molecular weight components in earlier separators and progress to lighter components in subsequent separators without pressurizing or expending additional energy.
FIG. 4 is a block diagram of sub-system ( 100 ) in counter-flow operation. Typically, this embodiment is used in pharmaceutical applications where there objective os stripping lighter components from a polymer solution. In this embodiment, sub-system ( 100 ) includes vertical reactor ( 7 ) and the dissolved and the un-dissolved components are separated inside the vertical reactor ( 7 ) during operation, thus eliminating the need for cyclone separator ( 14 ) as shown in FIG. 4 . It should be noted, however, that a single or multiple separation vessel such as cyclone separator ( 14 ) may be added to sub-system 100 as required to fractionate the soluable components into different fractions according to their molecular weights.
Referring now to FIG. 5 , the preferred action within reactor 7 is shown. Reactor ( 7 ) is preferably perpendicular and long in length to increase the contact time between the processed fluid and the supercritical fluid. The nature of the flow inside the reactor is not turbulent in comparison with the co-flow process. The supercritical fluid again enters from one end of the reactor. The jet spray of the chemical fluid is preferably done at a 45° angle opposing the flow of the supercritical fluid. As discussed above, high-pressure jet spray micro-orifices ( 20 ) atomize the fluid to micro droplets inside the supercritical fluid reactor ( 7 ) resulting in a mixing of the two fluids and the solubilization of some components into supercritical fluid. The solubilization of the dissolved components in the supercritical fluid depends on the atomization of the injected fluid into the stream of supercritical fluid.
The flow of the supercritical fluid in the vertical reactor is upward. During the contact time between the supercritical fluid and the atomized injected fluid, the dissolvable components will be carried upward by the supercritical fluid. The higher density of the un-dissolved components will result in the sedimentation down ward due to the gravity. The accumulated un-dissolved components can be removed periodically from the bottom of the reactor itself. The dissolved components can be separate from the supercritical fluid using one cyclone separator ( 10 ). A magneto drive impeller shaft is not used inside the reactor ( 7 ) in the counter-flow process. An ultrasonic gun ( 21 ), discussed above, optionally may be used as it works by increasing micro agitation without disturbing the opposite flows of the supercritical fluid (up) and the processed fluid (down).
In either of the preferred embodiments, the system of the present invention is usually closed during operation but may be open if recycling of the supercritical fluid is not desired in small-scale research operation. Temperature sensors, not shown in the Figures, monitor the temperature of the fluids in reactors ( 7 , 13 ), and the cyclone separators ( 14 ) ( 10 ). That information may be relayed to a central control system, which may, in turn, control the heat source. Temperature and pressure are not only necessary in controlling the conditions in the supercritical fluid reactors ( 7 , 13 ) of the system, but are necessary in controlling conditions when multiple separators are used. Those of ordinary skill in the art will recognize that pressure gauges, valves, and other devices will be needed to properly operate the system shown in FIG. 1 and the reactors shown in FIGS. 2 and 4 . Such devices are well known in the art and have been omitted from these Figures for purposes of clarity. Moreover, the present invention may be easily scaled with respect to flow and volume.
In either of the preferred embodiments, the supercritical fluid acts as a solvent selectively dissolving certain components of the processed fluid. Table 1 is an example of some of the conventional supercritical fluids that are commercially available and may be used in the present invention.
TABLE 1
Physical Parameters of Selected Supercritical Fluids
Critical
Super-
Temper-
Critical
Critical
ature
Pressure
Fluid
T c (° C.)
P c (atm)
CO 2
31.3
72.9
N 2 O
36.5
72.5
NH 3
132.5
112.5
CH 4
82.1
45.8
C 2 H 6
32.2
48.2
C 3 H 8
96.8
40.0
C 4 H 10
152.0
37.5
C 5 H 12
196.6
33.3
SF 6
45.5
37.1
Xe
16.6
58.4
CCl 2 F 2
111.8
40.7
CHF 3
25.9
46.9
All conventional solvents and detergents, such as methanol, ethanol, hexane, acetic acid, N 2 O, etc., can be used as a co-modifier to enhance the solubility parameters of supercritical fluids as well as to increase specificity of the solvation power of the supercritical fluid. Modifiers (usually an organic solvent), usually increase the solvation power of the supercritical fluids. Modifiers may dissociate sample molecules by forming clusters around them. These clusters may dissolve more rapidly in supercritical fluids in comparison with sample molecules. Analog modifiers can make supercritical fluids more selective for certain types of components depending on their chemical structure. The analog modifier shares at least a common functional group with the component to be selectively solubilized by the supercritical fluids. By adding the modifier directly to the supercritical fluid, and monitoring their concentration on line, or by premixing modifiers with the fluids to be processed, the selectivity of the supercritical fluid can be “tuned” to the fluid being processed.
The molecules of CO 2 and propane (the preferred supercritical fluids) are both non-polar, and hence they can dissolve very little of polar components such as water and PCB's. The sludge, dirt, and heavy metals do not dissolve either in non-polar molecules. Propane has the advantage over CO 2 in having more solvation power toward similar hydrocarbon molecule in the used oil, as liquid, sub-critical, and supercritical phases of propane. Accordingly the propane/used oil ratio is much lower than that of CO 2 /used oil ratio. This is an advantage from energy consumption during operation.
Propane is the preferred supercritical fluid as it can dissolve at least five times more oil than CO 2 during operation and this means about five times less energy used to process the same amount of used oil in a continuous process. In the process Energy is used to Heat, Cool, Compress various phases of the solvent during operation. (See Subramanian, M Supercritical fluid extraction of oil sand bitumen from Uinta Basin, Utah, Ph.D. dissertation, University of Utah, Salt lake city, Utah, 1996).
Data regarding the soluability of water, sludge, dirt, heavy metal are well established for supercritical CO 2 and super/sub-critical propane, using static systems and path processes. For example, see Heng-JooNg et. al at D.B. Robinson Research Ltd., 9419-20 Avenue Emdmonton, Alberta, Canada T6N1E5.
At expected running conditions of 93.3 C (200 F) and 4000 psi. The equilibrium phase properties indicate that at 93.3 C (200 F) the dissolved water in those conditions is (674E−03). The propane concentration is (1.03E+03), and the CO 2 concentration is (3.91E+01). The data indicate that the solubility of water at equilibrium in CO 2 is 263 times more than that in Propane under the same condition. Water concentration, can be reduced at equilibrium from 6.74E−03 down to 1.88E−03 by reducing temperature isobonically in the first cyclone separator when multiple cyclone separators are used. This is clearly an advantage in the case of propane, where coalescent filtration may be eliminated, from the process to polish the final product. The same principles applies to larger polar molecules such as contaminating PCB's which has no solubility in non polar molecules such as propane and CO 2 .
The maximum pressure in a propane-based system is less than 5,000 psi for maximum efficiency, whereas in the CO 2 system the maximum pressure will be 10,000 psi to increase the solvation power of supercritical CO 2 . The downside of higher pressure is the tremendous increase in the cost of equipment and safety costs.
All materials not soluble in solvent are separated in the first cyclone separator in the co-flow process during operation and removed from the bottom of the reactor in the counter-flow process. These unwanted materials can be removed periodically from the separator or subjected to further treatment to make them non-toxic as the case with PCB's. PCB's can be rendered harmless with supercritical water oxidation by adding additional modules at the bottom outlet of cyclone separator ( 14 ). Since the system under pressure, there is no energy consumption regarding pressurization for any treatment of the separated material in cyclone separators ( 14 and 10 ).
The present invention may also be used in processes other than the purification of petroleum-based products. The fields of application include many industries such as chemical environmental, food, medical, enzymatic, pharmaceutical and recycling. The type of the supercritical fluid and the conditions of temperature and pressure, solvent ratio and other relate operation parameters are determined for each application to obtain the desired final product at minimal cost of system construction and system operation. A bench top research unit can be used to obtain the operation parameters. A pilot plant of medium capacity (one gallon/minute of processed material) is more suitable to give operational data regarding material and waste handling, energy consumption and total cost analysis of the process including the added premium per gallon of the processed waste fluid.
The difference in the solubility of various chemical components in supercritical fluids is the bases of the present invention. This principle can be used to recycle many industrial waste fluid such as used engine oil, used transformer oil, used ink, use cooking oil and many other industrial fluids. And removal of heavy metals from nuclear industry waste using detergent modified supercritical fluid.
Many chemical mixtures cannot be separated completely, into their individual components, because they are azotrope mixtures, e.g., water and ethanol. A 95% azotrope mixture of water and ethanol can be purified further to 99.9% of ethanol, due to high solubility of ethanol in the supercritical fluid CO 2 .
Food industry applications of the present invention are potentially many and they include removal of fatty material from food products such as removal of cholesterol from milk. Other examples of applications of the present invention include a continuous extraction and fractionation of butter oil, glycerides, citrus oil. Further examples of applications of the present invention include the continuous.
One of the many applications of the present invention is sub-critical/supercritical water oxidation, water and air (or hydrogen peroxide) can be mixed at a temperature and pressure above critical parameters of water (critical temperature 374° C. and critical pressure 216 atm), for example, oxidation of polychlorinated biphenyls with hydrogen peroxide, hydrolysis of nitrites at sub-critical water conditions, oxidation of methane into methanol with supercritical water, and the continuous photo-oxygenation of benzene in carbon dioxide.
Supercritical fluid reactions based applications of the present invention are continuous emulsion and dispersion polymerization of N-vinyl formamide in carbon dioxide, a continuous deacidification of vegetable oils, a continuous alkylination of isobutene and isobutene in supercritical water, a continuous reaction of alkyl aromatics and supercritical water, continuous production of polymeric material under supercritical fluid conditions.
Other examples of use of the present invention for fractionation of many types of copolymers include using polypropylene-polyethylene copolymers to remove the low and high molecular weight fractions and the production of medical grade products of very high value on a continuous manner. The process can be used as a recycling process for old polymeric rags and carpet. In this case the old rag material is dissolved in solvent, and fractionation and crystallization using the present invention is performed. Other examples of applications of the present invention, includes the continuous depolymerization of polymers and a continuous production of lipid free human plasma products.
Commercially available computer programs in industrial design and processing can simulate many of those applications. Phase equilibrium data for each component in the processed can be predicted based on the modified equation of state (Bing-Robinson). These programs can be used to predict the design parameters of the system at any scale to insure maximum efficiency of operation.
While the present invention has been described in conjunction with preferred embodiments thereof, those of ordinary skill in the art will recognize that many modifications and variations may be made. The following claims are intended to cover all such modifications and variations.
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A method for the continuous process of fluids is based on mixing the fluid with a supercritical fluid. The mixing of the two fluids may be accomplished using either a co-flow or counter-flow process. The process focuses on the difference in the solubilities of the desired and the undesired components into supercritical fluid and de-emphasizes the influence of the contaminating components of the fluid to be processed. The process of the present invention is particularly advantageous to the recycling of industrial waste fluids, such as used oil, wherein the process is carried out by jet spray micro-orifices atomization of waste material with a supercritical fluid to dissolve oil from the waste material. Additional mixing devices such as an ultrasonic gun may be employed. Thereafter, un-dissolved components are separated first and the dissolved fluid is then separated from the supercritical fluid. The process takes advantage of the unique gas-like properties of supercritical fluids for on-line treatment of the separated components. That treatment can be an on-line reaction, or using absorbents to remove certain components. Various apparatus for carrying out the method are also disclosed.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the drying of clothes using a clothes dryer. More particularly, the invention relates to providing a clothes dryer with a combined temperature sensor and electromechanical thermostat for measuring the inlet air temperature, and for controlling the heat source.
2. Description of Related Art
The drying of clothes via the application of heated air in a conventional clothes dryer is well-known in the prior art. Thermostats and thermistors with electronics are used in such dryers to control heat input, thereby preventing high clothes temperatures that can damage the clothes. Some dryers use both an inlet thermistor and an exhaust thermistor for monitoring air temperature, as well as a bi-metal thermostat for limiting the heat input. This known configuration, however, suffers from a number of shortcomings.
Initially, the above-mentioned system of the prior art has a delay between the time the inlet air temperature is sensed by the thermistor and the time the thermostat reacts to an increase in temperature. This delay in response time can result in excessively long drying times due to the thermostat turning the heating element off prematurely. This condition, known as nuisance cycling, lengthens the total amount of drying time necessary to completely dry the contents of the dryer.
Another shortcoming of the prior art is a lack of close correlation of the air temperature due to the distance and orientation between the inlet thermistor and the thermostat. This distance and orientation can lead to a difference in the temperature detected by each of the components.
Further, the prior art utilizes an inlet thermistor that is separate from the thermostat. Thus, two separate components must be manufactured and mounted to the dryer, thereby adding to the overall cost in both labor and materials.
Accordingly, it is desirable to develop a system that more efficiently controls the heat input in a clothes dryer while using the minimum amount of components to reduce overall cost.
SUMMARY OF THE INVENTION
The present invention meets the shortcomings of the prior art by providing a combined thermistor/thermostat located in the inlet of the heater box of a clothes dryer. The combined device measures the conductive, convective, and/or radiated heat of the heat source of the dryer and regulates the inlet air temperature to the clothes load, thereby providing a more real-time control of the overall dryer temperature and preventing the air temperature from getting too high. The invention disclosed herein combines a thermistor with its fast response time for monitoring inlet air temperature and a bi-metal thermostat wired directly to the heat source. One of the benefits of having a combined device is the close proximity of the two components. This proximity improves the reaction time of the control system to temperature changes, thereby preventing excessive fabric temperatures. The combined sensor of the present invention provides all the above benefits at a cost lower than that of prior art sensors since the thermistor and thermostat are assembled as a single piece instead of two separate components.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic view of a system utilizing the combined thermistor/thermostat sensor of the present invention.
FIGS. 2A and 2B are perspective views of the combined thermistor/thermostat sensor of the present invention.
FIG. 3 is a control diagram of the system utilizing the combined thermistor/thermostat sensor of the present invention.
FIG. 4 is a schematic view of an alternative system utilizing the combined thermistor/thermostat sensor of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
With reference to FIG. 1 , an electric clothes dryer 10 of the present invention is schematically shown, provided generally with a heater box 30 , a drum 60 , a blower 80 and an exhaust 90 . The heater box 30 is provided with an inlet 32 through which inlet airflow 20 passes, and a drum inlet grill 34 through which heated air exits the heater box 30 and enters the drum 60 of the dryer 10 . The air is heated in the heater box 30 by a heating element 36 , preferably a dual element heater. The blower 80 draws the air out of the drum 60 , through a lint screen 70 , and eventually through the exhaust 90 of the dryer, as exhaust airflow 120 . The dryer 10 further includes a thermal cut-off 50 and a thermal fuse 110 . The thermal cut-off 50 ensures a safe condition in the event of a heating element failure. The thermal fuse 110 removes power to the drum motor, thus stopping the airflow and containing any combustible material from being vented outside of the dryer.
The clothes dryer 10 is provided with a number of sensors for detecting the temperature of the airflow in the dryer. A combined thermistor/thermostat unit 40 is located in the inlet 32 of the heater box 30 while an exhaust thermistor temperature sensor 100 is located in the exhaust 90 of the dryer 10 . As shown in FIGS. 2A and 2B , the combined thermistor/thermostat unit 40 includes a thermistor temperature sensor 41 and an electromechanical bi-metal thermostat 42 within a body 43 . The thermistor 41 measures the inlet air temperature of the dryer, and the exhaust thermistor 100 measures the temperature of exhaust airflow 120 . The thermostat 42 opens the heating element circuit when the temperature exceeds a predetermined trip point and closes the heating element circuit when the temperature falls below a predetermined reset point.
The thermistor 41 of the combined sensor unit 40 may be a partially encapsulated NTC (negative temperature coefficient) semiconductor molded into a high temperature plastic probe. Alternatively, the thermistor 41 may be a fully encapsulated or metal enclosed device. The thermostat 42 may be of a bi-metal type single pole, single throw switch that opens when the metal is heated to the specified trip point. Thus, the combined unit 40 provides the fast response time of a thermistor along with the safety and reliability of a bi-metal thermostat within one component.
Referring to FIGS. 2A and 2B , the combined sensor unit 40 is depicted in further detail. In addition to the thermistor 41 and the thermostat 42 , the unit is provided with high voltage terminals 44 , which are connected in series with the heating element 36 , and terminals 46 for connection with a controller. The high voltage terminal 44 and the terminal 46 protrude from the body 43 . Further, the unit is provided with mounting means 48 for mounting in the desired location on the heater box 30 .
With reference to FIG. 3 , the combined sensor 40 is connected to both the heating element 36 and a controller 140 . Specifically, the thermostat 42 reacts to the inlet temperature to limit the heat input by the system. In the event that the thermostat's trip temperature is reached, the thermostat 42 would open the heating element circuit and turn the heating element 36 completely off.
Additionally, the thermistor 41 communicates with the controller 140 via a wire harness 130 . The thermistor 41 measures the temperature at the inlet of the heater box 30 , and then provides the temperature signal to the controller 140 . When the thermistor 41 senses that the temperature is becoming too high, the controller 140 operates the heating element 36 at half power until an inlet reset point is reached. Thus, one of the heating elements 36 remains active and continues to heat the airflow. Once the reset temperature is reached, the controller 140 then turns the heating element 36 back to full power. Alternately, the combined thermistor/thermostat 40 could be implemented with a single stage heating element. As a result of this function of the thermistor, the thermostat is prevented from reaching its trip temperature, thus preventing long dry times due to thermostat cycling.
With reference to FIG. 4 , the combined sensor 40 , described above, is shown in a gas dryer 10 ′. The gas dryer 10 ′ is provided generally with a heater box 30 ′, a drum 60 ′, a blower 80 ′ and an exhaust 90 ′. The heater box 30 ′ is provided with an inlet 32 ′ through which inlet airflow 20 ′ passes, and a drum inlet grill 34 ′ through which heated air exits the heater box 30 ′ and enters the drum 60 ′ of the dryer 10 ′. The air is heated in the heater box 30 ′ by burner 38 ′ that is controlled by a bi-level gas valve. The blower 80 ′ draws the air out of the drum 60 ′, through a lint screen 70 ′, and eventually through the exhaust 90 ′ of the dryer, as exhaust airflow 120 ′. The dryer 10 ′ further includes a thermal cut-off 50 ′ and a thermal fuse 110 ′. The thermal cut-off 50 ′ ensures a safe condition in the event of a burner or gas valve failure. The thermal fuse 110 ′ removes power to the drum motor, thus stopping the airflow and containing any combustible material from being vented outside of the dryer.
The gas dryer 10 ′ is provided with a number of sensors for detecting the temperature of the airflow in the dryer. A combined thermistor/thermostat unit 40 is located in the inlet 32 ′ of the heater box 30 ′ while an exhaust thermistor temperature sensor 100 ′ is located in the exhaust 90 ′ of the dryer 10 ′. As shown in FIGS. 2A and 2B , the combined thermistor/thermostat unit 40 includes a thermistor temperature sensor 41 and an electromechanical bi-metal thermostat 42 . The thermistor 41 measures the inlet air temperature of the dryer, and the exhaust thermistor 100 ′ measures the temperature of exhaust airflow 120 ′. The thermostat 42 opens the gas valve when the temperature exceeds a predetermined trip point and closes the gas valve when the temperature falls below a predetermined reset point.
The function of the combined sensor 40 in the gas dryer 10 ′ is generally the same as demonstrated above for an electric dryer 10 . Referring again to FIG. 3 , the thermistor 41 communicates with the controller 140 via a wire harness 130 . The thermistor 41 measures the temperature at the inlet of the heater box 30 ′, and then provides the temperature signal to the controller 140 . When the thermistor 41 senses that the temperature is becoming too high, the controller 140 operates the burner 38 ′ at half power until an inlet reset point is reached. Once the reset temperature is reached, the controller 140 then turns the burner 38 ′ back to full power. As a result of this function of the thermistor, the thermostat is prevented from reaching its trip temperature, thus preventing long dry times due to thermostat cycling.
Thus, the present invention provides a more real-time control of the overall dryer temperature, thereby preventing the temperature from getting too high and damaging clothes, and also reducing nuisance cycling in the dryer. Further, dryness accuracy and overall energy efficiency of the dryer are both improved.
The combined sensor of the present invention can be manufactured at a cost lower than that of prior art sensors since the thermistor and thermostat are assembled as a single piece instead of two separate components.
While certain features and embodiments of the present invention have been described in detail herein, it is to be understood that the invention encompasses all modifications and enhancements within the scope and spirit of the following claims.
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A clothes dryer has a system for regulating the inlet air temperature. The system includes a first sensor located in an inlet of the dryer and including a thermistor and a thermostat, a heat source located in a heater box adjacent the first sensor, and a second sensor located in an exhaust of the dryer. The thermistor measures the inlet air temperature of the dryer and cooperates with the controller to prevent the thermostat from reaching its trip temperature and turning off the heat source. Thus, damage due to excessive air temperatures in the dryer is prevented.
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This invention relates to a docking system for handheld electronic communication devices such as cellular telephones or the like, for use with structures or vehicles, and this application is a continuation of U.S. patent application Ser. No. 11/020,450, filed Dec. 22, 2004, to issue on 15 Jul. 2008 as U.S. Pat. No. 7,400,858, and application Ser. No. 11/728,487, filed Mar. 26, 2007 which is a continuation of Ser. No. 10/619,770, filed Jul. 15, 2003 now U.S. Pat. No. 7,197,285, which are each a continuation applications of Ser. No. 09/634,140, filed Aug. 8, 2000, now U.S. Pat. No. 6,885,845, which was a continuation of Ser. No. 08/604,105, filed Feb. 20, 1996, now U.S. Pat. No. 6,594,471, and is a Continuation-In-Part Application of U.S. patent application Ser. No. 08/581,065, filed Dec. 29, 1995, which is a Continuation-In-Part Application of our allowed co-pending U.S. patent application Ser. No. 08/042,879, filed Apr. 5, 1993, each being incorporated herein by reference, in their entirety.
BACKGROUND OF THE INVENTION
(1) Field of the Invention
(2) Prior Art
Extraneous radio frequency emission has become a serious concern of hand-held electronic communication devices such as portable facsimile machines, ground position indicators, and cellular telephone manufacturers and users alike. RF radiation is considered a potential carcinogen.
The proliferation of these hand-held devices is evident everywhere. A single hand-held device however, should able to travel with its owner and be easily transferably usable in automobiles, planes, cabs or buildings (including hospitals) as well as at offices and at desks with no restrictions on their use, and without causing concern with regard to the radiation therefrom. The hand-held devices should be portable for a user to carry in his pocket, yet be able to use that same cellular unit in such vehicle or building while minimizing such radiational effect therein.
It is an object of the present invention to permit a user of a portable hand-held electronic communication device such as a cellular telephone or the like, to conveniently use that same hand-held device/cellular phone in an automobile, plane or building, office/desk, or anywhere signal transmission is needed, and to permit such signal to reach its intended destination such as a communications network or satellite, without interfering with other electrical equipment and in spite of interfering walls of buildings or structure and/or other electrical equipment.
It is a further object of the present invention to minimize any radiation from such a portable device, such as a cellular telephone or the like, while such use occurs in an automobile, a building or an elevator, an airplane, a cab, or other public facility in which the user wishes to minimize his own exposure to stray radiation, and also to permit re-transmission of his signal, to avoid the necessity of connecting and disconnecting cables, and to permit a wide variety of cellular telephones such as would be utilized in a rental car where various manufactures' phones would be used, and to permit control of such re-transmission of signals where desired, so as to allow user/customer billing and monitoring thereof.
BRIEF SUMMARY OF THE INVENTION
The present invention comprises a docking system adaptable to an automobile, plane, building or desk for receipt of an electronic communication device such as a cellular telephone, portable computer, facsimile machine, pager or the like, to permit a user safe, environmentally safe, non-touching, radiationally communicative mating of the antenna of that device to a further transmission line through a juxtaposed pick-up probe, the signal coming in or going out through a communications network or further remote antenna.
The docking system may comprise a “zone” or “focal area” as a generally rectilinear area/volume on/in a desk or work surface on/in which the electronic communication device may be placed, such a surface or space being possible on a desk, or in a plane. That focal area may also, in a further embodiment, be comprised of one or more rooms in a building, such focal area having a pick-up probe thereat, in conjunction with a shield placed on/in the desk, room, vehicle or building to prevent the radiation from that communication device from traveling in any undesired directions within the desk, room, vehicle or building.
The focal area may be defined by a metal walled structure within or on which a broadband probe is arranged. The metal walled structure acts as a shield to minimize radiation from the communication device from passing therethrough. In a first embodiment, the shield may be comprised of a partial housing disposed within the upper work surface of a desk. The probe would be elongatively disposed within the partial housing and be in electrical communication with a transmission line such as coax cable, waveguide, or the like. The partial housing may have a planar dielectric layer thereover, which would also be co-planar with the surface of the desk. The communication device would be placed within the pickup zone of the focal area, and would be able to transmit and receive signals through the dielectric layer. The partial housing would act as the shield in the desk, to minimize radiation by the worker at the desk. In a further embodiment, the housing may be comprised of a thin, generally planar mat of conductive material, which mat may be flexible and distortable, for conformance to a particular work surface and for ease of storage capabilities. The mat has an upper layer of dielectric material (for example, plastic, foam or the like). A thin, flat, conformable coupling probe may be embedded into or printed onto the upper surface of the dielectric material. The mat may be utilized as a portable focal area for placement of a communication device thereon, or wrapped up in an enveloping manner therein.
A yet further embodiment of the present invention includes a control unit in the transmission line from the pickup probe to the further remote antenna. The control unit may comprise a filter or switch connected to a computer. The computer may accumulate billing information, control system functions, or act as a regulator for multiple users of the antenna coupling system.
The invention thus comprises a docking system for connecting a portable communication device to a further signal transmission line, the portable communication device having an externally radiative antenna, the system comprising a shield for restricting at least a portion of any radiation from the externally radiative antenna of said portable communication device, and a coupling probe mounted adjacent to the shield for radiatively coupling between the externally radiative antenna of the portable communication device and the further signal transmission line via radio frequency energy therebetween. The shield may be comprised of an electrically conductive material, or an attenuative material capable of blocking at least part of the radiofrequency radiation energy coming from the communication device(s) connected thereto. The shield defines a focal area for receipt and transmission of a radio frequency signal, when a communication device is placed within the focal area. The focal area or zone, may be selected from the group of structures consisting of a desk, a room in a building, or a tray or the like in a vehicle. The further signal transmission line may be connected to a further communication network and/or a further antenna connected to the transmission line, yet positioned at a location remote from the shield. The transmission line may have a control unit therein, the control unit being arranged to permit regulation of signals being transmitted through the transmission line. The control unit may comprise a computer arranged to monitor time or use of the docking system. The shield and the probe may be spaced apart by a dielectric material. The shield, the probe and the dielectric material may be flexible. The communication device may include at least two cellular telephones (or other portable communication devices) simultaneously connected to the remote antenna.
The invention also includes a method of coupling a portable communication device having an externally radiative antenna, to a signal transmission line having a further remote antenna thereon, for the purpose of effecting radio signal transmission therebetween, the method comprising the steps of arranging a radiation shield in juxtaposition with at least a portion of said radiative antenna of the portable communication device, mounting a coupling probe adjacent the shield and in communication with the signal transmission line, and placing the externally radiative antenna of the portable communication device close to the probe and the shield so as to permit radiative communication between the externally radiative antenna and the signal transmission line via the coupling probe. The method may include arranging the shield in or on a generally planar work surface so as to restrict the propagation of at least a portion of the radiation emanating from the communication device primarily only to the vicinity of the probe. The method may include attaching a control unit to the transmission line to permit regulation of electric signals therethrough, and adding a further communication device in juxtaposition with a further probe, the further probe also being in electronic communication with that control unit, so as to permit multiple simultaneous use of the transmission line and communication system and/or remote antenna therewith. The method of coupling the portable communication device to the signal transmission line, may also include the step of billing any users of the communication and/or remote antenna by monitoring and tabulating any signals received by and sent through the control unit.
It is an object of the present invention to provide a shielded antenna docking arrangement, which itself may be portable, for use with a portable communication device such as a cellular telephone, facsimile machine or ground position indicator or the like, such use occurring in a vehicle such as a plane, an automobile or a cab or in a public or private building, office desk or elevator.
BRIEF DESCRIPTION OF THE DRAWINGS
The objects and advantages of the present invention will become more apparent when viewed in conjunction with the following drawings in which:
FIG. 1 a is a perspective view of a focal area docking arrangement, as may be utilized with a desk;
FIG. 1 b is a partial view taken along the lines A-A of FIG. 1 a;
FIG. 2 a is a perspective view of a portable focal area docking system for portable communication devices;
FIG. 2 b is a view taken along the lines B-B of FIG. 2 a;
FIG. 3 a is a block diagram of a docking system having a sensor unit arranged therewith;
FIG. 3 b is a block diagram of a further embodiment of that shown in FIG. 3 a ; and
FIG. 4 is a side elevational view of a docking system, as it may be utilized in a vehicle.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the drawings in detail, and particularly to FIG. 1 a , there is shown a portable communication device docking arrangement 10 , to permit a portable communication device such as a hand-held cellular telephone 12 to be utilized thereon, such as on a desk 14 or adjacent to it, and as a personal communicator (i.e. cellular telephone, facsimile machine, pager or the like) which may also be carried on an individual.
Such a docking system 10 of the present invention may also be adaptable to an automobile, plane, or building for providing radiationally restrictive communication between a portable electronic communication device 12 such as a cellular telephone, portable computer, facsimile machine, pager, or the like, while allowing communicative mating of the radiative antenna of that device to a further transmission line and communication system and/or a more remote antenna, as recited and shown in our aforementioned patent applications, incorporated herein by reference in their entirety.
The docking system 10 may comprise a “zone” or “focal area” 16 as a rectilinear area/volume on/in a desk 14 or work surface on/in which the electronic communication device 12 may be placed, such a surface or space being in a structure such as an airplane. That focal area 16 has a pick-up coupling probe 22 thereat, as shown for example in FIG. 1 b , in conjunction with a shield 24 placed on/in the desk 14 , (or room, vehicle or building, as shown in FIGS. 3 a and 3 b ), to prevent the radiation (electromagnetic/microwave) emanating from that communication device 12 from traveling in any undesired directions within the desk, room, vehicle or building.
The focal area 16 may be defined by a metal walled housing structure 30 within which a broadband probe 22 is arranged, as shown in FIG. 1 b . The metal walled structure 30 acts as a shield to minimize undesired radiation from the communication device 12 from passing therethrough. In a first embodiment, the shield may be comprised of a partial housing 34 disposed within the upper work surface 36 of a desk 14 , as may be seen in FIG. 1 b . The pick-up probe 22 would be elongatively disposed within the partial housing structure 30 and be in electrical communication with a transmission line 32 such as coaxial cable, waveguide, or the like. The transmission line 32 would be in electrical communication with an electric communications network or distribution system 38 , and/or to a further remote antenna 40 , such as may be seen in FIGS. 1 b , 3 a and 3 b . The partial housing 30 may have a planar dielectric layer 42 thereover, which would also be co-planar with the surface of the desk 14 . The communication device 12 would be placed within the pickup zone of the focal area 16 , and would be able to transmit and receive signals through the dielectric layer 42 . The partial housing 30 would act as the shield in the desk, to minimize radiation directed towards the worker(s) at the desk.
In a further embodiment as shown in FIG. 2 a , the shield or housing may be comprised of a thin, generally planar mat 50 of conductive material, which mat 50 may be flexible and distortable, for conformance to any surface (human or otherwise), and may be folded or rolled up to minimize storage requirements. The mat 50 has an upper layer 52 made of a dielectric material (plastic, foam or the like). A thin, flat, conformable coupling probe 54 is embedded into or printed onto the upper surface of the layer of dielectric material 52 . The mat 50 may be utilized as a portable focal area for placement of a communication device thereon, or wrapped-up in an enveloping manner therein. The probe 54 is connected to a transmission line 56 , in electrical contact with a network or remote antenna, not shown in this figure.
A yet further embodiment of the present invention includes a control unit 60 , connected into the transmission line 62 from the pickup probe 64 to the further remote antenna 66 shown in FIGS. 3 a and 3 b . The control unit 60 may comprise a filter, switch, amplifier, attenuator, combiner, splitter, or other type of frequency converter, connected to a computer 68 . The computer 68 may be arranged to accumulate customer or billing information by functioning with a processor to print out use-data 69 , to maintain frequency control functions, or to act as a regulator for multiple users of the antenna coupling system IQ. There may be a plurality of pickup coupling probes 64 each connected to the control unit 60 and the transmission line 62 , one probe 64 in each of a plurality of shielded rooms 65 , each wall or work area (desk) having a shield, the rooms 65 shown in a building 67 , in FIG. 3 b.
The view shown in FIG. 4 , displays a portable communication device such as a facsimile machine or computer 70 supported on a tray 72 articulably mounted on the back of an airplane seat 74 . The tray 72 has a “focal area” 75 therewithin, as represented by the dashed lines 76 . The focal area 75 includes a conductive (preferably metallic) shield arranged beneath and partially surrounding a broadband probe 77 . The probe 77 transmits electrical signals radiated to and from a radiative antenna on or in the base of the portable communication device 70 . A transmission line 78 which may be comprised of coaxial cable, waveguide, or optical fibers, extends from the probe within the focal area, to a further remote antenna 80 mounted outside of the structure, which here, is identified as an airplane.
A control unit 82 , such as attenuators, heterodyne converters, amplifiers, bandpass filters, switches, or the like, may be arranged in communication with the transmission line 78 to monitor or control the time in the vehicle in which the communication device may be utilized, for example, to limit certain times when such devices may be utilized in an airplane, or to modulate the signal being transmitted or received by the remote antenna, and/or to monitor usage of the docking system for subsequent billing of those users.
Thus what has been shown is a unique system for minimizing the detrimental effects of radiation from common portable communication devices to their users, while improving the transmission capabilities and customer usage of such devices, overcoming the barriers such as buildings and vehicles in which such devices might otherwise be utilized, that would interfere with the flow of signals transmitted.
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The present invention comprises a docking system for connecting a portable communication device to a further signal transmission line. The docking system may be arranged within a workstation such as a desk or a tray. The system may also envelope a room in a building or be located in a vehicle, to control and restrict the radiative emission from the communication device and to direct such radiation to a further remote antenna and or signal distribution system connected to the transmission line.
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FIELD OF THE INVENTION
[0001] This invention relates in general to centrifugal pump stages, and in particular to a method of attaching radial and axial support bearing elements.
BACKGROUND OF THE INVENTION
[0002] Centrifugal pumps for petroleum production are made up of a large number of stages. Each stage has an impeller that is rotated by a shaft driven by an electrical motor. Each impeller is located within a stationary diffuser. Each diffuser has passages that extend downstream and radially inward toward the shaft for receiving fluid from an upstream impeller and delivering the fluid to a downstream impeller. Each impeller has a central inlet and passages that extend outward in a downstream direction for delivering well fluid to a downstream diffuser.
[0003] The rotation of the impeller causes down thrust. Typically, each impeller is free to float axially on the shaft, and transmits the down thrust to its mating diffuser. Furthermore, thrust washers are located between the mating surfaces for handling the rotating sliding engagement between the impeller and the diffuser.
[0004] One type of thrust washer is made of phenolic material, which is not particularly hard. Another type, which is used for abrasive well fluid conditions, is of a hard, wear resistant metal such as tungsten carbide. The diffuser and impeller are cast of a metal such as Ni-Resist. Normally, the thrust washer is attached to the impeller for rotation therewith, such as by adhesive or by an interference fit. One problem with adhesive is that the bonding surface of the impeller must be very clean and free of oil. Also, the adhesive has to have time to cure. Further, in high temperature wells, the temperature may exceed that of the adhesive, causing it to deteriorate. If the thrust washer begins to spin relative to the impeller, damage to the impeller may occur.
[0005] An interference fit requires a high tolerance for the mating components. Also, it may not be as reliable as the adhesive because variations in the force fit installation. The differences in the coefficient of expansion of the impeller and a tungsten carbide thrust washer could cause the thrust washer to become loose at high temperatures. An interference fit required to hold a tungsten carbide thrust washer at high temperatures may be so large that the thrust washer fractures during assembly.
[0006] The diffuser has an internal bearing support that receives a bearing sleeve for engaging the rotating shaft. The bearing sleeve is typically installed in the bearing support by heat shrink and force fit techniques. In high temperature operations, the differences in thermal expansion of the bearing sleeve can cause the bearing sleeve to become loose and fall out or to spin in the bearing holder of the diffuser. Force fits may not be successful when the plastic deformation of the bearing holder material of the diffuser causes the bearing to become loose at high temperatures. An interference fit required to hold the bearing sleeve at high temperatures may be so large that the bearing fractures during assembly.
SUMMARY OF THE INVENTION
[0007] The bearing element for a centrifugal pump assembly is installed in a receptacle of a bearing holder, which may be a portion of an impeller or a portion of a diffuser. The receptacle has a retaining wall located adjacent the bearing element. The retaining wall is permanently deformed against the bearing element to prevent rotation.
[0008] The mechanical deformation involves staking or bending portions of the retaining wall inward. These deformed portions are spaced circumferentially apart from each other around the retaining wall. Recesses may be provided on the outer diameter of the bearing element for receiving the deflected portions of the retaining wall therein. The recesses may be flats that are circumferentially spaced around the bearing element. The flats may be in axial planes or, they may be inclined bevels located at the intersection of the sidewall with an end of the bearing element.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] [0009]FIG. 1 is a partial sectional view of a portion of a pump stage constructed in accordance with this invention.
[0010] [0010]FIG. 2 is an axial sectional view of the impeller of the pump stage of FIG. 1.
[0011] [0011]FIG. 3 is a bottom view of the impeller of FIG. 1.
[0012] [0012]FIG. 4 is a top view of a die used for staking the thrust washer to the impeller of FIG. 2.
[0013] [0013]FIG. 5 is an axial sectional view of a die assembly that utilizes the die of FIG. 4.
[0014] [0014]FIG. 6 is an enlarged sectional view of a portion of the assembly of FIG. 5, showing the staking operation being performed with the die assembly of FIG. 5.
[0015] [0015]FIG. 7 is a sectional view of an alternate embodiment of a pump stage constructed in accordance with this invention.
[0016] [0016]FIG. 8 is a plan view of one of the thrust washers of the pump stage of FIG. 7.
[0017] [0017]FIG. 9 is a partial sectional view of the pump stage of FIG. 7.
[0018] [0018]FIG. 10 is a sectional view of the pump stage of FIG. 11, taken along the line 10 - 10 of FIG. 11.
[0019] [0019]FIG. 11 is a sectional view of a third embodiment of a pump stage constructed in accordance with this invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0020] Referring to FIG. 1, pump stage 11 is part of a centrifugal pump stage of a pump that is particularly used for petroleum production. Normally, such a pump has a large number of pump stages 11 , each having an impeller 13 that has a hub 15 mounted to a shaft 17 for rotation therewith. In most pumps, impeller 13 is free to move small distances in axial directions on shaft 17 . Impeller 13 has a plurality of passages 19 that extend from an upstream inlet outward to the periphery of impeller 13 . A skirt 21 surrounds the central inlet and depends downward or in upstream direction. A retaining wall 23 extends downward from the lower or upstream side of impeller 13 concentric with the axis and spaced radially outward from skirt 21 .
[0021] Skirt 21 and retaining wall 23 define an annular receptacle for receiving an outer thrust washer 25 . A second or inner thrust washer 27 may be located on impeller 13 . Thrust washers 25 , 27 are both secured in receptacles in a manner to cause them to rotate with impeller 13 . Because of the greater distance from the axis of shaft 17 , outer thrust washer 25 encounters more torque than inner thrust washer 27 .
[0022] Impeller 13 is rotatably carried within a diffuser 29 that is stationarily mounted in a housing (not shown). Diffuser 29 has fluid passages 31 that extend inward in a downstream direction for delivering fluid to the inlet of impeller 13 within skirt 21 . Skirt 21 slidingly engages the outlet of diffuser 29 . Diffuser 29 has an outer thrust surface 33 and an inner thrust surface 35 , both on the downstream end. Thrust surface 33 engages thrust washer 25 , while thrust surface 35 engages inner thrust washer 27 .
[0023] Referring to FIG. 3, retaining wall 23 has an inner side 37 and an outer side 39 that are joined by a rim 41 . Rim 41 is typically in a plane perpendicular to the axis of rotation of impeller 13 . After thrust washer 25 is placed in the receptacle next to retaining wall 23 , a plurality of deformed portions 43 are made in rim 41 . As can be seen in FIG. 3, deformed portions 43 enlarge the wall thickness of retaining wall 23 between inner side 37 and outer side 39 . Deformed portions 43 are spaced circumferentially around retaining wall 23 to mechanically stake or secure outer thrust washer 25 in place. Inner thrust washer 27 could be installed by the same manner, or it could be installed in a conventional manner, such as by adhesive.
[0024] Referring to FIG. 5, die assembly 45 is suitable for making the deformed portions 43 (FIG. 3), although other devices could also perform the staking operation. Die assembly 45 has a lower body 47 that rigidly supports an annular die 49 . Die 49 has a plurality of staking projections 51 , as shown in FIG. 4, which is a top view of die 49 . Each projection 51 is a sharp tooth-like member protruding from the upper surface of die 49 .
[0025] A lower support 53 is reciprocally carried within lower body 47 . Lower support 53 has a central cavity 54 and an annular upward facing rim 55 . Rim 55 is located radially inward a slight distance from die 49 for engaging thrust washer 25 . A plurality of coiled springs 57 bias lower support 53 upward. A fastener 59 extends axially through lower support 53 for retaining lower support 53 with lower body 47 , but allowing axial movement of lower support 53 relative to lower body 47 . A plunger 61 is located above or opposite lower body 47 . Plunger 61 is adapted to engage the downstream end of impeller 13 and may be hydraulically or mechanical driven. Plunger 61 has central passage 63 for receiving hub 15 of impeller 13 .
[0026] In the operation of die assembly 45 , impeller 13 is placed on die 49 with its wall 23 in contact with projections 51 and its skirt 21 located within cavity 54 . Lower support 53 will be in contact with outer thrust washer 25 . Plunger 61 is placed against the downstream end of impeller 13 with hub 15 located in passage 63 . Plunger 61 is stroked toward body 47 . As illustrated in FIG. 6, this causes projections 51 to embed into retaining wall rim 41 , radially deforming inner and outer sides 37 , 39 (FIG. 3). This deformation also causes some deformation of thrust washer 25 , creating an interference fit. Springs 57 allow lower support 53 to move downward slightly as plunger 61 moves impeller 13 further toward die 49 . If a staking procedure is to be used with inner thrust washer 27 , a different die assembly would be required as it would need to pass through skirt 21 and engage the retaining wall surrounding inner thrust washer 27 .
[0027] [0027]FIG. 7 illustrates an alternate embodiment. Pump stage 65 is particularly to be used in abrasive applications, such as where well fluid has an appreciable content of sand. Impeller 67 rotates within diffuser 69 . An impeller thrust washer 71 is mounted to impeller 67 for transferring downward thrust to a diffuser thrust washer 73 that is stationarily mounted to diffuser 69 . Both thrust washers 71 , 73 are preferably formed of a hard wear resistant material such as tungsten carbide. Thrust washers 71 , 73 engage each other in rotating sliding contact.
[0028] Referring to FIG. 9, thrust washers 71 , 73 are identical in this embodiment, each having an outer diameter containing a radially extending lip 75 . Also, lip 75 of each thrust washer 71 , 73 has a plurality of flats 77 . In this embodiment, three flats 77 are shown spaced 120° from each other. Each flat 77 extends in an axial plane that is parallel with an axial plane that passes through the axis of thrust washer 71 or 73 . Lip 75 has a smaller radial dimension at each flat 77 , and if desired, could be substantially eliminated at each flat 77 . Impeller 67 has a cylindrical retaining wall 79 that receives of lip 75 of thrust washer 71 . A skirt 81 depends from impeller 67 , surrounds the inlet of impeller 67 , and slidingly engages an outlet portion of diffuser 69 .
[0029] Deformed portions 83 are formed in the rim of retaining wall 79 adjacent each flat 77 . Deformed portions 83 bear against each flat 77 to prevent rotation of thrust washer 71 . Flats 77 avoid having to deform any portion of the tungsten carbide washer 71 to create an interference fit. The staking operation for deformed portions 83 may be as described in connection with the first embodiment. The plan view of FIG. 8 discloses shallow recesses 87 formed in the mating surface of impeller thrust washer 71 . These recesses assist in lubrication and do not form a part of this invention.
[0030] Similarly, diffuser 69 has a retaining wall 85 that closely receives the lip of diffuser thrust washer 73 . It has deformed portions also that engage flats on the outer diameter of diffuser thrust washer 73 . The same procedure as described in connection with the first embodiment may be used for performing the staking operation.
[0031] Referring to FIG. 11, portions of two pump stages 89 are shown, these stages being a third alternate embodiment. Impellers 91 , 93 are located within diffusers 95 , 96 , respectively. Each diffuser 95 , 96 has an outer wall or shell 97 that is stationarily mounted within a housing (not shown). Each diffuser has a central hub 99 that provides radial support for one of the impellers 91 , 93 . Central hub 99 also receives down thrust from one of the impellers 91 , 93 . Each diffuser 95 , 96 has passages 101 that extend downstream and inward to an intake of one of the impellers 91 , 93 . A central cavity 103 is formed within outer shell 97 . Fluid from upstream impeller 91 flows through central cavity 103 to diffuser passages 101 of downstream diffuser 96 .
[0032] Each diffuser 95 , 96 also has an integral bearing support 107 formed in central cavity 103 . Bearing support 107 has an axial bore that serves as a receptacle to receive a stationary bearing sleeve 109 . Bearing sleeve 109 is fixed to bearing support 107 and receives within it a rotating bushing 111 that is mounted to shaft 112 . In an abrasion resistant pump, bearing sleeve 109 and bushing 111 may be made of a hard wear resistant material such as tungsten carbide.
[0033] To retain bearing sleeve 109 stationarily within bearing holder 107 , a plurality of flats or bevels 113 are formed on one end of bearing sleeve 109 , as shown in FIG. 10, and spaced circumferentially around the outer diameter of bearing sleeve 109 . Each bevel 113 is a flat surface that is inclined relative to an axial plane parallel to an axial plane passing through the axis of shaft 112 . Each bevel 113 joins an end surface 115 with an outer diameter 117 of bearing sleeve 111 . A plurality of circumferentially spaced-apart deformations 118 are located in one of the end surfaces 115 of bearing holder 107 , preferably the downstream end. Deformations 118 permanently deform a portion of bearing holder 107 into engagement with one of the bevels 113 . Deformations 118 may be formed generally in the same manner as described in connection with the first embodiment. Because of bevels 113 , no deformation of bearing sleeve 109 is required. Thrust washers 119 may be attached conventionally with adhesive, or they may be installed in a mechanical staking operation as in the other embodiments.
[0034] The invention has significant advantages. The mechanical staking operations avoids having to clean all oil from the impeller prior to securing a thrust washer. It avoids having to delay further manufacturing operations to allow the adhesive to cure. The circumferentially spaced apart deformations do not require high tolerances of the outer diameter of the thrust washer, unlike conventional force fits. As no glue is required, high temperature operations will not cause the adhesive to deteriorate. Mechanical staking also avoids the disadvantage of interference fits between two different materials that have different coefficients of expansion.
[0035] While the invention has been shown in only three 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 method of installing an annular bearing element within a centrifugal pump utilizes a mechanical staking operation. The bearing element locates within a receptacle of a pump stage that is surrounded by a retaining wall. Once the bearing element is located within the retaining wall, the retaining wall is permanently deformed at various points against the bearing element. The bearing element, if of a hard wear resistant metal, may have flats for the circumferentially spaced apart deformations to locate within. The bearing element may be a thrust washer for transmitting downward thrust, or it may be a radial support bearing sleeve.
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TECHNICAL FIELD
This disclosure relates to wireless coverage detection and more particularly to systems and methods for using mobile devices for detecting the boundary of a measurable phenomenon, such as the signal quality of RF broadcasts.
BACKGROUND OF THE INVENTION
Providers of wireless services, such as, for example, cellular telephone service, currently detect holes in their coverage in two ways, drive testing throughout the coverage area and customers calling to report problems. One disadvantage of drive testing is that the RF field is undersampled in time, since each sample covers only a fraction of a second per month at any one location. Another disadvantage of drive testing is that the RF field is also undersampled in space, because most of the major roads are not driven their entire length and only some of the minor roads are driven. Drive testing misses all locations without a road, such as parks, stadiums, homes, offices, conference centers, etc. While drive testing attempts to weigh the samples by their importance (making sure to cover major roads, for example) this weighing is subjective and ad hoc, and applies a single weighing for all customers. In addition, drive testing is labor-intensive and requires a truck full of expensive equipment. A disadvantage of having customers call in complaints is that such a system is subjective and undersamples the signal even more seriously than does drive testing, both in time and space. In addition, called-in information is usually imprecise and it is also labor-intensive to record the called-in data.
BRIEF SUMMARY OF THE INVENTION
In one embodiment there is shown a system and method for determining the spatial boundary of measurable phenomenon, such as the quality of a broadcast signal at various locations within geographical areas covered by the broadcast signal. Data representing relative signal quality at various locations within the geographical area is created within a mobile device, such as a cell phone capable of receiving the broadcast signals. The data is stored, and refined, within the device so as to define weak signal quality areas within at least a portion of the geographical area traveled by the mobile device. The data stored within the mobile device is from time to time communicated to the central broadcast system. The refinement of the data in the device allows for long storage periods so that signal quality can be reported over long time spans. By collecting such data from a plurality of such devices, the central system can map the signal strength over the entire geographical area.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A shows geographical areas defined by a mobile device;
FIGS. 1B , 1 C, and 1 D show movement, expansion and contraction of the geographical area of FIG. 1 ;
FIGS. 2 , 3 , and 4 show flow charts of one embodiment of system operations;
FIG. 5 shows one embodiment of a mobile device;
FIGS. 6A , 6 B, 6 C, 6 D and 6 E show one embodiment of the steps for changing the size of cells; and
FIG. 7 shows one embodiment of a cellular system using the systems and methods described herein.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1A shows geographical area 11 where the user of a mobile device (for example, a cellular telephone) spends most of his/her time. The letter ‘A’ is positioned at the center of geographical area 11 . For discussion purposes, this is called the ‘home’ region and in discussing FIGS. 1A-1D the method discussed with respect to FIG. 2 will be used.
Assume now that the user moves a little bit and spends his/her time in region 12 shown with a ‘B’ at its center. In this situation region 11 will expand. FIG. 1B shows the expanded region 13 . In FIG. 1B the new home region has expanded on the north and east.
The expansion amount could be by just enough to include the user's new location or could be by an integral number of bins (cells), or by doubling the original size, etc.
FIG. 1C shows an example where the user remains within the confines of region 12 and, periodically, as will be discussed hereinafter, the region is reduced. For discussion purposes herein it should be noted that acts performed periodically can be performed at regular intervals or at random intervals. In this example, region 12 is reduced on all sides to form region 14 .
FIG. 1D shows that the home region, now region 15 , has again been expanded on the north and east to include areas of user movement. The home region now includes the new areas of user movement, and omits the areas where the user no longer goes. The home region has effectively moved to follow the user from A to B.
When the user goes far outside the home region (e.g., flies somewhere), the coordinates (and the data associated with the coordinates) are cached (home coordinate cache) and a new temporary region is created.
In addition, the system periodically increments a count associated with the region the user is currently in and periodically deletes from the cache the region with the smallest count. When one region count exceeds some threshold, the system has established a home region. Using this method, the system establishes which cached region is the user's home region. There may be a tie, or a near-tie, for first place, depending on the usage pattern. However, this does not matter since the important thing is to choose a region where the user spends a lot of time. In the embodiment shown, it takes four numbers to store the bin information. The numbers may be, for example, latitude/longitude, or distance (in bins, or some other unit) plus an angle from a known tower, or some other coordinate system (which need not be Cartesian).
By using more numbers: five (2 locations+angle) for a rotated rectangle, six for a triangle, eight for an arbitrary quadrilateral, etc. less restrictive region boundaries can be accommodated. To appreciate the value of less restrictive representations, imagine trying to represent a highway 100 feet wide and 20 miles long, running at a 45° angle. If the rectangle must have horizontal and vertical sides, it will be 14 miles on a side. If the system allows it to be rotated 45°, it only needs to be 100 feet on one side. The cache size of the home coordinate cache (as discussed above) can be as small as desired, as long as it contains at least two elements. The larger the cache, the greater the chance of converging quickly on “home.”
FIG. 2 shows one embodiment of a flowchart showing system and method 20 for determining the home region for storing data pertaining to signal strength. Process 201 starts with an initial home region. One embodiment for determining the home region is shown in FIG. 3 to be discussed hereinafter.
Process 202 determines whether the user has moved outside of the home region. If the user has moved outside the home region, process 203 determines if the user has moved beyond a given distance. If not, then the boundary is expanded via process 204 as discussed above. If the user has moved beyond a given distance, then the prior region's data is stored in a cache via process 205 . Process 206 then determines if the new location is in cache. If so, that cached region becomes the new home region. If not, then process 208 creates a new home region.
Process 209 periodically increments the count for the current region and process 210 periodically shrinks the current region. Either or both of these actions can be incremented periodically, such as every minute (hour), (day), etc., as desired. While uniform shrinking is discussed, an important factor is that shrinkage (whether uniform or nonuniform) is unbiased over the long run. Thus, the shrinkage need not be uniform across the region, and one side could be reduced at one time and a different side reduced at another time. The side or sides to be reduced could be determined in order (north, south, east, west, etc.) or in random order, and any number of sides can be reduced at a time.
As discussed above, this system will continually refine itself so that if a user has moved to a new home region, the new home region will soon become the official home region and the system will continue without anything being done by either the user or the central system to which the device will eventually report. In addition, as discussed above, the size of the area will continually refine downward (or upward) so that as the user's movements reduce (or increase) the home region also reduces (or increases).
FIG. 3 shows one embodiment 30 of a system and method for constructing a grid of cells describing the measurement of the phenomenon, for example, quality of wireless coverage. Process 301 constructs a cell grid over the region where the user presently is located. This cell grid can be as fine as memory will allow. Note that the memory can be different for different mobile devices, and thus, the size of grid area or the refinement therein can be different. Process 302 sets all cells to 0 initially. Processes 303 to 306 are several examples of a defined “bad” cell. In this context “bad” can be defined in any manner subjectively observable by the device and generally pertains to the quality of the signal. No signal is the ultimate bad quality. If desired, different levels of severity can cause a cell's count to be incremented more than once. Thus a dropped call is one example of a “bad” reading. If desired, bad readings can be graded such that a dropped call can be, say, the equivalent of two low RF signal readings, while other factors only give rise to a single incremented count.
Process 303 determines if a call has been dropped. If so, process 313 determines the cell where the dropped call occurred and an incremented count is made in that cell via process 323 . As discussed, this increment would be, for example, a 1 added to the cell to show that a call has been dropped in that cell by this device. Again, note that this information is maintained in the device itself, and is not, at this point, communicated to the central system.
Process 304 determines whether an attempted call has failed, if it has, process 314 finds which cell the call was attempted from. That cell is incremented via process 324 .
Process 305 to 305 N checks for other failure modes and the proper cells are located and incremented via processes 315 to 315 N and 325 to 325 N.
Process 306 checks to see if a periodic check of strength has failed, and if so, then process 316 finds which cell the signal strength has failed in and process 326 increments that cell. Process 306 works under periodic control of process 307 and can, if desired, be under random control, or triggered by external signals or any other manner desired.
Process 308 determines whether a triggering event for reducing the region has occurred. If it has, then system and method 40 , shown in FIG. 4 is entered and, as will be discussed in more detail hereinafter, operates to reduce the memory required for the active region so that more data can be stored for faulty cells.
Process 330 , FIG. 3 , determines if it is time to file the data with the central system. If it is, then data, via process 331 , is transferred from the cell phone to the central system. This transfer can occur periodically, randomly, or on command from the central system as will be discussed, this time can be once a year, or every several months, or sooner as desired. At some point in time, it may be proper to reset the cells to 0. If so, then the system triggers process 302 and system and method 30 will repeat.
Note that for processes 313 , 314 , 315 and 316 if the mobile device cannot determine its location, it does nothing.
FIG. 4 shows one embodiment 40 of a system and method for refining the boundary of the region of poor coverage, by giving cells not on the boundary coarse granularity, and cells on the boundary fine granularity. Processes 401 - 402 control coarse granularity with respect to adjacent cells which have approximately equal density of counts per unit area. These approximately equal cells are merged into a single cell, and the cell's count is set equal to the sum of the counts of the merged cells. Note that this process frees up memory, which is used in later steps. There is, in general, more than one solution. For example, if there is an L-shaped region of equal density, a decision must be made with respect to the corner belonging to the vertical or the horizontal piece. Any choice can be made here, as long as the merged regions are rectangular.
Similarly, any reasonable interpretation of ‘equal’ will work—exactly equal, within “n” counts/area, within “n” percent, etc. Thus, a user can decide how to design the system and method to take into account the desired interpretation of “all cells are equal”: (i.e.) the difference between neighbors is small, the difference between max and min is small, the difference between max and average is small, etc. Again, any method can be chosen, but it is good practice to use the difference between max and min; otherwise the method could be fooled by a smooth gradient.
Processes 403 - 406 control fine granularity. Process 403 divides each cell whose density is not “equal” to that of its neighbors into four cells. This uses the memory which was freed in the previous step. If there is not enough memory, as determined by process 404 to do this step, then division is ended as shown in process 403 .
Process 406 assigns a count to each new cell created in process 403 . The count is chosen as follows. Assume the original cell's count is C.
(1) If C<4, then set p=C/4, and set each new cell's count to 1 with probability p, and 0 with probability 1−p. (2) If C is exactly divisible by 4, then set each new cell's count to C/4. (3) Otherwise, let R be the remainder C mod 4, and let S=C−R. S is now exactly divisible by 4. Proceed as in step (1) with R and as in step (2) with S. The system then repeats processing as in FIG. 3 .
The above is but one embodiment for dividing the region near the boundary into smaller cells and partitioning the counts fairly. Any other method of representing the region as a hierarchic collection of variable-sized rectangles will also serve to keep the memory requirements approximately constant while providing detail near the boundary. For example, see Samet, H., 1988 “Hierarchical representation of collections of small rectangles.” ACM Computing Surveys Vol. 20 No. 4, 271-309.
FIG. 5 shows one example of a hand-held device 50 . In the example, device 50 is a cellular phone having display 51 , location detector 56 , signal strength detector 57 , processor 53 , memory 54 and counters 55 . Some or all of these elements may not be necessary or can be combined into one or more as desired. Note that the mobile device can be any type of device designed to receive wireless broadcast signals, such as, for example cell phones, PDAs, navigation systems, computers, vehicle control processors, etc.
FIG. 6A through FIG. 6E show steps that, by way of example, illustrate how cells are coalesced and split.
Step 1, as shown in FIG. 6A , shows an initial division of the home region into a uniform grid. The area inside circle 61 has poor coverage, and the area outside has good coverage as shown by the number of “bad” counts in the respective cells. Thus, after some time has passed, the cells with poor coverage have relatively large counts, and those with good coverage have relatively small counts. This initial arrangement has 64 cells, which, for illustration, we assume is all that the available memory will permit. The boundary of the region of poor coverage is marked by cells (or cell boundaries) with a small count on one side and a large count on the other.
After some time, (which may be a timed interval, or when the largest count exceeds a threshold, or when the sum of counts exceeds a threshold), as shown by process 308 , FIG. 3 , the system coalesces the grid elements whose incremented count densities are equal to their neighbors' count densities. Unless the service is very bad, most count densities will be equal (in the sense discussed above) to zero, so many cells will collapse into one, and the space required in the device memory for storage of data will be much less than for the original grid. Accordingly, memory is freed up if there is a large good area or a large bad area. As will be seen, this free memory is consumed by constructing an image of the boundary between good and bad areas. In principal, the boundary can be arbitrarily detailed, as long as it fits the available memory.
Step 2, as shown in FIG. 6B , shows the effect after coalescing neighboring cells which have ‘equal’ count density. In this example, cells within 2 of one another are considered equal. There are now 12 cells. Note that the four center cells within circle 61 (circle 61 being a spatial boundary of the measured phenomenon, a portion of which is outside the home region of this measuring device) having counts of 20, 21, 20 and 19 (80) have been reduced to a single cell having a count of 80 which is the sum of the original cells. Also note that all the non-boundary cells (cells not on the boundary of the circle) to the left of circle 61 are reduced to a single cell having a count of 6. Likewise, the three non-boundary cells (cells not on the boundary of the circle) above circle 61 are reduced to a single cell having a cell count of 3 while the nine non-boundary cells (cells not on the boundary of the circle) below circle 61 have been reduced to a single cell having a count of 1.
Step 3, as shown in FIG. 6C , shows the result after splitting those cells which were not coalesced with their neighbors. There are now 36 cells based upon a 4 for 1 split of each coalesced cell. The boundary of the region of poor coverage is marked as in Step 1, but since those cells are now smaller, the boundary is determined more precisely.
Step 4, as shown in FIG. 6D , shows the situation after the cells have been accumulating counts for some time. As would be expected, the cells in the area of poor coverage accumulate counts at a higher rate than do the cells in the better coverage areas.
Step 5, as shown in FIG. 6E , shows the result after a second round of coalescing neighboring cells which have ‘equal’ count density, and then splitting the cells that remain. Note the three cells at the bottom of circle 61 which have not been split. There are 63 cells in this FIGURE; further splitting would require more memory than had been used (64) for the initial cell count (see step 1, FIG. 6A ). (In step 1, the assumption is that the available memory has all been used). The algorithm stops splitting when there is insufficient memory to do so. The boundary of the region of poor coverage is still marked as in Step 1, but since those cells are now smaller, the boundary is determined even more precisely.
This process continues, stopped only by running out of memory, or by being restarted by process 332 , FIG. 3 . Note that as shown in FIGS. 6A-6E the boundary of the measured “bad” (or out of norm) phenomenon need not lie entirely within the region reported by the device. Thus, it may take several devices to properly describe the totality of the “bad” phenomenon.
Places where the signal quality is different at different altitudes are treated the same as places where the signal quality is different at different times; i.e. there will probably not be a consistent hole. If mobile devices know their location in three dimensions than the concept discussed in this patent can be generalized to three dimensions. This would only be practical if sufficient memory exists. However, since mobile phone locating methods do not work very well indoors or underground, three dimensions may not be practical. Note that a device may have been in a “bad” location many times and for one reason or another (for example, being turned off) not logged a “bad” signal.
FIG. 7 shows RF system 700 having RF communication tower 701 controlled by control system 702 . In the embodiment shown, RF tower 701 is a cellular tower communicating to cell phones 50 - 1 , 50 - 2 through 50 -n. These cell phones are mobile and can thus move throughout the coverage area or to other areas. As they each move, they will each contain within the device the incremented numbers recorded according to the system and method discussed above. Periodically, this information will be communicated to control system 702 for the purpose of allowing the central system to then determine problems within the coverage areas based upon actually occurring criteria as determined from mobile devices in the course of their normal end-user usage. Note that the “home” region of each device is defined based upon that device's actual movements and thus each home region will be different. This difference then assures that the entire coverage area is monitored.
The system and method described will over time compute the boundary of regions where the device was unable to support a call and will do this within fixed memory limits in a hand-held wireless device. The device will devote almost no memory to regions where service is adequate. The process will be more memory-efficient if there are a few large holes as opposed to many small ones. The devices used, for example, the cellular phones, will be ones that are in the region naturally, because they are being used on a commercial network for which they were intended and not as a piece of extraneous test equipment. Thus, in the embodiment shown, a cellular telephone is being used to make and receive calls and the population of cell phone users (not any particular one cell phone user) will tend to go into every possible location within any cellular region. Thus, the actual end-user device defines the locations for making measurements, and the region is not limited to places where test equipment can go. This then yields more natural test results since it is based on actual user experience over a wide population.
A large portion of the device memory is spent storing counts of instances of poor service. The process is more accurate if it runs longer (assuming stationary service holes), but this requires larger counts, hence wider counters, hence more memory. If a user spends, say, 15 minutes a day in a coverage hole and the system samples every 10 seconds, then an 8-bit counter will overflow in 3 days. Morris, Robert “Counting Large Number Of Events In Small Registers” Communications of the ACM, Volume 21 Number 10, pp. 841-842, Oct. 1978, which is hereby incorporated by reference herein, developed a technique whereby the logarithm of the count can be stored (the technique does not require computing logarithms). The result is approximate, but since the system is sampling a continuous phenomenon, and “equal” is already approximate, it can accept an approximate count. Using the Morris method, and accepting a standard deviation of about 10%, an 8-bit counter's range can be extended to 4 years. One can use sub-byte counters, but this brings little benefit because the log function grows slowly. A 7-bit counter under these conditions will span just 3 weeks. This type of counter can also be used for the counts in the cache.
This process evolves an ever-more-detailed image of the boundary of coverage holes, in bounded memory and using only 1-byte counters. The two main aspects of determining coverage locations and determining holes could run concurrently or alternately, or by constantly updating the counts in the cache, perhaps at a slower rate once the system has calculated a home location. Updating home location is necessary because the system might have made a wrong choice, or the user's behavior may have changed.
The concepts taught herein can be used for detecting the boundary of any phenomenon, as long as it's fairly stationary and mobile devices can detect that phenomenon. For example, a determination can be made of where there's a lot of background noise; where traffic consistently speeds up or slows down; the level of smog (if smog sensors are placed on mobile devices) or sunlight (if correction is made for time of day), etc. Also, while a cellular system has been described, the concepts taught herein could be used for any type of communication or broadcast transmission system, including, by way of example, WIFI, Internet and wireless computing, radar, and sensor.
Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the invention as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one will readily appreciate from the disclosure, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.
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A system and method is shown for determining the spatial boundary of certain measurable phenomena, such as broadcast signals, at various locations within geographical areas covered by the phenomenon. Data representing relative signal quality at various locations within the geographical area is created within a mobile device, such as a cell phone capable of receiving the phenomenon. The data is stored and refined within the device so as to define weak signal quality areas within at least a portion of the geographical area traveled by the mobile device. The refinement, which in one embodiment comprises coalescing and splitting stored data locations in the device allows for long storage periods by reducing memory requirements. By devoting the majority of memory to locations in the vicinity of the good/bad boundary, the most detailed picture possible of the boundary is achieved for a given amount of memory. By collecting such data from a plurality of such devices, a central system can map the signal strength over the entire geographical area.
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Field of invention
The present invention relates to a method for damping the natural vibrations and/or oscillations of movable pillar-stands carrying X-ray equipment, when making positional adjustments thereto.
Such a pillar-stand may be mounted to the ceiling, on the floor or on the wall of a room, and the equipment carried by said stand may comprise X-ray film exposure apparatus, a hospital bed or the like.
When the pillar-stand is suspended from the ceiling of a room, the stand often has an L-shape configuration, and the X-ray apparatus, hospital bed or the like is often positioned on a member which is movable in relation to the pillar-stand itself and which, either separately or together with the pillar-stand, has a U-shape, a C-shape or a similar shape.
A typical ceiling-hung pillar-stand often has the shape of an inverted L, and is mounted so as to be pivotable or adjustable about a vertical axis located in the upper part of said stand, at the end of the shorter leg thereof. The vertically extending, longer leg of the stand is provided with a further member which carries the X-ray equipment, such as exposure equipment and film-cassette holder or a hospital bed or the like.
This further member is normally arranged for vertical movement along the pillar-stand and is also mounted thereon for pivotal or rotary movement about a horizontal axis.
In the case of a typically ceiling-mounted pillar-stand of the aforedescribed kind, the height between ceiling and floor is 2.75 m, and the total height of the pillar-stand is slightly less than this measurement and measures, for example, about 2.5 m. When the pillar-stand carries X-ray equipment, the total weight may reach from 300 to 350 kg.
PRESENTATION OF THE UNDERLYING PROBLEMS RELEVANT TO THE INVENTION
One problem encountered with such pillar-stands, particularly with a pillar-stand mounted on the ceiling of a room, is that the stand can readily be set into free oscillation, e.g. when making positional adjustments, when the pillar-stand is swung about the vertical axis and/or the further part is swung about its horizontal axis.
Upon examination it has been found that the amplitude of this natural oscillatory movement in the case of a typical pillar-stand of the aforedescribed kind is about 2 mm, and that this amplitude is still close to 2 mm after a lapse of 12 seconds. After 36 seconds, the amplitude was found to have decreased to about 1 mm, and it took almost one minute before it could be said that the free oscillatory movement of the stand had ceased.
Tests have shown that when the pillar-stand is caused to oscillate or vibrate in an arbitrary direction -- e.g. by kicking the base of a ceiling-suspended pillar-stand -- the stand will relatively quickly begin to oscillate freely in one and the same plane, namely the plane exhibiting the lowest inertia against natural oscillation, in accordance with for example a central plane or symmetry plane which passes through the L-shaped stand and extends through its suspension point.
It will be understood that the course followed by natural oscillations of the aforedescribed kind constitutes a serious disadvantage, primarily because the X-ray exposure may be blurred as a result thereof. Thus, the phenomena of natural vibrations results, in turn, to the serious risk of necessitating the patient to be subjected to a repeated course of X-rays, with an increased X-ray dosage as a result thereof.
In order to further illustrate the decisive negative influence of the phenomena of natural oscillations on the final result, it can be mentioned that there are essentially three factors which contribute to the total blurring of an X-ray picture. These three factors are: geometric blurring blurring of the film system (limited resolution of the picture etc.), and movement blurring.
If these factors are assumed to have the numerical values a, b and c respectively, the total non-focussing or blurring effect is given by the expression ##EQU1## It will be seen herefrom that when one of these factors is substantially higher than the others, the higher factor will have a decisive effect on the end result.
By way of illustration it can be mentioned that a typical geometric non-sharpness may be as much as 0.2 mm in the case of an X-ray stand. A movement non-sharpness of a corresponding order of magnitude will typically occur at an exposure time of 0.01 seconds. Consequently, with an exposure time 10 times as long, i.e. 0.1 seconds, the movement non-sharpness will be 2 mm, i.e. will correspond to the amplitude of the natural oscillatory movement of a typical pillar-stand of the aforementioned kind. It is quite common to use much longer exposure times, up to 4-5 seconds.
When these values are inserted into the above formula, in which the film-blur is assumed to correspond to the value of the geometric blurring or non-sharpness, i e. 0.2, there is obtained a total blurring of ##EQU2##
The conclusion was reached that even though expensive equipment having low geometric blurring, and a film having high resolution were used on a pillar-stand which exhibits high natural-oscillation amplitudes, the last mentioned factor will dominate, and hence the quality of the picture would be unsatisfactory.
The pertinent parts of the aforementioned are also true when a pillar-stand mounted, for example, on the ceiling of a room, carries a hospital bed, while the X-ray equipment is so supported as to substantially be free of natural oscillation.
Consequently, the problem upon which the present invention is based is also relevant in this case.
BACKGROUND ART
The aforementioned problem has earlier been observed, and various solutions have been proposed in an attempt to overcome the problem.
For example, there is described in SE-B-147.339 (Siemens-Reiniger-Werke) a method of eliminating oscillation of an X-ray apparatus by electro mechanical means. In the arrangement therein described there is used a support means which comprises at least two rigid members which can be adjusted relative to one another and which support against a part which is separate from the apparatus and which is stationary relative to the apparatus part to be supported. The stationary part may, for example, comprise the ceiling of a treatment room.
Such arrangements, which utilize a fixed support point externally of the X-ray stand, are normally particularly complicated and constitute a serious limitation to the extent to which the X-ray frame can be moved.
Consequently, such arrangements are unsuitable and have not met with wide use in modern X-ray stands.
Other types of arrangements are described in U.S. Pat. No. 4,287,424 (Tomita et al) which teaches a plurality of damping mechanisms in connection with tomography; U.S. Pat. No. 4,181,347 (Clark) which teaches vibration damping for mobile X-ray units; and U.S. Pat. No. 4,050,551 (Schmedemann et al) which teaches an arrangement for damping oscillations or vibrations in conjunction with counterweights.
None of these known arrangements provides a satisfactory solution to the problem of quickly damping effectively the natural oscillations of a pillar-stand carrying X-ray equipment.
BRIEF DISCLOSURE OF THE INVENTION
The present invention eliminates the aforementioned disadvantages and fulfils the aforesaid object, and its widest aspect is mainly characterized by applying a pivotable mass in said stand at a distance from the attachment point of said stand; and by causing said mass to execute a dampened oscillatory movement in a counter direction to said natural oscillations of the stand, such as to rapidly extinguish said natural oscillatory movement.
The aforementioned mass may comprise a pivotable body, for example a pendulum or a suitably journalled body of some other design, which can be caused to execute dampened oscillatory movements when the pillar-stand begins to oscillate at its natural frequency.
Alternatively, the mass may also comprise a quantity of liquid contained in a container suitably placed in the stand.
Such a liquid mass can be caused to execute counter-oscillations in any direction. An oscillation-damping pendulum, or some other kind of body, can also be arranged so that its counter-directed oscillatory movements can be effected in any desired direction.
Preferably, however, and particularly when the mass has the form of a body such as a pendulum or a suitably journalled weight, the body is arranged to swing in a plane in which the pillar-stand exhibits the lowest inertia against natural oscillations.
As beforementioned, as a rule the phenomenon whereby the natural oscillatory movement of the pillar-stand will take place in the direction exhibiting the lowest inertia against the oscillations will manifest itself irrespective of the direction in which the natural oscillatory movement of the stand begins. Consequently, the counter-directional oscillatory movement should take place in this direction.
In principle, the counter-directional oscillatory movement of the mass can be initiated and/or created in any desirable manner. Thus, if so desired, drive means may be provided for imparting the counter-directional movement to the mass. Preferably, however, the natural oscillatory movement of the stand itself is utilized to impart the counter-directional oscillatory movement to the mass. This provides for effective damping of the natural oscillations of the stand in the absence of any such drive means.
Tests have shown that in the case of a typical ceiling-suspended pillar-stand of the aforementioned kind, an initiated natural oscillatory movement having an amplitude of about 2 mm can be caused to cease practically completely within the space of about 5 seconds, with the use of two pendulums suspended in the lower part of the stand and having a length of about 0.8 m and an individual weight of about 10 kg.
Suitably, two such pendulums are used, one on each side of the pillar-stand, since the central space of the stand is required for other purposes, for example for housing means by which the pendulum arm can be displaced, rotated, turned and/or braked in relation to the stand.
The oscillatory movements of the pendulum or pendulums are suitably dampened by a rubber cushion or like means mounted in a suitable position in the stand. Normally, it is preferred to dampen only one side of the pendulum by means of such damping means, since the characteristic feature of a pendulum is that it will swing equal distances in both directions relative to an 0-line, and consequently an additional damping means on the other side of the pendulum would fulfil no function.
The use of a pendulum arrangement of the aforementioned kind also affords a number of additional advantages which cannot be achieved with hitherto known natural-oscillation damping arrangements. One such advantage resides in the fact that when a pillar-stand of the aforementioned kind is manufactured in the factory, the stand is fully assembled and tested in the aforesaid respect. When using a pendulum arrangement of the aforedescribed kind, the relative positions of the pendulum and the stand under ideal circumstances can be marked on suitable parts of the pendulum and stand. The pillar-stand is then dismantled, for transportation to the place where it is to be used, and re-assembled. The aforementioned marks can then be used to ensure that the pillar-stand is correctly assembled at its place of use.
The aforesaid principle can be applied to varying degrees of fineness. A measurement can be made on one or two sides by means of an infrasonic or ultrasonic transmitter of the deviation from the ideal value, and to take advantage hereof when adjusting the position of the pillar-stand. When the deviation from the ideal position on both sides is 0, it will be ensured that the pillar-stand is correctly adjusted.
One or more pendulums of the aforementioned kind can be replaced with, for example, a weight carried by ball bearings and having magnetic properties, and arranged for movement backwards and forwards in a magnetic field generated by permanent magnets or electro magnets. This enables the desired soft damping of the weight or body to be achieved in a simple fashion. The damping means may have a form other than the aforedescribed weight or body, however.
When the mass comprises a liquid contained in a container, the container is conveniently provided with a baffle which suitably extends in a direction so that movements of the liquid are effectively dampened in a direction which falls in the plane in which the pillar-stand exhibits the lowest inertia against natural oscillatory movement.
In a further improvement of the method according to the invention, means for sensing and/or registering the amplitude of the natural oscillatory movement or damping movement may be connected to X-ray exposure means carried by the stand, such as to prevent exposure at least for certain shutter times when the amplitude of the oscillations exceeds a given value.
This comparatively simple method ensures that no exposure can be made when the natural oscillatory movement would result in an unacceptable blurred X-ray picture.
The invention also relates to a movably mounted pillar-stand for carrying X-ray equipment, the main characterizing features of the stand being set forth in the claims.
Additional aspects of the invention are disclosed in the following description, which is made with reference to a number of selected embodiments, illustrated in the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a ceiling-suspended pillar-stand for carrying X-ray equipment, in accordance with the present invention.
FIG. 2 is a perspective view in larger scale, illustrating the partially cut-away lower part of the stand illustrated in FIG. 1.
FIG. 3 is a cross-sectional view taken on the line III--III in FIG. 1.
FIG. 4 is a perspective view of the lower part of a stand according to FIG. 1 provided with a modified oscillation-damping arrangement.
FIG. 5 is a perspective view of another modified damping arrangement.
FIG. 6 is a perspective view of a ceiling-suspended pillar-stand in which the X-ray apparatus comprises a displaceable and pivotably adjustable hospital bed.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In FIGS. 1-3, the reference 1 identifies a movable ceiling-mounted pillar-stand for a carrying X-ray equipment. The stand is of an invert L-shape, the stand part 2 of which is of invert L-shape having an upper horizontal part 2a and a vertical part 2b which terminates at a distance from a support surface or floor 7.
The stand 1 has a U-shaped pendant-like part 3 which is displaceable along the vertical leg 2b of the pillar-stand and arranged for rotation around a horizontal axis (not shown) relative thereto. The displaceable and pivotable pendant-like part 3 carries X-ray equipment in the form of an X-ray emission device 4 and a cassetteholder 5 for an X-ray negative.
As beforementioned, the stand part 2 is suspended from a ceiling, namely from a swivel bearing 8 firmly mounted on the ceiling 9.
When the stand part 2 and/or the pendant-like part 3 are adjusted, natural oscillatory movements will be created in the plane exhibiting the lowest inertia against such oscillations, this plane lying along a central line or symmetry plane through the inverted L through the ceiling-suspension point.
If the damping means according to the present invention, hereinafter described, is rendered inoperative, for example by means of anchoring the pendulums 10 to the stand part by means of screw clamps (not shown), the amplitude of the natural oscillations of the frame at its lower part will approach 2 mm. A reduction to an amplitude of about 1 mm takes more than 30 seconds, and it is not until 60 seconds have passed that the natural oscillatory movement can be said to have ceased.
In order to stop the natural oscillatory movement more rapidly, there are used pendulums 10 having a length of about 0.8 m. The pendulums are pivotally mounted on a horizontal pivot 11. The pendulums may be made of steel and each has a weight of about 10 kg.
The pendulums 10 are arranged on mutually opposite side surfaces of the stand part 2, between reinforcing flanges extending vertically in said stand. The pendulums 10 are arranged to swing in the direction of the natural oscillations of the standpart 2. The pendulating movement of the pendulums is restricted by a rubber cushion 12 on one of the flanges 2c.
When the pillar-stand begins to oscillate at its natural frequency as a result of making the aforementioned adjustments, a counter-directional damped oscillatory movement is automatically generated by the pendulums 10, which causes the natural oscillatory movement to cease practically completely within the space of some 4 to 5 seconds.
FIG. 4 illustrates a modified damping arrangement in the form of a weight or body 10' having magnetic properties and being movable on ball or roller bearings 11'. Two permanent magnets or electromagnets 12' restrict movement of the body 10' when said body is set into motion by the natural oscillatory movement of the pillar-stand 2. When using an electromagnet, damping can be regulated by varying the voltage.
In this arrangement it is possible, by way of an alternative , to set the body 10' into motion by means of electromagnets 12', said movement being given a frequency different to the frequency of the natural oscillatory movement of the pillar-stand.
In the modification illustrated in FIG. 5, a body of liquid 10", for example oil, is contained in a container 15 located in the lower part of the stand. When the stand oscillates at its natural frequency, the liquid executes a splashing movement which dampens the natural oscillations of the stand. In order to improve the effect, the container 15 may be suitably provided with a baffle plate (not shown). The damping effect can also be modified by varying the amount of liquid in the container.
FIG. 6 illustrates a similar, ceiling-hung pillar-stand 2. The X-ray equipment of this embodiment comprises a hospital bed 5' which is displaceably and articulately mounted on the stand part 2. The natural oscillations created in the stand when adjusting the position of the hospital bed and negatively affecting the X-rays pictures taken with the aid of X-ray equipment (not shown) arranged separately of the pillar-stand 2 is reduced by means of the pendulums 10 pivotally arranged in the lower part of the stand. Thus, this arrangement will also extinguish the natural oscillatory movement of the stand within the space of a few seconds.
It should be mentioned that the aforementioned extinguishing time of from 4 to 5 seconds is normally long enough for the person operating the equipment to move from the stand to a position -- behind a lead screen -- from which the exposure can be made. Thus, the operator is able to make the exposure practically immediately from said isolated position.
FIG. 2 illustrates in chain lines an auxiliary means 16 for damping the oscillatory movement magnetically, for example.
In FIG. 3 there is illustrated at the bottom of the stand, in connection with respective pendulums 10, means 2d which, together with said pendulum, can be provided with markings which indicate the position adopted by a respective pendulum when the stand is ideally suspended. The markings can be made when testing the stand in the factory, prior to delivery. These markings enable the stand to be precisely positioned when mounting the same in the location where it is to be used.
The amplitude of the natural oscillatory movement or of the damping means can be sensed by means of a suitable device which is connected, via a data processor, to the exposure-release means of the X-ray equipment. In this way, it can be readily ensured that an exposure is only taken when the amplitude has been reduced to an acceptable value of any desired magnitude.
In a modified embodiment hereof, the maximum permitted amplitude may vary from case to case in correspondence with relevant exposure times. This is particularly favourable in respect of the pre-programming of exposure parameters, which is now a normal procedure.
One of normal skill in this art will realize that the damping arrangement itself may have a form different to those illustrated and above described.
Although the invention is primarily suited for ceiling-suspended pillar-stands, it will be understood that the invention can also be applied to other types of X-ray stands, such as floor-mounted stands or wall-mounted stands.
Should the pillar-stand exhibit substantially the same degree of inertia against natural oscillations in a number of directions, the damping means may comprise a pendulum which is journalled for rotation at one end thereof. the counter-directional pendulating movement of the pendulum will thus be dependent upon the direction in which the pillar-stand is caused to oscillate.
In the case of a floor-mounted stand, damping is improved when the pendulating mass, for example, the pendulum, is arranged in the upper part of the stand and is inversely directed, i.e. the attachment point is located lowermost.
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A movably mounted pillar-stand for carrying X-ray equipment, the pillar-stand preferably celling-suspended and having a pendulum arrangement or the like for the purpose of damping natural oscillatory movements. When natural oscillatory movements occur in the pillar-stand when making positional adjustment thereto, the natural oscillatory movement of the stand is effectively extinguished within the space of some few seconds by a damped, counter-directional pendulating movement imparted to the pendulating arrangement by means of the natural oscillatory motion of the stand.
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SUMMARY OF THE INVENTION
This invention relates to a power pack for a portable cellular telephone, the power pack having a concealed radio transmitter for use by a law enforcement agent or a witness cooperating with the government to broadcast to sound recording equipment at some distance away a conversation that might incriminate a criminal suspect.
Criminals generally, and particularly those trafficking illegally in controlled substances, are vigilant and suspicious of anything that might be used to record an incriminating conversation. A portable cellular telephone is not likely to arouse their suspicion because it is a common tool of their own trade. Nonetheless, every precaution should be taken to insure that the criminal suspect does not detect that the usual portable cellular telephone has a radio transmitter that is broadcasting what he or she is saying to a sound recording device located elsewhere.
In accordance with the present invention, the usual power pack for a portable cellular telephone is modified to carry a very small radio transmitter that will broadcast conversations conducted in the vicinity of the phone. The housing of the power pack is constructed to hold shorter batteries than those previously used but with enough capacity to operate the cellular telephone in the usual way for a reasonable period of time, as well as to hold a concealed radio transmitter, its antenna and its microphone. When the power pack in accordance with this invention is in place, there is no change in the usual operation of the cellular telephone, either in receiving or in transmitting messages. There is nothing visible on the outside of the phone and nothing in the way it is used that might be detected by or arouse the suspicion of the person under surveillance. The only change on the outside of the power pack is an unobtrusive push button for operating an on/off switch to connect the batteries to the concealed transmitter for broadcasting conversations that take place in the vicinity of the cellular telephone. This push button is one of three openings that are present on the usual power pack for a cellular telephone where electrical contacts are located.
A principal object of this invention is to provide a novel power pack for a portable cellular telephone which contains a concealed radio transmitter that is not part of the cellular telephone system but is used for law enforcement purposes to transmit conversations occurring in the vicinity of the phone.
Further objects and advantages of this invention will be apparent from the following detailed description of a presently preferred embodiment which is illustrated schematically in the accompanying drawings.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a cellular telephone of known design with a power pack containing a concealed radio transmitter in accordance with the present invention;
FIG. 2 is a view taken along the line 2--2 in FIG. 1 showing the power pack partly in end elevation from its outer side, i.e., the side away from the casing of the cellular telephone, and partly with its housing broken away to reveal the concealed transmitter, its antenna and its microphone;
FIG. 3 is a section taken along the line 3--3 in FIG. 1 at the inner side of the power pack, i.e., the side next to the casing of the cellular telephone;
FIG. 4 is an exploded perspective view of the power pack and concealed transmitter assembly in accordance with the present invention;
FIG. 5 is an elevational view of the power pack in its assembled condition taken from its inner side;
FIG. 6 is a longitudinal section taken along the line 6--6 in FIG. 5;
FIG. 7 is a cross-section taken along the line 7--7 in FIG. 5;
FIG. 8 is a cross-section taken along the line 8--8 in FIG. 5; and
FIG. 9 is a cross-section taken along the line 9--9 in FIG. 5.
Before explaining the disclosed embodiment of the present invention in detail it is to be understood that the invention is not limited in its application to the details of the particular arrangement shown since the invention is capable of other embodiments. Also, the terminology used herein is for the purpose of description and not of limitation.
DETAILED DESCRIPTION
FIG. 1 shows a power pack P on the back of a cellular telephone 10 of known design. The exterior of the housing 11 of the power pack is unchanged from a known design but in accordance with this invention its interior is modified to hold a concealed radio transmitter and shorter batteries than ordinarily are provided.
As shown in FIGS. 4, 7, 8 and 9, the power pack has an outer housing member 11 of generally U-shaped or channel-shaped cross-section, with a flat outer wall 12 and opposite side walls 13 and 14 joined the outer wall 12 at rounded corners along the length of this housing member. The lower end of the outer housing member is closed by a generally flat end wall 15. At the upper end the outer housing member has a flat end wall 16 formed with a semi-circular recess 17 in its edge away from the outer wall 12. As shown in FIGS. 7, 8 and 9, the side wall 13 along substantially its entire length has a shallow groove or recess 13a on the inside along its edge away from the outer wall 12. The opposite side wall 14 has a similar groove or recess 14a on the inside for virtually its entire length. As shown in FIG. 2, immediately above the bottom end wall 15 of outer housing 11, its outer wall 12 has three small rectangular openings 12a, 12b and 12c. As thus far described, the outer housing member 11 of the power pack is unchanged from the outer housing member of the power pack housing on a well-known cellular telephone, hereinafter referred to as "the prior art power pack housing."
Referring to FIG. 4, the outer housing member 11 has an interior wall or web 18 extending parallel to its end walls 15 and 16 and joined integrally to the outer wall 12 and the opposite side walls 13 and 14. This interior wall or web 18 is thin and flat and is located much closer to the upper end wall 16 than to the lower end wall 15 of housing member 11. In the prior art power pack housing this interior wall has occupied almost the full depth of the interior of the housing from one side wall 13 to the opposite side wall 14 and it defined one end of the battery chamber, the opposite end of which is defined by the lower end wall 15.
In accordance with one feature of the present invention, the interior wall 18 is cut away to have a wide rectangular recess or notch 19 of sufficient depth and width to receive a circuit board 20 which holds the components of a radio transmitter of known design. Preferably, the transmitter is a crystal controlled transmitter operating at a selected frequency within one of several VHF high band frequency ranges, including the 140-174 megaHertz range. Also, in accordance with this invention the outer housing member 11 is further modified by the addition of a second internal wall or web 21 extending parallel to and spaced below the interior wall 18. Wall 21 is formed with a rectangular recess or notch 22 of the same depth and width as the recess 19 in wall 18. As shown in FIG. 6, the transmitter circuit board 20 near its upper end rests on the upper interior wall 18 at the bottom of its recess 19 and, as shown in FIGS. 6 and 9, the transmitter circuit board near its lower end rests on the lower interior wall 21 at the bottom of its recess 22.
In accordance with another important feature of this invention, the inside of the outer wall 12 of the outer housing member 11 has a shallow recess 23 of generally rectangular outline. The lower edge 24 of this recess is about midway between the bottom end wall 15 and the lower interior wall 21 of housing member 11. The upper edge 25 of recess 23 is located a very short distance below the upper interior wall 18. The lower interior wall 21 has a shallow, wide, rectangular recess or notch 21' along its edge facing the recess 23 in outer wall 12.
Thus, the structural changes in the outer housing member 11 from the prior art power pack housing are the recess 19 in interior wall 18, the addition of the lower interior wall 21, and the provision of the shallow recess 23 on the inside of outer wall 12.
An antenna A of thin, flat, rectangular configuration is seated in the bottom of recess 23, as shown in FIG. 8. Potting compound 26 covers the antenna and fills the remainder of recess 23 not occupied by the antenna. Electrical wiring 27 (FIG. 2) connects the potted antenna A to the radio transmitter circuitry on circuit board 20.
The battery pack housing also has an inner member 28 (FIG. 4) which except for one structural change is the same as the inner member of the prior art power pack housing. This inner member 28 fits on the outer housing member 11 in a known manner, as shown in FIGS. 5, 7, 8 and 9, and it is located along the inner side of the power pack next to the casing of the cellular telephone 10. The opposite longitudinal side edges of the inner housing member 28 are snugly seated in the grooves 13a and 14a extending along the inside of the opposite sides 13 and 14 of the outer housing member 11 of the power pack.
As shown in FIGS. 4, at its upper end the inner housing member 28 has a hollow, rounded protrusion 29 which, as shown in FIG. 7, engages the inside of the back wall 12 of outer housing member 11. The upper part of protusion 29 is semi-circular in cross-section and it is seated snugly in the recess 17 in the upper end wall 16 of outer housing member 11. The lower part of protrusion 29 presents opposite flat side walls 30 and 31 (FIGS. 4 and 7) which are spaced inward from the respective sides 13 and 14 of outer housing member 11. Between wall 30 and side 14, the power pack housing assembly provides a space 32 (FIG. 7) which is empty in the prior art power pack housing.
In accordance with another feature of this invention, a microphone M is positioned in this space 32 and a small air hole 32a (FIGS. 4 and 7) is drilled in the rounded protrusion 29 on the inner housing member 28 to provide sound to travel in this space. This air hole is the only structural change in the outer housing member 28 from how it is in the prior art power pack housing. As shown in FIG. 3, microphone M is connected to the transmitter circuit on circuit board 20 by wiring 33 which extends past the upper interior wall 18 on one side of its recess 19.
Referring to FIG. 4, at its lower end the inner member 28 of the power pack housing has a bridge 34 which fits snugly inside the outer housing member 11 next to the inside of its lower end wall 15. This bridge supports two electrical contacts 35 and 36 which are accessible at respective openings 12b and 12c (FIG. 2) in the outer wall 12 of outer housing member 11. In this respect, the housing of the present power pack is unchanged from the prior art power pack housing. Between these contacts, bridge 34 supports a push button 37 which projects through opening 12a in the outer housing member. (In the prior art power pack, instead of this push button there is an electrical contact which is used for rapid charging of the batteries in the power pack). Push button 37 operates a push-on, push-off latching switch 38 (FIG. 3) for turning on and off the radio transmitter on circuit board 20. As shown in FIG. 3, switch 38 is connected by wiring 39 to the transmitter circuit board 20.
In accordance with another feature of the present invention, the batteries in the prior art power pack are replaced by an equal number of shorter batteries B of the same type and the same cross-sectional size as those previously used. These are rechargeable nickel-cadmium batteries and six of them have sufficient capacity to power the cellular telephone for about three hours. These batteries are disposed inside the power pack housing in a battery chamber 40 bounded on the bottom by the bridge 34 on inner housing member 28, on the top by the lower interior wall 21 of outer housing member 11, on the opposite sides by the side walls 13 and 14 of outer housing member 11, on the outside by the outer wall 12 of outer housing member 11, and on the inside by inner housing member 28. As shown in FIGS. 2 and 3, the batteries are arranged in two side by side columns of three each. The batteries are connected in series and are connected through the push button-operated switch 38 to the concealed transmitter on circuit board 20. The batteries also are connected to power the cellular telephone 10 in the normal manner. When the power pack of the present invention is used in place of the usual power pack on the cellular telephone, there is no change in the operation of the cellular telephone except for an acceptable reduction in the time between battery recharges. In addition to maintaining normal operation of the cellular telephone, the present power pack provides a concealed radio transmitter which a law enforcement officer can use without arousing suspicion that anything but a cellular telephone is being used in the normal way.
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The present power pack for a portable cellular telephone has a concealed radio transmitter for law enforcement use. The usual battery compartment in the housing of the power pack has a shortened battery compartment above which are located interior walls of the housing which are notched or recessed to support a printed circuit board carrying a radio transmitter. The housing has a shallow recess on the inside in which an antenna is potted. A space inside the housing receives a microphone for the radio transmitter. An opening near the lower end of the housing receives a push button switch for powering the transmitter from batteries in the shortened battery compartment.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is broadly concerned with methods of forming substituted guanidines utilizing nickel catalysts. More particularly, the methods comprise guanylating amines or pyrrolidines with guanylating agents such as thioureas or isothioureas in the presence of a nickel catalyst. Preferably, the nickel catalyst comprises nickel in the zero oxidation state. Suitable Ni(0) catalysts are preferably derived from nickel-boride alloys, nickel-phosphide alloys, aluminum-nickel alloys, nickel on kieselguhr, nickel on silica/alumina, and other nickel catalysts.
2. Description of the Prior Art
The guanidine functional group is an important structural component in many biologically active compounds. Due to their strongly basic character, guanidines are fully protonated under physiological conditions. The positive charge thus imposed on the molecule forms the basis for specific interactions between ligand and receptor or between enzyme and substrate, mediated by hydrogen bonds and/or electrostatic interactions. As a result, the guanidino group has been incorporated into many clinically useful drugs. For example, the guanidino group is used in H 2 -receptor antagonists such as cimetidine and tiotidine which are anti-ulcer agents. The guanidine functional group is also found in cardiovascular drugs (e.g., clonidine, guanethidine), anti-diabetic drugs (e.g., phenformin, metformin), anti-malarial drugs (e.g., chloroguanidine), antibacterial agents (e.g., streptomycin), as well as other drugs.
Due to their importance in drug development, synthetic procedures for the preparation of guanidines under mild reaction conditions and in high yields while using minimal amounts of reagents are of significant interest to the pharmaceutical industry. Mild reaction conditions are necessary during the synthesis process because harsh conditions will lower the yield of the reaction product due to decomposition or unwanted side reactions of the valuable drug precursor. Reducing the number and quantity of reagents minimizes the quantity of reagent by-products generated which must be removed from the drug product, thus resulting in decreased drug production costs. Finally, of particular importance are chemical synthesis methods that minimize or eliminate the use of toxic reagents or catalysts, particularly in large scale industrial drug production.
Typically, synthesis of guanidines involves treating amines with guanylating agents. The most commonly used agents include derivatives of pyrazole-1-carboxamidine, aminoiminomethanesulfonic acid, S-methylisothiouronium salts, S-alkylisothioureas, and protected thiourea derivatives.
Substituted and protected thioureas are widely employed in the preparation of substituted guanidines. Coupling reagents (e.g., Ph 3 P/CCl 4 and thiophilic metal salts such as HgO/S, HgCl 2 , CuCl 2 , and CuSO 4 ) have been extensively used in conjunction with thioureas for the guanylation of both aliphatic and aromatic amines. The initial step in these reactions involves the formation of intermediate carbodiimides which will then react with amines to give the corresponding guanidines. However, these reactions generally require an excess amount of reagents and/or longer reactions times in order to provide acceptable yields of the particular substituted guanidine. Furthermore, a distinct disadvantage to the use of mercuric salts in guanylation reactions is that the mercuric salts are toxic compounds. Finally, it is very difficult to separate the guanidines from the unreacted mercuric salts and the mercuric sulfide byproduct.
N-Unsubstituted S-methylisothioureas are useful for guanylating aliphatic primary and secondary amines. However, N-alkyl substituted S-methylisothioureas are inadequate at guanylating aliphatic primary and secondary amines due to the fact that this reaction is reversible and the byproduct methyl mercaptan must continually be removed from the reaction mixture in order to drive the reaction to completion.
There is a need for methods of guanylating amines in high yields which do not require the large quantities of coupling reagents and bases used in prior art methods.
SUMMARY OF THE INVENTION
The instant invention broadly comprises methods of forming substituted guanidines in the presence of a nickel catalyst. In more detail, guanylating agents are reacted with a compound selected from the group consisting of amines utilizing the nickel catalyst.
The nickel catalysts utilized in the inventive methods preferably comprise nickel in the zero oxidation state. Suitable Ni(0) catalysts are preferably derived from nickel-boride alloys, nickel-phosphide alloys, aluminum-nickel alloys, nickel on kieselguhr, and nickel on silica/alumina. Nickel catalysts are particularly advantageous due to their relatively inexpensive cost. Furthermore, the nickel catalysts are essentially completely recoverable after the guanylation reactions so that they may be reused. During the guanylation reactions, the nickel catalyst should be present at a level of less than about 10 molar % nickel, and preferably less than about 5 molar % nickel, based upon the total moles of guanylating agent(s) (e.g., isothioureas and/or thioureas) taken as 100%.
Preferred guanylating agents are thioureas and isothioureas, which have the respective general formulas ##STR1## wherein each of R 1 -R 4 is individually selected from the group consisting of hydrogen, protecting groups (i.e., a group which prevents the atom to which it is attached from reacting with any of the compounds present in the reaction mixture), aliphatic groups (branched and unbranched, preferably C 1 -C 22 ), and cyclic groups (preferably aromatic), and wherein X is selected from the group consisting of aliphatic groups (preferably lower alkyl C 1 -C 4 groups such as methyl groups) and cyclic groups (preferably aromatic or preferably C 3 -C 8 aliphatic cyclic groups).
At least one of R 1 -R 4 should preferably be a protecting group, and more preferably R 1 and R 3 are both protecting groups, with preferred protecting groups being selected from the group consisting of Boc groups (i.e., tert-butoxycarbonyl groups), Cbz groups (i.e., carbobenzyloxy groups), and arylsulfonyl groups. Arylsulfonyl groups include p-toluenesulfonyl groups and 4-methoxy-2,3,6-trimethylbenzylsulfonyl groups. Those skilled in the art will appreciate that the location of the particular protecting group(s) can be selected depending upon the desired final substituted guanidine. Particularly preferred protected thioureas and isothioureas include bis-Boc-protected thioureas and isothioureas. Of course, the protecting groups can be readily removed from the resulting guanidine using conventional methods.
In one embodiment, the methods of the invention comprise reacting a compound having the structure Formula I with an amine or pyrrolidine, wherein R 1 and R 3 of Formula I are Boc groups. In another embodiment, the invention comprises reacting a compound having the structure Formula II with an amine or pyrrolidine, wherein X of Formula II is selected from the group consisting of alkyl groups (and particularly methyl groups) and benzyl groups. Even more preferably, in this latter embodiment R 1 and R 2 of Formula II are phenyl.
In another embodiment, the methods of the invention comprise reacting pyrrolidine with a compound selected from the group consisting of ##STR2##
Particularly preferred thioureas and isothioureas are those selected from the group consisting of ##STR3##
While essentially any amine can be reacted with a guanylating agent in the presence of a nickel catalyst according to the invention, preferred amines are primary and secondary amines. Specific amines which work well with the instant methods include those selected from the group consisting of ##STR4##
The inventive reactions are preferably carried out at a temperature of from about -30-140° C., and more preferably at room temperature or under ambient conditions. It is preferable that the reaction be carried out in a solvent system. Suitable solvent systems comprise a solvent selected from the group consisting of DMF, THF, DMSO, and water mixed with any of the foregoing. Carrying out the reactions with a nickel catalyst and a thiourea as the guanylating agent will result in a percent yield (based upon the theoretical yield) of at least about 10%, preferably at least about 40%, and more preferably at least about 85%, after a reaction time of about 30 minutes. Carrying out the reactions with a nickel catalyst and an isothiourea as the guanylating agent will result in a percent yield (based upon the theoretical yield) of at least about 10%, preferably at least about 40%, and more preferably at least about 85%, after a reaction time of about 2 hours.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The methods of the instant invention can be utilized to synthesize N-substituted and N,N-disubstituted guanidines from bis-protected thioureas in the presence of a nickel catalyst. Suitable protecting groups include Boc groups and Cbz groups. The N protecting groups can be easily cleaved from the resulting guanidines under mild reaction conditions. These bis-protected thioureas can be utilized to guanylate both aromatic and aliphatic primary and secondary amines at room temperature with high yields. A general reaction scheme by which this guanylation takes place is shown in Scheme 1. ##STR5##
Those skilled in the art will appreciate that mono-, di-, tri-, and tetrasubstituted guanidines can be synthesized from N-protected thioureas in the presence of a nickel catalyst such as nickel-boride (nickel boride, nickel-boride, nickel boride alloy, and nickel-boride alloy are used interchangeably herein to refer to alloys comprising nickel and boride). Suitable protecting groups again include Boc and Cbz, as well as an N-arylsulfonyl group. These protected thioureas can be used to guanylate both aromatic and aliphatic amines. One general reaction by which this guanylation occurs is shown in Scheme 2. ##STR6##
N-Arylsulfonyl protected methylisothioureas can also be used to guanylate aliphatic and aromatic amines in the presence of a nickel catalyst. A general outline of this reaction is shown in Scheme 3. ##STR7## 1,3-diphenyl-S-methylisothiourea can be used to guanylate aliphatic and cyclic amines in the presence of a nickel catalyst. A general outline of this reaction is shown in Scheme 4. ##STR8##
While it is possible that the inventive guanylation reactions take place via a carbodiimide intermediate, because the reactions are taking place under neutral conditions it is believed that the mechanism by which the nickel catalyst promotes guanylation reactions is similar to that described by Ni et al., Nickel-Catalyzed Olefination of Cyclic Benzylic Dithioacetals by Grignard Reagents, J. Org. Chem. 56:4035-42 (1991), incorporated by reference herein. That is, it is believed that the nickel(0) species initially coordinates with the divalent sulfur of thiourea and then undergoes oxidative insertion of nickel into the carbon-sulfur double bond to give the three-membered cyclic intermediate Formula III shown in Scheme 5. ##STR9## The highly reactive cyclic intermediate Formula III yields the complex designated by Formula IV as a result of the nucleophilic attack of the amine and breaking of the carbon-nickel bond. Cleavage of the carbon-sulfur bond by elimination of the proton on the adjacent nitrogen forms the Formula V guanidine and a hydrido nickel(II) complex (which thermally decomposes to regenerate the Ni(0) species). A similar mechanism is believed to occur when the guanylating agent is a isothiourea.
EXAMPLES
The following examples set forth preferred methods in accordance with the invention. It is to be understood, however, that these examples are provided by way of illustration and nothing therein should be taken as a limitation upon the overall scope of the invention.
Example 1
Synthesis of Isothioureas and Thioureas
1. N,N'-Bis-tert-butoxycarbonylthiourea
Isothioureas were prepared for use in the exemplary guanylation reactions. N,N'-bis-tert-butoxycarbonylthiourea was prepared according to the protocol reported by Iwanowicz et al., Preparation of N,N'-Bis-tert-Butoxycarbonylthiourea, Synth. Commun., 23:1443-45 (1993). The reaction by which the N,N'-bis-tert-butoxycarbonylthiourea was formed is outlined in Scheme A. ##STR10##
Wherein Boc refers to tert-butoxycarbonyl.
2. N-Arylsulfonyl-S-methylisothiourea
N-Arylsulfonyl-S-methylisothiourea was prepared as described by Kent et al., Two New Reagents for the Guanylation of Primary, Secondary and Aryl Amines, Tetrahedron Lett., 37:8711-14 (1996). This reaction is outlined in Scheme B. ##STR11## 3. Synthesis of N,N'-diphenyl-S-benzylisothioureas and N,N'-diphenyl-S-methylisothioureas
A solution of halide (55 mmol) in acetone (25 ml) was added dropwise to a stirred suspension of thiocarbanilide (11.40 g, 50 mmol) and potassium carbonate (6.90 g, 50 mmol). The reaction mixture was stirred at ice bath temperature for about 30 minutes, followed by stirring at room temperature. The progress of the reaction was monitored by TLC. The reaction mixture was then filtered and the resulting precipitate washed 3 times with 15 ml portions of acetone. The combined filtrates were concentrated on a rotavapor. The residue was diluted with methylene chloride (100 ml) followed by two washings with 25 ml portions of water. The residue was then dried over sodium sulfate. The crude product was purified by passing it through a short silica gel column using a gradient of hexane and diethyl ether as eluents. Scheme C and its accompanying table outline the general reaction which took place as well as the halides used, the isothioureas resulting from the reaction, and the yield of those isothioureas.
__________________________________________________________________________Scheme C #STR12##Entries Halide Isothiourea Reaction time Yield (%)__________________________________________________________________________ 1 Mel 4 h 91 # - 2 #STR14## 6 h 99##__________________________________________________________________________
Example 2
Synthesis of N,N'-bis-tert-butoxycarbonyl Protected Guanidines Guanylation of Amines
Nickel-boride alloy (13 mg, 0.10 mmol, prepared by the reduction of nickel acetate or chloride with sodium borohydride in ethanol or water) was added to a solution of N,N'-bis-tert-butoxycarbonylthiourea (28 mg, 0.10 mmol, prepared in Part 1 of Example 1) and an amine (0.15 mmol) in dimethyl formamide (DMF) contained in a 15 ml screw cap vial. The solution was stirred at room temperature and the progress of the reaction was monitored by thin layer chromatography (TLC). The reaction mixture was then diluted with ethyl acetate (15 ml) and poured into 25 ml of water. The organic layer was separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The combined extracts were washed twice with 15 ml of water after which they were dried over sodium sulfate, evaporating the solvent. The residue was passed through a short silica gel column using a gradient of hexane and ether as eluents to give the pure guanidine. The general reaction is outlined in Scheme D. The particular amines utilized in the respective preparations as well as the reactions times, resulting guanidines, and yields of those guanidines are set forth in Table 1. ##STR16##
TABLE 1__________________________________________________________________________Guanylation of amines with N,N'-bis-tert-butoxycarbonylthiourea.Entries Amine Guanidine Reaction time Reaction temp Yield (%)__________________________________________________________________________ 1 90 min room temp. 91 - 2 #STR18## 90 min room temp. 94 - 3 #STR20## 2 h room temp. 97 - 4 #STR22## 2 h room temp. 89 - 5 #STR24## 3 h room temp. 91 - 6 #STR26## 90 min room temp. 92__________________________________________________________________________
Guanylation reactions of pyrrolidine with N,N'-bis-tert-butoxycarbonylthiourea were carried out under various reaction conditions utilizing a variety of solvents in order to optimize the suitable solvent conditions to run this reaction ("THF" refers to tetrahydrofuron and "DMSO" refers to dimethyl sulfoxide). The aqueous layer extraction was effected with methylene chloride rather than with ethyl acetate as was the case in Part 1 above. Scheme E outlines the general reaction while Table 2 sets forth the various solvents tested, reaction conditions, and the % yield of guanylated pyrrolidine. DMSO and DMSO-H 2 O (Entries 4 and 5, respectively) were the most effective solvents. ##STR28##
TABLE 2______________________________________Guanylation of pyrrolidine with N,N'-bis-tert-butoxycarbonylthiourea in different reaction conditions. Reaction Reaction Yield Entries Solvent(s) time temp. (%)______________________________________1 DMF 2 h room temp. 89 2 THF 3 h room temp. 100 3 THF-H.sub.2 O (3:1) 1 h room temp. 100 4 DMSO 1 h room temp. 100 5 DMSO-H.sub.2 O (3:1) 45 min room temp. 100______________________________________
Example 3
Synthesis of N-tosyl and N-mtr Protected Guanidines
Nickel-boride alloy (13 mg, 0.10 mmol) was added to a stirred solution of N-arylsulfonyl-S-methylisothiourea (0.10 mmols, prepared in Part 2 of Example 1) and an amine (0.15 mmol) in DMF contained in a 15 ml screw cap vial. The reaction mixture was heated in a sand bath, and the progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature followed by dilution with 15 ml of ethyl acetate. The reaction mixture was poured into 25 ml of water, and the organic layer was separated. The aqueous layer was extracted with 10 ml of ethyl acetate, and the combined extracts were washed twice with 15 ml of water. The solvent was then evaporated by drying over sodium sulfate. The crude product was purified by passing the product through a short silica gel column using hexane and diethyl ether as eluents. Tables 3 and 4 set forth the particular amines which were guanylated in this series of tests as well as the resulting guanidines and percent yields of those guanidines. Schemes F and G outline the general reaction taking place when guanidine is reacted with the particular N-arylsulfonyl-S-methylisothiourea. ##STR29##
TABLE 3__________________________________________________________________________Guanylation of amines with N-(p-toluenesulfonyl)-S-methylisothiourea. Reaction Entries Amine Guanidine time Reaction temp. Yield (%)__________________________________________________________________________ 1 #STR30## 8 h 100° C. 79 - 2 #STR31## 10 h 100.degre e. C. 91 - 3 #STR33## 18 h 100.degre e. C. 85__________________________________________________________________________ ##STR35##
TABLE 4__________________________________________________________________________Guanylation of amines with N-(2,3,6-trimethyl-4-methoxybenzene sulfonyl)- S-methylisothiourea. Reaction Reaction Entries Amine Guanidine time temp. Yield (%)__________________________________________________________________________ 1 26 906## ° C. 89 - 2 #STR37## 18 90° C. 92 - 3 #STR39## 36 90° C. 78__________________________________________________________________________
Example 4
Guanylation of Amines with N,N'-diphenyl-S-methylisothiourea and N,N'-diphenyl-S-benzylisothiourea
Nickel-boride alloy (13 mg, 0.10 mmol) was added to a solution of N,N'-diphenyl-S-methylisothiourea (24 mg, 0.10 mmol, prepared in Part 3 of Example 1) and an amine (0.15 mmol) in DMF contained in a 15 ml screw cap vial. The mixture was heated in a sand bath, and the progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature and diluted with ethyl acetate (15 ml). The organic layer was separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The combined organic extracts were washed twice with 15 ml portions of water, followed by drying over sodium sulfate. The residue was passed through a short silica gel column using a gradient of hexane and ethyl acetate as eluents to give the corresponding pure guanidine.
Scheme H outlines the general reaction scheme when aliphatic and benzylic amines were guanylated with N,N'-diphenyl-S-methylisothiourea. Table 5 lists the particular amines that were guanylated as well as the resulting guanidines and the yields of those guanidines. ##STR41##
TABLE 5__________________________________________________________________________Guanylation of aliphatic and benzylic amines with N,N'-diphenyl-S-methylisothiourea.Entries Amine Guanidine Reaction time Reaction temp. Yield (%)__________________________________________________________________________ 1 #STR42## 8 h 80° C. 96 - 2 #STR43## 15 h 80° C. 98 - 3 #STR45## 18 h 80° C. 98 - 4 #STR47## 18 h 80° C. 95 - 5 #STR49## 3 h 100.degre e. C. 95 - 6 #STR51## 17 h 100.degre e. C. 97 - 7 #STR53## 7 h 100.degre e. C. 94 - 8 #STR55## 7 h 100.degre e. C. 95__________________________________________________________________________
The guanylation of aromatic amines with N,N'-diphenyl-S-methylisothiourea is outlined in Scheme I, while Table 6 sets forth the particular amines which were guanylated as well as the resulting guanidines. Methylene chloride was utilized during the work-up procedures in place of ethyl acetate in these procedures. ##STR57##
TABLE 6__________________________________________________________________________Guanylation of aromatic amines with N,N"-diphenyl-S-methylisothiourea.EntriesAmine Guanidine Reaction time Reaction temp. Yield (%)__________________________________________________________________________ 1 #STR58## 6 h 65° C. 98 - 2 #STR59## 15 h 65.degree . C. 89 - 3 #STR61## 15 h 65.degree . C. 91__________________________________________________________________________
Scheme J outlines guanylation reactions of pyrrolidine with N,N'-diphenyl-S-methylisothiourea in various solvents. Table 7 sets forth the particular solvents that were utilized. Methylene chloride was used during the work-up procedures in place of ethyl acetate in this set of procedures. ##STR63##
TABLE 7______________________________________Guanylation of pyrrolidine with N,N'-diphenyl-S-methylisothiourea in different reaction conditions. Reaction Reaction Yield Entries Solvent(s) time temp. (%)______________________________________1 DMF 3 h 100° C. 95 2 THF 5 h 60° C. 100 3 THF-H.sub.2 O (3:1) 3 h 60° C. 100 4 DMSO 18 h room temp. 100 5 DMSO-H.sub.2 O (3:1) 4 h room temp. 100______________________________________
Scheme K shows the general reaction for the guanylation of amines with N,N'-diphenyl-S-benzylisothiourea, while Table 8 sets forth the structure of the particular amines that were guanylated as well as the resulting guanidines and their respective percent yields. ##STR64##
TABLE 8__________________________________________________________________________Guanylation of amines with N,N"-diphenyl-S-benzylisothiourea.Entries Amine Guanidine Reaction time Reaction temp. Yield (%)__________________________________________________________________________ 1 #STR65## 8 h 80° C. 91 - 2 #STR66## 10 h 80° C.__________________________________________________________________________ 88
EXAMPLE 5
Guanylation of Pyrrolidine in Presence of Varying Molar Concentrations of Nickel-Boride
N,N'-Bis-tert-butoxycarbonylthiourea was prepared as described in Part 1 of Example 1. Pyrrolidine was then guanylated at room temperature as described in Part 2 of Example 2 during the course of five test runs, with nickel-boride being present at nickel molar percents of 100 mol %, 50 mol %, 25 mol %, 10 mol %, and 5 mol % (all based on the total moles of N,N'-Bis-tert-butoxycarbonylthiourea taken as 100% by weight), respectively, during the test runs. The reaction scheme followed was identical to Scheme E above, with DMSO being the solvent. Table 9 sets forth the results of these runs.
TABLE 9______________________________________Guanylation of pyrrolidine with N,N'-bis-tert-butoxycarbonylthiourea in the presence of varying molar concentrations of nickel-boride. Nickel-Boride Reaction Entries (mol %) .sup.a Time Yield (%)______________________________________1 100 1 h 100 2 50 1 h 100 3 25 11/2 h 100 4 10 2 h 100 5 5 4 h 100______________________________________ .sup.a Nickel molar percent based upon the total moles of N,N'-Bistert-butoxycarbonylthiourea as 100%.
These results indicate that the nickel(0) derived from the nickel-boride acts as a catalyst during the guanylation reactions.
EXAMPLE 6
Guanylation of Pyrrolidine in the Presence of Various Nickel Catalysts
In this example, several commercially available nickel catalysts were tested to determine their effectiveness. Those catalysts were: nickel-phosphide alloy; aluminum-nickel alloy; nickel on kieselguhr; and nickel on silica/alumina. In each of the tests, 1 equivalent of N,N'-bis-tert-butoxycarbonylthiourea, 1.5 equivalents of pyrrolidine, and 1 equivalent of nickel catalyst in DMSO were utilized. Each reaction was carried out at room temperature. The data from these tests are recorded in Table 10.
TABLE 10______________________________________Guanylation of Pyrrolidine with N,N'-bis-tert-butoxycarbonylthiourea in the presence of various nickel catalysts. Reaction Yield Entries Nickel Catalyst Time (%)______________________________________1 nickel-phosphide 1 h 100 2 aluminum-nickel 1 h 100 3 nickel, ˜60 wt. % on kieselguhr 45 min. 100 4 nickel, ˜65 wt. % on silica/alumina 30 min. 100______________________________________
All of the nickel catalysts worked well and gave the corresponding guanidines in quantitative yields. The reactions were much faster when nickel on silica/alumina and nickel on kieselguhr were utilized as the catalysts compared to nickel-phosphide and aluminum nickel catalysts, with the reaction utilizing nickel on silica/alumina being extremely rapid. Commercially, aluminum-nickel catalysts will likely be the most important due to their relatively low cost. Finally, in comparing these results to those of Example 5, the catalysts listed in Table 10 would be effective in catalytic amounts as was the case with the nickel-boride.
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An improved method for guanylating amines is provided. Broadly, the amines are reacted with a guanylating agent in the presence of a nickel catalyst. Preferably, the nickel catalyst comprises nickel in the zero oxidation state. Suitable nickel(0) catalysts are derived from nickel-boride alloys, nickel-phosphide alloys, aluminum-nickel alloys, nickel on kieselguhr, and nickel on silica/alumina catalysts. Preferred guanylating agents are thioureas and isothioureas. In one embodiment, protecting groups are selectively attached to the guanylating agents to yield particular substituted guanidines. The preferred protecting groups are Boc groups, Cbz groups, and arylsulfonyl groups. The reactions are particularly well suited for guanylating primary and secondary amines. The methods of the invention can be carried out under ambient conditions to provide high yields of the corresponding guanidines, with the nickel catalyst being essentially completely recoverable for reuse.
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FIELD OF THE INVENTION
The present invention is related to low power non-isolated driver used for LED lighting and other non-isolated power supply appliance.
BACKGROUND OF THE INVENTION
LED lighting market is growing very fast and becoming more and more important. For the AC input source, most LED drivers adopt switching mode power supply (SMPS) based on flyback topology. The flyback SMPS circuit usually consists of AC input, PWM control circuit, transformer and constant voltage/current control circuit, wherein the output voltage/current control circuit are coupled through an optical coupling element to the primary side PWM control circuit. The PWM control circuit adjusts the switching duty cycle when line voltage or load is changed, so constant output current or voltage can be realized.
However, the cost of flyback SMPS circuit is relatively high and the total system size is big. For home appliance, it is ideal that the LED lighting driver is compact and can be placed in the lamp holder like CFL (compact fluorescent lamp). Thus the whole LED lighting system's installation will be easy. Also for compact LED lighting driver, isolating may not be needed if plastic lamp holder is used.
Therefore, it is necessary to provide new cost down solutions with less component count, small print circuit board size and better price/performance ratio.
SUMMARY OF THE INVENTION
The present invention is to provide basic cost down solutions for low power non-isolated LED driver application with higher system reliability, better line/load regulation, and short circuit protection characteristic.
The present invention provides a non-isolated LED lighting solution based on buck topology, in which the input side is connected to an AC or DC input, a PWM control circuit is connected to the buck converter switch, a capacitor filters the output voltage ripple and an output voltage/current control circuit provides feedback signal to the PWM control circuit.
The present invention is based on a low cost PWM control circuit with emitter switched architecture. The current mode PWM control circuit contains P 1 , P 2 and P 3 terminals. The P 1 terminal is to produce switching pulse which can be connected to the emitter of NPN transistor or the source of MOSFET, the P 2 terminal is used for both bias supply and feedback control, the P 3 terminal is the reference ground of the PWM control circuit.
The present invention provides an output voltage/current control circuit employing a low voltage PNP transistor and zener diode to compose voltage sense error signal amplification circuit, a resistor and a low voltage NPN transistor to compose current sense and amplification circuit, or adopt two resistors to form output voltage sensing circuit.
The present invention has such features of less component number, low total cost, high reliability, and better line/load regulation.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention detailed is illustrated by way of example and not limitation in the accompanying figures.
FIG. 1 shows one embodiment of low power non-isolated driver that has an approximately constant output current and output voltage clamping characteristic in accordance with the teachings of the present invention.
FIG. 2 shows the function block of the PWM control circuit.
FIG. 3 shows another embodiment of low power non-isolated driver that has an approximately constant current and output voltage clamping characteristic in accordance with the teachings of the present invention.
FIG. 4 shows the embodiment of low power non-isolated driver that the transistor, PWM control circuit and the output voltage/current control circuit are integrated.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention is a low power non-isolated driver which provides a basic cost down solutions for low power non-isolated LED driver application with higher system reliability, better line/load regulation, and short circuit protection characteristic. In particular, the present invention provides a non-isolated LED driver with approximately constant current and constant voltage characteristic based on a PWM control circuit.
FIG. 1 shows the first embodiment of a low power non-isolated driver that has an approximately constant current and output voltage clamping characteristic of the present invention. The AC or DC input 100 is rectified by diode 101 and filtered by capacitor 103 , inductor 102 and capacitor 104 . Then the high DC voltage is converted to a low voltage DC output 150 by a switch 108 , diode 129 , inductor 128 and filtered by the output capacitor 130 . The switch can be a high voltage transistor or a MOSFET which emitter terminal or source terminal is connected to a PWM control circuit 109 .
FIG. 2 is the function block of the mentioned PWM control circuit. Its main function circuits include: under voltage lockout with low startup current; precise voltage reference for internal comparators; PWM comparator with current limit control, feedback signal and band-gap input; short circuit comparator.
The current mode PWM controller contains P 1 , P 2 and P 3 terminals. The P 1 terminal is to produce switching pulse which can be connected with the emitter of NPN transistor or the source of MOSFET, the P 2 terminal is used for both bias supply and feedback control, the P 3 is the reference ground of the PWM control circuit.
See FIG. 1 and FIG. 2 . During start up, start up current through resistors 105 charges capacitor 110 , and also brings up P 1 pin voltage of the PWM control circuit 109 through transistor 108 BE junction. The internal regulator of the PWM control circuit 109 will charge P 2 pin voltage from P 1 pin. When P 2 voltage reaches the start up voltage, the regulator sourcing current will be stopped by internal UVLO comparator. Then the PWM control circuit 109 starts to output PWM signal at P 1 pin and controls the switch 108 turning on and off.
When the switch 108 turned on, input current will flow through rectifier 101 , switch 108 , PWM control circuit 109 , current sense resistor 114 and inductor 128 to the output. The current flow through PWM control circuit 109 is converted to a voltage by an internal resistor, and this voltage will compare with VREF by short circuit comparator. If output short circuit happens, the output current is limited by the PWM control circuit 109 . When the switch 108 turned off, the inductor 128 current will flow through fast recovery diode 129 and transfer energy to the output.
The output voltage/current control circuit is composed of components from 114 to 127 . When the switch 108 turned off, the diode 127 will turn on and voltage on capacitor 126 will be almost equal to the output DC voltage. The capacitor 126 voltage is compared with zener diode 125 clamping voltage and amplified by the low voltage small signal PNP transistor 122 , then filtered by compensation resistor 120 , capacitor 119 , capacitor 121 and feedback to the P 2 of the PWM control circuit 109 . If the DC output 150 voltage is higher than the reference value, the P 2 voltage of PWM control circuit 109 will also becomes higher and the PWM control circuit 109 will reduce the converter switching duty cycle or comes into skip cycle mode and low down the DC output 150 voltage. So the constant output voltage control is realized. The inductor 128 current is sensed by resistor 114 , filtered by resistor 115 , capacitor 116 and drives the low voltage small signal NPN transistor 117 BE junction. If the resistor 114 voltage higher than transistor 117 BE junction conduction voltage (about 0.7V), the transistor 117 will turn on and pull down the transistor 122 base junction voltage and output DC voltage will be reduced. So the output current is limited and approximately constant current control is realized.
When the switch 108 turned off, the inductor 128 energy will also charge capacitor 110 through diode 127 and 112 . The capacitor 110 will discharge and provide driving energy to the switch 108 when the PWM control circuit 109 turns on the switch 108 . The capacitor 110 voltage is clamped by zener diode 111 to prevent high voltage on 110 at very low or no load condition.
FIG. 3 shows another embodiment of a non-isolated power supply of the present invention. The difference between FIG. 3 and FIG. 1 is the output voltage/current control circuit. In FIG. 3 , the output DC voltage is sensed by two resistors 224 and 225 . There is no output voltage sensing error amplification circuit, so the output voltage precision of line/load regulation is not as good as FIG. 1 .
FIG. 4 is the solution with the integrated transistor, PWM control circuit and output voltage/current control circuit. The integrated circuit 360 has five terminals p 1 , p 2 , p 3 , p 4 and p 5 . The integration of the switch 308 , PWM control circuit and output voltage/current control circuit 309 can reduce the whole system size and improve the system reliability.
It is to be understood, however, that even though numerous characteristics and advantages of the present invention have been set forth in the foregoing description, together with details of the structure and function of the invention, the disclosure is illustrative only, and changes may be made in detail, especially in matters of shape, size, and arrangement of parts within the principles of the 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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The present invention mainly discloses low power non-isolated driver that can be used for LED lighting and other non-isolated power supply appliance, in which the input side is connected to an AC or DC input, a PWM control circuit is connected to the buck converter switch, a capacitor filters the output voltage ripple and an output voltage/current control circuit provides feedback signal to the PWM control circuit. The present invention has such features of less component number, low total cost, high reliability, and better line/load regulation.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation application of prior copending U.S. non-provisional application Ser. No. 12/614,005, filed Nov. 6, 2009 which claims benefit and priority under 35 U.S.C. §119(e) from U.S. Provisional Application 61/138,803 filed Dec. 18, 2008, entitled PRE-INSULATED STRUCTURAL BUILDING PANELS and also from U.S. Provisional Application 61/227,586 filed Jul. 22, 2009, entitled INSULATED STRUCTURAL WALL SYSTEM, the disclosures of which are incorporated by reference herein in their entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention is directed generally to a method and apparatus for pre-insulted structural panels. More particularly, the invention is directed to pre-insulated structural building panels configured with vertical support members, acoustical aspects and wiring friendly features, among other aspects.
2. Related Art
Building construction often employs pre-manufactured components such as building panels that may be assembled in the field to create walls and perimeters of buildings of all sorts. Often the components may include expandable polystyrene foam (EPS), or similar material. The EPS material may provide thermal insulating properties to a degree related to the thickness of the EPS panel.
Moreover, the various types of building components currently available typically have limited features that assist in the installation of the components or finishing off of the building wall surfaces and/or related building functions. Moreover, the currently available products provide limited acoustical dampening aspects.
Furthermore, current building components are often of relatively small size and may require multiple components to create a vertical dimension in the height of a wall, which may require extra installation time and costs.
Accordingly, there is a need for a method and apparatus that provides a pre-insulated building panel with improved features to reduce installation costs and time, while providing improved structural integrity to the resulting wall.
SUMMARY OF THE INVENTION
The invention meets the foregoing need and provides a method and apparatus for constructing a pre-insulated structural panel that includes vertical c-channels or profiles spaced apart for imparting structural integrity to the panel and the c-channels embedded in EPS foam to create the panel. One side of the panel may be configured with a tongue shaped edge that runs along one side of the panel. On the other side of the panel a groove shaped edge may be formed to mate with the tongue shaped edge of another panel when two panels are arranged side-by-side to form a wall section. A fastening plate may be employed to fasten two panels together when placed side-by-side.
In one aspect, a horizontal chase may be provided from one side of the panel to the other side to permit running of wiring through the panel and in a resulting wall. The chase of one panel aligns with a respective chase in another panel when installed. Moreover, a vertical chase may be provided between mated panels proximate the tongue and groove mated surfaces for running wiring or for providing an additional a structural member for added structural strength.
In another aspect, an apparatus for a pre-insulated building component is provided that includes a plurality of vertical support channels embedded in an insulating material to produce a first panel and a second panel, a groove end configured in one side of each panel, and a tongue end configured in another side of each panel, wherein the tongue end of the first panel mates with the groove end of the second panel to form a wall section.
In another aspect, an apparatus for a pre-insulated building component is provided that includes means for constructing an expandable polystyrene (EPS) wall section, wherein the means for constructing includes a means for attaching finishing materials at spaced apart intervals and the means for attaching provides lateral force resistance to the EPS wall section, means for accepting electrical wiring laterally through the interior of the EPS wall section and means for securing the wall section at a bottom end and at a top end, wherein the means for securing at the bottom end and the top end are connected by a means for connecting that traverses an entire height of the wall section.
In another aspect, a method for providing a pre-insulated building component is provided that includes providing a plurality of vertical support channels embedded in an insulating material to produce a first panel and a second panel, providing a groove end configured in one side of each panel, and providing a tongue end configured in another side of each panel, wherein the tongue end of the first panel mates with the groove end of the second panel to form a wall section.
Additional features, advantages, and embodiments of the invention may be set forth or apparent from consideration of the following detailed description, drawings, and claims. Moreover, it is to be understood that both the foregoing summary of the invention and the following detailed description are exemplary and intended to provide further explanation without limiting the scope of the invention as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings, which are included to provide a further understanding of the invention, are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the detailed description serve to explain the principles of the invention. No attempt is made to show structural details of the invention in more detail than may be necessary for a fundamental understanding of the invention and the various ways in which it may be practiced. In the drawings:
FIG. 1A illustrates in perspective view a pre-insulated structural panel configured according to principles of the invention;
FIG. 1B illustrates a frontal view of the embodiment of FIG. 1A ;
FIG. 1C illustrates a first side-view of the embodiment of FIG. 1A , configured according to principles of the invention;
FIG. 1D illustrates a second side-view of the embodiment of FIG. 1A ;
FIG. 1E illustrates an end-view of the embodiment of FIG. 1A ;
FIG. 2A is a front-view of an embodiment of a plurality of pre-insulated structural panels of FIG. 1A configured to form a wall, according to principles of the invention;
FIG. 2B is a top view of the embodiment of FIG. 2A ;
FIG. 2C is a side view of the embodiment of FIG. 2A ;
FIG. 3A is an illustration showing an embodiment of a wall section comprising a plurality of pre-insulated structural building panels constructed according to principles of the invention;
FIG. 3B is a top view of a section of a base plate and/or a header plate with attaching mechanisms, constructed according to principles of the invention; and
FIG. 3C is an end-on view of the section of FIG. 3B .
DETAILED DESCRIPTION OF THE INVENTION
The embodiments of the invention and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments and examples that are described and/or illustrated in the accompanying drawings and detailed in the following description. It should be noted that the features illustrated in the drawings are not necessarily drawn to scale, and features of one embodiment may be employed with other embodiments as the skilled artisan would recognize, even if not explicitly stated herein. Descriptions of well-known components and processing techniques may be omitted so as to not unnecessarily obscure the embodiments of the invention. The examples used herein are intended merely to facilitate an understanding of ways in which the invention may be practiced and to further enable those of skill in the art to practice the embodiments of the invention. Accordingly, the examples and embodiments herein should not be construed as limiting the scope of the invention, which is defined solely by the appended claims and applicable law. Moreover, it is noted that like reference numerals represent similar parts throughout the several views of the drawings.
FIG. 1A is a perspective view of a pre-insulated structural building panel, constructed according to principles of the invention, generally denoted by reference numeral 100 . The pre-insulated structural building panel 100 includes a plurality of c-channels 105 that runs the extent of the length (L) of the panel 100 . The panel 100 is typically installed with the length (L) oriented vertically, as shown perhaps more clearly in relation to FIG. 2A . The plurality of c-channels 105 may comprise steel channels having lips 135 formed in the sides of the c-channels 105 to embed the c-channels 105 into the expandable polystyrene (EPS) 140 during fabrication of the panels 100 . The EPS provides substantial structural support in combination with the c-channels 105 . In some embodiments, the c-channels 105 may comprise any metal or plastic type material. During fabrication or molding, the EPS may be injected or molded between opposing c-channels 105 located on both sides of the panel 100 , and also continuously between the c-channels 105 , whereby the EPS may be substantially continuous along the entire length and height of the panel 100 including between the opposing c-channels.
The panel 100 may be constructed to nearly any required dimension in thickness (t), width (w) and length (L). Common dimensions include about 4, about 8, about 10 or about 12 foot length, 4-6 inch thickness, and 4-6 feet width. But, nearly any dimensionality may be constructed, according to the application need or customer requirements.
The c-channels 105 may be placed at any spacing intervals, such as 4 foot centers, for example, and any spacing to imitate common (or traditional) spacing for “studs.” Two-foot center-to-center spacing is also quite common, as is 16 inch spacing. Nearly any spacing, including irregular spacing, may be provided. The c-channels 105 may comprise structural members to facilitate attaching finishing materials such as dry wall, panels, wood siding, vinyl siding, fiber-cement such as Hardiplank®, and the like. The surfaces of the panel 100 may be covered with stucco, gunite, resins, paints, or similar materials, as needed. The c-channels 105 laterally support the EPS and provide substantial weight bearing capability to support the building load generally and to provide attachment capability for siding materials.
A tongue side 110 and a groove side 120 may be formed along the length (L) of the panel 100 , and configured to form a tongue-in-groove assembly when two or more panels 100 are arranged side-by-side, to form a wall section 200 such as shown in relation to FIG. 2A , for example. The tongue side 110 is configured to mate with the groove side 120 of another panel. When so mated, a vertical chase 150 may be formed between the respective tongue and the groove edges as an interior chase along the length (L) of the mated panels 100 . The vertical chase 150 may be about one inch in width (i.e., between the lateral tongue edge and the lateral groove edge) to permit installation of wiring between the mated panels 100 . Alternatively, a structural strengthening member or stabilizer, such as a metal bar, perhaps having a length of about (L), may be inserted into the vertical chase 150 to provide added strength to the resulting wall, such as for added load bearing capacity, for example. An example of a structural strengthening member is described more fully in relation to FIG. 3 , below.
A horizontal chase 130 (as viewed when installed) may be formed (but not always necessary) during the molding fabrication process and configured to extend from the tongue side 110 to the groove side 120 , through the interior of the panel 100 . The horizontal chase 130 may be about 1½ inches in diameter, but any diameter suitable for a particular application may be constructed. This horizontal chase 130 may provide for accepting wiring runs such as electrical wiring (or perhaps even plumbing) so it may be inserted into or through the panel 100 at the building site to provide power and/or communications, for example. A chase 130 of one panel 100 may align with the chase of an adjacent panel 100 , so that wiring may run substantially unimpeded through multiple panels 100 . The horizontal chase 130 may be configured with a tapered opening 115 , as a lead-in for aiding in guiding inserted wires into the horizontal chase 130 , also assisting running of the wire from one panel 100 to an adjacent panel 100 .
The EPS portions 140 of the panels 100 may be molded to hold c-channels 105 in place relative to one another using molding techniques of various types. The EPS portions 140 provide substantial structural strength in combination with the c-channels 105 . The EPS portions 140 may be constructed with acoustical protrusions 125 on the outer surface of the EPS. The acoustical protrusions 125 may be about ⅛ inch in height, but may vary some. The acoustical protrusions 125 may provide a spacing factor or gap between the EPS outer surface and any applied siding or covering such as dry wall, for example. The extra spacing provided by the acoustical protrusions 125 significantly reduces acoustical noise from penetrating through a finished wall. The acoustical protrusions 125 may be spaced at regular (or perhaps irregular) intervals such as 2 inches, or so, from one another, but can vary, along an extent of a panel so that a sound barrier is also created in a vertical sense so that sound may be prevented, or at least reduced, in propagation ability in a vertical sense along the EPS surface. That is, the series of acoustical protrusions 125 may also inhibit sound propagation laterally along the EPS outer surface, in addition to creating a dampening effect by creation of the space factor or gap. Such a space factor or gap may be created between the EPS foam and any applied finishing materials such as dry wall sheet, siding, or finishing panels, for example, so that the protrusions 125 formed along the width of the EPS portions 140 thereby inhibit sound travel along the surface of the panel, especially, but not limited to, in a vertical sense.
FIG. 2A is a side view of a plurality of pre-insulated structural building panels 100 , configured to form a wall section 200 . The wall section 200 may be arranged so that a tongue side 110 is mated with a groove side 120 of another panel 100 . A fastening plate 160 may be used to fasten the plurality of panels 100 together.
FIG. 3A is an illustration of an embodiment of a wall section comprising a plurality of pre-insulated structural building panels constructed according to principles of the invention, the wall section generally denoted by reference numeral 300 . The pre-insulated structural building panels 305 , 310 comprising the wall section 300 are shown in two different lengths, for example 4 foot panels and 8 foot panels, arranged in a checkerboard fashion, with a longer size panel 310 layered on top of a shorter panel 305 (the pair shown in the left-hand side of FIG. 3A ), and then the pair coupled laterally by tongue-in-groove mating, as described previously, with a second pair of panels (the pair shown in the right-hand side in FIG. 3A ). The second pair of panels includes a shorter panel 305 layered on top of a longer panel 310 . The tongue-in-groove arrangement may be configured to form a vertical chase 150 for receiving a structural strengthening member 330 , such as a metal bar, that may extend the entire height of the layered panels (in this example, about 12 feet of extent). In this way, extra strengthening and/or extra stabilizing characteristics may be provided to enhance structural integrity of the side-by-side sets of panels. The checkerboard pattern itself also provides additional resistance to lateral movement of the panels 100 . The panels 305 , 310 may comprise any embodiments of panel 100 . Panels 305 and 310 are shown in FIG. 3A without any c-channels 105 (and several other features of FIGS. 1A-1C ) to permit enhancement of particular features being described in relation to FIG. 3A , but the c-channels 105 (and the other features of FIGS. 1A-1C ) may be interpreted as being included in the embodiment of FIG. 3A .
Further, an optional based plate 320 , mountable to a floor or other surface, may have lips 322 configured to receive the lower side of the respective lower panels 305 , 310 . The base plate 320 may serve at least in part to stabilize the wall section 300 to a floor, or similar surface, and may be of any length to match any number of side-by-side panels being installed for an application. The base plate 320 may be configured with one or more attaching mechanisms 335 (see the top view of the base plate/header plate as shown in FIG. 3B ), which may be holes, to secure the structural strengthening member 330 to the base plate 320 . Moreover, an optional header plate 325 may be employed at the top of the upper panels 305 , 310 to provide added structural integrity at the top of the wall section 300 . The header plate 325 may be configured similarly to the base plate 320 , as shown in relation to the end-on view of FIG. 3C . The header 325 may also have lips 322 and may also have attaching mechanism 335 to receive the structural strengthening member 330 . The header 325 may be secured to an appropriate structure for securing the wall section 300 at the top and may be of any length to match any number of side-by-side panels being installed for an application. The structural strengthening member 330 may be cut to length, as needed, which may be more than 12 feet in this example.
While the invention has been described in terms of exemplary embodiments, those skilled in the art will recognize that the invention can be practiced with modifications in the spirit and scope of the appended claims. These examples given above are merely illustrative and are not meant to be an exhaustive list of all possible designs, embodiments, applications or modifications of the invention.
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An apparatus and method for constructing pre-insulated structural panels is disclosed that has a tongue and groove assembly arrangement. Each panel may include one or more c-channels or profiles embedded in expandable polystyrene (EPS) foam to provide structural integrity to the panels, and resulting wall. The panels may be covered with siding, stucco, or similar materials. A chase may be formed horizontally in the panels to provide a wiring conduit through the panel. The panel may also provide when assembled, a vertical chase formed between the mated panels along the length of the panel for wiring. Acoustical properties may be formed in the surface of the EPS portions to provided added acoustical damping measures.
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CROSS-REFERENCE TO RELATED APPLICATION
This is a continuation-in-part of Application Ser. No. 334,201 filed Dec. 24, 1981 now abandoned.
BACKGROUND OF THE INVENTION
Preparations of Mg or Mg alloy granules in a friable salt matrix are taught, e.g., in U.S. Pat. No. 4,186,000; U.S. Pat. No. 4,182,498 and U.S. Pat. No. 4,279,641. In those patents there are taught methods in which molten mixtures of Mg (or Mg alloy) and salts are processed in a manner such that when the melts are cooled to the point of being frozen, the Mg is in dispersed form within the salt mixture. It is also disclosed there that the friable salt matrix is broken up in a manner such that the round granules of Mg are freed from entrapment in the salt matrix for removal from the salt, except that there remains on each granule a tightly-bound protective salt layer.
In U.S. Pat. No. 4,186,000 and U.S. Pat. No. 4,279,641 (incorporated herein by reference) there is disclosed the freezing of the molten mixture of Mg and salts by the technique of pouring the melt onto a revolving chilled roller on a flaking machine where the melt freezes as a thin sheet and is broken up into flakes by the action of the scraper blade. It has been found that in some melts, there is a tendency for some of the molten Mg particles to "stretch" into elongated particles due to the gravity flow (slippage) down the roller surface before the Mg becomes frozen. Then when the Mg freezes, the elongated (sometimes "stringy") shape is retained by the frozen Mg; this is not a welcome result when it is desired that the Mg granules be round, or at least nearly round in shape.
In order to provide a chilled surface on which the molten mixture could be cooled on a continuous feed basis, while avoiding the adverse effects of gravity encountered by the sliding of the melt down the non-horizontal surface of a chilled roll, the present novel rotary table flaker was designed. This novel rotary cooling table (also called a rotary table flaker) may also be used for chilling other melts on a horizontal, moving surface from which they are scrapped by a blade after being appropriately chilled.
SUMMARY OF THE INVENTION
A flat, planar, horizontal, circular, rotatably mounted sheet or plate, in operable combination with a fixated rotation means, a cooling means, a feed means for feeding a molten material to the surface as it rotates, and a means for scraping said material from the surface at a point distal from said feed means is employed in a process wherein a molten material is fed to the rotating plate, is cooled to remove heat from the fed material, and the cooled material is scraped from the plate before the material can rotate to the point at which the molten material is fed to the rotating plate. The speed of rotation is less than that which would cause movement of the material across the surface of the plate by centrifugal action.
DETAILED DESCRIPTION OF THE INVENTION
FIGS. 1 and 2, and 3 are graphic representations of various embodiments to serve as visual aids in describing the process and apparatus of the present invention.
FIG. 1 is a schematic elevation to illustrate a revolvable table surface or plate (1) having a top planar surface (2) and a bottom surface (3). The plate (1) is rotated by support means (5) by the operation of rotation means (4). Rotation means (4) is fixed in place by supports (6). Concentrically mounted in the center of plate (1) is a raised circular portion (7) which provides a vertical, concentric surface (8). Molten material is fed to surface (2) of plate (1) by feed means (9) as a relatively thin sheet. The molten material becomes cooled before it reaches scraper blade (10) and is scraped off into a material receptacle (11). Cooling means (12) and/or (13) are employed as needed to remove heat and cool the material before it reaches the scraper (10) which is closely positioned near or against surfaces (2) and (8). The feed means (9) may be oscillated, by means not shown, to lay down a serpentine ribbon on the revolving plate; the speed of the oscillation can be regulated or programmed to lay down a substantially constant thickness. Attachments and supports for cooling means (12) and (13), for feed means (9), for scraper (10), and for receptacle (11) are not shown for purposes of conciseness, but it is easily understood that such supports and attachments can be made adjustable. For instance, the scrapper (10) may be adjusted to various distances from feed means (9), or feed means (9) may be adjusted to various distances from scraper (10) as desired. Also, the rotational speed of plate (1), the cooling rate provided by the cooling means, and/or the rate of flow of the feed material through feed means (9) can be adjusted by amounts commensurate with the desired results. It will be realized that the rotational speed of the plate should be low enough to prevent centrifugal forces from causing flow of material toward the edge of the plate before it reaches the scraper blade.
FIG. 2 is a schematic top-view to illustrate counter-clockwise rotation of plate (1), the feeding of molten material through feed means (9), the cooling through use of cooling means (12) and the operation of scraper (10) against surfaces (2) and (8) which scrapes the material into receptable (11). Obviously, the apparatus can be designed to run clockwise, if desired.
FIG. 3 represents a side-view, not to scale, where the cross-hatching represents cross-sectional views of some of the parts. Plate (1) is shown as having a top surface (2) and a bottom surface (3). Plate (1) communicates by way of shaft (5) to rotation means (4) which is fixated to base (15) by support or attachment means (6). Feed means (9) illustrates a slotted feed means instead of a circular feed means; this slotted feed means can lay down a relatively thin layer of the molten material, the thickness of the layer being adjustable by varying the flow rate of the feed, by adjusting the width of the feed slot, and/or by adjusting the speed of rotation of plate (1). Scraper (10) operates against surfaces (8) and (2) to scrape the cooled material into receptacle (11). The material in receptacle (11) may be conveyed, by means not shown, to storage or further processing such as by using a conveyor or to a grinder and then to a conveyor.
When quite large, heavy metal plates are used, especially where very high temperatures are employed, it is often advisable to employ liquid coolants to the bottom side (3) of plate (1) to obtain the desired heat transfer from the metal plate. One embodiment which is beneficial in providing such cooling is as shown in FIG. 3, where two concentric vertical walls descend from surface (3), wall (19) being relatively near the center of plate (1) and wall (20) being relatively near the outer edge of plate (1). The portion of surface (3) which is bounded by walls (19) and (20) may be sprayed by nozzles of cooling means (13) which protrude through a fixated pan (21). The pan (21) is provided with an inner vertical circular wall extending upwardly to lie close to revolving wall (19) and an outer vertical circular wall to lie close to, and on the outside of, revolving wall (20). The pan (21) is equipped with drain means (14) to carry away the cooling liquid which falls from surfaces (3). Support members (22) hold pan (21) in place.
Also, with reference to FIG. 3, when a large heavy metal plate (1) is used especially at high temperature, it is advisable to employ supplemental support means to help avoid sagging or warping of the plate. This supplemental support may be provided, as illustrated, by employing support rollers (16) which revolve on spindles or axles (17) in support members (18) which are fastened to a base (15). Several such rollers may be used, though only two are shown in FIG. 3.
In FIG. 3, cooling means (12) is shown as a conduit having a plurality of nozzles or openings to direct cooling gas to the material on plate (1), but the precise arrangement shown is not the only arrangement which may be used. The cooling gas may, in some cases, be air or may be an inert gas such as nitrogen, helium, carbon dioxide, etc. Whether or not the cooling gas is adversely reactive with the material to be cooled is dependent on the material.
The molten material which may be fed to the rotating plate may be of heterogenous or homogenous composition, so long as it is substantially friable, plastic, or brittle when cooled so that the scraper can cause the material to be scraped from the plate. Of particular interest is a molten salt composition, especially one which contains small particles of metal dispersed therein, and which, when frozen, comprises a heterogenous, but brittle, mixture of frozen metal particles entrapped in a frozen, friable salt matrix. The following example illustrates an embodiment of the present process, but the present concept is not limited to the specific example shown.
EXAMPLE 1
A molten mixture comprising about 40% by weight of molten magnesium dispersed as small particles in a molten matrix of salt (i.e., a mixture of predominantly alkali metal halide, alkaline earth metal halide and a small amount of metal oxides) is fed to a non-central portion of the top side of a flat, horizontal, rotating, circular steel plate. The manner of feeding the molten material caused it to lay down on the plate as a relatively thin layer. As the plate revolves, the material is cooled to a solid by cooling means to remove heat from the material. By the time the rotating material reaches a scraper, it is in the form of a brittle, friable solid, and the scraper causes it to break into flakes or fragments of irregular size and shape and fall from the plate into a receptable.
The illustrations and embodiments disclosed herein are representative, and variations therefrom may be made without departing from the present novel concepts.
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A horizontally positioned rotating table is provided with a rotation means, a means for feeding molten material to the topside of the table as it is rotated, a means for cooling the molten material, and a means for scraping the cooled material from the table. This table is especially useful in continuously receiving a molten salt containing molten metal, cooling it to a friable solid, and scraping the friable solid from the table for further processing.
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CROSS-REFERENCE TO PRIOR APPLICATIONS
[0001] This application claims benefit to German Patent Application No. DE 10 2009 014 023.9, filed on Mar. 23, 2009, which is hereby incorporated by reference herein.
FIELD
[0002] The invention relates to a dishwasher with a cleaning compartment whose front can be closed by a door that can pivot at its bottom section around a horizontally running axis, with a device for illuminating the cleaning compartment and/or the front portion of the cleaning compartment, and with a control device for switching the illuminating device on and/or off as a function of the closing position of the door.
BACKGROUND
[0003] Certain dishwashers with a device for illuminating the cleaning compartment and/or the front portion of the cleaning compartment are well known from the state of the art. This measure is intended to make it easier to load and unload dishes. In order to lower energy consumption, it is a known procedure for the illuminating device to only switch on when the door is open. For this purpose, the control devices used comprise microswitches that are actuated by the door. Moreover, approximation switches such as, for example, Hall sensors, are known that are actuated when the metal door is almost closed. These switches have the drawback that they are only actuated by a completely or at least almost completely closed door. If the door of the dishwasher is open by a small gap, as is commonly done, for example, at the end of the cleaning program in order to assist the drying, then the illuminating device remains switched on for a long time. This results in increased energy consumption.
[0004] German patent application DE 10 2005 028 449 A1 describes a motor-driven closing piston for a door closing mechanism.
[0005] German patent application DE 10 2004 023 509 A1 describes attachment of a tension spring and of deflection rollers to the housing of a dishwasher.
[0006] German patent application DE 10 2005 028 449 A1 describes an automatic door opening device.
SUMMARY
[0007] In an embodiment, the present invention provides a dishwasher including a cleaning compartment having a front portion that can be closed by a door. The door is configured to pivot at a bottom section thereof around a horizontally running axis. An illuminating device configured to illuminate at least one of the cleaning compartment and the front portion of the cleaning compartment. A control device switches the illuminating device on or off based on the opening position of the door. The control device includes a switching element that is actuated by a Bowden cable arranged on the door in order to compensate for the weight of the door.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] An embodiment of the invention is shown purely schematically in the drawings and is described in greater detail below. In the drawings:
[0009] FIG. 1 is a dishwasher with cleaning compartment illumination;
[0010] FIG. 2 is a view of the door of the dishwasher with a Bowden cable, deflection rollers and a switching element; and
[0011] FIGS. 3 a - d are views illustrating various opening stages of the door and the associated position of the switching element.
DETAILED DESCRIPTION
[0012] In an embodiment, the present invention provides a dishwasher including a device for illuminating the cleaning compartment, in which the light remains switched off, also when the door is open by a small gap.
[0013] Advantages that can be achieved with the invention ensue from the fact that the control device comprises a switching element that is actuated by a Bowden cable arranged on the door in order to compensate for the weight of the door. As a result, on the one hand, already present structural elements can be used, and on the other hand, it is easy to achieve that the light is only switched on once a specific door opening angle has been reached.
[0014] In an advantageous embodiment, the Bowden cable is arranged on the door in such a way that its swiveling causes a swiveling motion of at least one section of the Bowden cable, said motion being sufficient to actuate the switching element. This causes an uncoupling of the Bowden cable and the switching element. Here, it is advantageous for the Bowden cable to act on a spring-mounted piston that, when it is depressed, triggers the activation of a microswitch.
[0015] Moreover, it is advantageous for the illuminating device to be switched on once the opening angle of the door is more than approximately 10°. In this manner, in order to initially assist the drying, a sufficient air exchange is possible through the door, which is open by a small gap, without the light being switched on.
[0016] FIG. 1 shows a dishwasher 1 with a cleaning compartment 2 whose front can be closed by a swiveling door 3 . The door closing mechanism has a known motor-driven closing piston 4 . that is only sketched in the figure. In this manner, the door 3 can also be automatically opened by a small gap by means of the program control 5 , also in the locked state. Moreover, the dishwasher 1 has a lamp 6 for illuminating the cleaning compartment 2 and/or the front portion of the cleaning compartment. In order to allow the lamp 6 to be switched on and off as a function of the closing position of the door 3 , a switching element 7 is provided whose structure and functions are explained below.
[0017] The lower end of the door 3 has an angled piece 8 with an arm 9 that projects perpendicularly out of the plane of the door and into the interior of the appliance. In a recess (not visible) located at the end of the arm 9 , a Bowden cable 11 is secured by means of an eye 10 . The Bowden cable 11 is deflected over two rollers 12 and 13 , and its other end 14 is connected to a tension spring 15 (see FIGS. 3 a to 3 d ). The entire device serves to compensate for the weight of the cladding (not shown here) that serves as a panel for the front of the door 3 , matching it to the other cabinet doors in the kitchen. The attachment of the tension spring 15 and of the deflection rollers 12 and 13 to the housing of the dishwasher 1 may be in a known matter. In FIGS. 3 a to 3 d , it can merely be seen that the upper deflection roller 13 is mounted on the vertical leg 16 of a support 17 whose horizontal leg 18 serves to mount the door 3 so that it can swivel. Furthermore, a holding plate 19 is also attached to the leg 16 , said holding plate 19 having a microswitch 20 and an actuator 21 ; also see FIG. 2 . The actuator 21 comprises a stamp 22 , a roller holder 23 and a pressure roller 24 . The bolt-like end 221 of the stamp is surrounded by a spring 222 and is held by the roller holder 23 in such a way that it can be moved lengthwise. In this manner, the roller holder 23 can be moved against the force of the spring 222 in the direction indicated by the double-headed arrow. The side of the roller holder 23 facing the microswitch 20 has a switching cam 231 with which the switching tappet 201 of the microswitch can be actuated.
[0018] FIGS. 3 a to 3 d show the sequence of movements during the opening of the door 3 . When the door 3 is closed ( FIG. 3 a ), the arm 9 extends horizontally, i.e. parallel to the standing plane of the dishwasher 1 and, due to the deflection roller 13 , the end of the Bowden cable 11 on the door side encloses an angle of approximately 30° relative to the imaginary parallel of the standing plane. The pressure roller 24 rests on the Bowden cable 11 , at this time, the roller 24 and the roller holder 23 are in a lower position in which the switching cam 231 is still at a distance from the switching tappet 201 . FIG. 3 b shows the door in a position in which it is open by about 10°. This opening angle can be established manually by the user or else automatically by an opening device. The arm 9 that also executes the swiveling motion of the door 3 pulls the Bowden cable 11 upwards, so that it is swiveled counterclockwise by about 15°. In this process, the Bowden cable 11 lifts the pressure roller 24 along with the roller holder 23 so that the switching cam 231 is moved until shortly before the switching tappet 201 . Consequently, the cleaning compartment light (lamp 6 ) is not yet switched on in this position. When the door 3 ( FIG. 3 c ) is opened further, the Bowden cable 11 is swiveled counterclockwise once again by 10°. As a result, the pressure roller 24 is raised even further and the switching cam 231 pushes the switching tappet 201 inwards. The microswitch 20 relays the triggered switching command to the program control 5 , which now switches on the lamp 6 . As an alternative, the lamp 6 can also be switched on directly by the microswitch 20 . It can be seen in FIG. 3 d that the switching tappet 201 is pressed inwards, also when the door 3 is completely open, and that the cleaning compartment light (lamp 6 ) thus remains switched on.
[0019] While the invention has been described with reference to particular embodiments thereof, it will be understood by those having ordinary skill in the art that various changes may be made therein without departing from the scope and spirit of the invention. Further, the present invention is not limited to the embodiments described herein; reference should be had to the appended claims.
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A dishwasher includes a cleaning compartment having a front portion that can be closed by a door. The door is configured to pivot at a bottom section thereof around a horizontally running axis. An illuminating device is configured to illuminate at least one of the cleaning compartment and the front portion of the cleaning compartment. A control device switches the illuminating device on or off based on a opening position of the door. The control device includes a switching element that is actuated by a Bowden cable arranged on the door in order to compensate for the weight of the door.
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FIELD OF THE INVENTION
The invention pertains to methods for correcting the water permeability contrast for heterogeneous subterranean formations. In one aspect, the invention pertains to prolonged permeability contrast correction of underground strata. In a particular aspect, the invention pertains to gelable aqueous polymer solutions employing components which are biocidal, particularly important in treatments wherein formation waters containing sulfate reducing bacteria are encountered. In a further aspect, the invention pertains to methods of waterflooding.
BACKGROUND OF THE INVENTION
In older oil-producing fields, water channeling through the high permeability zones in an oil reservoir will by-pass a large amount of oil-in-place. The more permeable zones of the subterranean formation tend to take most of the injected fluids. While initially this is acceptable in sweeping oil from such zones of relatively high permeability, it subsequently becomes undesirable as the oil content of such strata becomes depleted since much of the subsequently injected floodwater or other fluid by-passes the relatively less permeable zones and provides little benefit in enhancing further hydrocarbon recoveries.
Indepth plugging of a relatively high-permeability zone is to be preferred, so as to convert the zone into a much lower permeability zone. Then, subsequently injected floodwater will tend to enter the previously by-passed but now relatively more permeable hydrocarbon bearing zones and thus mobilize increased amounts of hydrocarbons therefrom.
A variety of means of subterranean formation permeability corrections have been developed. U.S. Pat. No. 3,762,476 (Gall, Oct. 2, 1973) describes the use of a variety of polymers in conjunction with crosslinking solutions of various multivalent metal cations complexed with certain sequestering/retarding anions selected from the recited group consisting of acetate, nitrilotriacetate, tartrate, citrate, and phosphate. The crosslinking solution is injected after the first polymer-thickened solution injection, frequently after and before interspacing brine slugs, followed by injection of further polymer solution, which sequence can be repeated. U.S. Pat. No. 4,018,186 (Gall et al, Apr. 19, 1977), describes similar materials further with employment of controlled pH.
However, many of the materials have been deficient in hard brines (brines containing calcium and/or magnesium ions) in regard to providing a high level of effectiveness on a large scale, avoiding undue sedimentation and strata plugging, inadequate formation of gel, and the like.
A problem with bacteria also has become increasingly apparent in oil field work. Bacteria in the available feedstock surface water and in the deep subterranean structures, particularly sulfate reducing bacteria, do exist and thrive under what had seemed very adverse conditions. Sulfate reducing and other bacteria encountered in subterranean strata have become increasingly troublesome because of the production of hydrogen sulfide which causes corrosion, "sours" the oil in place and causes the precipitation of insoluble compounds such as iron sulfide which can cause the undesirable plugging of pores in the formation.
Needed have been treatments with materials which are effective as crosslinking agents and also possess bactericidal properties.
Heretofore, of the sequestered cationic materials employed in gelling polymers, aluminum citrate solutions have been the crosslinking agents of preference for economy and availability. However, a real problem has persisted in that to make up the aluminum citrate solutions fresh water must be used. Since tremendous volumes of injection solutions are involved in flood work, providing large quantities of fresh water of injection quality at the well sites has indeed been a serious problem in many locations.
Needed are effective crosslinking agents, which can be used in hard brine solutions, and at the same time possess biocidal properties particularly toward sulfate reducing bacteria.
BRIEF DESCRIPTION OF THE INVENTION
We have discovered gelable compositions suitable for injection into subterranean formations and methods for applying to at least one wellbore compositions which comprise water, a water-thickening amount of a polymer capable of gelling in the presence of a polyvalent metal crosslinking agent of biocidal properties, such as chromium propionate, and which are useful in high brine solutions. Thus, we have discovered gelable compositions possessing important biocidal properties.
Our compositions and processes have the advantages of being aqueous compositions which can be made up in available-at-the-well-site hard brine waters without the need for supplying fresh water, and the crosslinking agent itself is biocidal. This provides bacterial control in the solution of the crosslinking agent itself, assists in providing control of bacteria in the injection lines through which the biocidal solution flows, thus assisting in minimizing corrosion and maintaining protection in metal conduits. Further, it exhibits bactericidal properties in the deep strata, controlling the population of sulfate reducing bacteria, which otherwise provide undesirable metabolic products such as H 2 S in-situ which can cause precipitation of iron sulfide and lead to plugging in locations where such is undesirable, sometimes interrupting or disrupting or destroying the effectiveness of floods for recovering hydrocarbon reserves.
It is an object of our invention to provide both near well and indepth permeability contrast correction compositions and methods of plugging more permeable strata in subterranean formations. It is an object of our invention to provide methods for treating an underground formation for improved recovery of hydrocarbon values. It is a further object of our invention to provide crosslinking agents which are bactericidal in properties to assist in bacteria control in the available feedstock surface water and connate water in underground strata in conjunction with the gelable polymer compositions.
Other aspects, objects, and the various advantages of this invention will become apparent upon reading the specification and the appended claims.
DETAILED DESCRIPTION OF THE INVENTION
Surprisingly, we have found that certain anions of sequestering (retarding) capabilities, particularly such as propionate, are bactericidal. This is surprising, indeed, since the closely related homologue acetate is not bactericidal.
In accordance with our invention, we provide high brine-tolerant biocidal injection compositions. We further provide methods which employ the compositions, e.g. by sequential injection of a water-thickening amount of a water-soluble or water-dispersible polymeric viscosifier, brine injection, injection of the biocidal sequestered polyvalent metal cation solution of defined characteristics, preferably followed by a further brine injection, and/or preferably by a further injection of a water-soluble water-dispersible polymeric viscosifier.
CROSSLINKING AGENTS
The crosslinking agents are solutions of multivalent (polyvalent) metal cations which are effective in type and concentration to gel the selected polymer when within the gelation pH range. Such polyvalent metal ions preferably are one or more of Al 3 .spsp.+, Ti 4 .spsp.+, Zn 2 .spsp.+, Sn 4 .spsp.+, Zr 4 .spsp.+, and Cr 3 .spsp.+. Presently preferred are Al 3 .spsp.+ and Cr 3 .spsp.+, though Cr 3 .spsp.+ is presently much more preferred in high salinity hard brines.
Presently preferred is chromium(III). The preferred chromium(III) or other polyvalent metal cations are employed in the form of complexes with an effective sequestering or chelating amount of one or more chelating or sequestering anions of biocidal character. The biocidal chelating or sequestering component retards the onset and rate of gelation of the polymer, and as well provides the surprising and highly important biocidal property. Chromium is the preferred cation in high salinity brines including hard brine. High salinity brine contains on the order of at least about 100,000 ppm total dissolved solids. Thus, the combination of the particular chelating or sequestering agent with biocidal character in conjunction with the preferred chromium(III) cation confers high brine tolerance as well as biocidal character.
While propionate presently is a most preferred, and adipate is considered a preferred biocidal anion, further suitable for use in our invention are other types of biocidal anions of chelating and sequestering character. Various bactericidal materials include:
A. Substantially water-soluble carboxylic acids of three to five carbons and the corresponding water-soluble carboxylate salts, preferably propionate, and to a lesser extent butyrate because of its decreasing water-solubility.
B. Halogenated and/or nitro-substituted monocarboxylic acids of two to five carbon atoms and the corresponding water-soluble carboxylate salts, such as 2,2-dichloropropionic acid, 2,2-dibromobutyric acid, trifluoroacetic acid, tribromoacetic acid, trichloroacetic acid, 2,3-dibromopropionic acid, 2,2-dichlorovaleric acid, 3-nitropropionic acid, triiodoacetic acid, 3(2,2,2-trichloroethoxy)propionic acid, 4-nitro-2-chlorobutyric acid, 2-bromo-2-nitropropionic acid, 2-nitroacetic acid, and the like, alone or in admixture.
C. Hydroxylated, halogenated, and/or nitro-substituted phenyl group-containing carboxylic acids of 8 to 11 total carbon atoms and the corresponding water-soluble salts such as 2,4-dihydroxyphenyl acetic acid, 2,4-dichlorophenyl acetic acid, 3(2',4'-dibromophenoxy)propionic acid, 3(3',5'-dinitrophenoxy)propionic acid, 3-phenyl-2,3-dibromopropionic acid, 3,5-dinitrosalicylic acid, 3(3'-bromo-4'-nitrophenyl)propionic acid, 3(3',4'-dihydroxyphenyl)propionic acid, and the like, alone or in admixture, and
D. Adipic acid and water-soluble adipate salts.
The desired solution of chromium(III) or other polyvalent metal cation with the sequestering or chelating agent of bactericidal properties selected from the materials as described above can be prepared in various manners.
PREPARATION OF CHROMIUM SOLUTION
For example, chromium or other selected metal powder can be slurried with the acid form of the chosen anion in suitable proportions, sometimes with heating and/or with small amounts of aqueous hydrochloric acid to assist in initiating the reaction, until a desired solution is obtained. In the case of chromium(III), particularly chromium propionate, clear deep green solutions are obtained.
Sufficient retarding/sequestering anion should be present to completely associate with the chromium or other polyvalent metal cation employed. Ratios of anion:chromium or other polyvalent metal cation for a stable solution are readily determinable.
Any convenient method of preparing the chromium propionate or other polyvalent metal cation salt of bactericidal properties can be employed. For example, suitable inorganic salts can be admixed with the selected chelating/sequestering salt or acid form in suitable molar proportions.
A solution of polyvalent metal ion can be prepared from a suitable water-soluble salt or compound of the metal, such as the chloride or the like, by admixing the metal salt or compound with sufficient amounts of water to make up a desired or convenient stock concentration. Fresh water may be helpful for solubility characteristics of some salts as is known.
The sequestering agent usually is supplied or available as the sodium salt, or in some cases as the free acid. A stock solution is made up in water to a convenient concentration, such as about 1 to 5 weight percent of sequestering agent.
The polyvalent metal salt solution and the sequestering agent solution then can be admixed in suitable porportion to result in the sequestered polyvalent metal ion solution. The amount of chelating or sequestering anion employed presently is considered to be an amount preferably sufficient to substantially associate with the metal ions present in the solution. The pH of the injection solution can be adjusted as desired to assist in gelling, depending on the polymer, as is known.
Generally, the molar ratio of sequestering agent to chromium or other polyvalent metal cation varies over the broad range of about 1:2 to 8:1, preferably about 2:1 to 4:1, most preferably about 2.5:1 to 3.5:1, but should be gauged such as to achieve a clean solution substantially clear without precipitate in each case. For example, with chromium salts, clear dark green colored solutions are desired.
In the case of propionate, and the preferred chromium polyvalent metal, a minimum of about 4 moles of propionate per mole of chromium, more preferably about 8 moles of propionate are considered desirable. It is contemplated that minor proportions of non-biocidal carboxylic acids such as acetic acid can be used in combination, e.g., with propionic acid to improve the economics of the overall operations without significantly diminishing the biocidal effectiveness of the chromium propionate system.
POLYMERS
Polymers suitable for use in this invention are those capable of gelling in the presence of polyvalent metal ion crosslinking agents. Polymers suitable for use in this invention, i.e., those capable of gelling in the presence of crosslinking agents within a gelation pH range, including biopolysaccharides, cellulose ethers, and acrylamide-based polymers.
Suitable cellulose ethers are disclosed in U.S. Pat. No. 3,727,688 (herein incorporated by reference). Particularly preferred cellulose ethers include carboxymethylhydroxyethyl cellulose (CMHEC) and carboxymethyl cellulose (CMC).
Suitable biopolysaccharides are disclosed in U.S. Pat. Nos. 4,068,714 (herein incorporated by reference). Particularly preferred is polysaccharide B-1459 which is a biopolysaccharide produced by the action of Xanthomonas campestris bacteria. This biopolysaccharide is commercially available in various grades under the trademark Kelzan® (Kelco Company, Los Angeles, Calif.).
Suitable acrylamide-based polymers are disclosed in U.S. Pat. No. 3,749,172 (herein incorporated by reference). Particularly preferred are the so-called partially hydrolyzed polyacrylamides possessing pendant carboxylate groups through which crosslinking can take place. Thermally stable polymers of acrylamide, such as poly(N-vinyl-2-pyrrolidone-co-acrylamide), poly(sodium-2-acrylamido-2-methyl-1-propanesulfonate-co-acrylamide-co-N-vinyl-2-pyrrolidone), and poly(sodium-2-acrylamido-2-methyl-1-propanesulfonate-co-acrylamide), are particularly preferred for applications in high salinity environments at elevated temperatures. Selected terpolymers also are useful in the present process, such as terpolymers derived from acrylamide and N-vinyl-2-pyrrolidone comonomers with lesser amounts of termonomers such as vinyl acetate, vinylpyridine, styrene, methyl methacrylate, and the like.
Other miscellaneous polymers suitable for use in the present invention include partially hydrolyzed polyacrylonitrile, polystyrene sulfonate, lignosulfonates, methylolated polyacrylamides, and the like.
Presently preferred are the acrylamide based polymers, particularly the polyacrylamides and the partially hydrolyzed polyacrylamides.
The concentration or water-thickening amount of the water-soluble/dispersible polymer in the aqueous solution/dispersion can range widely and be as suitable and convenient for the various polymers, and for the degree of gelation needed for particular strata. Generally, the concentration of polymer in its aqueous solution/dispersion is made up to a convenient strength of about 100 to 20,000 ppm, preferably about 200 to 5,000 ppm.
Any suitable procedures for preparing the aqueous admixtures of the crosslinkable polymer can be used. Some of the polymers may require particular mixing conditions, such as a slow addition of finely powdered polymer into the vortex of stirred water, alcohol pre-wetting, protection from air (oxygen), preparation of stock solutions from fresh rather than salt water, or the like, as is known for such polymers.
PREFLUSH (OPTIONAL)
Prior to employment of the gelable compositions, the strata can be subjected to a conditioning preflush step.
The optional preflush employs aqueous solution with a lower level of hardness and/or total dissolved solids (tds) than that of the stratum connate water, of preferably containing substantially no hardness cations though it may be saline. The purpose of the preflush is to alter the salinity of the connate water by flushing the formation, generally with about one to three times the pore volume of the zone to be treated.
Since it is known that enhanced oil recovery chemicals such as surfactants and polymeric viscosifiers are adsorbed and/or precipitated to a greater extent in the presence of electrolytes and hardness cations in particular, the preflush alleviates this potential problem by sweeping out a certain fraction of such electrolytes. A typical NaCl preflush brine contains, e.g., on the order of about 0.2 to 2 weight percent total dissolved solids.
COMPOSITIONS FOR INJECTIONS
The amount of crosslinking agent used depends largely on the amounts of polymer in the injected polymer solution. Lesser amounts of polymer, e.g., require lesser amounts of crosslinking agent. Further, it has been found that for a given concentration of polymer that increasing the amount of crosslinking agent generally substantially increases the rate of gelation. Of course, as soon as the injected polyvalent metal cation contacts the previously injected gelable polymer, gelation can begin. Rate and extent of gelation depend on proportion of each, and pH as is known which should be in a gelation pH range. Although a molar ratio can be estimated, generally the molar ratio of polyvalent metal cations to crosslinkable side groups on the polymeric viscosifier will vary with polymer molecular weight, polymer concentration and salinity. The concentration of polyvalent metal cations in the injected slug varies over the broad range of 25 ppm to 5,000 ppm, preferably over the range of 100 ppm to 2,000 ppm.
The total quantity of in situ gelable treating composition employed, e.g., in a near well treatment, can be expressed in terms of the pore volume of the area to be treated. For example, if a region (one or more stratum or portion thereof) to be treated is taking upwards of 80 volume % of the volume of injected fluid, a packer can be set to direct the treating composition into this zone. The quantity of treating composition can vary widely, depending on the effects desired, but generally from about 100% to 120% of the pore volume of the zone to be treated with the upper limit being governed merely by the practical limitations of pumping expense and chemical costs. For indepth treatment, the volume of the thief zones can be estimated by the use of tracers. From these results, the suitable amounts of polymer and crosslinking agent can be determined.
In the sequential treatment involving the injection of polymer-brine-crosslinking agent-brine-polymer the volumes of the respective brine slugs should be sufficient to prevent face plugging by delaying the mixing of crosslinking agent and polymer. Less than a suitable volume of brine slug, thus, can result in face plugging whereas greater than a suitable volume of brine slug can result in less effective treatment due to poor contacting of polymer and crosslinking agent.
A representative treatment sequence is given below.
1. A pre-flush with brine (optional).
2. Injection of a determined volume of polymer solution/dispersion.
3. Injection of a further brine volume to push the polymer on out into the (presently) more permeable strata.
4. Injection of the chromium(III) propionate solution (or other bactericidal chromium solution).
5. Injection of another brine volume to push the gel-triggering chromium propionate solution on into the (more permeable) strata to there initiate gelation and create a plug.
6. Injected floodwater is diverted into what formerly was less permeable but now is the more (relatively) permeable, and hydrocarbon-rich strata.
AQUEOUS DRIVE FLUID
The aqueous drive generally follows the permeability contrast correction process of our invention. The aqueous drive employs available field brines and/or fresh water if the latter is obtainable.
The aqueous drive, since it follows the gelation treatment, is diverted to the (formerly) relatively less permeable oil-rich zones since the permeability contrast correction process slows or substantially prevents the flow of aqueous drive fluid through the (originally) more permeable but oil-poor zones (so-called thief zones). A successful permeability contrast correction operation generally is signaled at the production well by a lowering of the water/oil ratio in the produced fluid.
Subsequent to the permeability contrast correction, the water/oil ratio may gradually increase again after prolonged injection of the drive water. A gelation retreatment of the formation can be carried out, if desired.
It is contemplated that the permeability contrast correction could also be followed by other enhanced oil recovery operations such as surfactantflooding and the like as well as the aforementioned aqueous drive.
The gel-plugging can be substantially reduced or eliminated following the gelation plugging at any time convenient thereafter by injecting an agent such as sodium hypochlorite which is recognized in the art for its effectiveness in degrading polymeric viscosifiers such as polyacrylamides.
EXAMPLES
Examples provided are intended to assist one skilled in the art to a further understanding of our invention. Particular materials employed should be considered as exemplary and not limitative. The examples are a part of our disclosure. The specification including text, examples, data, and claims, should be viewed as a whole in considering the reasonable and proper scope of our invention.
Example I
This example describes the preparation of chromium(III) propionate from chromium metal and propionic acid with aqueous hydrochloric acid.
Chromium metal powder (2.06 g, 40 mmoles) was slurried with propionic acid (7 mL, 6.9 g, 94 mmoles) and water (1 mL, 1 g, 55.5 mmoles) in a 100 mL beaker. A small magnetic stir bar was placed in the beaker and the reaction mixture was warmed to 40°-50° C. on a stirrer hot plate as 1 mL of 1M aqueous hydrochloric acid was added to the stirred mixture. The reaction started immediately after the HCl addition as evidenced by the development of a green color in the reaction mixture. The reaction mass was stirred and heated at 40°-50° C. for 2-3 hours before allowing the reaction mixture to stand fourteen hours at ambient temperature.
The reaction mixture was re-warmed to 40°-50° C. and the supernatant blue-green colored solution was decanted into another 100 mL beaker. The remaining chromium powder was contacted with an additional 4 mL (50 mmoles) propionic acid, 1 mL of water, and 2 drops of 1M aqueous hydrochloric acid. The further reaction was allowed to continue for several hours before the second solution was combined with the above separated blue-green supernatant. An additional 2 mL (25 mmoles) propionic acid was added to this combined solution and the resulting mixture was digested at 50°-70° C. for a period of two hours. During the digestion period, distilled water was added portionwise to maintain total volume and the blue-green colored solution became a dark green colored mixture. After cooling to ambient temperature, sufficient distilled water was added to bring the final volume to 50 mL. This stock solution contained 0.8 mmole Cr per mL (4.16 wt % Cr; 41,600 ppm Cr).
Portions of this stock solution were diluted to provide, respectively, test solutions containing 1000 ppm Cr(III), 500 ppm Cr(III) and 250 ppm Cr(III) for use in laboratory core runs. For example, 24 mL of the above stock solution diluted to 1000 mL provided a liter of test solution containing 1000 ppm chromium. Similarly, 12 mL and 6 mL of the stock solution diluted, respectively, to 1000 mL provided test solutions containing 500 ppm chromium and 250 ppm chromium, respectively.
Example II
This example describes runs which demonstrate the capacity of chromium(III) propionate (prepared in Example I), to crosslink polyacrylamide to establish high residual resistance factors in Berea sandstone cores.
The cores were cast in epoxy and equipped with five pressure taps located at the entry end of the core and located at 1", 2.5", 5" and 5.5" away from the entry end of the core. The cores were 6" in length and the pressure taps were numbered nonconsecutively from the core entry as 1, 2, 4, 3 and 5. Pressure taps 1, 2 and 3 were oriented perpendicularly to the fluid flow through the core whereas pressure taps designated as 4 and 5 were oriented (on opposite sides of the cores) in a plane making a dihedral angle of 120° with the plane of pressure taps 2 and 3. With respect to the distal end of the core, pressure tap 5 was located 1/2" from the end of the core; pressure tap 3 was located 1" from the end of the core; pressure tap 4 was located 31/2" from the end of the core; pressure tap 2 was located 5" from the end of the core; and pressure tap 1 (at the entry of the core) was located 6" from the end of the core.
The cores were evacuated, saturated with brine under vacuum and finally saturated under 75 psi of back pressure. The cores were then preflushed with at least one pore volume of brine and initial permeability to brine was calculated. During the lab runs, pressure readings were monitored at the pressure taps with pressure transducers.
The core treatment consisted of the sequential injection of 2, 0.1, 0.4 to 0.5, 0.2 and 1 to 1.5 pore volumes of polymer solution, brine solution, chromium propionate solution, brine solution and polymer solution, respectively. The frontal advance rate of the injected fluids ranged from 2 to 10 ft/day. The polymer solution concentration was 500 ppm polyacrylamide in the designated brine. The three different core runs were carried out, respectively, with brine solutions containing 1000 ppm, 500 ppm and 250 ppm Cr. The brine used in the core runs was prepared by dissolving 50.8 g NaCl in sufficient water to give one liter of brine solution (20000 ppm Na+) (approximately 5 wt % NaCl).
Two sets of residual resistance factors were calculated for each of the chromium(III) propionate test solutions. These calculations were based on the pressure readings monitored by the pressure transducers. The first set of values is based on pressure differences between the pressure taps and reflects the effectiveness of the treatment on that part of the core located between the designated pressure taps. The second set of values is based on the pressure difference between a designated pressure tap and the distal or exit end of the core. The residual resistance factor (RRF) indicates the extent of the brine's mobility reduction through the core after the treatment, e.g., a RRF value of 10 indicates that brine mobility through the core or a portion of the core was reduced 10-fold by the sequential injection of polymer solution, brine solution, chromium(III) propionate solution, brine solution, polymer solution. The residual resistance factors (RRF) are summarized below in Tables I and II:
TABLE 1______________________________________First Set of RRF (Residual Resistance Factor) ValuesCorePerme-ability CrCore (Milli- (III) RRF.sup.a RRF.sup.b RRF.sup.c RRF.sup.d RRF.sup.eNo. darcies) ppm 1,2 2,4 4,3 2,3 4,5______________________________________1 949 1000 (160)* NM# NM# (55.1)* 89.42 978 500 27.7 20.8 23.4 20.8 22.93 678 250 37.1 16.7 11.8 13.9 NM#______________________________________ .sup.a RRF 1,2 represents the RRF value calculated from monitored pressur readings taken at pressure taps 1 (core entry) and 2 (1" from tap 1). The treatment zone considered was the first inch of the core. .sup.b RRF 2,4 represents the RRF value calculated from monitored pressur readings taken at pressure taps 2 and 4 located, respectively, 1" from core entry and 2.5" from core entry (a treatment zone of 1.5"). .sup.c RRF 4,3 represents the RRF value calculated from monitored pressur readings taken at pressure taps 4 and 3 located, respectively, 2.5" from core entry and 4" from core entry (a treatment zone of 1.5"). .sup.d RRF 2,3 represents the RRF value calculated from monitored pressur readings taken at pressure taps 2 and 3 located, respectively, 1" from core entry and 4" from core entry (a treatment zone of 3"). .sup.e RRF 4,5 represents the RRF value calculated from monitored pressur readings taken at pressure taps 4 and 5 located, respectively, 2.5" from core entry and 5.5" from core entry (a treatment zone of 3"). *These values represent approximations because massive gels formed near the pressure taps and prevented good contact between the pressure sensor and the flowing fluid. NM# represents "Not Measured".
Referring to the results in Table I, it is evident that the treatment becomes more effective (increasing RRF values) as the concentration of chromium in the test solution is increased from 250 ppm to 500 ppm to 1000 ppm.
TABLE II__________________________________________________________________________Second Set of RRF (Residual Resistance Factors) ValuesCore Permeability CR(III) RRF.sup.a RRF.sup.b RRF.sup.c RRF.sup.d RRF.sup.eCore No.(Millidarcies) ppm 1,E 2,E 3,E 4,E 5,E__________________________________________________________________________1 949 1000 109.5 (93.8)* 209.8 143.3 2692 978 500 165.4 (191.3)* 702.7 230.6 1382.53 678 250 25.9 22.3 59.2 24.4 NM#__________________________________________________________________________ *see footnote in Table I #See footnote in Table I .sup.a RRF 1,E represents the residual resistance factor for the entire 6 length of the core. .sup.b RRF 2,E represents the RRF for the last 5" of the core. .sup.c RRF 3,E represents the RRF for the last 1" of the core. .sup.d RRF 4,E represents the RRF for the last 3.5" of the core. .sup.e RRF 5,E represents the RRF for the last 0.5" of the core.
Referring to the results in Table II, it is evident that the RRF values increase as the zones of the core are considered in passing from core entry to core exit. It is noteworthy that the core run involving the use of the aluminum citrate system described hereinbelow exhibited the reverse trend in RRF values passing through the designated zones between core entry and core exit.
A comparative core run with aluminum citrate was carried out to illustrate the superiority of the propionate sequestered chromium(III) system over the citrate sequestered aluminum(III) system. The test solution of aluminum citrate was 500 ppm Al(III) and the Al to citrate ratio was 1.75/1. The procedure was the same as used above with the chromium propionate system and the results are summarized in Tables III and IV. The footnotes of Tables I and II are pertinent, respectively, to the core zone designations used in Tables III and IV.
TABLE III______________________________________First Set of RRF Values (Aluminum Citrate System) Core Perme abilityCore (Milli- Al(III) RRF.sup.a RRF.sup.b RRF.sup.c RRF.sup.dNo. darcies) ppm 1,2 2,4 4,3 2,3______________________________________A 885 500 4.3 2.2 3.8 3.12 978 500 27.7 20.8 23.4 20.8(Table (Cr.sup.+3)I)______________________________________ .sup.a-d see footnotes .sup.a-d Table I.
Referring to the results of Tables I and III, in particular to the 500 ppm Cr(III) run in Table I, it is evident that the RRF values in the Cr(III) propionate treatment sequence far exceeded the corresponding RRF values in the aluminum citrate treatment sequence.
TABLE IV__________________________________________________________________________Second Set of RRF Values (Aluminum Citrate System) Core Permeability Al(III) RRF.sup.a RRF.sup.b RRF.sup.c RRF.sup.d RRF.sup.eCore No. (Millidarcies) ppm 1,E 2,E 3,E 4,E 5,E__________________________________________________________________________A 885 500 2.9 3.2 3.5 3.7 2.332 978 500 165.4 (191.3)* 702.7 230.6 1382.5(Table II) (Cr.sup.+3)__________________________________________________________________________ .sup.a-e See footnotes .sup.a-e in Table II *See * footnote in Table II.
Referring to the results in Table IV and Table II, in particular to the 500 ppm Cr(III) run in Table II (also entered in Table IV), it is evident that the RRF values in the Cr(III) propionate treatment sequence far exceeded the corresponding RRF values in the aluminum citrate treatment sequence. Furthermore, in the aluminum citrate system it is apparent that the RRF values decrease as the zones of the core are considered in passing from core entry to core exit whereas the reverse trend prevails in the chromium(III) propionate system.
Example III
This example demonstrates the excellent performance of the chromium(III) propionate system (250 ppm Cr) in a hard brine. The core run was carried out in the same manner as described in Example II above except the NaCl brine was replaced with a hard brine (synthetic South Burbank Unit brine) containing, respectively, 23000 ppm, 5000 ppm, 1050 ppm and 960 ppm sodium, calcium, barium and magnesium. The RRF value results are summarized in Tables V and VI. The footnotes of Tables I and II are pertinent, respectively, to the core zone designations used in Tables V and VI.
TABLE V__________________________________________________________________________First Set of RRF Values in Hard Brine Core Permeability Cr(III) RRF.sup.a RRF.sup.c RRF.sup.d RRF.sup.eCore No. (Millidarcies) ppm 1,2 4,3 2,3 4,5__________________________________________________________________________B 704 250 10.2 31.6 15.4 33.2(Hard Brine)3** 678 250 37.1 11.8 13.9 NM#(From Table I)(NaCl Brine)__________________________________________________________________________ *Synthetic South Burbank Unit hard brine was used in core B. **5.0 wt % NaCl brine was used in core number 3. #NM represents "Not Measured". .sup.a,c-e See footnotes .sup.a,c-e in Table I.
Referring to the results in Table V it is evident that the RRF values in the hard brine were generally higher than those in the soft NaCl brine.
TABLE VI__________________________________________________________________________Second Set of RRF Values in Hard Brine* Core Permeability Cr(III) RRF.sup.a RRF.sup.b RRF.sup.c RRF.sup.d RRF.sup.eCore No. (Millidarcies) ppm 1,E 2,E 3,E 4,E 5,E__________________________________________________________________________B 704 250 164.7 197.7 740.5 301.4 1266.4(Hard Brine)3** 678 250 25.9 22.3 59.2 24.4 NM#(From Table II)(NaCl Brine)__________________________________________________________________________ *See footnote in Table V. **See footnote in Table V. NM See footnote in Table V. .sup.a-e See footnotes .sup.a-e in Table II.
Referring to the results in Table VI, it is evident that the RRF values of the chromium(III) propionate system in SBU (Synthetic South Burbank Unit) hard brine were much higher than observed in the 5 wt % NaCl brine of core run number 3 (from Table II). The RRF values remained relatively constant during the passage of 75 pore volumes of hard brine after-flush. This indicates the potential capacity of the chromium(III) propionate system to provide a long-lived permeability contrast correction even in the presence of hard brine.
The permeability contrast correction obtained with the aluminum citrate system was not nearly so long-lived, e.g., during the passage of 75 pore volume of hard brine after-flush, the RRF value was lowered by 2/3 of its magnitude calculated after three pore volumes of brine after-flush. These results generally indicate the greater capacity of the chromium(III) propionate system over the aluminum citrate system for permeability contrast correction particularly in the presence of hard brines.
Example IV
This example presents results which substantiate the biocidal activity of the chromium(III) propionate system toward sulfate reducing bacteria (SRB). These results are presented to buttress the thesis that the biocidal activity of the system is attributable to the propionate anionic sequestering group rather than to the chromium cation.
The test employed consisted of mixing 1 mL of the test material with 10 mL of Arkansas-Burbank water containing sulfate anion and 1 mL of sulfate reducing bacteria (SRB) culture in a serum bottle. After 24 hours, 0.1 mL of the resulting mixture was placed in a SRB growth medium containing an iron nail in a bottle. The bottle was placed in an incubator at 120 F. for either 28 days or until the appearance of black ferrous sulfide which ever occurred first. The appearance of FeS is an indication of SRB growth; if no FeS was observed then the test material was designated as biocidal. In such testing, chromium(III) propionate, chromium(III) adipate and chromium(III) trifluoroacetate showed biocidal activity.
A similar test was carried out on chromium(III) acetate to demonstrate that the next lower homolog was not biocidal toward SRB. Two samples were tested for biocidal activity toward sulfate reducing bacteria (SRB). One sample was commercially available chromium(III) acetate from Fisher Scientific Co. and the other sample was prepared in the laboratory by the reaction of chromium metal and acetic acid in a manner analogous to the procedure used in Example I for making chromium propionate from chromium metal and propionic acid. The biocidal tests were carried out at 250 ppm, 500 ppm and 750 ppm chromium(III) acetate. Since all of the tests showed growth of SRB within 24 hours, it was concluded that chromium(III) acetate is not biocidal toward sulfate reducing bacteria.
Another control run was carried out with chromium(III) citrate to support the thesis that Cr(III) cation is not the biocidal entity in chromium(III) propionate. The citrate anion is a well-known metabolite for microorganisms. Since concentrations of 250 ppm, 500 ppm and 750 ppm chromium(III) citrate did not inhibit SRB growth, it was concluded that the Cr(III) cation is not biocidal toward sulfate reducing bacteria.
On the basis of the above test results, it appears that chromium(III) propionate is biocidal toward SRB whereas the next lower homolog, i.e., chromium(III) acetate, is not biocidal. It appears that the SRB biocidal activity is contributed by the propionate sequestering group rather than the Cr(III) cation.
The disclosure, including data, has illustrated the value and effectiveness of our invention. The examples, the knowledge and background of the field of the invention and the general principles of chemistry and of other applicable sciences have formed the bases from which the broad description of our invention including the ranges of conditions and the generic groups of operant components have been developed, and formed the bases for our claims here appended.
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A water permeability correction process, and composition therefor, to improve the sweep efficiency of waterflooding which involves the sequential injection of (1) an optical aqueous preflush slug to adjust connate water salinity, (2) an aqueous sequestered polyvalent metal cation, such as chromium, wherein the sequestering anion is bactericidal, such as propionate, (3) a gelable polymeric viscosifier, such as polyacrylamide, and, preferably, (4) an aqueous drive fluid.
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TECHNICAL FIELD
[0001] The invention relates to a device for producing nanofibers or microfibers from solutions, emulsions, liquid suspensions or melts containing a spun substance.
BACKGROUND ART
[0002] Currently there are numerous devices for electrostatic spinning of solutions, emulsions, liquid suspensions or melts containing a spun substance. Described are systems producing nanofibers comprising both nozzle and nozzleless arrangements. These devices are structurally demanding and their operation has a number of shortcomings, including clogging of nozzles, which leads to an interruption of the operation or reduction in productivity.
[0003] As far as the nozzleless devices are concerned, the formation of nanofibers occurs directly from the surface of spun solutions which can be in the form of a thin film. Two-layer systems are also used, wherein the lower layer is formed by a ferromagnetic suspension and the upper layer by a solution of spun polymer. After application of the magnetic field, sharp vertical cones of the ferromagnetic liquid are formed that serve as nuclei from which the nanofibers are produced.
[0004] Other device is based on the aeration of a spun polymer solution in order to create a high concentration of bubbles on the surface of the solution, wherein a lowering of the surface tension takes place and the hubbies form seeds of nanofibers created by virtue of the electric field.
[0005] Another device is based on a slowly rotating cylinder which is partially immersed in a solution of the spun polymer. During the rotation of the cylinder, a deposit of a specific amount of the solution on the roller takes place, resulting in a formation of a continuous film from which on the upper part by virtue of a strong electric field so-called Taylor cones serving as nuclei of nanofibers are formed.
[0006] Electrostatic spinning methods are characterized by a low speed of the process; they are technically complicated and expensive. The electrostatic spinning is limited by the necessity of a high voltage electric field.
[0007] There are also devices used that are not based on the application of electrospinning. For the formation of nanofibers, these usually take advantage of centrifugal force or a gas stream. A rotating disk is used, on the surface of which a thin film of spun solution is produced by means of the centrifugal force.
SUMMARY OF THE INVENTION
[0008] Said disadvantages of the devices for producing fibers or microfibers from solutions emulsions, liquid suspensions, or melts containing spun suspension can largely be removed by means of the solution according to the invention whose principle consists in that it comprises a chamber in which a hollow shaft is assembled, on which at least one rotating disc with an output gap is mounted. The chamber is generally provided with a source of the flowing gas and a collection area. In an alternative embodiment, the chamber is provided with a number of side by side arranged hollow shafts on which rotating discs are mounted.
[0009] It is preferred that at least one hollow shaft is provided with two superposed rotating discs. At least one rotating disc is composed of two successive parts, wherein between the upper part and the lower part the outlet gap is formed around the circumference thereof. The size of the outlet gap between the upper part and the lower part of rotating disc may be formed by a spacer element, in particular a spacer ring.
[0010] It is preferred that at least one part of the rotating disc has a frustoconical shape. At least one rotating disc may be provided with a pressure element, such as pressure nut. At least one disc or discs disposed in a chamber which is made of heat resistant material may be provided with means for their heating.
[0011] The inner space of the hollow shaft is connected with the output gap of each of the rotating discs by means of openings and at the other end with a rotary unit for supplying the polymer and further with the drive motor.
[0012] The source of the flowing gas in the chamber is a compressor or a fan. The collecting area can be either a movable conveyor made of a breathable fabric or a rotating collector or a bag of a porous mesh. The collecting area may be electrically charged.
[0013] The present invention in comparison with the current state of the art prevents drying films of polymer solutions on the surface of rotating discs, it reduces the amount of defects of produced nanofibers and microfibrous layers, especially drops. It facilitates the centrifugal spinning of melts, because there occurs no cooling of the melt on the surface of the rotating elements.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] An exemplary embodiment of the device for producing nanostructured and microstructured materials is shown in enclosed drawings, wherein
[0015] FIG. 1 shows an overall diagram of the entire device,
[0016] FIG. 2 shows a spindle with a hollow shaft and a disc in the perspective illustration and partial longitudinal section,
[0017] FIG. 3 shows a specific embodiment of the disc according to the invention without a spacer and
[0018] FIG. 4 shows a specific embodiment of the disc according to the invention with a spacer.
DETAILED DESCRIPTION OF THE INVENTION
Example 1
Preparation of Nano- or Microfibers from a Polyvinyl Alcohol Solution
[0019] To prepare polyvinyl alcohol micro- or nanofibers, a commercial solution of polyvinyl alcohol Sloviol R16, 16% (wt./Wt.) of solid content (Fichema) was used. The polyvinyl alcohol solution was pumped from the first liquid reservoir 17 by the first pump 18 through a connecting hose 19 via the first safety valve 20 and the first check valve 21 at a rate of 2-12 ml/min., and fed through an inlet 22 of liquid into the rotation unit 10 from which it further entered into a hollow shaft 3 disposed in a tube 5 of a spindle. Via openings 16 was the polyvinyl alcohol solution sprayed from the inner space 6 of the hollow shaft 3 into the inner space of the rotating disc 2 having a conical shape with a diameter of 120 mm, between the upper part 7 and the lower part 8 thereof The output gap 4 of the conical disc 2 was set up using a spacer ring 13 on the width of 200 micrometers as shown in FIG. 4 , The rotating disc 2 was positioned over the base plate 23 with channels 32 for the distribution of the drying gas into the chamber 1 in the form of a tube 5 of a plexi-glass having the diameter of 35 cm and the height 40 cm. In the base plate 23 entered at a rate of 0.7 m 3 /s drying air preheated to a temperature of 25° C. from a source 11 , which is formed by a compressor and a heater. The rotating disc 2 with the hollow shaft 3 was rotated via an intermediate transmission 15 by means of a drive motor 14 at a speed of 1 to 5000 revolutions per minute. The stream of preheated air carried away the nano- or microfibers generated by the centrifugal force on the edge of the outlet gap 4 into a collection chamber 12 provided with an orifice having a width of the slot 24 of 5 cm and a length of 35 cm and a sliding belt 25 formed by a permeable nonwoven Spunbond having a basis weight 18.8 g/m 2 . The shift velocity was 10 cm/min. The nano- or microfibers were stored in the form of a continuous layer on the surface of the sliding belt 25 of the permeable nonwoven.
[0020] At a constant flow of the polyvinyl alcohol solution 10 ml/min, increased a rate of fiber formation with an increasing rotational speed of the disc in the range 1 to 3,000 revolutions per minute. Upon further increasing the rotation speed, the rate of the fiber formation did not further increase and the incidence of defects in the fibers network has increased in the form of droplets. Therefore, further experiments were carried out at a rotation speed of 3000 revolutions per minute. At this speed of rotation and other conditions described above has increased the basis weight of the fibers in a linear manner within the range of the polyvinyl alcohol solution flow from 2 to 8 ml/min. Maximum productivity was observed at the flow rate 10 ml/min, Further acceleration of the flow to 12 ml/min, under the conditions described. above seemed to be counter-productive already, because neither the fiber formation nor the exploitation of polyvinyl alcohol increased, conversely, they have even slightly declined. At the same time the incidence of defects in the form of microdroplets has increased. Under these conditions, it appeared as optimal the flow in the range of 8-10 ml/min. Under these conditions, the basis weight of the layer of polyvinyl alcohol fibers was in the range of 7-10 g/m 2 . Maximum speed of the fiber formation at a flow rate of 8 ml/min., and a speed of rotation of 3000 revolutions per minute was 20 g per hour. The distribution of the nanofibers was homogeneous both in the microscopic and macroscopic level across the whole belt width, which represented 35 cm. The diameter of the majority of fibers observed was in the range of 400 to 800 nanometers.
[0021] The above procedure was repeated with the exception that two rotating discs 2 of the same construction, located on one hollow shaft 3 superimposed with a spacing of 10 cm were used, and the flow rate of the polyvinyl alcohol solution and the shift of the belt 25 of permeable nonwoven were doubled. Under these conditions the rate of the fiber formation at a flow rate of 16 ml/min and the rotation speed of 3000 revolutions per minute managed to increase to 38 g per hour. There were no significant changes in the basis weight of the fibers and their quality.
Example 2
Preparation of Nano- or Microfibers from Polyamide 6
[0022] For the preparation of micro or nanofibers polyamide 6 were used pellets of polyamide 6 (Rhodin Technyl). From these pellets was prepared a solution 15% (wt./wt.) in 85% (wt./wt.) formic acid (Penta) at a temperature of 80° C. This solution was pumped from the first liquid reservoir 17 by the first pump 18 through the connecting hose 19 via the first safety valve 20 and the first check valve 21 at a rate of 6-16 ml/min., and fed through the inlet 22 of liquid into the rotation unit 10 from which it further entered into the hollow shaft 3 disposed in the tube 5 of the spindle. Via openings 16 was the polyamide 6 solution sprayed from the inner space 6 of the hollow shaft 3 into the inner space of the rotating disc 2 between the upper part 7 and the lower part 8 thereof. The disc 2 having a conical shape with a diameter of 120 mm provided with the pressure element 9 in the form of a nut was used, as it can be seen from FIG. 3 . The pressure of the presser nut was gradually changed so that an opening of the outlet gap 4 occurs at a pressure in the range of 4-400 bar. The rotating disc 2 was positioned over the base plate 23 with channels 32 for the distribution of the drying gas into the chamber 1 in the form of a tube 5 of a plexi-glass having the diameter of 35 cm and the height of 40 cm. In the base plate 23 entered at a rate of 0.6 m 3 /s drying air preheated to a temperature of 35° C. from a source 11 , which is formed by a compressor and a heater. The rotating disc 2 with the hollow shaft 3 was rotated via an intermediate transmission 15 by means of a drive motor 14 at a speed of 1 to 5000 revolutions per minute. The stream of preheated air carried away the nano- or microfibers generated by the centrifugal force on the edge of the outlet gap 4 into a collection chamber 12 provided with an orifice having a width of the slot 24 5 cm and a length 35 cm. At a height of 5 mm above the slit 24 of the aperture, a rotating collector of fibers in the form of a roller made of fine steel mesh having a diameter of 10 cm and provided with a motor imparting the collector a rotation of 10 rpm., was positioned longitudinally horizontally.
[0023] Nano- or microfibers were deposited evenly over the whole surface of the rotary collector in the form of a continuous layer of a thickness of almost 3 mm in the form resembling a soft cotton wool. When increasing the pressure in the interior of the disc between the upper part 7 and the lower part 8 thereof, a reduction in diameter of the fibers has occurred. While at a pressure of 4 bar the fiber diameter was in the range 600 to 900 nm, at a pressure of 400 bar the diameter was already in the range of 200 nm to 400 nm. The rate of the fibers formation was in the range of 50 g to 135 g per hour, depending on the conditions. The optimal flow rate was 14 ml/min.
[0024] In another experiment, a chamber 1 made of plexi glass and having a cuboidal shape with a length of 2 m and a width and a height of 50 cm was used, in which two rotating discs 2 were placed side by side, with pressure elements 9 in the form of nuts. The discs 2 were placed at a distance of 1 m apart. Optimal conditions were used for spinning the polyamide 6 solution as identified in the above described experiment. The flow in each disk was 14 ml/min. The pressure in the inner space of the disk ? between the upper part 7 and the lower part thereof was 60 bar. The collection of the fibers in the collecting space 12 was carried out using a slot having a width of the aperture 24 of 20 cm and a length of 2 m and a sliding belt 25 of the permeable Spunbond nonwoven having a basis weight of 18.8 g/m2, also with a width of 2 m. The speed of displacement of the belt was 10 cm/min. The nano- or microfibers have been stored in the form of a continuous layer on the surface of the belt 25 of a permeable fabric. The distribution of the nanofibers was homogeneous both in the microscopic and macroscopic level across the whole belt width, which represented 35 cm. The diameter of the majority of fibers observed was in the range of 400 to 800 nanometers. The basis weight of the fibers was in the range of 4-6 g/m 2 .
Example 3
Encapsulation of Probiotic Bacteria into Gelatin Microfibers
[0025] For the encapsulation of probiotic bacteria, a 10% (wt./wt.) suspension of the microbial preparation BA (1.10 9 CFU/g) (Milcom) containing the probiotic strains of genera Lactobacillus acidophilus and Bifidobacterium bifidum freeze-dried with powdered milk in distilled water was used. Further, a solution of 30% (wt./wt.) of pig skin gelatin, 300 bloom, type A (Sigma-Aldrich) in 40% (vol./vol.) acetic acid was used. The gelatin solution at a temperature of 45° C. was pumped from the first reservoir 17 of liquid by means of the first pump 18 via the first connecting pipe 19 through the first safety valve 20 and the first check valve 21 at a rate of 5 ml/min. Simultaneously, a bacterial suspension was pumped from the second reservoir 26 of liquid by means of the second pump 27 via the connecting hose 19 through the second safety valve 28 and the second check valve 29 at a rate of 5 ml/min. The gelatin solution and bacterial suspension were mixed in a mixing chamber 30 having a volume of 5 ml. The resulting bacterial suspension in the gelatin solution was fed through the inlet 22 of liquid into a rotation unit 10 from which it further entered the hollow shaft disposed in the tube 5 of the spindle. Through the openings 16 , the suspension was further sprayed from the inner space 6 of the hollow shaft 3 into the inner space of the rotating disc 2 of a conical shape with a diameter of 120 mm, between its upper part 7 and the lower part 8 . The output gap 4 of the conical disc 2 was set using the spacer element 13 to the width of 150 microns, as shown in FIG. 4 . The rotating disc 2 was positioned over the base plate 23 with channels 32 for the distribution of the drying gas into the chamber 1 in the form of a tube made of fine steel mesh 35 cm in diameter and the height 40 cm. Into the base plate 23 entered the drying air preheated to a temperature of 40° C. from a source 11 , which is formed by a compressor and a heater, at a velocity of 0.8 m 3 /s.
[0026] The rotating disc 2 with the hollow shaft 3 was rotated via an intermediate transmission 15 by means of a drive motor 14 at a speed of 3500 revolutions per minute. The stream of preheated air carried away the nano- or microfibers generated by the centrifugal force on the edge of the outlet gap 4 of the rotating disc 2 into a collection chamber 12 provided with an orifice having a width of the slot 24 of 10 cm over which a bag made of a permeable nonwoven Spunbond having a basis weight 18.8 g/m 2 . The shift velocity was 10 cm/min. The microfibers were stored in this bag in the form resembling a soft cotton wool.
[0027] The yield was 80 g of the microfibers with the encapsulated bacterial culture in one hour of the operation. A microscopic analysis confirmed the presence of bacterial cells encapsulated within the microfibers having a diameter of between 5 and 10 microns. Standard methods for microbiological analysis showed that there was only a small decrease in vitality of the original bacterial culture, expressed as a number of colony-forming units (CFU), by one order, Microbiological tests confirmed a significant protective effect of the encapsulating against a simulated acidic environment of the stomach and against the action of bile acids.
Example 4
Preparation of Fibers from the Melt the Polyhydroxyalkanoate
[0028] A melt of polyhydroxy alkanoate (Nanjing Huichen Co., Ltd., China) was prepared in the first reservoir 14 of a solution equipped with an induction heating, and maintained at a temperature of 300 degrees Celsius. The entire device was thermally insulated.
[0029] The melt was pumped from the first reservoir 17 of a solution by the first pump 18 via the insulated connecting hose 19 made of a profiled steel strip through the first safety valve 20 and the first check valve 21 at a velocity of 10 ml/min., and fed through the inlet 22 of a liquid into the rotation unit 10 from which it further entered into the hollow shaft 3 disposed in the tube 5 of the spindle. Through openings 16 were the melt sprayed from the inner space of the hollow shaft 6 into the inner part of the rotating disc 2 of a conical shape, with a diameter of 120 mm, between the upper part 7 and the lower part 8 thereof. The output gap 4 of the conical disc 2 has been set using the spacing element 13 to the width of 50 microns, as it is apparent from FIG. 4 . The rotating disc 2 was positioned over the base plate 23 equipped with channels 32 for the distribution of the drying gas into the chamber 1 in the form of an insulated steel tube having the diameter of 35 cm and the height of 40 cm. Into the base plate 23 , the drying air preheated to 250° C. from a source 11 , which was formed by a compressor and a heater, entered at a velocity of 1 m 3 /s. The rotating disc 2 with the hollow shaft was rotated via an intermediate transmission 15 by means of a drive motor 14 at a speed of 1 to 5 000 revolutions per minute. The stream of preheated air carried away the nano- or microfibers generated by the centrifugal force on the edge of the outlet gap 4 into a collection chamber 12 provided with an orifice having a width of the slot 24 of 5 cm and a length of 35 and a sliding belt made of a fine steel mesh.
[0030] The basis weight of the fibers was in the range of 8-10 g/m 2 . The distribution of the nanofibers was homogeneous both in the microscopic and macroscopic level across the whole belt width, which represented 35 cm. The diameter of the majority of fibers observed was in the range of 400 to 800 nanometers. The rate of fibres production was 600 g per hour.
INDUSTRIAL APPLICABILITY
[0031] Due to preventing the drying of films of polymer solutions on the surface of rotating discs and a reduced quantity of defects fibrous layers, a device for the production of fibers or microfibers from solutions, emulsions, melts or liquid suspensions containing a spinnable polymer according to the invention may be advantageously used to produce nanofibers or microfibers, where a high productivity work is required. The device also facilitates the centrifugal spinning of melts, because no cooling of the melt on the surface of the rotating elements takes place.
LIST OF REFERENCE NUMBERS
[0032] 1 —chamber
[0033] 2 —disc
[0034] 3 —hollow shaft
[0035] 4 —output gap
[0036] 5 —tube
[0037] 6 —inner space
[0038] 7 —upper part
[0039] 8 —lower part
[0040] 9 —pressure element
[0041] 10 —rotary unit
[0042] 11 —source of the gas flow
[0043] 12 —collection area
[0044] 13 —spacer element
[0045] 14 —drive motor
[0046] 15 —intermediate transmission
[0047] 16 —openings
[0048] 17 —first reservoir
[0049] 18 —first pump
[0050] 19 —connecting hose
[0051] 20 —first safety valve
[0052] 21 —first check valve
[0053] 22 —liquid inlet
[0054] 23 —base plate
[0055] 24 —slot
[0056] 25 —sliding belt
[0057] 26 —second reservoir
[0058] 27 —second pump
[0059] 28 —second safety valve
[0060] 29 —second check valve
[0061] 30 —mixing chamber
[0062] 31 —heating device
[0063] 32 —channel for gas distribution
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A device for producing nanofibers or microfibers from solutions, emulsions, liquid suspensions or melts containing a spun substance, comprises a chamber in which a hollow shaft is assembled, on which at least one rotating disc with an output gap is mounted, The chamber is generally provided with a source of the flowing gas and a collection area. In an alternative embodiment, the chamber is provided with a number of side by side arranged hollow shafts.
It is preferred that at least one hollow shaft is provided with two superposed rotating discs. At least one rotating disc is composed of two successive parts, wherein between the upper part and the lower part an outlet gap is formed around the circumference thereof. The size of the outlet gap between the upper part and the lower part of rotating disc may be formed by a spacer element, in particular a spacer ring.
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BACKGROUND OF THE INVENTION
1. Field of the Invention:
The present invention relates to a bitline precharge circuit for a semiconductor memory device, and more particularly relates to a bitline precharge circuit for precharging the bitlines connected to memory cells arranged in matrix.
2. Description of the Related Art:
An exemplary configuration of a conventional SRAM (static random access memory) is shown in FIG. 10. In this SRAM, multiple word lines WL and multiple bitline pairs BIT and /BIT are arranged in the row direction and the column direction, respectively. The same number of memory cells MRC as the number of the rows are connected to each bitline pair BIT and /BIT associated with each column Col. These memory cells MRC connected to a bitline pair BIT and /BIT on an identical column Col are connected to respectively different word lines WL, while the memory cells MRC which are connected to bitline pairs BIT and /BIT on different columns Col and disposed on the row are connected to one and the same word line WL. For the sake of simplifying the description, it should be noted that FIG. 10 illustrates only two word lines WL 1 and WL 2 corresponding to two rows, only two bitline pairs BIT 1 & /BIT 1 and BIT 2 & /BIT 2 corresponding to two columns Col 1 and Col 2 , only two memory cells MRC 1 and MRC 2 connected to the bitline pair BIT 1 and /BIT 1 on the first column Col 1 and only two memory cells MRC 3 and MRC 4 connected to the bitline pair BIT 2 and /BIT 2 on the second column Col 2 . As shown in FIG. 10, the memory cells MRC 1 and MRC 3 on the same row are connected to the same word line WL 1 and the memory cells MRC 2 and MRC 4 on the same row are connected to the same word line WL 2 .
The pair of bitlines BIT 1 and /BIT 1 on the first column Col 1 are connected to data lines D 1 and /D 1 , respectively, via associated column selector circuits 3 on the first column Col 1 , while the pair of bitlines BIT 2 and /BIT 2 on the second column Col 2 are connected to data lines D 2 and /D 2 , respectively, via associated column selector circuits 3 on the second column Col 2 . Each of the column selector circuits 3 is a circuit for connecting the bitlines BIT and /BIT to the data lines D 1 and /D 1 or D 2 and /D 2 via a single N-MOSFET (N-channel metaloxide-semiconductor field effect transistor) N 11 , the ON/OFF states of which are controlled by a column select signal Y. It is noted that the column select signal Y is a control signal for selecting a specified column Col and that different column select signals Y are used for the respective columns Col. Specifically, the pair of column selector circuits 3 on the first column Col 1 are controlled by a column select signal Y 1 on the same first column Col 1 , while the pair of column selector circuits 3 on the second column Col 2 are controlled by a column select signal Y 2 on the same second column Col 2 . Herein, the data line pair D 1 and /D 1 are connected to the bitline pair BIT 1 and /BIT 1 adjacent thereto and the data line pair D 2 and /D 2 are connected to the bitline pair BIT 2 and /BIT 2 adjacent thereto.
The bitline pair BIT 1 and /BIT 1 on the first column Col 1 are connected to a power supply V cc via associated bitline precharge circuits 1 on the first column Col 1 , while the bitline pair BIT 2 and /BIT 2 on the second column Col 2 are connected to the power supply V cc via associated bitline precharge circuits 1 on the second column Col 2 . Each of the bitline precharge circuits 1 is constituted by a single NMOS transistor N 1 shown in FIG. 11, in which the drain D thereof is connected to the power supply V cc , the source S thereof is connected to the associated bitline BIT or /BIT and a precharge signal EQ 0 is input to the gate G thereof. Thus, each bitline precharge circuit 1 connects the bitline BIT or /BIT to the power supply V cc when the precharge signal EQ 0 is at an H level (equal to the level of the power supply voltage V cc ). Moreover, as shown in FIG. 10, a pair of bitlines BIT and /BIT on each column Col are connected to each other via an NMOS transistor N 12 , the ON/OFF states of which are controlled by the precharge signal EQ 0 . It is noted that the precharge signal EQ 0 is a control signal commonly used among the respective columns Col.
In the SRAM having such a configuration, during a precharge period before a write operation or a read operation is performed, the precharge signal EQ 0 rises to the H level, thereby connecting all the bitline pairs BIT and /BIT to the power supply V cc via the NMOS transistors N 1 of the bitline precharge circuits 1. However, since the ON state of the NMOS transistor N 1 cannot be maintained unless the potential difference between the gate G and the source S thereof is equal to or larger than a threshold voltage Vth, the potential on the bitline pair BIT and /BIT can only be charged up to a voltage which is lower than the power supply voltage V cc by the threshold voltage Vth and which becomes a precharge level. This NMOS transistor N 1 has a high threshold voltage Vth because of the influence of a substrate bias and the like. For example, assuming that the power supply voltage V cc is 4 V, the threshold voltage Vth becomes about 1.5 V. Thus, the precharge level becomes equal to about 2.5 V, which is an approximately intermediate voltage between the power supply voltage V cc of 4 V and the voltage of a ground GND of 0 V. Furthermore, when the precharge signal EQ 0 rises to the H level, a pair of bitlines BIT and /BIT on each column Col are connected to each other via the NMOS transistor N 12 so that the voltages or the precharge levels of the bitlines BIT and /BIT are equalized.
It is noted that the terms "power supply" and "ground" mean a pair of powers having such a relationship that the potential difference obtained by subtracting the ground voltage from the power supply voltage always becomes positive.
When the precharging of all the bitlines BIT and /BIT is completed in the above-described manner, a row is selected by activating any of the word lines WL (setting the word line WL at the H level, for example) and at the same time, a column Col is selected by setting any of the column select signals Y at the H level, thereby writing the data input to a pair of data lines D 1 and /D 1 or D 2 and /D 2 to the memory cell MRC on the selected row via the pair of bitlines BIT and /BIT on the selected column Col or outputting the data read out from the memory cell MRC through the pair of data lines D 1 and /D 1 or D 2 and /D 2 via the pair of bitlines BIT and /BIT.
On the other hand, if any of the word lines WL is activated during such a write operation or read operation, the memory cells MRC on all the columns Col which are disposed on the row corresponding to the activated word line WL are connected to the associated bitline pairs BIT and /BIT. Thus, if data which has been written or read during a previous write or read operation remains on these bitlines BIT and /BIT, then it takes a long time to read out the data stored in the memory cells MRC, or in some cases, the data may be possibly destroyed. Thus, before the write operation or the read operation is performed, all the bitlines BIT and /BIT are required to be precharged to the precharge level intermediate between the power supply voltage V cc and the ground voltage GND by using the bitline precharge circuits 1.
However, as shown in FIG. 10, a parasitic capacitance C is generated between the bitline /BIT 1 on the first column Col 1 and the bitline BIT 2 on the second column Col 2 which are adjacent to each other, for example. Thus, when the potential of the bitline /BIT 1 on the selected column Col 1 is abruptly varied by the input of data during a write operation, the precharge level on the non-selected bitline BIT 2 adjacent to the bit-line /BIT 1 is sometimes varied considerably, owing to a coupling (or an electrostatic induction) caused by the parasitic capacitance C. As the gap between adjacent bitlines BIT and /BIT becomes finer for fulfilling the requirements of downsizing a chip and increasing the storage capacity, the parasitic capacitance C generated therebetween increases correspondingly. As a result, the influence of the coupling is also increased. However, during a read operation, since the potential on the bitline BIT 1 is slightly varied, the influence of the coupling is relatively small.
In this case, if a memory cell MRC is of a C-MOS (complementary MOS) type, a bitline pair BIT and /BIT can be rapidly charged from such a memory cell MRC. Thus, the potential variation on a non-selected bitline BIT or /BIT resulting from the coupling caused by the parasitic capacitance C is substantially negligible. However, in the SRAM, in order to downsize a chip and improve the response characteristics thereof, a memory cell MRC of a high-resistance pull-up type or a high-resistance pull-down type is often used.
As shown in FIG. 12, a high-resistance pull-up type memory cell MRC includes two NMOS transistors N 21 , and N 22 . The drains D of the NMOS transistors N 21 and N 22 are connected to a power supply V cc via high resistances R 1 and R 2 , respectively. The sources S of the NMOS transistors N 21 and N 22 are connected to a ground GND. And the gates G of the NMOS transistors N 21 and N 22 are connected to the drains D of the other NMOS transistors N 22 and N 21 , respectively. The drains D of these NMOS transistors N 21 and N 22 are also connected to a pair of bitlines BIT and /BIT via NMOS transistors N 23 and N 24 or switching elements (the gates of which are connected to a word line WL), respectively. Thus, in this high-resistance pull-up type memory cell MRC, in the situation where the word line WL rises to the H level and whereby the NMOS transistors N 23 and N 24 are turned ON, if the potential on a bitline BIT is too low, then it takes a long time to charge the bitline BIT from the power supply V cc via the high resistance R 1 , even when the drain D of the NMOS transistor N 21 holds an H level state, for example. As a result, in the meantime, the potential of the gate G of the NMOS transistor N 22 may become low so that the NMOS transistor N 22 may be inverted from ON into OFF. Consequently, the data stored in the NMOS transistor N 22 is possibly destroyed. In other words, in the case of using such a high-resistance pull-up type memory cell MRC, if the potential on a non-selected bitline BIT or /BIT becomes low because of the coupling caused by the parasitic capacitance C, then the data stored therein is more likely to be destroyed.
In the configuration shown in FIG. 10, assuming that the potential variation on a selected bitline /BIT 1 is denoted by ΔVb1 and the parasitic grounded capacitance of the bitline BIT 2 adjacent to the bitline /BIT 1 is denoted by Cb2 (C is a parasitic capacitance therebetween), the potential variation ΔVb2 on the bitline BIT 2 can be represented as:
ΔVb2=ΔVb1·C/Cb2
In addition, assuming that the inversion potential of the high-resistance pull-up type memory cell MRC shown in FIG. 12 is denoted by Vm, the potential V on the adjacent non-selected bitline BIT 2 is required to satisfy the following relationship:
V>Vm+ΔVb2
Thus, during a write operation, when the word line WL 1 and the column select signal Y 1 rise to the H level and the input of data to the bitline /BIT 1 largely lowers the potential on the bitline /BIT 1 , for example, the potential V on the non-selected bitline BIT 2 adjacent to the bitline /BIT 1 is also lowered because of the coupling. Thus, if the potential V on the bitline BIT 2 becomes equal to or lower than Vm+AVb2, then the data stored in the memory cell MRC 3 is destroyed.
For example, assume a case shown in FIG. 13. As shown in FIG. 13, when the precharging is completed at a time t 11 by the fall of the precharge signal EQ 0 to the L level (i.e., the voltage level of the ground GND=0 V), the potential on a selected bitline pair BIT 1 and /BIT 1 has reached a normal precharge level or the voltage V 2 (about 2.4 V), whereas the potential on a nonselected bitline pair BIT 2 and /BIT 2 has reached only the voltage V 1 (about 2.25 V) lower than the voltage V 2 because of the influence of the previous access. When the word line WL 1 rises to the H level at a time t 12 , the potential on one /BIT 1 of the selected bitline pair once increases because of the influence of the previous access and then decreases considerably to the vicinity of 0 V.
In such a case, the potential on one BIT 2 of the non-selected bitline pair which is adjacent to the bitline /BIT 1 also increases slightly once, and then decreases considerably. Consequently, at a time t 13 , the voltage levels at internal nodes ND 1 and ND 2 of the memory cell MRC 3 are inverted so that the data stored therein is destroyed.
On the other hand, a high-resistance pull-down type memory cell MRC includes two PMOS transistors (or P-channel MOSFETs) P 21 and P 22 , as shown in FIG. 14. The sources S of the PMOS transistors P 21 and P 22 are connected to a power supply V cc . The drains D of the PMOS transistors P 21 and P 22 are connected to a ground GND via high resistances R 1 and R 2 , respectively. And the gates G of the PMOS transistors P 21 and P 22 are connected to the drains D of the other PMOS transistors P 22 and P 21 , respectively. The drains D of these PMOS transistors P 21 and P 22 are also connected to bitlines BIT and /BIT via NMOS transistors N 23 and N 24 (the gates of which are connected to a word line WL), respectively. Thus, in this high-resistance pull-down type memory cell MRC, in the situation where the word line WL rises to the H level and whereby the NMOS transistors N 23 and N 24 are turned ON, if the potential on a bitline BIT is too high, then it takes a long time to discharge from the bitline BIT to the ground GND via the high resistance R 1 , even when the drain D of the PMOS transistor P 21 holds an L level state, for example. As a result, in the meantime, the potential on the gate G of the PMOS transistor P 22 may increase so that the PMOS transistor P 22 may be inverted from ON into OFF. Consequently, the data stored in the PMOS transistor P 22 is possibly destroyed. In other words, in the case of using such a high-resistance pull-down type memory cell MRC, if the potential on a non-selected bitline BIT or /BIT increases because of the coupling caused by the parasitic capacitance C, then the data stored therein is more likely to be destroyed.
Thus, in a conventional SRAM, if the potential on a selected bitline pair BIT and /BIT is largely varied by the input of data, then the potential precharged on an adjacent bitline pair BIT and /BIT is also varied because of the coupling caused by the parasitic capacitance C. Consequently, such an SRAM has problem in that the data stored in a non-selected memory cell MRC on the adjacent bitline pair BIT and /BIT is possibly destroyed.
In order to solve such a problem, it has conventionally been proposed to provide electrostatic shielding wires, to which the ground GND is always connected, between two adjacent bitlines BIT and /BIT. However, in order to provide such electrostatic shielding wires, the gap between adjacently disposed bitlines BIT and /BIT must be widened. As a result, a new problem is caused in that it becomes difficult to fulfill the requirement of downsizing a chip.
SUMMARY OF THE INVENTION
According to the present invention, a bitline precharge circuit for a semiconductor memory device is provided. The semiconductor memory device includes: a plurality of word lines arranged in a row direction; a plurality of bitlines forming a plurality of bitline pairs which are arranged in a column direction; and a plurality of memory cells connected between each of the plurality of bitline pairs via a plurality of switching elements, the switching elements being controlled by respectively different ones of the word lines. The bitline precharge circuit charges a potential on all of the bitlines to a precharge level which is approximately intermediate between a power supply voltage and a ground voltage before a write operation or a read operation is performed. The bitline precharge circuit is characterized by including a write precharge circuit for further varying the potential on the bitlines, which has been charged to the precharge level, by a predetermined level before the write operation is performed.
In one embodiment, the write precharge circuit further varies the potential on the bitlines, which has been charged to the precharge level, to a higher potential by the predetermined level.
In another embodiment, the write precharge circuit further varies the potential on the bitlines, which has been charged to the precharge level, to a lower potential by the predetermined level.
In still another embodiment, each of the memory cell is an SRAM memory cell of a high-resistance pull-up type which includes a first and a second NMOS transistor and in which drains of the first and second NMOS transistors are connected to a power supply via respective high resistances, sources of the first and second NMOS transistors are grounded and gates of the first and second NMOS transistors are connected to the drain of the second NMOS transistor and the drain of the first NMOS transistor, respectively.
In still another embodiment, each of the memory cell is an SRAM memory cell of a high-resistance pull-down type which includes a first and a second PMOS transistor and in which sources of the first and second PMOS transistors are connected to a power supply, drains of the first and second PMOS transistors are grounded via respective high resistances and gates of the first and second PMOS transistors are connected to the drain of the second PMOS transistor and the drain of the first PMOS transistor, respectively.
In still another embodiment, the precharge circuit includes an NMOS transistor associated with each of the bitlines and is configured such that a drain of the NMOS transistor is connected to a power supply, a source of the NMOS transistor is connected to the associated bitline and a precharge signal rising to an H level during a precharge period is input to a gate of the NMOS transistor, and the write precharge circuit includes a PMOS transistor associated with each of the bitlines and is configured such that a source of the PMOS transistor is connected to a power supply, a drain of the PMOS transistor is connected to the associated bitline and a write precharge signal, falling to an L level during a predetermined period immediately before the write operation and after the precharge period, is input to a gate of the PMOS transistor.
In still another embodiment, the PMOS transistor of the write precharge circuit is constituted by a TFT.
In still another embodiment, the precharge circuit includes a first NMOS transistor associated with each of the bitlines and is configured such that a drain of the first NMOS transistor is connected to a power supply, a source of the first NMOS transistor is connected to the associated bitline and a precharge signal rising to an H level during a precharge period is input to a gate of the first NMOS transistor, and the write precharge circuit includes a second NMOS transistor, which is associated with each of the bitlines and has a threshold voltage lower than a threshold voltage of the first NMOS transistor, and is configured such that a drain of the second NMOS transistor is connected to a power supply, a source of the second NMOS transistor is connected to the associated bitline and a write precharge signal, rising to the H level during a predetermined period immediately before the write operation and after the precharge period, is input to a gate of the second NMOS transistor.
In still another embodiment, the precharge circuit includes a PMOS transistor associated with each of the bitlines and is configured such that a source of the PMOS transistor is connected to the associated bitline, a drain of the PMOS transistor is grounded and a precharge signal falling to an L level during a precharge period is input to a gate of the PMOS transistor, and the write precharge circuit includes an NMOS transistor associated with each of the bitlines and is configured such that a drain of the NMOS transistor is connected to the associated bitline, a source of the NMOS transistor is grounded and a write precharge signal, rising to the H level during a predetermined period immediately before the write operation and after the precharge period, is input to a gate of the NMOS transistor.
In still another embodiment, the precharge circuit includes a first PMOS transistor associated with each of the bitlines and is configured such that a source of the first PMOS transistor is connected to the associated bitline, a drain of the first PMOS transistor is grounded, and a precharge signal falling to an L level during a precharge period is input to a gate of the first PMOS transistor, and the write precharge circuit includes a second PMOS transistor, which is associated with each of the bitlines and has a threshold voltage lower than a threshold voltage of the first PMOS transistor, and is configured such that a source of the second PMOS transistor is connected to the associated bitline, a drain of the second PMOS transistor is grounded, and a write precharge signal, falling to the L level during a predetermined period immediately before the write operation and after the precharge period, is input to a gate of the second PMOS transistor.
According to the present invention, during a write operation, a write precharge circuit varies the potential on a bitline into a level which has further been varied from the precharge level by a predetermined voltage. Thus, even in the case where the potential on a non-selected bitline adjacent to a bitline selected during the write operation has been varied because of an electrostatic induction, the potential variation on the non-selected bitline can be compensated for beforehand by the write precharge circuit, thereby preventing the data stored in a memory cell connected to the adjacent nonselected bitline from being destroyed.
In addition, according to the present invention, the write precharge circuit further varies the potential on a bitline into a level higher than the precharge level by a predetermined voltage. Thus, even when a memory cell of such a type that the data stored therein is likely to be destroyed by the decrease of the bitline potential is used, the data stored in a non-selected memory cell can be protected.
Moreover, according to the present invention, the write precharge circuit further varies the potential on a bitline into a level lower than the precharge level by a predetermined voltage. Thus, even when a memory cell of such a type that the data stored therein is likely to be destroyed by the increase of the bitline potential is used, the data stored in a non-selected memory cell can be protected.
Furthermore, according to the present invention, the write precharge circuit further varies the potential on a bitline into a level higher than the precharge level by a predetermined vol age. Thus, even when an SRAM memory cell of such a high-resistance pull-up type that the data stored therein is likely to be destroyed by the decrease of the bitline potential is used, the data stored in a non-selected memory cell can be protected.
Furthermore, according to the present invention, the write precharge circuit further varies the potential on a bitline into a level lower than the precharge level by a predetermined voltage. Thus, even when an SRAM cell of such a high-resistance pull-down type that the data stored therein is likely to be destroyed by the increase of the bitline potential is used, the data stored in a non-selected memory cell can be protected.
Furthermore, according to the present invention, when a precharge signal rises to the H level during a precharge period, the NMOS transistor of a precharge circuit is activated, thereby charging an associated bitline up to a voltage lower than the power supply voltage by a threshold voltage (i.e., the precharge level). In the case of performing a write operation, a write precharge signal holds an L level for a predetermined period thereafter, thereby activating the PMOS transistor of a write precharge circuit and allowing the bitline to be charged up to the power supply voltage. Thus, this bitline potential can be varied into a higher potential by a predetermined level to be determined by the predetermined period during which the write precharge signal holds the L level.
Furthermore, according to the present invention, a TFT (thin film transistor) is formed on the NMOS transistor of the precharge circuit by depositing a poly-silicon thin film or the like thereon, thereby forming a PMOS transistor for a write precharge circuit. Thus, even if such write precharge circuits are provided, it is possible to prevent the layout area from being increased.
Furthermore, according to the present invention, during the precharge period, the first NMOS transistor of a precharge circuit is activated, thereby charging an associated bitline up to a voltage lower than the power supply voltage by a first threshold voltage (i.e., the precharge level). In the case of performing a write operation, a second NMOS transistor of a write precharge circuit remains active for a predetermined period thereafter, thereby charging the bitline up to a voltage lower than the power supply voltage by a second threshold voltage. Since the second threshold voltage is lower than the first threshold voltage, the potential on the bitline can be varied into a higher potential by a difference between the first and the second threshold voltages. In addition, since the first and the second NMOS transistors can be formed on the same well, it is possible to prevent the layout area from being increased because of the division of the well.
Furthermore, according to the present invention, when a precharge signal falls to the L level during a precharge period, the PMOS transistor of a precharge circuit is activated, thereby discharging an associated bitline to a voltage higher than the ground voltage by a threshold voltage (i.e., the precharge level). In the case of performing a write operation, a write precharge signal holds an H level for a predetermined period thereafter, thereby activating the NMOS transistor of a write precharge circuit and allowing the bitline to be discharged to the ground voltage. Thus, this bitline potential can be varied into a lower potential by a predetermined level to be determined by the predetermined period during which the write precharge signal holds the H level.
Furthermore, according to the present invention, during the precharge period, the first PMOS transistor of a precharge circuit is activated, thereby discharging the associated bitline up to a voltage higher than the ground voltage by a first threshold voltage (i.e., the precharge level). In the case of performing a write operation, a second PMOS transistor of a write precharge circuit remains active for a predetermined period thereafter, thereby discharging the bitline up to a voltage higher than the ground voltage by a second threshold voltage. Thus, since the second threshold voltage is lower than the first threshold voltage, the potential on the bitline can be varied into a lower potential by a difference between the first and the second threshold voltages. In addition, since the first and the second PMOS transistors can be formed on the same well, it is possible to prevent the layout area from being increased because of the division of the well.
Thus, the invention described herein makes possible the advantage of providing a bitline precharge circuit for a semiconductor memory device which can prevent the data stored in a memory cell on a non-selected bitline from being destroyed owing to the interference of a selected bitline adjacent to the non-selected bitline by making a write precharge circuit further vary the potential level on a bitline, which has been precharged by a precharge circuit, by a predetermined amount during a write operation without any need for providing electrostatic shielding wires.
This and other advantages of the present invention will become apparent to those skilled in the art upon reading and understanding the following detailed description with reference to the accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram showing a configuration of an SRAM in the first example of the present invention.
FIG. 2 is a circuit diagram showing a configuration of a bitline precharge circuit in the first example of the present invention.
FIG. 3 is a circuit diagram showing a specific exemplary configuration of the bitline precharge circuit in the first example of the present invention.
FIG. 4 is a timing diagram showing the relationship between a precharge signal EQ 0 and a write precharge signal /WPR in the first example of the present invention.
FIG. 5 is a timing diagram illustrating a write operation of the SRAM in the first example of the present invention.
FIG. 6 is a circuit diagram showing another specific exemplary configuration of the bitline precharge circuit in the first example of the present invention.
FIG. 7 is a circuit diagram showing still another specific exemplary configuration of the bitline precharge circuit in the first example of the present invention.
FIG. 8 is a circuit diagram showing a specific exemplary configuration of a bitline precharge circuit in the second example of the present invention.
FIG. 9 is a circuit diagram showing another specific exemplary configuration of the bitline precharge circuit in the second example of the present invention.
FIG. 10 is a block diagram showing a configuration of an SRAM in a conventional example.
FIG. 11 is a circuit diagram showing an exemplary configuration of a bitline precharge circuit in the conventional example.
FIG. 12 is a circuit diagram showing an exemplary configuration of a conventional high-resistance pull-up type memory cell.
FIG. 13 is a timing diagram illustrating a write operation of the SRAM in the conventional example.
FIG. 14 is a circuit diagram showing an exemplary configuration of a conventional high-resistance pull-down type memory cell.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Hereinafter, the embodiments of the present invention will be described with reference to the accompanying drawings.
EXAMPLE 1
FIGS. 1 to 7 show a first example of the present invention. It is noted that the components having the same functions as the components of the conventional example shown in FIGS. 10 to 14 will be identified by the same reference numerals.
In this first example, a bitline precharge circuit for an SRAM including memory cells of the high-resistance pull-up type shown in FIG. 12 will be described. In this SRAM, as shown in FIG. 1, multiple word lines WL, multiple pairs of bitlines BIT and /BIT and multiple memory cells MRC are disposed and interconnected in the same way as in the conventional example shown in FIG. 10. Also, in the same way as in the conventional example shown in FIG. 10, a bitline pair BIT 1 and /BIT 1 on the first column Col 1 and a bitline pair BIT 2 and /BIT 2 on the second column Col 2 are connected to pairs of data lines D 1 & /D 1 and D 2 & /D 2 , respectively, via the associated column selector circuits 3 and the bitlines of each pair are connected to each other via an NMOS transistor N 12 . Furthermore, a parasitic capacitance C is similarly generated between adjacent bitlines BIT and /BIT, e.g., between bitlines /BIT 1 and BIT 2 .
The pair of bitlines BIT 1 and /BIT 1 on the first column Col 1 are connected to a power supply V cc via the associated bitline precharge circuits 1 on the first column Col 1 , while the pair of bitlines BIT 2 and /BIT 2 on the second column Col 2 are connected to the power supply V cc via the associated bitline precharge circuits 1 on the second column Col 2 . In each bitline precharge circuit 1, the associated bitline BIT or /BIT is connected to the power supply V cc via a precharge circuit 1a and a write precharge circuit 1b, as shown in FIG. 2.
The precharge circuit 1a has the same configuration as that of the conventional bitline precharge circuit 1 shown in FIG. 11. That is to say, the precharge circuit 1a is implemented as a single NMOS transistor N 1 in which the drain D thereof is connected to the power supply V cc , the source S thereof is connected to the associated bitline BIT or /BIT and a precharge signal EQ 0 is input to the gate G thereof. The write precharge circuit 1b is a circuit which can charge the associated bitline BIT or /BIT to a potential higher than that of the precharge circuit la when a write precharge signal WPR is activated. The write precharge circuit 1b may be implemented as a single PMOS transistor P 2 shown in FIG. 3 in which the source S thereof is connected to the power supply V cc , the drain D thereof is connected to the associated bitline BIT or /BIT and a write precharge signal /WPR is input to the gate G thereof. It is assumed that the exemplary bitline precharge circuit 1 shown in FIG. 1 includes the write precharge circuit 1b shown in FIG. 3.
A precharge signal EQ 0 is a control signal which holds an H level (or remains active) during a precharge period between times t 0 and t 1 before a write operation or a read operation is performed, as shown in FIG. 4. When the precharge signal EQ 0 rises to the H level, the NMOS transistors N 1 constituting the precharge circuits 1a in respective bitline precharge circuit 1 are turned ON so that all the bitlines BIT and /BIT shown in FIG. 1 are connected to the power supply V cc . It is noted that, in this case, the potential on the bitlines BIT and /BIT is charged to the precharge level lower than the power supply voltage V cc by the threshold voltage Vth of the NMOS transistor N 1 , as described above. Also, when the precharge signal EQ 0 rises to the H level, the bitlines BIT and /BIT of each pair on each column Col are connected to each other via an NMOS transistor N 12 so that the voltages at the precharge level are equalized.
The write precharge signal /WPR used for the write precharge circuit 1b shown in FIG. 3 is a control signal which holds an L level (or remains active) between the time t 1 when the precharge signal EQ 0 falls to the L level and a time t 2 which is later than the time t 1 by a predetermined time period and immediately before a write operation is started, only in the case of the write operation as shown in FIG. 4. Such a write precharge signal /WPR can be produced by inputting a timing signal TM and a write enable signal WE, which holds the H level for a predetermined period after the fall of the precharge signal EQ 0 to the L level, to a NAND gate 2 as shown in FIG. 1. That is to say, since the write enable signal WE rises to the H level (or activated) only during the write operation, the write precharge signal /WPR remains at the H level (inactive) even after the precharge period has passed in the case of a read operation. Conversely, in the case of the write operation, the write precharge signal /WPR holds the L level for a predetermined period after the precharge period has passed.
When the write precharge signal /WPR falls to the L level, the PMOS transistors P 2 constituting the write precharge circuits 1b in the respective bitline precharge circuits 1 are turned ON, thereby connecting all the bitlines BIT and /BIT shown in FIG. 1 to the power supply V cc . Furthermore, in this case, since the PMOS transistors P 2 can hold the ON state irrespective of the potential on the bitlines BIT and /BIT, the potential on the bitlines BIT and /BIT can be charged up to the power supply voltage V cc . However, it takes a rather long time to charge the bitlines BIT and /BIT in accordance with the current drivability of the PMOS transistors P 2 and the like. Thus, by adjusting the length of the predetermined period during which the write precharge signal /WPR holds the L level, the potential on the bitlines BIT and /BIT is charged to a voltage which is surely higher than the voltage charged during the precharge period but sufficiently lower than the power supply voltage V cc . As a result, the predetermined period during which the write precharge signal /WPR holds the L level becomes a period sufficiently longer than the precharge period in actuality.
Under the above-described configuration, in the SRAM of the first example, the bitline precharge circuits 1 turn ON only the NMOS transistors N 1 of the respective precharge circuits 1a, thereby charging the bitlines BIT and /BIT to a normal precharge level during the read operation. However, since the potential variation on the bitlines BIT and /BIT is relatively moderate during this read operation, adjacent bit-lines BIT and /BIT are hardly affected by the coupling caused by a parasitic capacitance C. Consequently, in this case, the data stored in a memory cell MRC can be read out rapidly and surely in the same way as in a conventional example.
On the other hand, in the case of a write operation, assuming that a word line WL 1 and a column select signal Y 1 rise to the H level, for example, the potential of a bitline /BIT 1 on a selected column Col 1 is varied abruptly and considerably so that an adjacent bitline BIT 2 on a non-selected column Col 2 is significantly affected by the coupling. Furthermore, since a non-selected memory cell MRC 3 connected to a pair of bitlines BIT 2 and /BIT 2 on the column Col 2 is of a high-resistance pull-up type shown in FIG. 12, if the potential on the bitline BIT 2 falls because of the coupling, then the data stored in the memory cell MRC 3 is more likely to be destroyed. However, the bitline precharge circuit 1 of the first example turns ON the NMOS transistor N 1 of each precharge circuit 1a before the write operation is started, charges each pair of bitlines BIT and /BIT to the precharge level and then turns ON the PMOS transistor P 2 of each write precharge circuit 1b, thereby varying the potential on each pair of bitlines BIT and /BIT into a voltage higher than the precharge level by a predetermined level. Thus, even when the potential on the bitline BIT 2 on the column Col 2 becomes low because of the coupling caused by the parasitic capacitance C, this potential variation is caused at a voltage level higher than a conventional level so that it is possible to prevent the data stored in a non-selected memory cell MRC 3 from being destroyed.
For example, assume a case shown in FIG. 5. As shown in FIG. 5, when the precharging is completed at the time t 1 by the fall of the precharge signal EQ 0 to the L level, the potential on the pair of bitlines BIT 1 and /BIT 1 has reached a normal precharge level or the voltage V 2 (about 2.4 V), whereas the potential on the pair of bitlines BIT 2 and /BIT 2 has reached only the voltage V 1 (about 2.25 V) lower than the voltage V 2 because of the influence of the previous access. Even in such a case, since the write precharge signal /WPR falls to the L level during a short predetermined time between the times t 1 and t 2 , the potential on the pair of bitlines BIT 2 and /BIT 2 can be charged by the write precharge circuit 1b to the voltage V 2 (about 2.4 V). Thus, even if the word line WL 1 rises to the H level at a time t 3 , the potential on the bitline /BIT 1 once increases because of the influence of the previous access and then decreases considerably to the vicinity of 0 V and the potential on the bitline BIT 2 also increases slightly once and then decreases considerably, the voltage levels at internal nodes ND 1 and ND 2 of the memory cell MRC 3 are not inverted. As a result, even if the write operation is completed at a time t 4 when the word line WL 1 falls to the L level and the precharge signal EQ 0 rises again to the H level, the data stored in the memory cell MRC 3 is not destroyed.
It is noted that the write precharge circuit 1b of each bitline precharge circuit 1 is exemplified as a PMOS transistor P 2 shown in FIG. 3 in the foregoing description. The PMOS transistor P 2 is generally formed on the same semiconductor substrate on which the NMOS transistor N 1 constituting each precharge circuit 1a is formed. However, as shown in FIG. 6, the PMOS transistor P 2 may be implemented as a P-channel TFT. The TFT is a MOSFET formed by using a poly-silicon thin film or the like to be deposited as an uppermost layer on a semiconductor substrate or the like. Thus, the TFT may be formed so as to be overlapped over the uppermost layer of the NMOS transistor N 1 via an insulating layer so that it is possible to prevent the layout area from being increased even if the write precharge circuits 1b are provided.
Furthermore, the write precharge circuit 1b may also be implemented as an NMOS transistor N 2 having a threshold voltage Vth 2 lower than the threshold voltage Vth 1 of the NMOS transistor N 1 constituting the precharge circuit 1a as shown in FIG. 7. The NMOS transistor N 2 is configured such that the drain D thereof is connected to the power supply V cc , the source C is connected to the associated bitline BIT or /BIT and an "H-active" write precharge signal WPR (an "H-active" signal is regarded as having been activated when it is at an H level in accordance with a positive logic) is input to the gate G thereof. When the precharge signal EQ 0 rises to the H level, the bitline precharge circuit 1 charges an associated bitline BIT or /BIT to a voltage lower than the power supply voltage V cc by the threshold voltage Vth 1 via the NMOS transistor N 1 of the precharge circuit 1a. When the write precharge signal WPR rises to the H level (or activated) during the write operation, the bitline precharge circuit 1 charges the bitline BIT or /BIT to a voltage lower than the power supply voltage V cc by the threshold voltage Vth 2 via the NMOS transistor N 2 of the write precharge circuit 1b. Since the threshold voltage Vth 2 is lower than the threshold voltage Vth 1 , the voltage charged by the write precharge circuit 1b becomes higher than the voltage charged by the precharge circuit 1a. Thus, the NMOS transistor N 2 can also function in the same way as the write precharge circuit 1b shown in FIGS. 3 and 6. Furthermore, when the write precharge circuit 1b is implemented as such a NMOS transistor N 2 , the NMOS transistor N 2 has the same channel type as that of the NMOS transistor N 1 of the precharge circuit 1a. Thus, since these NMOS transistors N 1 and N 2 can be formed on the same well on a semiconductor substrate, it is possible to prevent the layout area from being increased because of the division of the well.
EXAMPLE 2
FIGS. 8 and 9 illustrate the second example of the present invention. In FIGS. 8 and 9, the components having the same functions as those of the components of the first example shown in FIGS. 1 to 7 will be identified by the same reference numerals and the description thereof will be omitted herein.
In this second example, a bitline precharge circuit for an SRAM including memory cells of a high-resistance pull-down type shown in FIG. 14 will be described. The SRAM of the second example has substantially the same configuration as that of the SRAM of the first example shown in FIG. 1 but is different from the SRAM of the first example in that the bitlines BIT and /BIT are connected to a ground GND via the respective bitline precharge circuits 1. That is to say, in this second example, each bitline precharge circuit 1 is configured such that the associated bitline pair BIT and /BIT are connected to the ground GND via a precharge circuit 1a and a write precharge circuit 1b, respectively.
The precharge circuit 1a is implemented as a single PMOS transistor P 3 in which the source S thereof is connected to the associated bitline BIT or /BIT, the drain D thereof is connected to the ground GND, and an "L-active" precharge signal /EQ 0 (an "L-active" signal is regarded as having been activated when it is at an L level in accordance with a negative logic) is input to the gate G thereof. Thus, when the precharge signal /EQ 0 falls to the L level (or activated) during the precharge period before a write operation or a read operation is performed, the PMOS transistor P 3 is turned ON so that the associated bitline BIT or /BIT is connected to the ground GND. It is noted that, in this case, the potential on the bitline BIT or /BIT is discharged to the precharge level higher than the voltage of the ground GND by the threshold voltage Vth of the PMOS transistor P 3 . Also, when the precharge signal /EQ 0 falls to the L level, each pair of bitlines BIT and /BIT on each column Col are connected to each other via a MOS transistor (not shown) so that the voltages on these bitlines are equalized.
The write precharge circuit 1b is a circuit which can charge the associated bitline BIT or /BIT to a voltage lower than that of the precharge circuit 1a when a write precharge signal WPR is activated, and may be implemented as a single NMOS transistor N 4 as shown in FIG. 8 in which the drain D thereof is connected to the associated bitline BIT or /BIT, the source S thereof is connected to the ground GND and an "H-active" write precharge signal WPR is input to the gate G thereof.
Thus, in the case of the write operation, when the write precharge signal WPR rises to the H level (or activated) during the predetermined period after the precharge signal /EQ 0 has risen to the H level (or deactivated) and before the write operation is performed, the NMOS transistor N 4 is turned ON so that the associated bitline BIT or /BIT is connected to the ground GND. Furthermore, in this case, since the NMOS transistor N 4 can hold the ON state irrespective of the potential on the bitlines BIT and /BIT, the potential on the bitlines BIT and /BIT can be discharged down to the voltage of the ground GND.
However, it takes a rather long time to discharge the bitlines BIT and /BIT in accordance with the current drivability of the NMOS transistor N 4 and the like. Thus, by adjusting the length of the predetermined period during which the write precharge signal WPR holds the H level, the potential on the bitlines BIT and /BIT is charged to a voltage which is surely lower than the voltage charged during the precharge period but sufficiently higher than the voltage of the ground GND.
Under the above-described configuration, in the SRAM of the second example, the bitline precharge circuit 1 turns ON only the PMOS transistor P 3 of the precharge circuit 1a, thereby charging the bitlines BIT and /BIT to a normal precharge level during a read operation. In addition, since the bitlines BIT and /BIT are not greatly affected by the coupling caused by the parasitic capacitance C, the data stored in a memory cell MRC can be read out rapidly and surely.
On the other hand, in the case of a write operation, the potential on an adjacent non-selected bitline BIT or /BIT is varied because of the coupling caused by the parasitic capacitance C. Furthermore, since the memory cell MRC of this example is of a high-resistance pull-down type shown in FIG. 14, if the potential on the non-selected bitline BIT or /BIT increases because of the coupling, then the data stored in the memory cell MRC on the non-selected bitline BIT or /BIT is more likely to be destroyed. However, the bitline precharge circuit 1 of the second example turns ON the PMOS transistor P 3 of the precharge circuit 1a before the write operation is started, charges the associated bitline BIT or /BIT to the precharge level and then turns ON the NMOS transistor N 4 of the write precharge circuit 1b, thereby further varying the potential on the bitline BIT or /BIT into a voltage lower than the precharge level by a predetermined level. Thus, even when the potential on the adjacent non-selected bitline BIT or /BIT increases because of the coupling caused by the parasitic capacitance C, this potential variation is caused at a voltage level lower than a conventional level so that it is possible to prevent the data stored in a non-selected memory cell MRC from being destroyed.
It is noted that the write precharge circuit 1b of the bitline precharge circuit 1 is exemplified as an NMOS transistor N 4 shown in FIG. 8 in the foregoing description. However, as shown in FIG. 9, the write precharge circuit 1b may also be implemented as a PMOS transistor P 4 having a threshold voltage Vth 4 lower than the threshold voltage Vth 3 of the PMOS transistor P 3 of the precharge circuit 1a. The PMOS transistor P 4 is configured such that the source S thereof is connected to the associated bitline BIT or /BIT, the drain D is connected to the ground GND and an "L-active" write precharge signal /WPR is input to the gate G thereof.
When the precharge signal /EQ 0 falls to the L level, the bitline precharge circuit 1 discharges the associated bitline BIT or /BIT to a voltage higher than the voltage of the ground GND by the threshold voltage Vth 3 via the PMOS transistor P 3 of the precharge circuit 1a. When the write precharge signal /WPR falls to the L level (or activated) during the write operation, the bitline precharge circuit 1 discharges the bitline BIT or /BIT to a voltage higher than the voltage of the ground GND by the threshold voltage Vth 4 via the PMOS transistor P 4 of the write precharge circuit 1b. Since the threshold voltage Vth 4 is lower than the threshold voltage Vth 3 , the voltage charged by the write precharge circuit 1b becomes lower than the voltage charged by the precharge circuit 1a. Thus, the PMOS transistor P 4 can also function in the same way as the write precharge circuit 1b shown in FIG. 8. Furthermore, when the write precharge circuit 1b is implemented as such a PMOS transistor P 4 , the PMOS transistor P 4 has the same channel type as that of the PMOS transistor P 3 of the precharge circuit 1a. Thus, since these PMOS transistors P 3 and P 4 can be formed on the same well on a semiconductor substrate, it is possible to prevent the layout area from being increased because of the division of the well.
Moreover, in the second example, the NMOS transistor N 4 of the write precharge circuit 1b shown in FIG. 8 may also be implemented as a TFT.
In the first and the second examples, the present invention has been described as being implemented as a bitline precharge circuit 1 for an SRAM. However, the present invention is also applicable to bitline precharge circuits for various other semiconductor memory devices having similar problems to be solved.
As is apparent from the foregoing description, in the bitline precharge circuit for a semiconductor memory device according to the present invention, even in the case where the potential on a non-selected bitline has been varied because of an electrostatic induction from a bitline selected during a write operation, the potential variation can be compensated for beforehand by a write precharge circuit, thereby preventing the data stored in a memory cell connected to the non-selected bitline from being destroyed.
In this case, if an SRAM memory cell of such a high-resistance pull-up type is used in which the data stored therein is likely to be destroyed by the decrease of the bitline potential, the write precharge circuit further varies the potential on the bitline into a level higher than the precharge level by a predetermined level, thereby offsetting the potential variation of the bitline to a lower voltage and protecting the data stored in a non-selected memory cell. On the other hand, if an SRAM memory cell of such a high-resistance pull-down type is used in which the data stored therein is likely to be destroyed by the increase of the bitline potential, the write precharge circuit further varies the potential on the bitline into a level lower than the precharge level by a predetermined level, thereby offsetting the potential variation of the bitline to a higher voltage and protecting the data stored in the non-selected memory cell.
Furthermore, if a PMOS transistor for a write precharge circuit is implemented as a TFT formed on the NMOS transistor of the precharge circuit, it is possible to prevent the layout area from being increased. Moreover, if the MOS transistor of the write precharge circuit has the same channel type as that of the MOS transistor of the precharge circuit, then these MOS transistors can be formed on the same well. Thus, it is possible to prevent the layout area from being increased because of the division of the well.
Various other modifications will be apparent to and can be readily made by those skilled in the art without departing from the scope and spirit of this invention. Accordingly, it is not intended that the scope of the claims appended hereto be limited to the description as set forth herein, but rather that the claims be broadly construed.
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According to the present invention, a bitline precharge circuit for a semiconductor memory device is provided. The semiconductor memory device includes: a plurality of word lines arranged in a row direction; a plurality of bitlines forming a plurality of bitline pairs arranged in a column direction; and a plurality of memory cells connected between each of the plurality of bitline pairs via a plurality of switching elements, the switching elements being controlled by respectively different ones of the word lines. The bitline precharge circuit charges a potential on all of the bitlines to a precharge level which is approximately intermediate between a power supply voltage and a ground voltage before a write operation or a read operation is performed and is characterized by including a write precharge circuit for further varying the potential on the bitlines, which has been charged to the precharge level, by a predetermined level before the write operation is performed.
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CROSS REFERENCED APPLICATIONS
[0001] This application claims benefits from provisional application No. 60/437,772 filed Jan. 3, 2003 and provisional application No. 60/503,126 filed Sep. 15, 2003, the complete disclosures of which are incorporated herein by reference.
FIELD OF INVENTION
[0002] This invention pertains to a training aid for improving the path of a golfers putting stroke and also for improving the ball contact made during the putting stroke. The training aids of the present invention may resemble a standard golf putter comprised of a shaft with a grip and a putter head. The putter head will unconventionally be allowed to rotate around the shaft in order to provide both visual and physical feedback regarding the quality of the putting stroke and ball contact.
BACKGROUND OF INVENTION
[0003] There are two critical components to a good golf-putting stroke. The first key to a good stroke is comprised of a repeatable back swing and forward swing that follows along an intended target line in a pendulum motion. Secondly, the putting stroke should ensure that the ball is struck with the center of the putter head to impart a consistent forward roll along the intended target line. Inconsistencies in either of those two key components can cause putts to travel off-line or to not travel the intended distance. These inconsistencies result in more missed putts and undesirably higher golf scores. This invention pertains to a golf putter with unique features that will improve a golfers ability to make a repeatable putting stroke by providing physical and visual feedback due to any inconsistencies to one or both of the key swing components during the stroke.
[0004] A wide variety of inventions and devices exist to help improve a golfer's putting stroke. U.S. Pat. No. 6,482,099 describes a laser alignment device that can be easily attached to a club or putter shaft. This laser device will emit a line of light on the ground creating a target line for the putter head to follow. While this line is useful for alignment purposes, it may encourage the golfer to rotate their head slightly and look in front of the ball during the putting stroke instead of keeping the eyes focused on the ball until it is struck. Not watching the ball as it is struck frequently results in putts that are miss-hit and not struck in the center of the putter head. These putts tend to stray off line and not travel the intended distance. In addition, since the laser device is attached to the shaft of the club, any inadvertent rotation of the shaft during the putting stroke will also rotate the alignment marking line that is transmitted on the ground. This alignment adjustment may not be easily perceivable to the user and putts may be missed if the putter head follows the altered alignment marking.
[0005] U.S. Pat. No. 6,458,039 describes a putting training device that consists of a curved track and an engagement feature on the bottom of a putter head that forces the putter head to follow the curved track during a putting stroke. The curved track lies relatively flat in the middle of the golfer's stance where the ball is placed prior to putting. The track gradually increases in height as it moves back and away from the golfer. This increase in height represents the pendulum motion a good putting stroke would follow. The features of this invention encourage a putting stroke that travels straight back and straight through along the target line and also encourage that the ball be struck in the center of the putter head, both of which are desirable results. However, this type of apparatus is a cumbersome device for a golfer to carry and use in different locations. In addition, this device may not be well suited for all different body types. For instance, a shorter golfer may not make a stroke with the same pendulum arc that a taller golfer may make. Using a track not fitted for your swing path or body type may begin to develop some uncomfortable aspects throughout the stroke by forcing your stroke along an unnatural path. This can affect the fluidity of the putting stroke. Therefore, it may be required that each curved track be custom fitted for each particular golfer body type which can be expensive for the consumer.
SUMMARY OF THE INVENTION
[0006] The present invention provides a golf putter that can be used both indoors on a carpet or floor and also outdoors on a golf putting green or similar surfaces by both left-handed and right-handed golfers. It is a further aspect of the invention that it may be used in all arenas either as a training aid or as a standard golf putter depending on how the various features of the invention are configured. If the putter is used as a training aid, it is an aspect of the invention to improve the path of a golfer's putting stroke. A good putting stroke is comprised of a repeatable back swing and a forward swing that follows an intended target path in a pendulum motion. To accomplish this intention, the putter head will unconventionally be allowed to rotate around the shaft in order to provide both visual and physical feedback regarding the quality of the putting stroke. If the putting stroke were to undesirably travel off line during the stroke, the putter head would rotate and the golfer will be able to visually see the rotation of the putter head and become aware of the poor putting stroke. Or, the rotation of the putter head would result in the ball being struck at some angle other than perpendicular to the intended target line, causing the ball to travel off the intended target line, which the golfer would visualize at impact.
[0007] As the golfers ability to make a repeatable straight-back, straight-through stroke improves, it may be desirable to add a feature to the putter head that makes the putter head more susceptible to small imperfections of the putting stroke to fine tune the golfers stroke even further. To accomplish this, it is a further optional aspect of the invention that an adjustable counterweight may be attached to or removed from the putter head as desired. The counterweight may be attached to the putter head on a “Y” shaped support device. In this configuration, the two tips of the fork of the “Y” shaped support would be attached to the two ends of the putter commonly referred to as the “toe” (end of the putter farthest from the golfer) and “heal” (end of the putter nearest the golfer). This method of attachment would allow the counterweight to be attached to the stem of the “Y” shaped support and be located directly behind the center of the length dimension of the putter head. The counterweight would ideally be allowed to slide closer to, or further away from the putter head along the stem of the “Y” shaped support as desired. Positioning the weight farther away from the putter head increases the length of the moment arm by which the counterweight can impart a rotational force on the putter head and cause the head to rotate around the shaft. A longer moment arm will impart more torque on the putter head with less force and would therefore increase the susceptibility of the putter head to rotation as a result of small imperfections of the putting stroke, such as an off-line stroke path. Conversely, locating the counterweight closer to the putter head will decrease the length of the moment arm thereby reducing the putter heads susceptibility to rotation from small imperfections of the putting stroke. It is a further aspect of the invention that heavier or lighter counterweights may be interchangeably utilized to meet a particular feel or susceptibility level as desired by the user.
[0008] It is another aspect of the invention that the length of the stem of the “Y” be adjustable by either extending or retracting the length of the stem, thereby allowing the counterweight to be placed a desired distance from the putter head. To easily extend or retract the length of the stem, it is a further aspect of the invention that the stem of the “Y” shaped wire may be comprised of a telescopic structure. It is yet a further aspect of the invention that the counterweight be located at the tip of the telescopic structure thus providing the ability to easily extend or retract the counterweight to the desired level of difficulty.
[0009] It is a further aspect of the invention that the putter head have additional optional mounting holes for inserting the tips of the “Y” wire along the centerline of the width of the putter head. These holes may be spaced apart from one another, beginning from the heal and the toe of the putter head and moving closer inward towards the shaft of the putter. Inserting the tips of the “Y” wire into the mounting holes that are closer to the heal and toe of the putter will increase the susceptibility of the putter head to rotation. Having the tips spaced far away from the shaft increases the rotational force moment arm that tips will impart a rotational force across onto the bearing. Depending on the skill level of the golfer, a novice golfer may want to place the tips of the “Y” wire into mounting holes closer to the putter shaft to reduce the length of the moment arm and make the putter head less susceptible to rotation due to an improper stroke. As the golfer's putting stroke improves, the tips of the “Y” wire can be gradually moved further away from the shaft to increase the level of difficulty.
[0010] To further improve the visual feedback provided to the golfer, it is another aspect of the invention that the putter has alignment markings on the top of the putter head. These alignment markings can be both parallel and perpendicular to the intended target line of the putt. The alignment markings that are parallel to the putting path assist the golfer in properly aligning the putter head along the intended-putting path. The alignment markings perpendicular to the putting path provide the golfer with additional visual feedback if the putter head begins to undesirably rotate during the putting stroke. These markings assist the golfer in noticing subtle rotations of the putter head.
[0011] It is another aspect of the invention when used as a training aid to improve a golfer's ability to strike the ball repeatedly with the center of the putter head, commonly referred to as a “sweet spot”. A putt that is struck with the center of the putter head travels with a consistent forward roll along the intended target line. By allowing the putter head to rotate around the putter shaft, putts hit inadvertently off center will cause the putter head to rotate and visually inform the golfer of the miss hit. The farther off center the ball is struck, the more the putter head will rotate providing additional information on how far off center the putt was struck. This feedback will work for both putts hit off either the toe or heal of the putter. Putts hit near the toe of the putter will cause the putter head to rotate clockwise around the shaft for a right-handed golfer. Putts hit towards the heal of the putter will cause the putter head to rotate counter clockwise for a right-handed golfer. The rotational directions are reversed if the golfer is putting left-handed.
[0012] If desired to use the invention as a standard golf putter, the invention provides various locking features that can be incorporated and used to immobilize the putter head to prevent it from rotating about the shaft. A locking feature will allow the golfer to use the same putter as both a training aid and as a standard putter thereby keeping the size, shape and weight of the putter the same, which is important. If a golfer were to practice with a putting device that is heavier than the standard putter the golfer uses during a round of golf, the golfer's putting stroke may become quick due to the lighter weight of the standard putter. This is a similar result to a baseball player that takes several practice swings with a weight attached to the bat prior to hitting a pitch from an opposing player. Practice swings with a heavier bat help the baseball player to increase their bat speed during their actual hitting attempt by providing both a physical and psychological feel that the bat is lighter. An increased bat speed will increase the distance a baseball will travel when struck. Therefore, a golfer putting with a putter that is lighter than the practice putter used may encourage a putting stroke that is faster than required and hit putts that travel longer than intended. The reverse also holds true. If a golfer were to practice with a putting device that is much lighter than the normal putter used, when the heavier putter is used during competition or play, a golfer's putts may not travel the entire intended distance due to the reduced swing speed.
[0013] There are numerous methods for incorporating locking or immobilization features into this invention. Three such locking features are described in detail here within. However, it should be appreciated that other locking features that are obvious to someone skilled in the art may be incorporated into this invention.
[0014] In one aspect of the invention, the locking feature is attached onto the shaft of the putter. In this configuration, a rigid appendage could be affixed to the shaft as a portion of the locking feature and be forced to rotate along with any rotation of the shaft. Threaded or unthreaded holes may be incorporated through the thickness of the appendage into which threaded or unthreaded rigid members can be inserted. One or more corresponding receiving holes could also be incorporated into the putter head that could simultaneously receive the rigid members that are passed through the appendage. The rigid members should also contain certain features that allow the members to be easily inserted or removed by hand without the need for a special tool. The rigid members would then be in contact simultaneously with the putter head and the appendage. Since the appendage is affixed to the shaft, the putter head would only rotate along with any rotation of the putter shaft and not be allowed to rotate around the shaft thus allowing the putter to be used as a conventional putter.
[0015] In another aspect of the invention, the locking mechanism will be comprised of a threaded feature extending outward from the end of the putter shaft nearest the head of the putter. In this aspect, the threaded feature extends beyond the lower edge of the rotational device towards the bottom of the putter head. One or more rubber, metal, plastic or similar washers with inner diameters slightly larger than the diameter of the putter shaft could then be inserted over the threaded device and putter shaft and allowed to make contact with the rotational device. The washers can be secured in place with a threaded nut inserted onto the threaded device and tightened securely. Tightening the nut securely will ensure that sufficient pressure is applied to the rotational device by the washer thus preventing the rotational device from moving and thus preventing the putter head from rotating around the shaft. The locking nut should also contain certain features that allow the nut to be tightened or loosened by hand without the need for a special tool.
[0016] In a further aspect of the invention, the locking mechanism would be accomplished by threading the inner diameter of the putter shaft at the end of the putter nearest the putter head. One or more rubber, metal, plastic or similar washers with inner diameters slightly larger than the diameter of the putter shaft could then be inserted over the putter shaft and allowed to make contact with the rotational device. The washers can be secured in place with a threaded rigid member inserted into the threaded inner diameter of the putter shaft and tightened securely. Tightening the threaded rigid member securely will ensure that sufficient pressure is applied to the rotational device by the washer thus preventing the rotational device from moving and thus preventing the putter head from rotating around the shaft. The threaded rigid member should also contain certain features that allow the member to be tightened or loosened by hand without the need for a special tool.
[0017] It is another aspect of the invention that a device may be attached to the putter that will return the putter head to the desired staring position that is perpendicular to the intended target line of the putt. While it shall be appreciated that a variety of solutions may be employed to achieve this result, the preferred embodiment would utilize an elastic mechanism for returning the putter head perpendicular to the target line after each stroke. The return mechanism would be comprised of a ring with one or more elastic strings attached to the ring. The ring itself would be rigidly attached to the putter shaft and be allowed to rotate along with the putter shaft. The elastic strings could be attached to one or more ends of the putter head along the centerline of the putter width. Ideally, the elastic string would provide sufficient resistance to allow the putter head to return to the desired starting position but should not provide so much resistance that it restricts the ability of the putter head to rotate during the stroke or impact. The putter head would essentially act like a saloon style door that will swing back and forth but eventually return to the staring position perpendicular to the intended target line.
[0018] These and other aspects of the invention will become more apparent from the following detailed description of the invention when taken in conjunction with the accompanying figures.
BRIEF DESCRIPTION OF FIGURES
[0019] [0019]FIG. 1 illustrates three components of the invention, a shaft, a rotational device and a putter head that is allowed to rotate around the shaft.
[0020] [0020]FIG. 2 illustrates a bottom view of the three components of the invention described in FIG. 1.
[0021] [0021]FIG. 3 illustrates the invention with a locking mechanism that is comprised of a rigid appendage and rigid objects that can be used to immobilize the putter head for use as a standard golf putter when training is not desired.
[0022] [0022]FIG. 4 illustrates the invention along with a locking mechanism that is comprised of a threaded rigid object at the end of the putter shaft. Washers and a locking nut can then be threaded onto the threaded rigid object creating sufficient pressure against the rotational device to prevent the head from rotating.
[0023] [0023]FIG. 5 illustrates the invention along with a locking mechanism that is comprised of a threaded rigid object that can be threaded into the inner diameter of the putter shaft. The head of the threaded rigid object is shaped in a manner that will exert sufficient pressure against the rotational device and prevent the head from rotating.
[0024] [0024]FIG. 6 illustrates the invention along with the counterweight and “Y” shaped support device.
[0025] [0025]FIG. 7 illustrates the invention along with a return mechanism that will force the putter head back into a square alignment position with the intended target line after each stroke.
DETAILED DESCRIPTION OF THE INVENTION
[0026] Referring to the figures below, FIG. 1 shows a perspective view of an embodiment of a practice putting apparatus 5 that is encompassed by the present invention. Apparatus 5 shows a putter shaft 20 connected to putter head 10 by a rotational device 30 . Putter shaft 20 can be made from a multitude of materials including, but not limited to, aluminum and similar alloys, steel and similar alloys, graphite, wood or similar substances. Putter head 10 can be made from a multitude of materials including, but not limited to, aluminum and similar alloys, steel and similar alloys, brass, copper, iron, nickel or similar materials. Putter shaft 20 is connected to putter apparatus 5 by first passing freely through hole 13 of putter head 10 . Hole 13 has a slightly larger diameter than the outer diameter 21 of shaft 20 so that no friction or contact is made and putter head 10 can rotate around shaft 20 . Putter shaft 20 can then be connected to the inner diameter 31 of rotational device 30 . One method for connecting shaft 20 to inner diameter 31 utilizes an interference friction fit between the two features. This interference friction fit can be accomplished by using a putter shaft 20 where the end of shaft 20 where the interface with rotational device 30 occurs has an outer diameter 21 that is equal to or slightly larger than inner diameter 31 of rotational device 30 . Rotational device 30 may be forced onto shaft 20 via pressure, or, rotational device 30 may be heated to an elevated temperature to temporarily expand inner diameter 31 of rotational device 30 to reduce the pressure required to assemble rotational device 30 onto shaft 20 . When rotational device 30 cools, inner diameter 31 contracts and increases the interference friction between the rotational device 30 and shaft 20 . The interference friction would not be so great that it would inhibit rotational device 30 from rotating properly. However, the interference friction should be sufficient enough to maintain the mechanical connection between the rotational device 30 and shaft 20 for many years and over various temperature ranges and weather conditions that the putter may be exposed to during practice or a round of golf.
[0027] Another method that can be used to attach rotational device 30 to shaft 20 is to use a putter shaft 20 with an outer diameter 21 that is smaller than inner diameter 31 of rotational device 30 . The space that would exist between outer diameter 21 and inner diameter 31 could then be filled with epoxy, glue or other substance that would create a mechanical bond between outer diameter 21 and inner diameter 31 . This mechanical bond would be sufficient enough to maintain the mechanical connection between rotational device 30 and shaft 20 for many years and over various temperature ranges and weather conditions that putter apparatus 5 may be exposed to during practice or a round of golf.
[0028] In order to improve the visual feedback provided to the golfer by the invention, alignment markings 80 could be included as a feature on the top of putter head 10 as shown in FIG. 1. Alignment markings 80 can be parallel or perpendicular to the intended target line 100 of the putt. The intent of alignment markings 80 that are parallel to the putting path is to assist the golfer in properly aligning the putter head along intended target line 100 . The intent of alignment markings 80 perpendicular to target line 100 is to provide the golfer with additional visual feedback if putter head 10 begins to undesirably rotate during the putting stroke. These markings allow the golfer to more easily notice subtle rotations of putter head 10 .
[0029] Referring now to FIG. 2, rotational device 30 is attached to putter head 10 by similar methods used to attach rotational device 30 to putter shaft 20 . An interference friction fit can be created between rotational device 30 and putter head 10 . To accomplish this, inner diameter 11 of hole 15 , at the bottom surface of putter head 10 , will be equal to or slightly smaller than outer diameter 32 of rotational device 30 . The rotational device 30 may be forced into hole 15 via pressure, or hole 15 may be heated to an elevated temperature to temporarily expand the inner diameter 11 and reduce the pressure required to assemble rotational device 30 into putter head 10 . When hole 15 cools, inner diameter 11 contracts and increases the interference friction between outer diameter 32 of rotational device 30 and inner diameter 11 of hole 15 . The interference friction would not be so great that it would inhibit rotational device 30 from rotating properly. However, the interference friction should be sufficient enough to maintain the mechanical connection between rotational device 30 and putter head 10 for many years and over various temperature ranges and weather conditions that putter apparatus 5 may be exposed to during practice or a round of golf.
[0030] Another method that can be used to attach rotational device 30 to putter head 10 is to create hole 15 with inner diameter 11 that is larger than the outer diameter 32 of the rotational device 30 . The space that would exist between inner diameter 11 and the outer diameter 32 could then be filled with epoxy, glue or other substance that would create a mechanical bond between the inner diameter 11 of hole 15 and outer diameter 32 of rotational device 30 . This mechanical bond would be sufficient enough to maintain the mechanical connection between rotational device 30 and putter head 10 for many years and over various temperature ranges and weather conditions that putter apparatus 5 may be exposed to during practice or a round of golf.
[0031] [0031]FIG. 3 shows a perspective view of another embodiment of the invention described in detail in FIG. 1 along with locking features that can immobilize the putter head and prevent the putter head 10 from rotating around shaft 20 if desired. The apparatus shown in FIG. 3 contains all of the same aspects, such as shaft 20 , rotational device 30 , putter head 10 and alignment markings 80 , that are mentioned in the detailed description for FIG. 1. The additional aspects shown in FIG. 3 make up the locking mechanism and are comprised of rigid appendage 40 with one or more threaded or unthreaded holes 41 and one additional hole 42 passing through appendage 40 . Hole 42 will be used to rigidly affix appendage 40 to shaft 20 . Hole 41 of rigid appendage 40 could be used along with threaded or unthreaded rigid object 50 and one or more threaded or unthreaded hole 12 in putter head 10 that align with hole 41 . To immobilize putter head 10 , rigid object 50 would pass through hole 41 of appendage 40 and simultaneously pass through hole 12 in putter head 10 making both appendage 40 and putter head 10 rotate along with the rotation of shaft 20 , preventing putter head 10 from rotating independently.
[0032] [0032]FIG. 4 shows a perspective view of a further embodiment of the invention described in detail in FIG. 1 along with locking features that can immobilize putter head 10 and prevent putter head 10 from rotating around shaft 20 if desired. The embodiment shown in FIG. 4 contains all of the aspects and methods for attaching the components, such as shaft 20 , rotational device 30 , putter head 10 and alignment markings 80 , that are mentioned in the detailed description for FIG. 1. The additional aspects shown in FIG. 4 make up the locking mechanism and consist of a threaded rod 70 , one or more washers 90 , and a locking nut 60 . Threaded rod 70 , extends outward from the bottom of shaft 20 and can be attached to shaft 20 through a variety of methods. These methods include but should not be limited to a mechanical interference fit, a chemical-mechanical bond such as epoxy, glue or cement, or other similar methods to secure threaded rod 70 to shaft 20 . When assembled and shaft 20 is securely attached to rotational device 30 as described in the detailed description of FIG. 1, threaded rod 70 , should extend beyond the bottom of rotational device 30 . Threaded rod 70 should extend far enough so that one or more washers 90 and locking nut 60 can be assembled onto threaded rod 70 . The inner diameter 91 of washer 90 , should be slightly larger than outer diameter 71 of threaded rod 70 and larger than outer diameter 21 of shaft 20 so that washer 90 can be forced up against the bottom of rotational device 30 . Locking nut 60 is assembled after washer 90 and is allowed to tighten up against washer 90 in order to increase the pressure and friction washer 90 imparts on rotational device 30 . Locking nut 60 and washer 90 should be able to provide sufficient pressure and friction to prevent rotational device 30 from rotating and effectively immobilize putter head 10 to prevent it from rotating about shaft 20 . Washer 90 can be created from a variety of metal, plastic and/or rubber materials. Metal washers could be used to increase the overall weight of the putter if desired. Plastic or rubber washers tend to have a higher coefficient of friction and therefore would reduce the amount of pressure locking nut 60 would have to impart in order to prevent rotational device 30 from rotating.
[0033] [0033]FIG. 5 shows a perspective view of yet another embodiment of the invention described in detail for FIG. 1 along with locking features that can immobilize the putter head and prevent putter head 10 from rotating around shaft 20 if desired. The apparatus shown in FIG. 5 contains all of the same components and methods for attaching the components, such as shaft 20 , rotational device 30 , and putter head 10 , that are mentioned in the detailed description for FIG. 1. FIG. 5 also shows a threaded locking rod 130 that can be passed through the rotational device and threaded into the inner diameter 22 of shaft 20 . Head 135 of the locking rod 130 is shaped in a manner that will allow head 135 to make sufficient contact pressure and friction against rotational device 30 to prevent rotational device 30 from rotating and effectively immobilize putter head 10 and prevent it from rotating about shaft 20 . In additional pressure against rotational device 30 is required, washer (not shown) can be inserted prior to the insertion of locking rod 130 similar to the methods described in the detail description for FIG. 4. Additionally, locking head 135 may be shaped in such a manner that will allow locking rod 130 to be threaded or inserted into inner diameter 22 of shaft 20 by hand without the use of special tools.
[0034] [0034]FIG. 6 shows a perspective view of the invention described in detail for FIG. 1. The apparatus shown in FIG. 6 contains all of the same components and methods for attaching the components, such as shaft 20 , rotational device 30 , and putter head 10 , that are mentioned in the detailed description for FIG. 1. FIG. 6 also shows counterweight 120 and “Y” shaped support structure 110 . Support Structure 110 is comprised of stem 115 along with the two ends 111 . Counterweight 120 could be made from a variety of materials including, but not limited to metals such as steel, galvanized steel, brass, aluminum, copper, or tin. Counterweight 120 is located along stem 115 and is allowed to slide along stem 115 to move closer to or farther away from putter head 10 as desired. The friction between stem 115 and counterweight 120 should be sufficient enough to retain counterweight 120 in a desired location along stem 115 yet still be easily adjustable by hand with out the use of special tools. Locating counterweight 120 farther away from putter head 10 will increase the putter's susceptibility to rotation due to imperfections in a putting stroke. If counterweight 120 is not maintained directly behind the center of putter head 10 throughout the putting stroke, the momentum of the stroke will impart a force onto counterweight 120 . Force acting on counterweight 120 will in turn impart a rotational force onto rotational device 30 and cause putter head 10 to rotate around shaft 20 . Placing counterweight 120 farther away from putter head 10 increases the length of the moment arm that imparts the rotational force onto rotational device 30 . A longer moment arm increases the amount of rotational force applied to rotational device 30 . Therefore, a longer moment arm requires less force from counterweight 120 to impart sufficient rotational force to cause putter head 10 to rotate. With counterweight 120 placed farther away from putter head 10 , a more consistent putting stroke with a straight-back and straight-through pendulum motion is required to keep counterweight 120 positioned directly behind the center of mass of putter head 10 throughout the stroke. Conversely, positioning counterweight 120 closer to putter head 10 will decrease the length of the moment arm thus making putter head 10 less susceptible to rotation.
[0035] Any rotational force imparted onto putter head 10 by counterweight 120 is transmitted through support structure 110 where it connects to putter head 10 at ends 111 . As an additional means of adjusting the difficulty level of the putting aid, it is a further aspect of this invention that support structure 110 be flexible enough to allow ends 111 to flex and align with holes 105 in putter head 10 . To allow for flexibility, support structure 110 could be made from a variety of materials including, but not limited to metals such as steel, galvanized steel, brass, aluminum, copper, tin, or plastics such as polycarbonate, polycarbonate/ABS blends, polystyrene, polyethylene, or PVC. Similar to the positioning of counterweight 120 , positioning ends 111 into holes 105 that are located farthest away from shaft 20 increases the length of the moment arm between ends 111 and rotational device 30 , thereby making putter head 10 more susceptible to rotation. Conversely, positioning ends 111 into holes 105 that are closer to shaft 20 will decrease the length of the moment arm thus making putter head 10 less susceptible to rotation. Varying the length of the moment arm between these key features allows for the invention to be adjustable to all skill levels.
[0036] [0036]FIG. 7 shows a perspective view of the invention described in detail for FIG. 1. The apparatus shown in FIG. 7 contains all of the same components and methods for attaching the components, such as shaft 20 , rotational device 30 , and putter head 10 , that are mentioned in the detailed description for FIG. 1. FIG. 7 also shows features of a return mechanism comprised of ring 150 and one or more elastic strings 145 . In this configuration, ring 150 would be rigidly attached to putter shaft 20 and be allowed to rotate along with putter shaft 20 . One end of elastic string 145 is attached to ring 150 . The other end of elastic string 145 is attached to insertion feature 160 with geometry capable of mating with hole 105 on putter head 10 . Insertion feature 160 can be made from a variety of materials including, but not limited to metal, plastic, rubber, or wood. Insertion feature 160 should be shaped in such a manner so that it is easily inserted or removed from hole 105 by hand, without the use of any special tools. The intention of elastic string 145 is to return putter head 10 to the desired starting position that is perpendicular to the intended target line at the beginning of the putting stroke. As putter head 10 rotates, tension force will constantly be loaded and unloaded in elastic string 145 until all energy is dissipated and putter head 10 is returned to its original starting position. Locating insertion feature 160 into hole 105 that is farthest away from shaft 20 will increase the tension in elastic string 145 prior to the start of the stroke. More initial tension in elastic string 145 will cause the energy imparted on the strings through the rotation of putter head 10 to dissipate more quickly. Therefore, putter head 10 would return more quickly to its starting position, where all forces acting on the putter head are neutral until the putting device is set into motion again. Conversely, locating insertion feature 160 into hole 105 that is closer to shaft 20 would reduce the initial tension in elastic string 145 and allow putter head 10 to rotate back and forth for more iterations before coming to rest. This flexibility in pre-loading the tension of elastic string 145 allows the user to adjust how quickly putter head 10 returns based upon the users preference.
[0037] While particular forms of the invention have been illustrated and described, it will be apparent that various modifications can be made without departing from the spirit and scope of the invention.
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The present invention provides a golf training putter comprises a putter head that is connected to a shaft in a manner which enables the putter head to rotate around the shaft.
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BACKGROUND OF THE INVENTION
Non-woven fabrics are well known and have many varied uses, particularly in the textile industry. Such non-woven materials are useful as interliners for adhesive purposes or for support with fabrics and films. In many instances, the non-wovens can be made self-supporting and then used in fabricating garments, particularly where such garments are used one time and then discarded, such as in hospital operating rooms, and the like. These non-woven materials are made from a variety of fibers, such as, for example, cotton, wool, flax, glass, viscose rayon, cellulose acetate, acrylonitrile polymers (acrylics), polyamides (nylon), polyesters, etc. However, most of the known methods for producing non-woven fabrics from said fibers involve expensive and time consuming steps.
As an example of such time and expense is the manufacture of non-wovens from polymeric materials, such as acrylonitrile polymers, polyamides, polyesters, polyurethanes, and the like. First of all, the polymer must be spun in the form of a bundle of continuous filaments, treated and washed, cut into staple fibers, dried and baled. Thereafter, at a textile mill, the fibers are further treated, as by carding, to form a web in which the fibers are randomly distributed. Then the fibers are bonded together at the crossover points, i.e., wherever they cross or come in contact with another fiber. Such bonding is usually done with the use of adhesive compositions or by heating the fibers so that they soften sufficiently and fuse with other fibers at the contact points. Most of such non-woven fabrics tend to be stiff and have a harsh hand.
A recently developed process is being employed to overcome the aforesaid difficulties. In this process, the polymeric material is melted and passed through an extruder to a forming or shaping die. The polymeric material is extruded in the form of a film and immediately formed into a cellular or reticulated structure by means of a blowing agent. Overlapping of fibrils results in the structure and the material has the appearance of a non-woven fabric and is useful in the same end uses. This process has proved successful with many polymeric materials, such as polyethylene and the like. However, when making a lace-like structure from polyurethane, using said process, the hole size of the product formed is frequently too large and also nonuniform to give a commercially useful product. Polyurethanes are particularly useful for this kind of product since they impart good flexibility and have good binding properties. However, it is desirable to have a stiffer hand in the reticulate lace-like structure. Therefore, means of producing a reticulate lace-like structure from polyurethanes wherein the fiber structure changes sufficiently to give small holes and good uniformity thereof, along with a stiffer hand, is most desirable.
SUMMARY OF THE INVENTION
It has unexpectedly been found that a stero reticulated lace-like structure can be produced from a polyurethane which has greatly reduced hole size, more overlapping fibers or fibrils and multiple layers thereof, more uniform hole size, and a stiffer hand. This reticulated structure is obtained by extruding a polymeric blend comprising a polyurethane and a polymer selected from acrylic polymers, polyamides and a polymer formed from acrylonitrile-butadienestyrene (ABS). The polymeric mixture or blend is extruded in the form of a film and simultaneously given a cellular or stereo reticulate structure by means of a blowing agent.
DETAILED DESCRIPTION
In connection with the description of the invention which follows, reference is made to the drawing in which:
FIG. 1, is a photomicrograph of a reticulated lace-like structure or web made from polyurethane alone; and
FIG. 2, is a photomicrograph of a stero reticulated lace-like structure or web made from a polymer blend of a polyurethane and an acrylic terpolymer.
The polyurethane elastomers useful in the practice of the present invention are those which are substantially free of cross-links. These elastomers are prepared by reacting 1.0 mol of an essentially linear hydroxyl-terminated polyester having a molecular weight between about 600 and about 2500 with about 1.1 to 3.1 mols of a diphenyl diisocyanate in the presence of about 0.1 to 2.1 mols of a free glycol containing from 4 to 10 carbon atoms. The ratio of free glycol to diphenyl diisocyanate must be balanced so that there is essentially no free unreacted diisocyanate or glycol remaining after the reaction to form the elastomer. The amount of glycol employed will depend upon the molecular weight of the polyester used. The elastomer is formed by heating the mixture of reactants.
Useful polyesters include those prepared from the esterification of such dicarboxylic acids as adipic, succinic, pimelic, suberic, azelaic, sebacic, and the like or their anhydrides. Preferred dicarboxylic acids are those having the formula HOOC--R--COOH, where R is an alkylene radical containing 2 to 8 carbon atoms.
The glycols utilized in the preparation of the polyester by reaction with the aliphatic dicarboxylic acid are straight chain glycols containing between 4 and 10 carbon atoms, such as butanediol-1,4, hexamethylenediol-1,6, octamethylenediol-1,8, and the like. In general, glycols having the formula HO(CH 2 ) x OH, where x is a number from 4 to 8, are employed.
In making the polyurethane elastomers, a diphenyl diisocyanate is employed, such as 4,4'-diphenyl methane diisocyanate, diphenyl methane-p,p'-diisocyanate, dichlorodiphenyl methane diisocyanate, dimethyl diphenyl methane diisocyanate, diphenyl dimethyl methane diisocyanate, dibenzyl diisocyanate, diphenyl ether diisocyanate, and the like. The amount of diphenyl diisocyanate used is dependent upon the amount of free glycol and polyester and should be an amount equivalent to these latter two reactants so that there are essentially no free unreacted isocyanate and hydroxyl groups remaining in the reaction product. A convenient method for determining how much glycol to add to the polyester prior to reaction of the mixture of polyester and glycol with the diphenyl diisocyanate is to add enough glycol to the polyester so that the mixture has an average hydroxyl number molecular weight of about 400 to 800 and more preferably from 400 to 550. It will be apparent that the higher the molecular weight of the polyester the more glycol that will be required to obtain the desired hydroxyl content in the mixture of free glycol and polyester.
The acrylic polymers useful in blending with the polyurethane elastomers, in the practice of the present invention, are those comprising in 100 parts by weight of resin from about 40 to 97 parts by weight of a lower acrylic acid ester, from about 0 to 45 parts by weight of a methacrylic acid ester and from about 3 to 15 parts by weight of an α,β-olefinically unsaturated carboxylic acid having a terminal CH 2 =C group and having from 3 to 4 carbon atoms. These acrylic polymers can be represented by the formula: ##STR1## wherein R represents hydrogen and methyl, R 1 represents an alkyl radical having 1 to 10 carbon atoms, such as methyl, ethyl, propyl and decyl, R 2 represents methyl and ethyl, x represents from 3 to 15 weight percent based on the combined weight of x, y and z; y represents from 40 to 97 weight percent based on the combined weight of x, y and z; z represents from 0 to 45 weight percent based on the combined weights of x, y and z; the sum of numerical values of x plus y plus z is always 100 and the groups x, y and z are present in the polymer in a heterogeneous relative order.
The lower acrylic acid esters useful in making the polymers or resins for the present invention include those in which R 1 in the above formula is an aliphatic hydrocarbon group having from 1 to 10 carbon atoms, such as methyl acrylate, ethyl acrylate, n-propyl acrylate, isopropyl acrylate, 2-ethylhexyl acrylate, n-butyl acrylate, isobutyl acrylate, and secondary butyl acrylate. The most preferred lower acrylic acid esters are methyl acrylate and ethyl acrylate.
The lower methacrylic acid esters useful in this invention include those in which R 2 in the above formula is an aliphatic hydrocarbon group having from 1 to 2 carbon atoms, such as methyl methacrylate, and ethyl methacrylate, the preferred compound or monomer being methyl methacrylate.
The α,β-olefinically unsaturated carboxylic acids include acrylic acid and methacrylic acid.
The acrylic polymers or terpolymers used in the present invention are prepared by well-known polymerization techniques, for example, bulk, solvent, suspension and emulsion polymerization. Terpolymers of lower alkyl acrylates, lower alkyl methacrylates and acrylic or methacrylic acids are shown and described in U.S. Pat. Nos. 2,760,886; 2,790,735; 2,934,509; 3,454,509; and 3,460,945, among others. When making these terpolymers, the polymerization reaction is catalyzed by a free radical generating catalyst, such as a peroxide or a hydroperoxide. Among the typical useful catalysts of this type, there may be named as examples hydrogen peroxide, benzoyl peroxide, caproic peroxide, tertiary butyl peroxide, caprylyl peroxide, cumene hydroperoxide, and the like. Various other additives may be employed in the polymerization reaction, such as dispersants, emulsifiers, and the like, as is well-known to those skilled in the art.
The mixture or blend of polymers of the present invention may be made in any desirable way, such as melt blending, for example. However, it is preferred to mix or blend the polymers while dry and in a granular condition. This can be accomplished using any conventional equipment for blending dry polymers or other materials, such as roll mixers, and the like. When blending the polymers, it is sufficient to use an amount of the acrylic polymer of about 3 to about 25 parts by weight, based upon 100 parts by weight of the polyurethane polymer. Preferably, an amount of acrylic polymer in the range of about 3 to about 15 parts by weight is employed.
It has been found desirable, and in many cases necessary, to employ a lubricant in the polymer blend. The reason for this is that when the reticulated structure is passed over a guide roll or through a pair of nip feed rolls to the windup roll, it has a tendency to stick to said rolls. Also, blocking can occur on the windup roll and when trying to unwind the reticulated structure therefrom, it has a tendency to stick to itself making unwinding difficult, if not impossible in many cases. We have found that the use of small amounts of a paraffin wax in the polymer blend alleviates the problems of sticking and blocking. Usually, an amount of paraffin wax in the range of about 0.1 part to about 3 parts by weight, based upon 100 parts by weight of the polyurethane polymer, is sufficient. Preferably, 0.1 part to 2 parts by weight of paraffin wax are employed.
The paraffin wax may be added to the polymer blend in different ways. For example, the wax may be dry blended in the polymer blend as by tumbling and rolling in a drum. In fact, the wax can be blended in at the same time that the polyurethane polymer and acrylic terpolymer are dry blended together. It has been found, however, that improved distribution and balance of the wax in the polymer blend is achieved if the wax is added to the polymerization mix or recipe prior to polymerization when making the polyurethane polymer.
In order to obtain the cellular or stereo reticulated lace-like structure of the instant invention, a suitable blowing agent is employed in the polymer blend. The blowing agent is dry blended in the polymer blend. The polymer blend is now a homogeneous foamable composition which is fed into a hopper which feeds a conventional screw extruder. The extruder and the annular extrusion die attached to the exit end thereof are heated by any suitable means, such as by electrical resistance type band heaters, and the like. The polymer blend is maintained in unfoamed condition in the extruder by means of pressure until its exit from the die into an area of atmospheric pressure. Upon exiting from the die, the pressure is released on the gaseous material formed from the blowing agent thus causing a cellular structure in the extrudate to form a lace-like reticulated material, or fabric, such as shown in FIG. 2 of the drawing.
Various blowing agents, or foaming agents, are useful in the present invention. Such agents as will produce, or cause to be produced, a normally gaseous material at the conditions of extrusion, such as nitrogen, for example, are most useful, although other chemically or physically decomposable blowing agents are useful. The particular blowing agent employed is dependent upon the polymer blend used and the properties desired in the final reticulated material. With regard to chemical blowing agents, which may be used in the present invention, are the azo-, N-nitroso- and sulfonyl hydrazide compounds such as, for example, azobisformamide, azobisisobutyronitrile, diazoaminobenzene, p,p'-oxybis-(benzenesulfonylhydrazide), N,N'-dinitrosopentamethylenetetraamine, p,p'-azobis-(benzenesulfonylsemicarbonamide), diethylazoisobutyrate, 1,3-bis-(xenyl)triazine, 4,4'-oxybis-(benzenesulfonylhydrazide), and the like, p.p'-oxybis-(benzenesulfonylsemicarbazide), barium azodicarboxylate, sodium borohydride, and the like. Physical blowing agents include such compounds as the low boiling liquid hydrocarbons, such as hexane, heptane, pentane, etc., dichlorodifluoromethane, trichlorofluoromethane, 1,2-dichlorotetrafluoroethane, and the like. Usually an amount of a blowing agent in the range of about 0.1 to about 2 weight parts per 100 weight parts of polymer blend is sufficient to achieve the objects of the present invention. The blowing agent is used in amounts of from about 0.1 to about 3.0 weight parts per 100 weight parts of polymer blend.
In those instances where it is necessary to use high extrusion temperatures in order to get proper gas release from the blowing agents, and there is concern about polymer degradation, various catalysts or activators may be employed which generally lower the temperatures of gas release of the blowing agents. These blowing activators are known to those skilled in the art and include, among others, such compounds as metal soaps and metal salts and oxides. As examples, there may be named lead stearate, zinc stearate, titanium dioxide, silica, salts of zinc, lead, barium, cadmium, and the like.
In addition to the blowing agents mentioned above, an inert gas, such as freon, can be employed. This is accomplished by injecting the gas into the extruder through a port in that section wherein the polymer blend is in the molten state. The gas is under pressure and expands causing foaming upon leaving the extrusion die into the atmosphere.
In making the cellular or stero reticulated lace-like structure or fabric of the present invention the polymer blend is fed to an extruder by means of a hopper mounted thereon. The extruder used is of the screw type and may be of any particular size. We have found, however, that a 31/2 inch line produces very good results. An extrusion die having an annular opening therein is mounted on the exit end of the screw extruder and both the extruder and annular die are heated by suitable means, as hereinbefore pointed out. The extruder and die are maintained at a temperature in the range of about 300° F. to about 400° F. Preferably, the temperature is maintained in the range of 340° F. In actual commercial practice the temperature will vary along the length of the extruder and the die but within the ranges of temperature given above. For example, in a typical run the temperature in the solids section of the screw extruder will be 370° F., in the melt section 380° F. and in the die 370° F. The temperature regulation is dependent on a number of conditions, such as the size and shape of the screw, the rpm of the screw, the dwell time of the melt in the extruder, since a too long dwell time may cause some degradation of the polymers which is to be avoided.
The annular opening in the die may be of any convenient size in diameter depending upon such factors as rate of extrusion, size of the expander ring, hereinafter described, width of the finished fabric, and the like. We have found that for the purposes of our invention, an annular opening having a diameter of about 12 inches is satisfactory.
The foamed reticulated fabric is drawn from the annular opening in the die by means of an expander ring which has a diameter about 2 to 5 times that of the annular die opening. A diameter of about 48 inches has been found to be satisfactory. The expander ring is segmented and each segment is positively rotated about its own axis in the direction of travel of the fabric. Thus the fabric is attenuated as it passes over the expander ring and the holes therein, formed by the blowing agent, are extended or stretched in the longitudinal direction. The expansion of the gas from the blowing agent causes the formation of a myriad of fibrils, which are readily discernible in FIG. 2 of the drawing.
Immediately after immergence from the die, and prior to the expander ring, the reticulated structure, or fabric, is quenched with air at room temperature. The cooling is accomplished by means of a cooling ring mounted adjacent the exit end of the die and having a series of openings or jets around the inner periphery thereof. The openings are located so that the jets of air are directed against the emerging reticulated fabric in a direction away from the die so as not to cool the die. Usually it is necessary to bring the temperature of the fabric down close to the hardening temperature of the polymer blend. The reason for this is to build up the viscosity of the polymer blend so that it may be oriented to a high degree. Since this cooling of the emerging reticulated fabric must be done quickly, it is sometimes desirable, or even necessary to precool the air prior to contacting the fabric. Whether or not precooling of the air is necessary depends on the rate of extrusion, and other working conditions.
The orientation or setting of the reticulated lace-like structure or fabric is biaxial, that is, both in the longitudinal and transverse directions. The orientation or setting takes place between the extrusion die and the expander ring. The segmented expander ring is driven at such a speed that not only does the expansion of the tubular fabric going from the die diameter to the diameter of the ring contribute to the orientation but also the stretching thereof due to the speed of the expander ring. This orientation is also referred to as radial orientation. This radial orientation can be assisted by slowly rotating the die at 1 rpm. or less. This rotation also contributes to the uniformity of the fabric.
Biaxial orientation of the reticulated structure imparts high tensile strength thereto. However, one must be careful not to overstretch since this will reduce the strength of the structure or fabric. Generally, the reticulated structure is stretched in both the longitudinal and transverse direction at least twice its original dimension. Preferably, the stretching will be in the range of 2 to 12 times the original dimension. Generally, the orientation in the longitudinal direction is higher than in the transverse direction.
After orientation, the reticulated fabric passes between the feed rolls to a windup roll, which is rotated at the same speed as the feed rolls. Since the reticulated fabric is extruded in the form of a tube, it is wound up as double ply fabric. However, if it is desired to wind the fabric in single plies, two wind up rolls can be used. A slitting means can be employed between the feed rolls and the windup rolls and the edges of the fabric slit or cut thus separating the fabric into 2 single plies each of which is wound separately.
The weight of the reticulated fabric can be varied over a wide range by changing the width of the annular opening in the extrusion die and also by adjusting the rate of extrusion. Generally, a fabric having a single ply weight in the range of 0.2 to 4.0 ounces per square yard is satisfactory. Where the reticulated fabric is to be used as an adhesive interlayer in a laminated fabric structure, a weight of 0.5 to 1.0 oz./sq.yd. is sufficient. Of course, increased weight can be obtained by employing more than one ply of the reticulated fabric.
In the present invention finely divided fillers can be employed in the polymer blend prior to extrusion thereof. The small particle size fillers do not affect void structure but they do tend to promote fiber formation with fewer and smaller film-like junction areas. Most of the well known filler materials may be used in the present invention. These fillers are usually inorganic materials, such as calcium salts, for example. We have found that diatomacious earth is particularly useful in our polymer blends.
In the following example, which is merely intended in an illustrative and not a limitative sense, a series of runs were made using varying polymeric compositions. In the example, all parts and percents are by weight unless otherwise indicated.
The polyurethane used in the runs was made by reacting together an adipate glycol, 1,4-butanediol and a diisocyanate in accordance with the process described in U.S. Pat. No. 2,871,218 to Schollenberger. In addition to the compounds listed above, 2 parts of paraffin wax was added prior to polymerization with the compounds constituting 100 parts. When polymerization was complete, the polyurethane was cooled and set and then granulated. Several blends of the polyurethane were then made with varying amounts of a granular acrylic terpolymer having the following composition: ethyl acrylate -- 58%; methyl methacrylate -- 32%; and acrylic acid -- 10%. The polyurethane, acrylic terpolymer and chemical blowing agent were dry blended by tumbling in a drum. The blowing agent employed was Ficel EPA, an azo dicarbonamide blowing agent.
The polymer blend was then extruded to form the reticulated lace-like fabric. A 31/2 inch extruder was used and Table I shows typical extruder and line conditions employed for polyurethane alone and when blended with the acrylic terpolymer.
TABLE I__________________________________________________________________________ Expander Drow rolls Basis Weight Blowing Extrusion Temp., ° F. Roll Speed Speed Oz/sq. yd.Polymer Agent % Melt Die RPM AMPS Ft./Min. Ft./Min. (2 ply)__________________________________________________________________________Polyurethane 1 370 360 20 45 54 58 1.03Polyurethane +Acrylic polymer 1.25 380 370 22 45 37 42 1.08__________________________________________________________________________
The products produced are shown in FIGS. 1 and 2 of the drawing which are photomicrographs taken at a magnification of 3X. The differencre in hole size and overall structure can be clearly seen in the Figures. More importantly, the fabric from the polymer blend has a stiffer hand which is desirable, particularly with respect to ease of handling in subsequent operations. The degree of fibrillation, or the amount of formation of fibrils, was good for polyurethane alone and excellent for the polymer blend.
The following table shows data of other runs, including the use of freon as the blowing agent. The degree of fibrillation is determined by visual examination of the fabrics under magnification. In the table, Poly-U is 100 parts polyurethane, ATP is acrylic terpolymer, and EPA is the azo dicarbonamide blowing agent, all as hereinabove described.
TABLE II__________________________________________________________________________ Expander Drow Extrusion Roll Rolls BasisRun Blowing Temp. of Speed Speed Weight Degree ofNo. Polymer Agent Melt Die RPM AMPS Ft./min. Ft./min. Oz./sq.yd. Fibrillation__________________________________________________________________________1 Poly-U. - 100 pts. Freon 380 370 14 50 31 38 1.00 Medium2 Poly-U. - 100 pts. EPA-0.5% 370 350 13 50 37-71 37-76 0.40 Good3 Poly-U. - 100 pts. EPA-1.0% 365 340 14 62 79 83 0.63 Good4 Poly-U. - 100 pts. ATP - 15 pts. EPA-1.0% 350 345 21 40 68 73 0.85 Excellent5 Poly-U. - 100 pts. ATP - 7.5 pts. EPA-1.0% 350 345 21 48 68 73 0.92 Excellent6 Poly-U. - 100 pts. ATP - 3.75 pts. EPA-1.0% 330 330 22 57 58 62 0.86 Medium7 Poly-U. - 100 pts. ATP - 15 pts. EPA-1.0% 335 345 22 58 58 62 0.86 Medium8 Poly-U. - 100 pts. ATP - 3.75 pts. EPA-1.0% 345 350 12 45 43 47 0.66 Good9 Poly-U. - 100 pts. ATP - 7.5 pts. EPA-1.0% 350 350 18 60 44 53 0.84 Excellent__________________________________________________________________________
Again we see the superior results obtained when an acrylic polymer is blended with the polyurethane. In all the runs made the reticulated lace-like fabric did not stick to the expander roll nor the feed rolls and further, no blocking occurred on the windup roll. This was due to the presence of the paraffin wax. It is noted that when the extrusion temperature is lowered it affects the results in the finished product.
The reticulated lace-like fabrics produced in the Example were employed as adhesive interlayers in laminated or heat pressed fabrics, such as polyester cotton -- polyester cotton, polyester knit -- polyester knit, denim -- denim, nylon - nylon, and like. The bonding temperature varies with the fabric and the type platens used. Temperatures in the range of 225° to 400° F. were employed. Using the "T-Peel Test" (ASTM Test No. D1876) wherein the angle of peel is 90°, T-Peel strengths in the range of 2.0 to 7.0 pounds per square inch were obtained. The T-Peel strengths are in the range of good to excellent for this type of reticulated fabric and obtained along with a stiffer hand and smaller hole size and increased number of fibrils or increased fibrillation.
The addition of the acrylic polymer tightens the network structure, improves extrusion stability and promotes product uniformity. Numerous other advantages of the present invention will be apparent to those skilled in the art.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention, which is to be limited only by the reasonable scope of the appended claims.
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The present invention relates to a stereo reticulated lace-like structure formed from a mixture of polymeric materials, which structure is formed by extruding a film of the polymeric mixture and simultaneously imparting a cellular or reticulate structure to said film by means of a blowing agent. The resultant stereo reticulated structure has the appearance of overlapping layers of fibers or fibrils with small interstices therebetween even though the structure is formed from a continuous film.
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RELATED APPLICATION
This application is a Divisional of, and claims the benefit of priority to U.S. patent application Ser. No. 12/043,759, filed on Mar. 6, 2008, entitled Relocatable Habitat Unit, and currently co-pending.
FIELD OF THE INVENTION
The present invention pertains generally to Relocatable Habitat Units (RHUs) for use in simulating an environment for a military combat training scenario. More particularly, the present invention pertains to an RHU that can be assembled and disassembled on-site, using panels that can be maneuvered, positioned and interconnected by no more than two men. The present invention is particularly, but not exclusively, useful as a system and method for the complete assembly of an RHU using only a same, single, hand-operated tool.
BACKGROUND OF THE INVENTION
Military training must necessarily be conducted in an environment that will simulate anticipated combat operations as accurately as possible. For a comprehensive training program, this requires the ability and flexibility to relocate and set-up several different types of training environments. In general, training sites may need to selectively simulate either an urban, suburban or an open terrain environment.
For a training site, the realism that can be attained when simulating a particular environment can be dearly enhanced by introducing indigenous persons (i.e. actors) into the training scenario. Further, in addition to the indigenous persons, urban and suburban environments can be made even more realistic when trainees are confronted by obstacles, such as buildings (e.g. habitats). In most instances, such structures can be relatively modest. Nevertheless, their integration into the training scenario requires planning.
Providing realistic buildings for a training environment requires the collective consideration of several factors. For one, the buildings need to present a visual perception that is accurate for the particular training scenario. Stated differently, they need to “look the part”. For another, it is desirable that structures assembled on the training site be capable of disassembly for relocation to another training site and subsequent use. With this last point in mind, an ability to easily assemble and disassemble a building (i.e. training aide) is a key consideration.
Heretofore, military combat training scenarios have been conducted either on open terrain, or at locations where there have been pre-existing buildings. The alternative has been to bring prefabricated components of buildings to a training site, and then assemble the components to create the building. Typically, this has required special equipment and considerable man-hours of labor.
In light of the above, it is an object of the present invention to provide a construction set and method for assembling and disassembling an RHU, at a training site, with as few as two persons. Still another object of the present invention is to provide a construction set that requires the use of only a same, single, hand operated tool for the assembly and disassembly of an entire RHU. Yet another object of the present invention is to provide a construction set for the assembly and disassembly of an entire RHU that is relatively simple to manufacture, is extremely simple to use, and is comparatively cost effective.
SUMMARY OF THE INVENTION
A Relocatable Habitat Unit (RHU) in accordance with the present invention is assembled using a plurality of substantially flat panels. For this assembly operation, each panel includes male (M) and female (F) connectors. Specifically, these connectors are located along the periphery of the panel. Importantly, all of the male connectors can be engaged with a respective female connector using the same tool. Thus, an entire RHU can be assembled and disassembled in this manner. Further, each panel is sufficiently lightweight to be moved and positioned by one person. As a practical matter, a second person may be required to use the tool and activate the connectors as a panel is being held in place by the other person.
In detail, a construction set for use with the present invention includes a plurality of panels and only the one tool. Each panel has a periphery that is defined by a left side edge, a right side edge, a top edge and a bottom edge. Selected panels, however, can have different configurations that include a door or a window. Still others may simply be a solid panel. In particular, solid panels are used for the floor and ceiling (roof) of the RHU. Essentially, there are wall panels, floor panels, and ceiling panels. Each panel, however, regardless of its configuration, will include at least one male connector and at least one female connector that are located on its periphery.
In addition to the wall, floor, and ceiling panels, the construction set also includes corner connections and ceiling attachments. Specifically, corner connections are used to engage wall panels to each other at the corners of the RHU. The ceiling attachments, on the other hand, allow engagement of roof panels with the top edges of wall panels.
The placement and location of male (M) and female (F) lock connectors on various panels of the construction set is important. Specifically, along the right side edge of each wall panel, between its top edge and bottom edge, the lock configuration is (FMMF). Along its left side edge, the lock configuration is (MFFM). Further, along the top edge the lock configuration is (MM), and along the bottom edge it is (M or F [depending on the connector of the floor panel]).
Unlike the panels, the corner connections are elongated members with two surfaces that are oriented at a right angle to each other. The lock configurations for a corner connection are (F-F) along one surface and (-FF-) along the other surface. Like the corner connections, the ceiling attachments also present two surfaces that are at a right angle to each other. Their purpose, however, is different and accordingly they have a (FF) lock configuration on one surface for engagement with the fop edge of a wall panel. They also have either a (MM) or a (FF) configuration along the other surface for connection with a ceiling panel.
Importantly, in addition to the above mentioned panels, connections and attachments, the construction set of the present invention includes a single hand tool. Specifically, this hand tool is used for activating the various male (M) connectors for engagement with a female (F) connector. For the present invention, this tool preferably includes a hex head socket, a drive that holds the hex head socket, and a ratchet handle that is swivel attached to the drive.
For assembly of the RHU, the first task is to establish a substantially flat floor. This is done by engaging male (M) connectors on a plurality of floor panels with female (F) connectors on other floor panels. The floor is then leveled using extensions that can be attached to the floor. Next, a wall is erected around the floor of the RHU by engaging a male connector on the right side edge of a respective wall panel with a female connector on the left side edge of an adjacent wall panel. Recall, the lock configurations on the left and right edges of wall panels are, respectively, (FMMF) and (MFFM). Additionally, the bottom edge of each panel in the wall is engaged to the floor using mutually compatible male (M) and female (F) connectors. Finally, the roof is created for the RHU by engaging male (M) connectors on ceiling panels with female (F) connectors on other ceiling panels. The ceiling attachments are then engaged to the assembled roof. In turn, the ceiling attachments are engaged to the top edge of a wall panel using mutually compatible male (M) and female (F) connectors. All connections for the assembly of the RHU are thus accomplished using the same tool.
BRIEF DESCRIPTION OF THE DRAWINGS
The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which:
FIG. 1 is a perspective view of an assembled Relocatable Habitat Unit (RHU) in accordance with the present invention;
FIG. 2 is an exploded perspective view of an RHU;
FIG. 3 is an elevation view of three panels for an RHU shown positioned for connection of their respective male (M) and female (F) connectors;
FIG. 4 is a perspective view of a single wall panel of an RHU positioned for engagement with a corner section and a ceiling attachment; and
FIG. 5 is a perspective view of portions of two panels from an RHU, with portions broken away to show the interaction of male (M) and female (F) connectors in their operational relationship with a tool that is used to assemble the RHU in accordance with the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring initially to FIG. 1 , a Relocatable Habitat Unit (RHU) in accordance with the present invention is shown and is generally designated 10 . As shown, the RHU 10 includes a plurality of individual panels, of which the generic panel 12 (sometimes hereinafter referred to as a wall panel) is exemplary. The panel 12 is substantially flat, and is rectangular in shape with a width “w” of approximately four feet and a length “l” of approximately eight feet (i.e. the panel 12 is a 4×8). Alternatively, a panel 12 may be dimensioned as a 4×4. The depth of the panel 12 can vary slightly but, in general, will only be two or three inches. Preferably, the panel 12 is made of a light-weight composite polymer foam type material.
For the present invention there are essentially three different types of panels 12 . These are generally denominated by their structural function in the RHU 10 and are: a wall panel 12 , a ceiling panel 14 and a floor panel 16 . Further, the wall panels 12 may have any of three different configurations. Specifically, these configurations are shown in FIG. 1 , and are: a door panel 18 , a solid panel 20 and a window panel 22 . Regardless of configuration, however, the exterior of each wall panel 12 can be dressed to appropriately simulate the desired indigenous environment. FIG. 1 also shows that the RHU 10 is supported by a plurality of adjustable extensions, of which the extensions 24 a and 24 b are exemplary.
FIG. 2 shows that in addition to the panels 12 , the RHU 10 includes a plurality of corner connections 26 , of which the corner connections 26 a and 26 b are exemplary. Further, FIG. 2 shows there is a plurality of ceiling attachments 28 , of which the ceiling attachments 28 a and 28 b are exemplary. As will be more fully appreciated with further disclosure, these corner connections 26 and ceiling attachments 28 are used to interconnect panels 12 .
It is an important aspect of the present invention that the panels 12 , the corner connections 26 and the ceiling attachments 28 have compatible male (M) and female (F) locking connectors. For example, FIG. 3 shows a door panel 18 , a solid panel 20 and a window panel 22 placed in side-by-side relationship with their respective M and F locking connectors positioned for engagement. Details of the structure involved will, perhaps, be best appreciated by cross referencing FIG. 3 with FIG. 4 .
In FIG. 4 a panel 12 is shown to have a substantially rectangular periphery 30 that is defined by a left side edge 32 , a right side edge 34 , a top edge 36 and a bottom edge 38 . Further, FIG. 4 shows that the panel 12 includes a ledge 40 that extends along the bottom edge 38 and outwardly from the periphery 30 . The purpose of ledge 40 is to rest on a floor panel 16 of an assembled RHU 10 (i.e. when a wall panel 12 has been engaged with the floor panel 16 ), to thereby provide additional support for the panel 12 .
FIG. 4 also shows that a corner connection 26 is an elongated member having a first surface 42 and a second surface 44 . For purposes of the present invention, the first surface 42 needs to be oriented at a right angle (i.e. orthogonal) to the second surface 44 . Importantly, the first surface 42 is provided with F locking components that are aligned as (F-F). Thus, the first surface 42 of corner connection 26 is compatible with the alignment (MFFM) shown for locking connectors on the left side edge 32 of the panel 12 . Stated differently, the top and bottom M lock connectors on the left edge 32 of panel 12 will lock, respectively, with the top and bottom F lock connectors on first surface 42 of corner connection 26 . Note also that the alignment of locking connectors on the second surface 44 of corner connection 26 is (-FF-), This is likewise compatible with the alignment (FMMF) that is typical for the right side edge 34 of a panel 12 (see also FIG. 3 ).
Like the corner connections 26 , the ceiling attachments 28 are elongated members. Also, the ceiling attachments 28 have a first surface 46 and a second surface 48 . Like the corner connections 26 , the first surface 46 of the ceiling attachment 28 needs to be oriented at a right angle (i.e. orthogonal) to its second surface 48 . The similarities end there, however. As shown in FIG. 4 , the second surface 48 of the ceiling attachment 28 includes a pair of F locking connectors that will interact with respective M locking connectors along the top edge 36 of the panel 12 . On the other hand, the first surface 46 may have either M or F locking connectors for engagement with a ceiling panel 14 .
The interaction of M and F locking connectors will be best appreciated with reference to FIG. 5 . There it will be seen that the present invention employs a tool, generally designated 50 . As shown, the tool 50 includes a hex head 52 that is connected to a drive 54 . It will be appreciated by the skilled artisan that the hex head 52 shown in FIG. 5 , however, is only exemplary of head configurations that may be used for the present invention, In any event, the drive 54 is connected to a swivel ratchet 56 that, in turn, is connected to a handle 58 . As envisioned for the present invention, this tool 50 is all that is required to assemble the RHU 10 .
Still referring to FIG. 5 , it will be seen that the panel portions 12 a and 12 b have respective F and M locking connectors. As envisioned for the present invention, all M and F locking connectors used for the RHU 10 of the present invention are substantially identical. In detail, the M locking connector is shown to include a hex socket 60 with an attached cam lock 62 . Further, the cam lock 62 is shown to have an upper ramp 64 and a lower ramp 66 that are inclined so there is an increasing taper extending from end 68 back to the hex socket 60 . In contrast, the F locking connector on panel 12 a is shown to include an upper abutment 70 and a lower abutment 72 .
For an engagement between an M and an F locking connector, the connectors need to first be juxtaposed with each other. This can be accomplished in any of several ways. For instance, either side edges 32 / 34 of panels 12 are juxtaposed to each other (e.g. see FIG. 3 ); ceiling panels 14 and floor panels 16 are respectively juxtaposed (see FIG. 2 ); a corner connection 26 is juxtaposed with a side edge 32 / 34 of a panel 12 (e.g. see FIG. 4 ); a ceiling attachment 28 is juxtaposed with the top edge 36 of a panel 12 or with a ceiling panel 14 ; or the bottom edge 38 of a panel 12 is juxtaposed with a floor panel 16 . In each case, it is important that an M locking connector be positioned opposite an F locking connector.
Once an M and an F locking connector have been properly positioned with each other, as indicated above, the hex head 52 of tool 50 is inserted into the hex socket 60 . The tool 50 is then turned in the direction of arrow 74 . This causes the ramps 64 / 66 of cam lock 62 to respectively go behind the abutments 70 / 72 . The M and F locking connectors are then engaged.
In accordance with the present invention, assembly of the RHU 10 is best accomplished by following a predetermined sequence of steps. First, a plurality of floor panels 16 is engaged together to form a floor for the RHU 10 . The floor is then positioned and leveled by adjusting the extensions 24 that are provided for that purpose. Next, starting at a corner for the RHU 10 , a corner connection 26 is engaged with panels 12 . Note: at this point the respective ledges 40 on panels 12 are positioned to rest on the adjacent floor panel 16 . Also, the bottom edges 38 of the wall panels 12 are engaged through M/F locking connections to the adjacent floor panel 16 . This continues until all wails of the RHU 10 have been erected. As intended for the present invention, door panels 18 , solid panels 20 and window panels 22 can be used as desired in the assembly of the walls for the RHU 10 .
After the walls of RHU 10 have been erected, the roof is created. Specifically, ceiling attachments 28 are engaged, as required, with a single ceiling panel 14 (see FIG. 2 ). This ceiling panel 14 , with its ceiling attachments 28 , is positioned so the ceiling attachments 28 can be connected, via M/F locking connectors, to the top edges 36 of respective panels 12 . Additional ceiling panels 14 and their associated ceiling attachments 28 can then be similarly created, positioned and connected to other ceiling panels 14 and other wall panels 12 , to complete the roof. The RHU 10 is thus assembled, and appropriate set dressing can then be added.
Importantly, all of the tasks described above for the assembly of an RHU 10 are accomplished using only the tool 50 . Axiomatically, it follows that the entire RHU 10 is held together with only a plurality of M/F locking connections.
While the particular Relocatable Habitat Unit as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims.
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A construction set and method for assembling a Relocatable Habitat Unit (RHU) requires a plurality of flat panels that include male (M) and female (F) connectors located on their respective peripheries. The entire RHU can then be assembled using a single, hand-operated tool to engage a selected M with a selected F. First the floor is established and leveled. Next, starting at a corner, the walls are erected around the floor. Finally, the roof is created. A same, hand-operated tool is used for each task.
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FIELD OF THE INVENTION
[0001] This invention relates to the use of extracellular matrix components derived from stem cells in skin-related applications.
BACKGROUND
[0002] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Skin care products for anti-aging and anti-wrinkle applications operate through a variety of mechanisms. This includes products that promote moisture retention for hydration of the skin surface, application of nutrients to nourish skin cells, and reducing exposure to noxious agents, among many others (for example, PCT App. No. PCT/US2010/044162 and U.S. Pat. No. 7,887,858). Skin tissue possesses inherent properties of self-renewal and regeneration as a result of complex biochemical interactions within different skin layer compartments (epidermis and dermis). The present invention relates to skin cosmetics and methods of manufacture, including cosmetics that feature constitutive extracellular matrix (ECM) components derived from cultured stem cells. Purified and isolated ECM from cultured stem cells also provides a consistent and renewable source of biologically active molecules, which can be used for anti-aging and anti-wrinkle applications by enhancing the regenerative capacity of the skin. Furthermore, manufacturing from cell cultures minimizes the potentially deleterious effects and problems posed by contamination, impurities and immunogenicity.
[0004] Constitutive ECM components from animal tissue, such as different kinds of protein collagens and elastin, glycoprotein fibronectin and laminin are widely used in the cosmetic, biomedical and pharmaceutical industries. Although these ECM proteins are typically extracted from pooled tissues, mainly from bovine origin, some human ECM products have been obtained from adult cadaveric tissues. These sources of ECM components pose risks to users from the presence of possible infectious and immunogenic agents. Further, animal or human sources of ECM components may vary in efficacy and consistency, due to variability in extrinsic environmental exposure (e.g. UV exposure, dietary intake) or intrinsic heterogeneity in individual or groups of source organisms. Such sources may suffer from molecular cross-linking due to UV exposure, or be degraded or excessively modified by non-enzymatic glycation.
[0005] Other ECM components, including for example, collagen and collagen-derived products also can be produced recombinantly (for example, U.S. Pat. No. 6,992,172). However, recombinant proteins can have different patterns of cross-linking and other post-translation modifications that are provided in living cells. Thus, recombinantly produced ECM components may lack the intricate molecular arrangements necessary for fully activating the regenerative capacity of the skin and halting the progressive degradation of skin compartments due to aging or environmental exposure.
[0006] A new source of ECM products is desirable in which active ECM components such as proteins, glycoproteins, and proteoglycans are produced in a controlled environment. This approach minimizes exposure to infectious and immunogenic agents, reduces environmental and biological variability, and improves efficacy with biologically compatible and biologically activated molecules. Aspects of the invention described herein provide methods of manufacture of ECM products from clonally expanded embryonic stem (ES) cells, adult stem cells or any other type of pluripotent or multipotent cell capable of self-renewal.
[0007] Embryonic stem cells are pluripotent cells that give rise to multipotent stem cells, which in turn are capable of differentiating into virtually all cell types in an organism. Embryonic stem cells possess properties of self-renewal that allow virtually unlimited propagation in cell cultures without differentiation. Embryonic stem cells are available from a variety of organisms including mice, primates (U.S. patent application Ser. No. 11/033,335; U.S. Pat. Nos. 5,843,780, 6,200,806, and 7,582,479), and humans (U.S. patent application Ser. No. 09/975,011; Thomson et al. “Embryonic Stem Cell Lines Derived from Human Blastocysts,” Science. 282 (1998): 1145-47). The differentiation and self-renewal properties of the ES cell provide a consistent and renewable source of biological material, which can be adapted for delivering biologically active molecules for use in anti-aging and anti-wrinkle applications.
[0008] Cultured ES cells can form embryoid bodies (EBs), which are small clusters of multipotent progenitor cells, some of which are already committed to a specific lineage. Therefore, EBs can be defined as organized stem cell-derived cell clusters containing progenitor cells partially committed to the various lineages originating from the 3 germ layers (endoderm, mesoderm, ectoderm). These clusters may contain both pluripotent and multipotent stem cells, herein referred to as a stem cell clusters (SCCs). Differentiation of ES cells into SCCs promotes expression, production and development of various ECM components, including proteins, glycoproteins, and proteoglycans, that are involved in skin maintenance and repair mechanisms. SCCs form spontaneously in cell cultures, following withdrawal of factors supporting pluripotency (e.g., growth factors, serum, matrix or adherence substrate) and in physical conditions supporting aggregation into clusters (e.g., semi-solid solutions, low adherence tissue culture surfaces, hanging drop suspension).
[0009] While ES cells and SCCs have been well-studied, the use of ECM components prepared or derived from cultured ES cells for cosmetic applications has not been recognized and developed. There remains a need in the art for consistent and renewable sources of ECM components from cultured ES cells. There also remains a need in the art for additional cosmetic formulations that achieve anti-wrinkle, anti-aging and other therapeutic and/or cosmetic benefits.
SUMMARY
[0010] The following embodiments and aspects thereof are described and illustrated in conjunction with compositions and methods which are meant to be exemplary and illustrative, not limiting in scope. The present invention provides a method for obtaining at least one extracellular matrix component, the method comprising the steps of culturing mammalian embryonic stem cells (“ESCs”) to form a culture of ESCs, extracting from the culture of ESCs or differentiated ESCs the at least one extracellular matrix component. In one embodiment, the mammalian ESCs are murine ESCs. In another embodiment, the mammalian ESCs are cultured on feeder cells. In another embodiment, method further comprises the step of inducing differentiation in the culture of ESCs prior to the step of extraction. In another embodiment, method further comprises treating the culture of ESCs with dispase or collagenase prior to the step of inducing. In another embodiment, the inducing step further comprises transferring the culture of ESCs to a container under conditions which reduce the likelihood of adherence of the culture of ESCs to a surface of the container. In another embodiment, the inducing step further comprises inducing the culture of ESCs in a media solution. In another embodiment, method further comprises the step of rocking a container containing the culture of ESCs. In another embodiment, method further comprises inducing the culture of ESCs in a hanging drop. In another embodiment, the step of extracting further comprises contacting the culture of ESCs with a salt, a detergent and/or an acid, and separating the culture of ESCs from the at least one extracellular matrix component. In another embodiment, method further comprises the step of purifying the at least one extracted extracellular matrix component. In another embodiment, the step of purifying further comprises centrifugation, chromatography, precipitation, filtration and/or organic solvent extraction. In another embodiment, method further comprises the step of lyophilizing the at least one extracted extracellular matrix component. In another embodiment, the at least one extracellular matrix component is a collagen. In another embodiment, the method further comprises contacting the at least one extracellular matrix component with a protease. In another embodiment, the at least one extracellular matrix component is a proteoglycan. In another embodiment, the at least one extracellular matrix component is elastin. In another embodiment, the at least one extracellular matrix component is laminin or fibronectin.
[0011] Another embodiment of the present invention provides a composition comprising at least one extracellular matrix component extracted from a culture of mammalian embryonic stem cells (“ESCs”) or differentiated ESCs and a cosmetically-acceptable carrier. In one embodiment, mammalian ESCs are murine ESCs. In another embodiment, the mammalian ESCs are cultured on feeder cells. In another embodiment, the at least one extracellular matrix component is produced by a process, comprising culturing ESCs to form a culture of ESCs, inducing the ESCs to differentiate, and extracting from the culture of ESCs the at least one extracellular matrix component. In another embodiment, the composition further comprises treating the culture of ESCs with dispase or collagenase prior to the step of inducing. In another embodiment, the inducing step further comprises transferring the culture of ESCs to a container under conditions which reduce the likelihood of adherence of the culture of ESCs to a surface of the container. In another embodiment, the inducing step further comprises inducing the culture of ESCs in a media solution. In another embodiment, the step of extracting further comprises contacting the culture of ESCs with a salt, a detergent and/or an acid, and separating the culture of ESCs from the at least one extracellular matrix component. In another embodiment, the present invention further comprises the step of purifying the at least one extracted extracellular matrix component. In another embodiment purification step further comprises centrifugation, chromatography, precipitation, filtration and/or organic solvent extraction. In another embodiment, the composition further comprising the step of lyophilizing the at least one extracted extracellular matrix component. In another embodiment, the at least one extracellular matrix component is a collagen. In another embodiment, the at least one extracellular matrix component is treated with a protease. In another embodiment, the at least one extracellular matrix component is a proteoglycan. In another embodiment, the at least one extracellular matrix component is elastin. In another embodiment, the at least one extracellular matrix component is laminin or fibronectin.
[0012] The present invention further provides a method of manufacturing a composition comprising the steps of providing at least one extracellular matrix component extracted from a culture of mammalian embryonic stem cells (“ESCs”) or differentiated ESCs and adding a cosmetically-acceptable carrier to the at least one extracellular matrix component. In one embodiment, the mammalian ESCs are murine ESCs. In another embodiment, the at least one extracellular matrix component is a collagen. In another embodiment, the at least one extracellular matrix component is a proteoglycan. In another embodiment, the at least one extracellular matrix component is elastin. In another embodiment, the at least one extracellular matrix component is laminin or fibronectin.
[0013] The present invention also provides a method of treatment comprising the steps of providing a composition comprising at least one extracellular matrix component extracted from a culture of mammalian embryonic stem cells (“ESCs”) or differentiated ESCs, applying the composition to a subject, whereby the subject is treated. In another embodiment, the mammalian ESCs are murine ESCs. In another embodiment, the at least one extracellular matrix component is a collagen. In another embodiment, the at least one extracellular matrix component is a proteoglycan. In another embodiment, the at least one extracellular matrix component is elastin.
[0000] In another embodiment, the at least one extracellular matrix component is laminin or fibronectin.
[0014] The present invention further provides the use of a composition comprising at least one extracellular matrix component extracted from a culture of mammalian embryonic stem cells (“ESCs”) or differentiated ESCs in the manufacture of a cosmetic composition to treat a subject treatable by application of the composition.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Exemplary embodiments are illustrated in referenced figures. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive.
[0016] FIG. 1 is a depiction of a process embodiment for the formation of SCCs. Cells from a stock of actively growing ES cells are transferred into culture media and dispersed into individual drops of media, which are then placed inverted in a culture plate. As cells within each drop grow, they form spherical multicellular aggregates herein referred to as Stem Cell Clusters or SCCs (also known as embryoid bodies). The SCCs are transferred to an adherent culture plate and further expanded in culture for 12 days. On day 15, the resulting SCCs are harvested and the ECM extracted.
[0017] FIG. 2 is a depiction of the presence of ECM elaborated by stem cells grown in culture under conditions favoring formation of SCCs. Murine SCCs were grown in culture for the indicated periods of time and then harvested for histological examination. Frozen sections were prepared and then processed for standard H&E staining, followed by visualization at two different magnifications (lower magnification: 4 days FIG. 2A , 10 days FIG. 2B , 15 days FIG. 2C ; higher magnification: 10 days FIG. 2D , 14 days FIG. 2E ). As the SCCs expand in culture, they produce extracellular matrix visible as an amorphous hyaline material interspersed in the intercellular space (arrows). Thus, SCCs represent a suitable source of ECM components elaborated by pluripotent and multipotent stem cells in culture.
[0018] FIG. 3 is a depiction of the major types of collagen produced by stem cells grown in culture in the form of SCCs, including collagen IV. SCCs were harvested after 14 days in culture as described in FIG. 2 and frozen sections were prepared for immunostaining using antibodies against collagen I ( FIG. 3A ), III ( FIG. 3B ) and IV ( FIGS. 3C&D ). Immune complexes were detected with Alexa Fluor® 594-conjugated goat anti-mouse IgG and visualized under a fluorescence microscope. It is evident that SCCs can produce the major types of collagens, including collagen IV. Collagen IV is a distinctive type of non-fibrillar collagen that forms sheet-like aggregates predominantly found in basement membranes and at the dermal-epidermal junction (DEJ). The DEJ is a specialized structure separating the epidermis and dermis, which plays a key role in the normal barrier function of the skin.
[0019] FIG. 4 is a depiction of an embodiment of the process for the extraction and fractionation of ECM components and incorporation of purified component fractions into formulations for cosmetic applications. Pluripotent ES cells are grown under culture conditions favoring formation of SCCs, which are then harvested and processed for extraction of collagen-enriched ECM components. Extracts are prepared either by solubilization with an organic acid (e.g. lactic, acetic) aided by gentle digestion with pepsin or by cell lysis using a combination of a non-ionic detergent and NH 4 OH. The resulting collagen-enriched fractions are characterized by measuring the abundance of soluble collagen and/or hydroxyproline content. These purified extracts are then incorporated into suitable cosmetic formulations containing appropriate emollients and preservative agents and microencapsulated into liposomes or nanoparticle carriers. Cosmetic performance is then established in human volunteers by determining the safety and stability profile, as well as moisturization and wrinkle reduction efficacy.
[0020] FIG. 5 is a depiction of a biochemical analysis of ECM extracts prepared from SCCs confirming the presence of collagen IV and collagen I, components that represent abundant elements of the normal ECM. SCCs were harvested after 14 days in culture (see FIG. 2 ) and crude fractions prepared using a partial pepsin/acid extraction as described in FIG. 4 . FIG. 5A , the protein composition of the extracts was initially assessed by electrophoretic fractionation of proteins (SDS-PAGE) in serially titrated samples, showing a predominant band with an apparent molecular mass of 50 kDa. FIG. 5B , the predicted peptides resulting from a pepsin digest of collagen IV indicate the presence of two 50 kDa peptides (P1 and P2), which originate from each of the α Col IV tropocollagen chains (α1 IV and α2 IV). Aumailley and Timpl, “Attachment of Cells to Basement Membrane Collagen Type IV,” J. Cell Biol. 103 (1986): 1569-1575. Peptide P3 is further digested into much smaller fragments that would migrate towards the bottom of the gel. FIG. 5C , the presence of peptides with collagen IV and collagen I immunoreactivity was determined in extract samples (AMS) by ELISA using specific anti-Col IV and anti-Col I antibodies. Signal detected in the AMS samples was compared to the serially-diluted standards to estimate the relative concentration of collagen IV- and collagen I-related peptides. These results suggest that soluble ECM extracts prepared from cultured SCCs contain collagens I and IV, providing independent biochemical evidence consistent with the immunological detection of these collagens in intact SCCs.
DETAILED DESCRIPTION
[0021] All references cited herein are incorporated by reference in their entirety as though fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Singleton et al., Dictionary of Microbiology and Molecular Biology 3 rd ed., J. Wiley & Sons (New York, N.Y. 2001); March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 5 th ed ., J. Wiley & Sons (New York, N.Y. 2001); and Sambrook and Russel, Molecular Cloning: A Laboratory Manual 3 rd ed ., Cold Spring Harbor Laboratory Press (Cold Spring Harbor, N.Y. 2001), provide one skilled in the art with a general guide to many of the terms used in the present application.
[0022] One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods and materials described. For purposes of the present invention, the following terms are defined below.
[0023] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[0024] The term “stem cells” as used herein, are cells that are not terminally differentiated and are therefore able to produce cells of other types. Stem cells are divided into three types, including totipotent, pluripotent, and multipotent. “Totipotent stem cells” can grow and differentiate into any cell in the body, including extraembryonic tissues (e.g. placenta) and thus, can form the cells and tissues of an entire organism. “Pluripotent stem cells” are capable of self-renewal and differentiation into any cell or tissue type, except extraembryonic tissues. In contrast to pluripotent cells, “multipotent stem cells” are unspecialized cells that can propagate indefinitely and differentiate into specialized cells with specific functions. In this respect, multipotent stem cells are essentially committed to differentiate into specific cell types. The term “stem cells”, as used herein when referring to cells obtained from any animal source, refers to either multipotent or pluripotent stem cells capable of self-renewal and differentiation. Examples include embryonic stem cells, induced pluripotent stem cells, induced multipotent stem cells, skin stem cells, umbilical cord, hematopoietic stem cells, neural stem cells, and mesenchymal stem cells. “Stem cells”, as used herein where referring to cells obtained from any non-animal source, refers to totipotent, multipotent, or pluripotent stem cells capable of self-renewal and differentiation. Examples include dedifferentiated cells obtained from plants, fruits and vegetables.
[0025] The term “embryonic stem cells” (ES cells) is used herein as it is used in the art and is a type of stem cell. Sources of ES cells include those derived from the inner cell mass of human blastocysts or morulae, which can be serially passaged as cell lines, and wherein use of the cell line for various methods and compositions does not directly involve the destruction of an embryo. Further exemplary stem cells include induced pluripotent stem cells (iPSCs) generated by reprogramming a somatic cell by expressing a combination of factors, including Oct 3/4, Sox2, c-Myc, Klf4, Nanog and lin28. The iPSCs can be generated using fetal, postnatal, newborn, juvenile, or adult somatic cells. As an alternative, potential induction of somatic cells into multipotent stem cells would further provide a suitable source of ECM materials.
[0026] Stem cells can be from any species of organism. Embryonic stem cells have been successfully derived in, for example, mice, multiple species of non-human primates, and humans, and embryonic stem-like cells have been generated from numerous additional species. Thus, one of skill in the art can generate embryonic stem cells from any species, including but not limited to, human, non-human primates, rodents (mice, rats), ungulates (cows, sheep, etc), among others. Similarly, iPSCs can be from any species. These iPSCs have been successfully generated using mouse and human cells. Furthermore, iPSCs have been successfully generated using embryonic, fetal, newborn, and adult tissue. Accordingly, one can readily generate iPSCs using a donor cell from any species.
[0027] Stem cells can be obtained from plant, fruit, and vegetables species, following the dedifferentiation of adult cells obtained from the plant, fruit, and vegetables species in cell cultures. When placed on a solid medium surface, such as agar, adult cells from the plant, fruit, and vegetables species are induced to dedifferentiate into pluripotent stem cells capable of self-renewal and differentiation into virtually every cell type found in the source plant, fruit, or vegetable.
[0028] The term “differentiation” of stem cells in general as used in the present invention means the change of pluripotent stem cells into multipotent cells committed to a specific lineage and/or cells having characteristic functions, namely mature somatic cells.
[0029] “Treatment” or “treating” refers to therapy, prevention or prophylaxis and particularly refers to the administration of medicine or cosmetics or the performance of medical or cosmetic procedures with respect to a subject. Treatment may be for prophylactic purposes to reduce the extent or likelihood of occurrence of a disease state, disorder or condition. Treatment may also be for the purpose of reducing or eliminating symptoms of an existing disease state, disorder, condition, or undesirable appearance. Treatment may directly eliminate infectious agents or other noxious elements causing a disease state, disorder or a condition. Treatment may alternatively occur through enhancement and stimulation of an organism's natural immune system, such as promoting or facilitating repair and regeneration of damaged or disease cells and/or tissue. Treatment may also occur by supplementing or enhancing the body's normal function, such as the formation of collagen.
[0030] “Subject” or “patient” refers to a mammal, preferably a human, in need of treatment for a condition, disorder or disease.
[0031] “Cosmetically effective amount” as used herein is the quantity of a composition provided for administration and at a particular dosing regimen that is sufficient to achieve a desired appearance, feel, and/or protective effect. For example, an amount that results in the prevention of or a decrease in the appearance and/or symptoms associated with an undesirable condition, such as wrinkles, fine lines, skin thinness, loss of skin elasticity or suppleness, or other characteristics of skin associated with aging, UV, chemical exposure, adverse climate (e.g., temperature, humidity), dietary intake, biological agents, environmental oxidants, among others.
[0032] The present invention relates to a method for isolating and purifying extracellular matrix components (ECM), through culturing of mammalian ES cells (native or induced), inducing the mammalian ES cell to form SCCs, and extracting from these SCCs at least one ECM component. The mammalian ES cell can be derived from any suitable mammal, including a primate, rodent, or a human ES cell. One stem cell embodiment includes a non-primate, mammalian ES cell. According to various methods, ES cells can be cultured on a layer of support feeder cells, but preferably, are cultured in the absence of feeder cells. The cells can be treated with enzymes during culture, including dispase or collagenase.
[0033] The ES cells are induced to form SCCs by any suitable technique. For example, the cultured cells can be transferred to a container under conditions which prevent adherence of the cells to a surface of the container. The cells can be rocked in a suitable media solution, or can be cultured in hanging drops to prevent adhesion to the cell culture surfaces. Alternatively, they can also be grown in a culture vessel made with a material that does not support adhesion of cultured cells.
[0034] The ECM components can be extracted from SCCs by a variety of methods, including treatment of the cell with a salt, a detergent or an acid, and then separating the cells from the ECM components. The extracted ECM components can then be further purified by any suitable method. For example, the extracted ECM components can be purified, enriched or concentrated by centrifugation, chromatography, precipitation, filtration or organic solvent extraction, or any combination of these and other biochemical techniques. Alternatively, ECM components can be extracted from cultured ES cells that are kept in their native, undifferentiated multipotent stage or cultured ES cells that are subjected to induced or spontaneous differentiation without necessarily being derived from SCCs. It is appreciated that crude preparations of multiple ECM components may be prepared through whole cell extracts obtained directly from cultured ES cells, partially differentiated ES cells not requiring SCC formation, or through cells obtained from SCC differentiation. However, purification of specific ECM components, substantially free of non-ECM molecules (e.g., nucleic acid, intracellular proteins), enhances efficacy of various compositions, by eliminating molecules possessing inert or interfering properties at the skin surface and increases safety by removing potentially immunogenic factors.
[0035] According to the methods, the ECM component can be a collagen-containing extract, wherein the extracted ECM is treated with a protease to purify the collagen. Suitable proteases include: papain, chymo-papain, bromelain, protease VIII, or protease X. The ECM component to be purified also can be a proteoglycan, including, for example, hyaluronic acid, chondroitin sulfate, or heparan sulfate. The ECM component also can be elastin, laminin or fibronectin, as well as any other previously functionally active elements that form part of the ECM produced by ES cells.
[0036] Aspects of the present invention also include compositions of at least one ECM component purified from an embryoid body according to the methods of the present invention. Such compositions are suitable for a variety of applications, including cosmetic applications. The components also can be used as matrix components or stimulants or inhibitors for cell culture.
[0037] Other aspects of the present invention also provide methods delivering to a subject a cosmetically effective amount of a composition of the present invention. The extracted or purified ECM components can also be used directly in a subject to neutralize or inhibit endogenous proteases (e.g. matrix metalloproteinases or MMPs), induce cell growth, enhance production of regenerative factors, or to create a niche for cell homing at desired tissues or organs. The ECM components also can be applied to treat skin disorders including scars, burn, abrasion, incision, contusion or laceration. The ECM components also can be applied to treat skin defects or deformations including folds, wrinkles, distensions, asymmetries and other defects that are correctible using ECM. For such treatments, the composition is typically delivered intradermally, subcutaneously, surgically or topically.
[0038] Embryonic Stem Cells.
[0039] Embryonic stem cells are unique cells capable of self-renewal and differentiation into cell types derived from all three embryonic germ layers (mesoderm, endoderm, and ectoderm). Embryonic stem cells are derived from the inner cell mass of mammalian blastomeres and can be grown as cell lines plated on either mitotically-inactivated fibroblasts “feeder” support cells or under feeder-free conditions using a support matrix (e.g., gelatin, matrigel, collagen). More recently, ES cells can be grown in chemically defined conditions without the use of animal serum, thereby eliminating the risk of exposure to xenogenic pathogens. Clinical grade human ES cells lines have also been established, wherein initial isolation and subsequent culturing of ES cells has been performed entirely without the use of non-human animal products. Ellerström et al., “Derivation of a Xeno-Free Human Embryonic Stem Cell Line,” Stem Cells. 24 (2006): 2170-6.
[0040] Generally, ES cells possess cellular morphology of round shape, large nucleolus and scant cytoplasm. Embryonic stem cells from different species can be characterized by various sets of markers associated with pluripotency, as known in the art. For example, undifferentiated mouse ES cells possess a compact, round, multi-layer cluster morphology and express several cellular markers associated with pluripotency. This includes transcription factors Oct-4, Sox-2, and Nanog, surface antigen SSEA-1, and high levels of alkaline phosphatase (AP) expression. In contrast, pluripotent human ES cells possess a sharp-edged, flat, tightly-packed colony morphology, although similar markers can be used to characterize pluripotency in human ES cells. This includes expression of Oct-4, Sox-2, and Nanog with high levels of AP expression, and surface antigens SSEA-3, SSEA-4, TRA-1-60, TRA-1-81. A variety of established biochemistry, cell and molecular biology techniques can be used to detect the expression of these pluripotent markers, including flow cytometry, reverse transcription PCR (RT-PCR), quantitative real-time PCR (qRT-PCR), western blotting, enzymatic staining, among others. Other techniques can establish the pluripotent capacity of cell cultures, including teratoma formation in immunodeficient mice. Forming teratomas in mice requires injection of pluripotent ES cells into immunodeficient mice and observing formation of differentiated cell types from all three embryonic germ layers.
[0041] Mouse embryonic stem cells have been widely available as established cell lines for over 20 years. Examples of established mouse cell lines include ES-057BL/6, J1, R1, R1/E, ESF 158, RW.4, AB2.2, B6/BLU, CE-1, CE3, and CCE. Further examples include those listed in databases for distributors such as ATCC, Jackson Laboratory, Taconic, among others. Today, various human ES cell lines are established and readily available for distribution from commercial and non-commercial sources, thereby eliminating the need for directly manipulating embryos as source materials. Examples of established ES cell lines include H1, H7, H9, H13, H14, HES3-6, CHB1-12, HUES1-66, BG01V, among many others. This also includes iPSC cell lines, such as DMD-IPS1, DMD-IPS2, DS1-IPS4, HD-IPS1, HD-IPS4, IPS(FORESKIN)-1, IPS(FORESKIN)-2, IPS(FORESKIN)-3, IPS(FORESKIN)-4, IPS(IMR90)-1, IPS(IMR90)-2, IPS(IMR90)-3, IPS(IMR90)-4, among many others. Further examples of human ES and iPSC cell lines include those registered in the University of Massachusetts International Stem Cell Registry.
[0042] Culturing Embryonic Stem Cells.
[0043] The methods of the present invention can be used with any mammalian ES cell line including new stem cell lines derived from mammalian blastocysts or any induced stem cells of somatic origin. In one embodiment, the stem cells are human ES cells, primate stem cells, rodent stem cells, bovine stem cells, or porcine ES cells. Importantly, ES cells are capable of self-renewal and can be propagated indefinitely in cell cultures, thereby providing a consistent and renewable source of biological material.
[0044] The selection of ES cell will depend on the application. For example, human embryonic stem cells may be the most desirable source for use in extracting collagen for injection. Where the use is topical, the stem cell source may be derived from another species, including murine or mammalian embryonic stem cells.
[0045] The ES cells can be maintained in culture according to suitable methods known in the art. It is advantageous to prevent ES cells from differentiating until it is desirable to induce formation of SCCs or any other manipulation resulting in differentiation of stem cells. Differentiated cells possess reduced proliferative capacity and diminished capacity to mature into various cell types. A number of methods of culturing both mouse and human ES cells are known and described in the art (for example, U.S. patent application Ser. No. 11/027,395 and 10/507,884; U.S. Pat. Nos. 7,455,983, 7,297,539 and 7,439,064). Briefly, ES cells can be cultured on a substrate of mitotically-inactivated support feeder cells or cultured under defined conditions in the absence of feeder cells (Ludwig et al., “Derivation of Human Embryonic Stem Cells in Defined Conditions,” Nature Biotechnology. 24 (2006): 185-187; Ludwig et al., “Feeder-Independent Culture of Human Embryonic Stem Cells,” Nature Methods 3 (2006): 637-646). Other techniques and methods for culturing stem cells can be found in Turksen, ed., Embryonic Stem Cells: Methods and Protocols , Humana Press (Totowa, N.J. 2002); Notarianni and Evans, Embryonic Stem Cells: A Practical Approach, Oxford University Press (U.S.A. 2006); and Robertson, ed., Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, Oxford IRL Press (Washington D.C. 1987).
[0046] A variety of growth factors are utilized for the expansion and maintenance of undifferentiated ES cells without the use of support feeders. For example, mouse ES cells can be readily expanded in the presence of leukemia inhibitory factor (LIF) supplemented with serum or under chemically-defined conditions. Human ES cells require more complex solutions, but also can be expanded under feeder-free and/or chemically-defined conditions. One example includes the use of knockout serum replacement (KO-SR), basic fibroblastic growth factor (bFGF) on matrigel, as described in Xu et al., “Feeder-Free Growth of Undifferentiated Human Embryonic Stem Cells,” Nature Biotech. 19 (2001): 971-4. Other combinations include the use of Wnt3a (or Wnt/β-catenin pathway agonists), TGFβ, Activin A, and Nodal, in combination with bFGF (Nieden, ed., Embryonic Stem Cell Therapy for Osteo - Degenerative Diseases: Methods and Protocols , Humana Press (Totowa, N.J. 2010)). Another example includes use of April, BAFF (B cell activating factor), Wnt3a, insulin, transferrin, albumin, cholesterol, in combination with bFGF (Ludwig et al., 2006; Lu et al., “Defined Culture Conditions of Human Embryonic Stem Cells,” Proc. Nat. Acad. Sci., 103 (2006): 5688-5693).
[0047] Large Scale Production of Embryonic Stem Cells.
[0048] Embryonic stem cells can be grown in large scale cultures according to suitable methods known in the art. Generally, expansion of pluripotent stem cells and later differentiation into multipotent stem cells or specialized cell types depends on physiochemical environment, nutrients and metabolites and the presence/absence of growth factors. Polak and Mantalaris, “Stem Cells Bioprocessing: An Important Milestone to Move Regenerative Medicine Research into the Clinical Arena,” Ped. Res. 63 (2008): 461-466.
[0049] A well-established technique to provide a suitable physiochemical environment for large scale expansion of ES cells is the use of cell culture flasks (e.g., T75, T150, T175 flask) or cell trays. Thomson, Trends in Biotech. 25 (2007): 224-230. Embryonic stem cells grown in cell culture flasks or trays can adhere directly to an untreated cell culture surface, can be deposited on a layer of support matrix (e.g., gelatin, matrigel, collagen) to provide a semi-adherent state of attachment, or are grown in suspension without attachment. Traditionally, advantages of “two-dimensional” culture systems include simplicity, ease of handling, and low cost. Several cell culture flasks or trays can be combined together to form cell “factories”, thereby providing an easy and straightforward means to grow progressively larger numbers of cells. Placzek et al., “Stem Cell Bioprocessing: Fundamentals and Principles,” J. R. Soc. Interface. 7 (2009): 209-232. A further advantage includes convenient access to cells for harvesting or addition/supplementation of nutrients and metabolites. Additionally, cell culture flasks or trays provide few physical interfaces/openings, which lowers the risk of contamination or infiltration of contaminating particles. Often, cell culture flasks or trays are grown in static cell cultures, wherein diffusion is the primary means for mass transport of nutrients, metabolites, oxygen and other factors. Static culturing imparts little or no shear mechanical stress on cells, thereby maintaining cell viability, morphology and integrity.
[0050] Static cell culture techniques may be modified or adapted to provide physical or biomechanical features to improve expansion of undifferentiated ES cells or to promote development of specific cellular phenotypes. Examples of physical features include use of natural or synthetic scaffolds, which increase available surface area for cellular attachment and growth. Use of “three-dimensional” culture surfaces thereby proves higher cell densities in the expansion of undifferentiated ES cells. Similar improvements can be obtained through modification of the cell culture vessel surface, including use of recessed and/or elevated patterns, grooves, micro- and nano-chambers to increase surface area for cellular attachment (Thomson, 2007).
[0051] Biomechanical features include dynamic culture conditions to improve delivery of nutrients, metabolites, oxygen and other factors involved in stem cell growth and maintenance. Whereas static culturing relies primarily on diffusion for mass transport, dynamic culture conditions, enhance mass transport by altering fluid velocity in a cell culture (Thomson, 2007). Common examples include perfusion and stirring of cell culture media.
[0052] Use of dynamic cultures via stirring, has been reported to lead up to a 10-fold increase in cell density compared to traditional methods (Zandstra et al., “Stem Cell Bioengineering,” Ann. Rev. Biomed. Eng. 3 (2001): 275-305). A limitation of dynamic culturing conditions is creation of shear stress (i.e., the force exerted over cells due to the flow of media), which may lead to deleterious effects on stem cell viability if media velocity is too high. In contrast, low media velocities have been reported to result in cell clumping, which lowers overall mass transport conditions. Other techniques known in the art rely on microcarriers or encapsulation of cells to capture various features of both static (i.e., cell attachment with reduced shear stress) and dynamic (i.e., higher mass transport) cell culturing techniques.
[0053] Stem Cell Clusters.
[0054] Cultured stem cells can be induced to form SCCs, which are partially differentiated clusters of ES cells that spontaneously form following removal of pluripotent support factors and under physical conditions promoting cell aggregation. Differentiation of ES cells into SCCs promotes the expression, production and development of ECM components involved in skin maintenance and repair mechanisms, including proteins, glycoproteins, and proteoglycans. Differentiating ES cells into SCCs results in a loss of expression of ES cell pluripotent markers and induced expression of gene markers associated with multipotent cells derived from all three embryonic germ layers (ectoderm, endoderm, and mesoderm). A viable alternative to induced differentiation without formation of SCCs entails the use of appropriate culture conditions that directly promote multipotency via germ layer differentiation in the original ES culture. These differentiated cells are also regarded as a suitable source of ECM materials.
[0055] One of skill in the art can select a method appropriate for the type of mammalian ES cell being used. For example, SCCs can be formed from murine ES cells according to the methods described in Doetschman et al., “The In Vitro Development of Blastocyst-Derived Embryonic Stem Cell Lines: Formation of Visceral Yolk Sac, Blood Islands and Myocardium,” J. Embry. Exper. Morph. 87 (1985): 27-45; Keller, “In Vitro Differentiation of Embryonic Stem Cells,” Curr. Op. Cell Biol. 7 (1995): 862-869; and U.S. Pat. No. 5,914,268. An SCC can be formed, for example, by culturing a murine ES cell in an SCC cell medium that includes platelet-poor fetal bovine serum, preferably from about 1 day to about 7 days. Alternatively, others commonly used methods involve removal of LIF and serum to eliminate factors supporting ES cell pluripotency, coupled with physical methods to promote cell aggregation (e.g., hanging drop suspension, low adherence tissue culture surface, semi-solid solutions such as methylcellulose).
[0056] When the ES cells are primate ES cells, SCCs can be formed by suitable methods known in the art. Similar to mouse ES cells, human ES cells also spontaneously form SCCs when factors supporting pluripotency are removed, in the absence of serum and/or with the use of media and culture vessels which limit adherence to tissue culture surfaces (for example, U.S. Pat. No. 6,602,711). Briefly, ES cells growing on a substrate, such as feeder cells, are removed from the substrate and cultured under conditions that prevent adherence to a new container and which favors formation of SCCs. Examples include use of petri dishes, low adherence tissue culture surfaces, semi-solid solutions such as methylcellulose, hanging drop suspension, among others (Iskovitz-Eldor et al., “Differentiation of human Embryonic Stem Cells into Embryoid Bodies Comprising the Three Embryonic Germ Layers,” Mol. Med. 6 (2000): 88-95; Yang et al., “Novel Method of Forming Human Embryoid Bodies in a Polystyrene Dish Surface,” Biomacromolecules, 8 (2007): 2746-2752.) Differentiated SCCs can be removed from the substrate by mechanical force (e.g., centrifugation, physical separation) with or without the use of dissociating enzymes.
[0057] Primate ES cells (e.g., Rhesus or human, U.S. Pat. No. 5,843,780; Thomson et al., “Embryonic Stem Cells Lines Derived From Human Blastocysts,” Science. 282 (1998) 1145-1147) are cultured on mitotically inactivated (3000 rads γ-radiation) mouse embryonic fibroblasts, prepared at 5×10 4 cells/cm 2 on tissue culture plastic previously treated by overnight incubation with 0.1% gelatin (Robertson, 1987). Culture medium consists of 79% Dulbecco's modified Eagle medium (DMEM; 4500 mg of glucose per liter; without sodium pyruvate), 20% fetal bovine serum (FBS), 0.1 mM 2-mercaptoethanol, 1 mM L-glutamine and 1% nonessential amino acid stock (GIBCO).
[0058] One allows colonies to form clumps over a period of hours. ES cell colonies can then be removed from the tissue culture plate using physical or chemical methods that keep the ES cells in clumps. For dispase or collagenase removal of ES cell colonies from the culture plate, the culture medium is removed from the ES cells. Dispase (10 mg/ml in ES culture medium) or collagenase (1 mg/ml solution in DMEM or other basal medium) is then added to the culture plate. The culture plates are returned to the incubator for 10-15 minutes.
[0059] After dispase treatment the colonies can either be washed off the culture dishes or will become free of the tissue culture plate with gentle agitation. After collagenase treatment the cells can be scraped off the culture dish with a 5 ml glass pipette. Some dissociation of the colonies occurs, but this is not sufficient to individualize the cells. After chemical removal of the cells from the tissue culture plate, the cell suspension is centrifuged gently for 5 minutes, the supernatant is removed and discarded, the cells are rinsed, and the cells are resuspended in culture medium with or without serum.
[0060] Mechanical removal of the cells is achieved by using a pulled glass pipette to scrape the cells from the culture plate. Cell clumps can be immediately resuspended, without centrifugation, in fresh tissue culture medium.
[0061] Once colonies are removed from the tissue culture plate, the ES cells should remain in suspension to promote SCC formation. This can be achieved by, for example, gently and continuously rocking the cell suspension. Cell suspensions are aliquoted into wells of 6-well tissue culture dishes, placed inside a sealed, humidified isolation chamber, gassed with 5% CO 2 , 5% O 2 and 90% N 2 and placed on a rocker. The rocker is housed inside an incubator maintained at 37° C. The culture plates can be rocked continuously for at least 48 hours and up to 14 days.
[0062] Every 2 days, the plates are removed from the rocking device, the culture medium is removed, and fresh culture medium is added to the cells. The culture dishes are then returned to the rocking environment. Cells will also remain in suspension when cultured in suspension culture dishes without rocking, or when cultured in the absence of serum, which provides attachment factors. All cells are cultured at about 37° C., in a humidified, controlled gas atmosphere (either 5% CO 2 , 5% O 2 and 90% N 2 or 5% CO 2 in air).
[0063] Following culture in suspension for up to 11 days, SCCs are dispensed by mechanical or chemical means and can be allowed to reattach to tissue culture plates treated with gelatin or matrix, in ES medium. Displaced, plated SCCs will form flattened monolayers and can be maintained by replacing medium every 2 days.
[0064] Extracellular Matrix Components.
[0065] While the examples provided describe ECM extraction from differentiated cells obtained via SCC formation, it is appreciated that such techniques are readily understood to be applicable to cultured ES cells or partially differentiated ES cells not requiring SCC formation. The ECM either produced by via SCCs formation or otherwise stated in accordance with alternate embodiments described herein, has a number of components, including structural proteins: collagen and elastin, glycoproteins: laminin and fibronectin; proteoglycans: hyaluronic acid, chondroitin sulfate, heparan sulfate; and other factors useful in the maintenance and regeneration of the skin. According to the methods of the present invention, the ECM derived from the SCCs can be used as a crude preparation, or can be further purified to individual components or fractions containing multiple components.
[0066] Extraction of the ECM can be accomplished by suitable techniques known to one of skill in the art. For example, methods for purifying ECM are described in Current Protocols in Cell Biology. John Wiley & Sons, 1998, sections 10.4, 10.9. Depending on the desired application, ECM preparations can be made in two and three-dimensional forms.
[0067] For example, a crude preparation of ECM can be prepared by treating the cultured cells with a dilute basic solution or a detergent. For example, the SCCs can be treated with 0.01 N NaOH or 0.1% triton-X. The cells can be removed from the solution by filtration. The resulting solution is highly enriched in the matrix components.
[0068] Alternatively, the SCCs can be homogenized in a salt solution (for example, in 3.6 M NaCl). The solute is centrifuged, and the insoluble material preserved after centrifugation at 10,000 rpm. The extraction with 3.6 M NaCl is repeated until no extractable material is observed by protein assays (Biorad analysis). The insoluble material is then extracted with DNAse (0.1%) and RNAse (0.1%), and finally 0.1% Triton X.
[0069] In other forms, crude preparations of ECM extracts may be prepared through whole cell extracts. In one example, whole cell extracts may be obtained by directly lysing cells without fractioning or removal of non-ECM components. Such whole cell extracts thereby contain not only ECM components, but other cellular structures and molecules, including nucleic acids, lipids, sugars, intracellular proteins, among others. However, it is further appreciated that purification of specific ECM components, wherein a purified composition is substantially free of non-ECM components may enhance efficacy by eliminating molecules possessing inert or interfering properties at the skin surface, while increasing safety by removing potentially immunogenic factors.
[0070] Purified preparations of ECM can be used to form a gel matrix for cell culture. Methods for the preparation of such a matrix are described in Current Protocols in Cell Biology. John Wiley & Sons, 1998, Unit 10.3.
[0071] Collagen Purification.
[0072] Collagen can be purified by any method known to one of skill in the art. For example, collagen can be purified by the methods described in Current Protocols in Cell Biology . John Wiley & Sons (New York, N.Y. 1998), Sec. 10.2.4. Briefly, homogenized cells from the embryoid body are homogenized repeatedly in 2 M guanidine followed by centrifugation. The supernatant is dialyzed to remove the guanidine.
[0073] Purified ECM or crude preparations of collagen can be further purified by enzymatic treatment with one or more proteases. For example, the ECM can be digested using papain, chymo-papain, bromelain, protease VIII, or protease X.
[0074] Either with or without an enzymatic treatment, the ECM can be further purified using any technique known to one of skill in the art. For example, the components can be separated by centrifugation, chromatography, precipitation, and other techniques for separating biological molecules.
[0075] Laminin-1 Purification.
[0076] Laminin-1 can be purified by suitable techniques known to one of skill in the art. For example, the methods described in Current Protocols in Cell Biology , Sec. 10.2.3 can be used. Briefly, the SCCs are homogenized in a 3.4 M NaCl solution. After centrifugation at 8000×g, the pellet is retained and suspended in 0.5 M NaCl. After centrifugation, the supernatant is retained and laminin-1 is purified by precipitation with ammonium sulfate, added to 30% saturation. The pellets containing laminin-1 are resuspended in a buffer solution and dialyzed to remove the ammonium sulfate. Laminin1 is then precipitated by bringing the NaCl concentration to 1.7 M, followed by centrifugation.
[0077] Stem Cells From Plants, Fruit, and Vegetables.
[0078] Stem cells have also been obtained from dedifferentiation of adult cells obtained from plants, fruit, and vegetables. Briefly, adult cells from these non-animal sources, can be placed in cell cultures on solid media surfaces composed of various ingredient promoting dedifferentiation. Induction into a callus, a mass of undifferentiated cells in cluster form, can occur in two to three weeks, and can continue to be cultivated until complete dedifferentiation of the adult cells is fully achieved (U.S. patent application Ser. No. 12/148,241). Calluses may be mechanically or chemically dissociated and grown in suspension media to provide greater numbers of cells for scale-up applications. As an example, dedifferentiated cells have been obtained from apples, such as Malus domestica . Extracts obtained from Malus domestica may be prepared for the purpose of cosmetic applications and have been shown to promote growth and proliferation of umbilical cord stem cells, hair follicle maintenance, and skin-related uses. Other examples of extracts from plants, fruits, and vegetables have been obtained from alpine rose, Rhododendron ferrugineum , grape, Vitis vinifera , and rasberry, Rubus idaeus.
[0079] Skin-Related Applications.
[0080] Skin consists of an outer layer of epidermis and an inner layer of dermis. The epidermis is made up of stratified squamous epithelium and is separated from the dermis by a specialized, underlying structure called basal lamina. The basal lamina is a layer of ECM on which the epithelium sits. The ECM of the basal lamina consists of several biomolecular components including collagens, proteoglycans and glycoproteins. Representative examples of collagens in the basal lamina include type IV collagen, examples of proteoglycans include hyaluronic acid, chondroitin sulfate, heparan sulfate, and entactin, while examples of glycoproteins include laminin and fibronectin. The heterogeneous molecules of the ECM provide structural integrity and biotrophic support for the maintenance and regeneration of surrounding tissues, further including the activity of skin stem cells within and below the basal lamina. As an example of the multi-faceted role resulting from interactions of various ECM components, various forms of protein collagens (e.g., Collagen I-VI) attach to negatively-charged proteoglycans (e.g., chondroitin sulfate, and heparan sulfate) and attract water molecules via osmosis to hydrate the ECM and surrounding cells.
[0081] This compartment also serves as a reservoir for growth factors and nutrients necessary for cell survival and maintenance. Anchoring to glycoproteins (e.g., fibronectin, laminin) tethers matrix components to cell surfaces, thereby providing signaling through associated receptors, including fibronectin-integrin and laminin-laminin receptor signaling. Signaling among ECM components serves to promote the continued production of ECM, while regulating expression and release of additional growth factors and nutrients from fibroblasts situated in the inner dermis and skin stem cells located within the basal lamina and epithelia. In addition to their presence in the basal layer of the epidermis, skin stem cells typically reside within niche structures associated with hair follicles. Fuchs et al., “Socializing With the Neighbors: Stem cells and Their Niche,” Cell. 116 (2004): 769-78; Fuchs, “The Tortoise and the Hair: Slow-Cycling Cells in the Stem Cell Race,” Cell. 137 (2009): 811-9. Since skin tissue is constantly regenerated during the life of an organism, these skin progenitor cells play a central role in the maintenance, repair and replacement of surrounding tissues. Gago, et al., “Age-Dependent Depletion of Human Skin-Derived Progenitor Cells,” Stem Cells . (27) 2009: 1164-72. However, these specialized skin progenitor cells also can suffer damage and depletion as a result of age and environmental insults.
[0082] Existing further within this context, type IV collagen is the predominant collagen present in the basal lamina. Khoshnoodi et al., “Mammalian Collagen IV”. Microsc. Res. Tech. 71 (2008): 357-70. Uniquely among collagens, type IV collagen is anchored through laminin, signals through laminin receptors, and due to the presence of additional C-terminus amino acids, lacks a glycine residue motif commonly found in other collagens. This causes formation of sheets of collagen IV characteristic of the basal lamina, in contrast to the triple-helical fibrillar structure characteristic of other forms of collagens. Berisio et al., “Crystal Structure of the Collagen Triple Helix Model [(Pro-Pro-Gly)(10)(3),” Protein Sci. 11 (2002): 262-70.
[0083] Skin aging is the result of cumulative alterations in skin structure, barrier function and appearance. These alterations are due to a combination of intrinsic chronological factors (e.g., advanced age) or extrinsic environmental exposure (e.g., UV, chemical exposure, temperature humidity, dietary intake, etc.). Wrinkles and thinning of the skin results from atrophy of the ECM components in the epidermis and dermis, including induction of ECM degrading enzymes such as matrix metalloproteinases (MMPs). Fisher et al., “Pathophysiology of Premature Skin Aging Induced by Ultraviolet Light,” New. Eng. J. Med. 337 (1997): 1419-28. Matrix metalloproteinases are a family of approximately two dozen proteases, which are specific for degrading particular extracellular components. Examples include collagenases (MMP-1, MMP-08, MMP-13, MMP-14, and MMP-18), which target triple-helical fibrillar collagens, and genlatinases (MMP-2 and MMP9), which are capable of degrading type IV collagen and gelatin. Prolonged induction and activation of MMPs leads to depletion and fragmentation of skin collagen, a reduction in collagen synthesis, depletion of growth factors and nutrients within reservoirs providing biotrophic support for skin cells, and diminished support from dermal fibroblasts and skin stem cells within the basal lamina and epithelia.
[0084] An additional mechanism leading to changed appearance of the skin is the combined effects of enzymatic and non-enzymatic cross-linking in relation to the turnover of ECM components such as collagen and elastin. Avery and Bailey, “Enzymic and Non-enzymic Cross-Linking Mechanisms in Relation to Turnover of Collagen: Relevance to Aging and Exercise,” Scand. J. Med. Sci. Sports 15 (2005): 231-40. Enzymatic cross-linking results from the catalytic activity of various enzymes, such as lysyl hydroxylase, lysyl oxidases, prolyl-hydroxylases, and are involved in hydroxylation of lysine residues in ECM components. In turn, catalytic activity leads to formation of di-valent and tri-valent cross-links, which bind long rod-like molecules within protein tissue fibers to reduce movement and slippage, thereby providing core mechanical strength to the fibers. Robins, et al., “The Chemistry of Collagen Cross-Links,” J. Biochem., 131 (1973): 771-80. Enzymatic cross-linking plays a vital role in the natural growth, maturation and turnover of skin proteins and establishment of its structural integrity. The other type of cross-linking, non-enzymatic cross-linking, is adventitious (i.e., occurring through external factors) and a prime example advanced aging effects, since the long half-life of proteins in the skin increases opportunities for such external factors (e.g. UV exposure, dietary intake) to produce deleterious effects associated with non-enzymatic cross-linking Baily et al., “Non-Enzymic Glycation of Fibrous Collagen Reaction Products of Glucose and Ribose,” J. Biochem. 305 (1995): 385-90. In contrast to enzymatic cross-linking, non-enzymatic cross-linking does not involves enzyme activity, but instead, results from glyco-oxidation (glycation) and lipo-oxidation reactions. Paul and Bailey, “Glycation of Collagen: The Basis of its Central Role in the Late Complications of Ageing and Diabetes,” Int. J. Biochem. 28 (1996): 1297-1310. A hallmark of the process is the formation of an intermediate Schiff base and Amadori rearrangement product, both of which undergo oxidation to form stable end-products known as advanced glycation end-products (AGE). (Avery and Bailey, 2005). Examples of AGE include FFI, pentosidine, NFC-1, malondialdehyde, among others. Importantly, the non-enzymatic cross-linking leads to intermolecular (e.g., interfibrillar) cross-linking between proteins and interferes with reactivity with other ECM components, thus reducing the optimal mechanical and effective functional properties of proteins within the skin. Thus, measurement of AGE products serves as a direct measure of the degree of glycation occurring in a sample of collagen and a proxy for the quality and integrity of ECM as a whole. The nature and extent of cross-linking in various skin proteins can be measured by a variety of techniques, including immunodetection of intermediate and end products of enzymatic and non-enzymatic processes, HPLC-based separation, optical detection of reactive species and presence/absence of associated by-products (e.g., CML and pyrraline), among others. Since ECM components obtained from SCCs are freshly made from cultured cells, there is a reduced degree of undesirable cross-linking present, particularly with respect to non-enzymatic glycation, thus possessing an important advantage over products obtained from animal sources.
[0085] Without being bound by any particular theory, the inventors believe that application of ECM purified/or obtained from ES cells will reverse or limit the deleterious effects of skin aging, through improved moisturization, neutralization of harmful enzyme degradation, and regeneration of skin components. First, application of ECM to the skin surface or within the epidermis, provides a source of negatively charged proteoglycans to increase retention of water for improved moisturization and hydration of the skin. Second, greater concentrations of ECM components, such as collagen, serve as enzyme substrates to neutralize or reduce the effects of MMP-degrading activity on cell and tissue surfaces. Third, enhancing levels of ECM components within the epidermis may activate signaling pathways associated with the normal regeneration and repair mechanism within skin tissues, including enhancing the response from fibroblasts and skin stem cells. Fourth, the ECM derived from cultured stem cells is freshly made, devoid of chemical cross-links or oxidative damage and is actively engaged in tissue development. Thus, this ECM may have inherent properties that would be desirable to delay skin aging and promote skin renewal.
[0086] Cosmetics.
[0087] Fractions of ECM can be processed and used in the form of solid powders, aqueous solutions (i.e., gels), partially emulsified aqueous solutions, or emulsifications (i.e., creams and lotions). Following isolation and purification, ECM components may be air-dried or freeze-dried in combination with heating/cooling, vacuum aspiration, centrifugation, and addition of salt or stabilizers to facilitate removal of moisture (for example, U.S. Pat. No. 7,115,388). Solid dried material may be ground or pummeled for longer-term storage or use in bulk industrial-scale manufacturing. Aqueous solutions can be formed from ECM, since the proteins and polypeptide chains in solution readily bind to each other via hydrogen bonding or through dispersion forces to form a three-dimensional mesh, wherein gel formation occurs. Addition of lipophilic components through mixing or stirring provides a partially emulsified aqueous solution, wherein a proportion of aqueous solution and oil component provides improved efficacy of skin cell growth, maintenance, and regeneration, with other desirable colligative properties such as improved adhesion and spreadability (i.e., extensivility). Various additives can be further provided in aqueous or oil components, including preservatives, pH adjusters, moisturizer, germicide, anti-inflammatory agent, dye, aromas, fragrances, antioxidants, ultraviolent absorbent, vitamin, alcohol, carbohydrates, or other components routinely used in skin care applications.
[0088] Extracellular components from SCCs can be formulated into a variety of cosmetic products. There are several benefits of incorporating stem cell extracts, including ECM components, as active ingredients in cosmetic products. Such extracts are typically colorless (or white), odorless, water-soluble, maintain stability and activity across a range of physiologically relevant pHs (i.e., 4-0-8.0), cosmetically effective as small amount of total product volume (i.e., 0.4%-1.0%), soluble and miscible. Collagen, for example, can be used for both topical, transdermal and internal applications.
[0089] Use of extracellular components derived from ES cells differentiated into SCCs has a number of advantages over current animal sources: 1) cultured ES cells can be maintained with reduced exposure to pathogens and infectious agents under laboratory conditions, eliminating reliance on animal or cadaveric sources possibly tainted with viruses, prions, or other disease causing agents; 2) extracellular membrane components derived from ES cells are a consistent and renewable source of biologically active ECM components, unaltered by the extrinsic factors such as environmental exposure or intrinsic biological variability, which affect animal or human sources of ECM. For example, ES cell-derived ECM has reduced cross-linkage, less oxidative damage, and lowered non-enzymatic glycation; 3) deriving ECM components from in vitro cultured ES cells provides critical post-translational modifications necessary for biological compatibility and activity, thereby improving efficacy for anti-aging and anti-wrinkle applications; and 4) ES cell-derived ECM is homogeneous and pathogen-free. This ECM may be prepared in vitro using a reproducible method of production and extraction.
Various Embodiments
[0090] Further described herein is a method for obtaining at least one ECM component. In one embodiment, the method comprises the steps of culturing a quantity of mammalian ES cells, inducing the quantity of mammalian ES cells to form one or more SCCs and extracting from the one or more SCCs the at least one ECM component. In another embodiment, the ES cell line has been derived without exposure to non-human animal products. In one embodiment, the mammalian ES cells are murine ES cells. In another embodiment, the mammalian ES cells are human ES cells. In another embodiment, the mammalian ES cells are induced pluripotent stem cells obtained from adult somatic cells. In another embodiment, the mammalian ES cells are cultured on feeder cells. In another embodiment, the mammalian ES cells are cultured in serum-free conditions. In another embodiment, the mammalian ES cells are cultured in chemically defined conditions. In another embodiment, the quantity of mammalian ES cells are treated with dispase or collagenase prior to the step of inducing formation of SCCs. In another embodiment, the ES cells are grown in a plurality of tissue culture flasks or cell trays.
[0091] The present invention further provides methods to improve SCC formation. In one embodiment, the inducing step further comprises transferring the quantity of mammalian ES cells to a container under conditions that reduce the likelihood of adherence of the mammalian ES cells to a surface of the container. In another embodiment, the inducing step is performed in a media solution. In another embodiment, the media solution is a semi-solid solution. In another embodiment, the media solution is serum-free. In another embodiment, the media solution comprises platelet-poor serum. In another embodiment, there is an additional step of rocking the container to reduce the likelihood of adherence. In an alternative embodiment, the inducing step uses mammalian ES cells in a hanging drop. In various embodiments, the time period of induction to form SCCs is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 day(s). In various embodiments, the SCCs are formed and are maintained as SCCs for a period of 1, 2, 3, 4, 5, or 6 day(s)s. In various embodiments, the SCCs are formed and are maintained as SCCs for a period of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 week(s).
[0092] The present invention further provides various methods to extract the extracellular component. In one embodiment, the step of extracting further comprises contacting the quantity of mammalian ES cells with a salt, a detergent and/or an acid, and separating the quantity of mammalian ES cells from the at least one ECM component. In another embodiment, the step further comprises the step of purifying the at least one extracted ECM component. In another embodiment, the step further comprises the step of purifying the at least one extracted ECM, comprising centrifugation, chromatography, precipitation, filtration and/or organic solvent extraction. In another embodiment, the step further comprises the step of lyophilizing the at least one extracted ECM component. In one embodiment, the at least one ECM component is a collagen. In another embodiment, the at least one ECM component is collagen IV. In another embodiment, the step further comprises contacting the at least one ECM component with a protease. In a different embodiment, the at least one ECM component is a proteoglycan. In one embodiment, the at least one ECM component is elastin. In another embodiment, the at least one ECM component is hyaluronic acid, chondroitin sulfate, or heparan sulfate. In a different embodiment, the at least one ECM component is a glycoprotein. In another embodiment, the at least one ECM component is laminin or fibronectin. In another embodiment, the at least one ECM component is substantially free of AGE. In various embodiments, the at least one ECM component comprises a quantity of AGE less than at least about 0.1%, at least about 0.5%, or at least about 1%, and may be as great as or more than about 5%, or about 10%, or about 15%, or about 20%, or about 25%, or about 35%, or about 50%, or about 80%, or about 90%. In various embodiments, the AGE is FFI, pentosidine, NFC-1, or malondialdehyde. In another embodiment, the ECM component is not substantially cross-linked.
[0093] The present invention further provides compositions derived from SCCs. In one embodiment, the composition comprises at least one ECM component extracted from SCCs and a cosmetically-acceptable carrier. In one embodiment, the at least one ECM component is a collagen. In a different embodiment, the at least one ECM component is produced by a process, comprising culturing a quantity of mammalian ES cells, inducing the quantity of mammalian ES cells to form one or more SCCs and extracting from the one or more SCCs the at least one ECM component. In one embodiment, the composition is derived from undifferentiated ES cells. In another embodiment, the composition is derived from partially differentiated ES cells not requiring SCC formation.
[0094] In various embodiments, the composition comprises one or more ECM components. In various embodiments, the composition comprises one or more ECM components selected from the group consisting of collagen, elastin, hyaluronic acid, chondroitin sulfate, heparan sulfate, laminin or fibronectin, and combinations thereof. In various embodiments, the composition comprises one or more ECM components of at least about 0.1%, at least about 0.5%, or at least about 1%, and may be as great as or more than about 5%, or about 10%, or about 15%, or about 20%, or about 25%, or about 35%, or about 50%, or about 80%, or about 90% or more (weight/weight). In various embodiments, the at least one ECM component comprises a quantity of AGE less than at least about 0.1%, at least about 0.5%, or at least about 1%, and may be as great as or more than about 5%, or about 10%, or about 15%, or about 20%, or about 25%, or about 35%, or about 50%, or about 80%, or about 90%. In various embodiments, the AGE is FFI, pentosidine, NFC-1, or malondialdehyde. In another embodiment, the ECM component is not substantially cross-linked.
[0095] In certain embodiments, the composition is a substantially pure solid or liquid. In other embodiments, the substantially pure solid or liquid comprises one or more ECM components selected from the group consisting of collagen, elastin, hyaluronic acid, chondroitin sulfate, heparan sulfate, laminin or fibronectin, and combinations thereof. In other embodiments, the composition is a substantially pure solid or liquid, substantially free of non-ECM components. In one embodiment, the composition is a substantially pure solid or liquid, substantially free of nucleic acid. In another embodiment, the substantially pure solid or liquid is substantially free of AGE. In other embodiments, the composition is a crude preparation solid or liquid. In one embodiment, the crude preparation is a whole cell extract. In other embodiments, the crude preparation comprises one or more ECM components selected from the group consisting of collagen, elastin, hyaluronic acid, chondroitin sulfate, heparan sulfate, laminin or fibronectin, and combinations thereof. In another embodiment, the crude preparation is substantially free of AGE.
[0096] In various embodiments, the composition comprises a solid powder, aqueous solution, partially emulsified aqueous solution, or emulsifications. In one embodiment, the aqueous solution is acidic. In one embodiment, the aqueous solution includes glycerin and ethanol. In another embodiment, partially emulsified aqueous solution, or emulsifications contain a proportion of aqueous solution and an oil component. In various embodiments, the oil component in compositions comprises at least about 0.3% or less to about 30% or more, such as at least about 0.5% to about 20% (weight/weight). In other embodiments, the oil components in compositions comprises at least about 0.5% to about 50%, such as 5% to 30% (weight/weight).
[0097] In various embodiments, the composition is mixed with additives in aqueous or oil components, comprising preservatives, pH adjusters, moisturizer, germicide, anti-inflammatory agent, dye, aromas, fragrances, antioxidants, ultraviolent absorbent, vitamin, alcohol, carbohydrates, or other components routinely used in skin care applications. In one embodiment, the preservative is sodium benzoate. In various embodiments, one or more additives is provided in compositions comprising at least about 0.0001%, at least about 0.01%, at least about 0.1%, at least about 0.5%, or at least about 1%, and may be as great as or more than about 5%, or about 10%, or about 15%, or about 20%, or about 25% or more (weight/weight).
[0098] In other embodiments, compositions are formulated with one or more ECM components as an active ingredient. In various embodiments, one or more ECM component provided in a composition comprises at least about 0.0001%, at least about 0.01%, at least about 0.1%, at least about 0.5%, or at least about 1%, and may be as great as or more than about 5%, or about 10%, or about 15%, or about 20%, or about 25% or more (weight/weight). In other embodiments, the cosmetically acceptable carrier in a composition comprises about 1% or less to about 99.9% or more, such as from about 10% to 90%, including about 25% to about 80% (weight/weight).
[0099] In various embodiments, the composition is formulated for topical application to the skin, such as the skin surrounding or comprising the eyes, mouth, nose, forehead, ears, neck, hands, feet, hair, and/or overall body. For example, the topical skin care composition may be in the form of a solution, serum, cream, lotion, body milk, emulsion, balm, gel, soap, conditioner, powder and the like. Alternatively, the topical skin care composition may be in the form of a shampoo, conditioner, serum, or toner. In other embodiments, the composition is formulated for topical application to hair or scalp.
[0100] In other embodiments, the composition is provided as an active ingredient in a composition formulated for topical application to the skin. In other embodiments, the composition is as provided as an active ingredient in a composition formulated for topical application to hair or scalp. In other embodiments, the composition is provided as an active ingredient in a composition formulated for cosmetic use. In other embodiments, the composition is provided as an active ingredient in a composition formulated for use as a treatment for a subject in need of treatment. Various skin-related conditions include appearance of aging, wrinkles, fine lines, thinness, diminished elasticity or suppleness, dry skin, undesirable apperance of pores, pronounced appearance of stretch marks and scars, undesiable color tone and hue, dermatitis, eczema, sunburn, inflammation, pruritic lesions, inflammatory and non-inflammatory lesions of the skin of a subject. Other conditions related to hair include baldness (i.e., alopecia), reduced shaft volume, structural deformations (e.g., split ends), low elasticity, brittleness, dullness, dryness, slow growth, among others.
[0101] The present invention further provide a method of preparing an exact from stem cells of a plant, fruit or vegetable source. In one embodiment, the method comprises isolating adult somatic cells from a plant, fruit or vegetable source, culturing the adult somatic cells on a solid medium containing components promoting dedifferentiation, inducing dedifferentiation of the adult somatic cells into a callus, disaggregating the callus into single cells in a liquid suspension medium. In another embodiment, the method further comprises homogenizing the liquid suspension into a broth extract and adding a liposome preparation.
[0102] In another embodiment, the method further comprises purification of at least one component from the extract.
EXAMPLES
Example 1
Production of Stem Cell Clusters from Embryonic Stem Cells
[0103] This example describes the production of a population of SCCs cells from an established ES cell population. Similar methods can be used for producing SCCs from other murine ES cell lines.
[0104] The 129-SvEv-tac ES cell line #501 derived from 12956/SvEv-Taconic mice (Primogenix), is maintained in Dulbecco's modified Eagles medium (DMEM) supplemented with 15% fetal calf serum (FCS), 1.5×10 −4 monothioglycerol (MTG), and leukemia inhibitory factor (LIF). The ES cells are passaged every 2-3 days at a dilution of approximately 1:15. Two days before the initiation of the differentiation cultures, undifferentiated ES cells are passaged into Iscove's modified Dulbecco's medium (IMDM) supplemented with the above components. Optionally, 50 μg/mL ascorbic acid may be introduced to increase matrix thickness and improved ECM yield. To induce differentiation into an SCC, the ES cells are trypsinized, washed, and counted using techniques standard in the art. The freshly dissociated ES cells are then cultured in IMDM containing 15% platelet-derived fetal bovine serum (PDS; obtained from Antech, Tex.; also referred to herein as platelet-poor fetal bovine serum, PP-FBS), 4.5×10 −4 M MTG, transferrin (300 μg), glutamine (2 mM). The ES cells are plated in a final volume of 10 ml at a concentration of about 3000 to about 4500 cells per ml of medium in 150 mm bacterial grade dishes. The ES cell population is then cultured in a humidified environment of 5% CO 2 , at a temperature of 37° C. After 3 days, SCCs are transferred back onto adherent plates and incubated in complete media with daily changes for an additional 12 days. The SCCs can be viewed under a Leitz inverted light microscope and will generally consist of groups of tightly packed cells, in which individual cells are not easily detectable.
Example 2
Extraction of Complete Extracellular Matrix from SCCs
[0105] This example describes the extraction of ECM from SCCs grown in T-150 flasks. SCCs generated in Example 1 are subjected to the following protocol. The culture flasks containing the SCCs are taken out of the incubator and the culture medium is carefully aspirated. The flasks are gently rinsed twice with 8 ml of PBS by touching the pipette against the flask wall. A solution of pre warmed (37° C.) extraction buffer (PBS containing 0.5% Triton X-100, 20 mM NH 4 OH) is gently added using 5 ml/flask. Cell lysis is monitored by inspection with an inverted microscope. Flasks are incubated at 37° C. until no more intact cells are visible. Remaining cellular debris is diluted by slowly adding 3 ml of PBS, taking care not to disturb the newly formed and freshly denuded matrix. Flasks are stored overnight at 4° C. The diluted debris is carefully aspirated the next day leaving a thin liquid layer to keep the matrix hydrated at all times.
[0106] The matrix layer is rinsed with 6 ml of PBS by gently adding and aspirating while keeping the matrix hydrated. The matrix is treated briefly with a solution of 5 ml of DNase I prepared in PBS supplemented with 1 mM CaCl 2 and 1 mM MgSO 4 and incubated for 30 min at 37° C. The enzyme solution is aspirated and the matrix carefully rinsed with two washes with 8 ml of PBS, aspirating the excess of PBS after slightly tilting the flasks and carefully aspirating the PBS collected on one side of the flask. The flasks are put on ice and 5 ml of solubilization buffer is added (5 M guanidine-HCl containing 10 mM DTT). The matrix is harvested by scraping the flasks with a cell scraper to one side and pipetting the mixture into a plastic centrifuge tube. The flasks are rinsed with 3 ml of solubilization buffer, combining with the previously harvested matrix into the same tube. The matrix mixture is centrifuged at 12,000×g at 4° C. and the supernatant is saved. The supernatant is then dialyzed against 0.5 M acetic acid with four changes in one day. The final dialyzate is evaporated by lyophilization and resuspended in 1/10 th the original volume with 0.5 M acetic acid. A small sample ( 1/10 th volume) is taken and submitted for total protein mass, standard amino acid analysis and hydroxyproline and hydroxylysine content. The rest is stored at −20° C. until further use and formulation.
Example 3
Extraction of Collagen-Enriched Extracellular Matrix from SCCs
[0107] This example describes the extraction of a collagen-enriched fraction associated with the ECM from SCCs grown in T-150 flasks. SCCs generated in Example 1 are subjected to the following protocol. The culture flasks containing the SCCs are taken out of the incubator and the culture medium is carefully aspirated. The flasks are gently rinsed twice with 8 ml of PBS by touching the pipette against the flask wall. An ice-cold solution of 0.5 M acetic or lactic acid containing 0.1 mg/ml pepsin is gently added, using 5 ml/flask. Flasks are incubated at 4° C. for 24 hr on a rocking platform with gentle rotation. The extract is carefully harvested and transferred to a centrifuge plastic tube. Flasks are rinsed with 3 ml 0.5 M ice-cold acetic or lactic acid, collecting the remaining cells and insoluble materials with a cell scraper to one side of the flask. This mixture is combined with the harvested extract and then centrifuged at 12,000×g for 15 min at 4 C. The total collagen fraction may be concentrated using a salting out procedure by slowly adding NaCl to a final concentration of 0.9 M.
[0108] The mixture is incubated overnight at 4° C. and the resulting precipitate is collected by centrifugation at 12,000×g for 15 min at 4° C. The precipitate is dissolved in ice-cold 0.5 M acetic or lactic acid and dialyzed against the same with four changes in one day. The final dialyzate may be evaporated by lyophilization and resuspended in 1/10 th the original volume with 0.5 M lactic or acetic acid. A small sample ( 1/10 th volume) is taken and submitted for total protein mass, standard amino acid analysis and hydroxyproline and hydroxylysine content. The rest is stored at −20° C. until further use and formulation.
Example 4
Extracts Prepared from Stem Cells from Plant, Vegetable and Fruit Sources
[0109] This example describes preparation of extracts from stem cells obtained from a plant, vegetable or fruit source. Adult somatic cells may be isolated from a plant, vegetable, or fruit organism and placed on solid medium in a culture vessel, wherein the solid medium contains components promoting the dedifferentiation of the adult somatic cells. Following induction of the dedifferentiation process through formation of a callus, the callus may be mechanically or chemically dissociated as single cells to be grown in suspension in liquid medium. Suspension cultures may require additional cultivation steps for scale up purposes. Extracts may be prepared from stem cell cultures through combining a homogenized whole cell broth with a liposome preparation for solubilization. Addition of a liposome component to the extract further provides an oil component to the aqueous solution, wherein various agents and carriers related to the use of cosmetics may be added (e.g., preservatives, stabilizers, antioxidants).
Example 5
Use of a Composition Containing Stem Cell Extracts for Anti-Wrinkle Treatment
[0110] This example describes the use of a composition containing stem cell extracts for anti-aging and anti-wrinkle treatment of the skin. The composition can appear as a cream, lotion, gel, toner, serum, or in other forms ordinarily known to be utilized for application of anti-wrinkle treatments. A quantity of the composition, for example 1 ml to 100 mL or more, is applied topically to a site of interest, such as the face or hands. Application may occur through obtaining a quantity of composition from a suitable container using a finger, squeezing the composition onto the skin surface, or directly applied through an applicator such as a pump. As necessary, the composition is spread over and/or rubbed into the site using hands or fingers, or a suitable device, such as an applicator tip. The composition may contain various components suitable for enhancing application to the skin area, such as ethanol to promote drying through evaporation or glycerin to promote spreading on the skin surface. The composition may be applied singularly or repeatedly as is necessary to achieve effect of anti-wrinkling effects, such as a reduction in appearance of fine lines and wrinkles, or anti-aging effects, such as improved tonicity and color on the skin.
Example 6
Use of a Composition Containing Stem Cell Extracts for Improving Appearance of Hair
[0111] This example describes the use of a composition containing stem cell extracts to improve the appearance of hair. The composition can be in the form of a shampoo, conditioner, serum, or in other forms ordinarily known to be utilized for application of hair treatments. A quantity of the composition, for example 1 ml to 100 mL or more, is applied topically to a site of interest, such as onto the hair surface or directly onto the scalp. Application may occur in association with a shower or bath, wherein the composition is massaged and rubbed into the hair and/or scalp and rinsed out using water, or may be a “leave-in” treatment, wherein the composition is applied to wet or dry hair and left in-place for an extended period before being removed by rinsing. The composition may be applied singularly or repeatedly as is necessary to achieve the effect of improved hair appearance, as demonstrated by increased size/volume of individual hairs, improved hair structure (e.g., fewer split ends at hair termini), or better elastic and mechanical properties. In related applications, the composition can be applied to the skin of the scalp for the purpose of reducing or eliminating hair loss, by promoting maintenance and regenerative mechanisms of skin cells which are involved with the routine growth and replacement of hair.
[0112] The various methods and techniques described above provide a number of ways to carry out the invention. Of course, it is to be understood that not necessarily all objectives or advantages described may be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the methods can be performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as may be taught or suggested herein. A variety of advantageous and disadvantageous alternatives are mentioned herein. It is to be understood that some preferred embodiments specifically include one, another, or several advantageous features, while others specifically exclude one, another, or several disadvantageous features, while still others specifically mitigate a present disadvantageous feature by inclusion of one, another, or several advantageous features.
[0113] Furthermore, the skilled artisan will recognize the applicability of various features from different embodiments. Similarly, the various elements, features and steps discussed above, as well as other known equivalents for each such element, feature or step, can be mixed and matched by one of ordinary skill in this art to perform methods in accordance with principles described herein. Among the various elements, features, and steps some will be specifically included and others specifically excluded in diverse embodiments.
[0114] Although the invention has been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that the embodiments of the invention extend beyond the specifically disclosed embodiments to other alternative embodiments and/or uses and modifications and equivalents thereof.
[0115] Many variations and alternative elements have been disclosed in embodiments of the present invention. Still further variations and alternate elements will be apparent to one of skill in the art. Among these variations, without limitation, are the sources of ECM and constituent products, the manufacturing techniques used to create cosmetic products, and the particular use of the products created through the teachings of the invention. Various embodiments of the invention can specifically include or exclude any of these variations or elements.
[0116] In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[0117] In some embodiments, the terms “a” and “an” and “the” and similar references used in the context of describing a particular embodiment of the invention (especially in the context of certain of the following claims) can be construed to cover both the singular and the plural. The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0118] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
[0119] Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations on those preferred embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. It is contemplated that skilled artisans can employ such variations as appropriate, and the invention can be practiced otherwise than specifically described herein. Accordingly, many embodiments of this invention include all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
[0120] Furthermore, numerous references have been made to patents and printed publications throughout this specification. Each of the above cited references and printed publications are herein individually incorporated by reference in their entirety.
[0121] In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that can be employed can be within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention can be utilized in accordance with the teachings herein. Accordingly, embodiments of the present invention are not limited to that precisely as shown and described.
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Methods of manufacturing collagen and other extracellular matrix components from SCCs are disclosed. The extracellular matrix components are useful in cosmetic applications, and can be manufactured free of immunogenic concerns and contaminants while controlling for other factors that commonly impact product quality and usefulness.
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CROSS-REFERENCE TO RELATED APPLICATIONS
The instant application claims priority to U.S. Provisional Application No. 60/600,651 filed Sep. 8, 2003, the disclosure of which is incorporated herein by reference in its entirety. The instant application is a continuation-in-part of U.S. patent application Ser. No. 10/679,371, entitled “Localized Network Authentication and Security Using Tamper-Resistant Keys,” filed Oct. 7, 2003, the disclosure of which is incorporated herein by reference in its entirety. The instant application is also related to U.S. patent application Ser. No. 10/679,268, entitled “Shared Network Access Using Different Access Keys,” filed Oct. 7, 2003, and U.S. patent application Ser. No. 10/679,472, entitled “Self-Managed Network Access Using Localized Access Management,” filed Oct. 7, 2003, the disclosures of which are both incorporated by reference in their entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to wireless networking, and more particularly, to an authentication and secure communication technique for Wi-Fi (IEEE 802.11) networks.
2. Description of Related Art
A Wireless Local Area Network (WLAN) is generally implemented to provide local connectivity between a wired network and a mobile computing device. In a typical wireless network, all of the computing devices within the network broadcast their information to one another using radio frequency (RF) communications. WLANs are based on the Institute of Electrical and Electronic Engineers (IEEE) 802.11 standard, which designates a wireless-Ethernet specification using a variety of modulation techniques at frequencies generally in the 2.4 gigahertz (GHz) and 5 GHz license-free frequency bands.
The IEEE 802.11 standard (“Wi-Fi”) enables wireless communications with throughput rates up to 54 Mbps. Wi-Fi (for “wireless fidelity”) is essentially a seal of approval certifying that a manufacturer's product is compliant with IEEE 802.11. For example, equipment carrying the “Wi-Fi” logo is certified to be interoperable with other Wi-Fi certified equipment. There are Wi-Fi compatible PC cards that operate in peer-to-peer mode, but Wi-Fi usually incorporates at least one access point, or edge device. Most access points have an integrated Ethernet controller to connect to an existing wired-Ethernet network. A Wi-Fi wireless transceiver connects users via the access point to the rest of the LAN. The majority of Wi-Fi wireless transceivers available are in Personal Computer Memory Card International Association (PCMCIA) card form, particularly for laptop, palmtop, and other portable computers, however Wi-Fi transceivers can be implemented through an Industry Standard Architecture (ISA) slot or Peripheral Component Interconnect (PCI) slot in a desktop computer, a Universal Serial Bus (USB), or can be fully integrated within a handheld device.
When network packets are formed, they typically result from a process known as encapsulation. FIG. 4 shows the “layered” sequence of packet formation well known as the “protocol suite.” See Richard Stevens, TCP/IP Illustrated, Vol. 1 (Addison-Wesley ISBN 0-201-63346-9). All network packets are typically identified by an Ethernet Header ( 150 ). The addition of 802.11 wireless functionality adds yet another layer below the link layer and is known as the 802.11 layer and this layer adds an additional 802.11 header ( 410 ). The Client Network Interface Card (NIC) ( 110 ) adds the 802.11 header ( 410 ) to the Ethernet packet and is used to transport the Ethernet packet across the wireless medium
On receipt of an 802.11 packet from an authenticated and associated Client NIC ( 110 ), the Access Point ( 140 ) will remove the 802.11 header ( 410 ) and place the remaining packet on the Ethernet cable ( 150 ). The Ethernet packet stripped of its 802.11 header is placed on the LAN as if the Client PC were directly connected on the LAN instead of being bridged by the combination of Client NIC ( 110 ) and Access Point ( 140 ). This process of stripping headers is known as “de-multiplexing”. As seen in FIG. 1 , the 802.11 network (WLAN, 130 ) comprises at least one Access Point ( 140 ) attached via Ethernet cable ( 150 ) to the wired network (LAN, 190 ). The Access Point ( 140 ) provides a wireless bridge for connecting clients PCs ( 120 ) to the LAN, 190 . The process of connection when security is not invoked is for the client NIC ( 110 ) to perform an Open Authentication to the Access Point ( 140 ). As the authentication is “open”, any Client will be automatically authenticated. The Access Point ( 140 ) grants permission to the Client NIC ( 110 ) to “associate” to the Access Point ( 140 ). The Client NIC ( 110 ) then “associates” to the Access Point ( 140 ) and the Client's PC ( 120 ) is now “bridged” to the LAN ( 190 ).
The process of bridging involves the Access Point ( 140 ) to manage the wireless traffic and remove the 802.11 header ( 410 ) placing the packet on the Ethernet cable as if the Client PC ( 110 ) were “hard-wired” to the network. In the case of Wired Equivalent Privacy (WEP) security, the process is identical except that the 802.11 authentication type is changed from “open” to “WEP’ and the predefined WEP parameters are used by the NIC ( 110 ) to encrypt communications from the Client PC ( 120 ) to the Access Point ( 140 ). The Access Point ( 140 ) decrypts all packets coming from the Client PC ( 120 ) using the pre-defined WEP parameters. Turning on WEP encryption prevents and Client NIC ( 110 ) not using the exact WEP parameters from connecting to the Access Point ( 140 ) and gaining access to the network ( 190 ). The WEP parameters thus are employed both for authentication and encryption purposes.
The Access Point ( 140 ) maintains the relationship between itself and the Client NIC ( 110 ) by means of the Client's MAC address ( 105 ). The Client's MAC address is the mechanism by which a Client's connection is managed by the Access Point ( 140 ). The Access Point ( 140 ) typically employs WEP security, a software algorithm that is used both for authentication purposes and to provide wireless link security. If WEP is turned on in the Access Point ( 140 ), no other users can connect to the Access Point without WEP turned on in their Client NIC ( 110 ) and the proper WEP parameters matching those in the Access Point turned on as well. This issue makes it impossible to support both people who desire security and those who do not at the same time.
The Institute of Electrical and Electronic Engineers (IEEE) has announced improvements to the security processes utilized in the 802.11 specifications. These improvements are known as Wireless Protected Access (WPA) and WPA2. Both improvements provider a greater degree of security over WEP, but still do not permit both secure and non-secure Clients to connect to the same Access Point. WPA2, in particular, requires new Access Point hardware and new Client NIC cards to be purchased by users who desire to use the improved WPA2 security. While a WPA2 Access Point will support WEP clients, it cannot support both WPA2 and WEP-based clients at the same time.
There are three typical types of authentication that are available for use with 802.11b networks: Open system; Shared Key; and IEEE 802.1X.
Open system authentication authenticates all wireless nodes using the Client NIC MAC Address ( 105 ), its wireless adapter hardware address. A hardware address is an address assigned to the network adapter during its manufacture and is used to identify the source and destination address of wireless frames.
For infrastructure mode, although some wireless APs allow you to configure a list of allowed hardware addresses for open system authentication, it is a fairly simple matter for a malicious user to capture frames sent on your wireless network to determine the hardware address of allowed wireless nodes and then use that hardware address to perform open system authentication and join your wireless network.
For ad hoc mode, there is no equivalent to configuring the list of allowed hardware addresses in Windows XP. Therefore, any hardware address can be used to perform open system authentication and join your ad hoc mode-based wireless network.
Shared key authentication verifies that the wireless client joining the wireless network has knowledge of a secret key. During the authentication process, the wireless client proves it has knowledge of the secret key without actually sending the secret key. For infrastructure mode, all the wireless clients and the wireless AP use the same shared key. For ad hoc mode, all the wireless clients of the ad hoc wireless network use the same shared key.
The IEEE 802.1X standard enforces authentication of a network node before it can begin to exchange data with the network. Exchanging frames with the network is denied if the authentication process fails. Although this standard was designed for wired Ethernet networks, it has been adapted for use by 802.11b. IEEE 802.1X uses the Extensible Authentication Protocol (EAP) and specific authentication methods known as EAP types to authenticate the network node.
IEEE 802.1X provides much stronger authentication than open system or shared key and the recommended solution for Windows XP wireless authentication is the use of EAP-Transport Level Security (TLS) and digital certificates for authentication. To use EAP-TLS authentication for wireless connections, you must create an authentication infrastructure comprising of an Active Directory domain, Remote Authentication Dial-In User Service (RADIUS) servers, and certification authorities (CAs) to issue certificates to your RADIUS servers and wireless clients. This authentication infrastructure is appropriate for large businesses and enterprise organizations, but is not practical for the home or small business office.
A solution to the use of IEEE 802.1X and EAP-TLS for the medium and small business is being developed. Windows XP Service Pack 1 and the Windows .NET Server 2003 family will both support Protected EAP (PEAP) and the Microsoft Challenge-Handshake Authentication Protocol, version 2 (MS-CHAP v2) EAP type. With PEAP and MS-CHAP v2, secure wireless access can be achieved by installing a purchased certificate on a RADIUS server and using name and password credentials for authentication.
Hot Spots typically provide no wireless link security. This is due to the fact that there is no mechanism for managing “keys” for transient users. The existing technology is vulnerable to hackers and the newer technology will not allow AES encryption to be run in the same Access Point as WEP-enabled customers. Hot Spots are faced with a situation wherein they cannot deploy the newer security technology as it means they will lose existing customers unless their customers also upgrade to the newer technology.
“Koolspan” functionality provides for mutual authentication of both the Client and the Network Edge device, typically an Access Point based on secure, tamper-resistant tokens on both sides of the wireless link. The modifier “Koolspan” refers to the authentication and secure communication technique(s) disclosed in U.S. patent application Ser. Nos. 10/679,371; 10/679,268; and 10/679,472, the disclosures of which are incorporated by reference in their entirety. As a product of this authentication process, a “Session Key” is independently generated on both sides of the link that is used to secure communications across the link for the duration of the session. Typically, the Access Point software is modified to provide for Koolspan authentication and to read an attached Koolspan token. Since this functionality requires modification of the Access Point software and an available port into which the token can be attached, not every Access Point can directly support Koolspan functionality. Existing wireless networks implement WEP security, the original security standard for 802.11 networks. This security mechanism is not safe and can be easily cracked. Newer technologies such as WPA and WPA2 are more secure, but will require new Access Points to be deployed and or new Network Interface Cards (NIC) for the user to install. It is highly desirable, therefore, that a means be provided that would allow the network to achieve Koolspan functionality without requiring the Access Points to be modified or replaced.
SUMMARY OF THE INVENTION
The present invention provides an external in-line device (“Subnet Box”) placed between the network and the access point to achieve Koolspan functionality without modifying the Access Point. Much like a dual-Ethernet ported firewall, the Subnet Box contains an embedded Koolspan token and will authenticate users based on pre-stored access rights.
In an embodiment of the invention, a method of facilitating authentication and security at an edge of a network is disclosed comprising the steps of: receiving a data packet; determining whether a source identifier exists in said data packet; and if the source identifier exists, retrieving a cryptographic key from local storage associated with the source identifier, and decrypting a portion of the data packet using the identified cryptographic key, and directing the data packet toward its recipient. The step of retrieving comprises the steps of: identifying a match to the source identifier, e.g., MAC address, within a pre-stored list of source identifiers; and loading a cryptographic key associated with a matching source identifier from the pre-stored list of source identifiers. If the source identifier doesn't exist, the method comprises identifying whether the data packet is a pass-through data packet, and then either directing the data packet toward its recipient if the data packet is identified as a pass-through data packet, or dropping the data packet if the data packet is not identified as a pass-through data packet.
In another embodiment of the invention, an apparatus is disclosed comprising: a first communications port for intercepting data packets communicated to and from a wired communications network; a second communications port for intercepting data packets communicated to and from a wireless access point, wherein the wireless access point is an edge device of the wired communications network; a database comprising a number of serial numbers each associated with a client token and a secret cryptographic key; and a processor for determining whether a computing device having a client token can access the wired communications network via the wireless access point. The processor establishes a secure tunnel between the computing device and the first communications port.
An advantage of the invention is that it provides an external solution that enables a totally secure tunnel across the wireless link, thereby allowing secure transmissions between the Subnet Box and the connected Client regardless of the intervening Access Point. Another advantage of the present invention is that it allows existing customers without a Koolspan token to “pass-through” the Subnet Box without security as before.
Another advantage of the invention is that it implement an authentication and wireless security technique at the edge of the network without requiring modification of the Access Point software/hardware. The invention works with all flavors of 802.11: “a”, “b”, “g” etc. and provides automatic security without needing to distribute keys across a wired or wireless network.
The foregoing, and other features and advantages of the invention, will be apparent from the following, more particular description of the preferred embodiments of the invention, the accompanying drawings, and the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
For a more complete understanding of the present invention, the objects and advantages thereof, reference is now made to the following descriptions taken in connection with the accompanying drawings in which:
FIG. 1 illustrates a conventional Wi-Fi network;
FIG. 2 illustrates a Wi-Fi network implementing a Subnet Box according to an embodiment of the invention;
FIG. 3 illustrates Subnet Box functionality according to an embodiment of the invention;
FIG. 4 illustrates a conventional encapsulation protocol stack;
FIG. 5 illustrates packet types according to an embodiment of the invention;
FIG. 6 illustrates a client driver according to an embodiment of the invention;
FIG. 7 illustrates “Koolspan” client packets according to an embodiment of the invention;
FIGS. 8 a - c illustrate processes implemented by the Subnet Box according to an embodiment of the invention;
FIG. 9 illustrates a process implemented by the Subnet Box according to an embodiment of the invention;
FIG. 10 illustrates an authentication process according to an embodiment of the invention; and
FIG. 11 illustrates a Subnet Box according to an embodiment of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Preferred embodiments of the present invention and their advantages may be understood by referring to FIGS. 2-3 and 5 - 11 , wherein like reference numerals refer to like elements, and are described in the context of a Wi-Fi network. Nevertheless, the present invention is applicable to wired and wireless communication networks in general.
The objects of the present invention are as follows: first, to implement Koolspan functionality across the wireless link (User ←(AP)→ a Subnet Box) using any 802.11-compliant Access Point without modification and second, to provide a facility that provides wireless link encryption for Koolspan-enabled clients and at the same time allowing non-Koolspan clients to pass through to the network across the wireless link. The Koolspan technique is an improved method of authentication and security that provides a secure Wi-Fi communications method and system employing a combination of physical keys, or tokens, that attach to existing computing devices and wireless access points. These keys are typically connected via a USB port, although other types of connections, e.g., Ethernet, PC-Card, serial, parallel, and the like may be employed. In overview, each component of the Wi-Fi network employs a physical key. For example, a client key is used to enable wireless connections on a user's computing device. An access point key (“AP key”) is used to activate at the access point the secure Wi-Fi functions described herein. Moreover, a master key is provided to enable and administer secure authentication and communications on the network. Each key comprises a serial number, which is forever unique, and must be unlocked using a personal identification number (PIN) known only to the owner, i.e., user, of the key. This PIN can be changed by the owner at any time.
Each physical key comprises a common network send (“NKS”) and a common network receive (“NKR”) cryptographic key used only during the authentication phase by all components on the LAN. Each physical key further includes a unique secret cryptographic key used in the second step of the authentication process. There is no mathematical relationship between key serial numbers and either the network send or network receive cryptographic keys, and the unique secret cryptographic key. The authentication process results in two random numbers that are known by both sides of the wireless channel and are uniquely generated per communications session. For example, when a client connects to an access point, the authentication process results in two unique random numbers being generated (one on each side of the connection). Only the random numbers are sent across the wireless channel and in each case these numbers are encrypted.
A transposed cryptographic key is used to encrypt all communications across the wireless channel between client and access point on behalf of the user. The transposed cryptographic key is preferably a 32-byte (256-bit) key generated using the random numbers generated during authentication and the client's secret cryptographic key. Using the serial number of the client's physical key, the access point knows the client's secret cryptographic key. Thus, both sides of the wireless channel know the secret key without it ever being transmitted between the two. The two random numbers are used to scramble the secret cryptographic key to generate a transposed version, which is finally used by both sides for secure data transmission after authentication.
Referring to FIG. 2 , the Koolspan authentication and security technique is implemented in an in-line device ( 160 ) called a “Subnet Box” that is inserted in between the Access Point ( 140 ) and the network ( 190 ). This technique does not require an authentication server, certificate server or any other network support.
In an exemplary embodiment of the invention, the Subnet Box comprises several hardware components as seen in FIG. 11 . These components include an field programmable gate array (FPGA) ( 1200 ) (e.g., an Altera FPGA), a Smart Card ( 1210 ), (2) Ethernet transceiver integrated circuits ( 1240 / 1260 ), two Ethernet ports ( 1250 / 1270 ), flash memory ( 1220 ) and synchronous SRAM memory ( 1230 ) integrated circuits. Additional interface components are also added to the design. The Subnet Box can be powered over Ethernet (POE) according to standard, well-known techniques ( 1260 ) or powered by an external AC adaptor ( 1230 ).
As seen in FIG. 11 , the block diagram of the Subnet Box, there are two Ethernet Ports. The wireless Access Point is connected to the first Ethernet Port ( 1270 ) and the Subnet Box is connected to the Network through the second Ethernet Port ( 1250 ). All packets sent from clients destined for the network must pass through the Subnet Box.
The FPGA ( 1200 ) acts as a control element of the Subnet Box. An Altera FPGA is a field-programmable gate array comprising approximately 6,000 logical elements. The internal configuration of the Altera Chip is programmed according to the desired hardware functionality. The Altera FPGA ( 1200 ) internal sub-sections are configured to include the NIOS 32-bit processor ( 1201 ), AES Crypto Engine ( 1203 ), a memory bus interface ( 1204 ), a Smart Card interface ( 1202 ) and a PCI-bus interface ( 1205 ).
The NIOS processor ( 1201 ) executes firmware instructions contained within the Flash Memory ( 1220 ) as interfaced through the Memory Bus Interface ( 1204 ). External data storage is provided in the Sync SRAM IC ( 1230 ). The NIOS processor ( 1201 ) reads the Smart Card data through the SIM I/F interface ( 1202 ) and processes Ethernet packets coming to/from the wireless Access Point through Ethernet Port ( 1270 ) via the Ethernet Transceiver IC ( 1260 ). The hardware interface to the Ethernet Transceiver IC ( 1260 ) is via the Altera FPGA ( 1200 ) PCI Interface ( 1205 ). Ethernet packets to/from the wired network are interfaced similarly via the Ethernet Transceiver IC ( 1240 ) and physical jack ( 1250 ).
While an Altera FPGA IC ( 1200 ) has been implemented in the preferred embodiment, an entirely different hardware configuration may be utilized to the same effect.
Subnet Box Functionality
As seen in FIG. 2 , all packets to/from the Client's PC ( 120 ) via the Client NIC ( 110 ) must go through the Subnet Box ( 160 ) before reaching the wired Ethernet network ( 190 ). The Access Point ( 140 ) is configured without WEP security and is left in “open” mode; that is, any 802.11 Client NIC ( 110 ) can authenticate and associate to the Access Point ( 140 ). All Client PCs ( 120 ) will be authenticated and bridged onto the Ethernet cable ( 150 ). Any Ethernet packet that is sent from the Client NIC will be ‘bridged’ onto the Ethernet cable ( 150 ) attached to the Access Point ( 140 ). The function of the Subnet Box is to permit Koolspan Client NICs ( 110 ) to establish a secure “tunnel” between the Client's PC ( 120 ) and the Subnet Box ( 160 ) providing security across the wireless 802.11 network. All traffic to/from the Client's PC ( 120 ) is encrypted using secure keys.
In the preferred embodiment, the secure keys are stored in a secure, tamper-resistant Smart Card ( 128 ) inside a Koolspan Token ( 125 ). The token is attached to the Client PC via one of many interfaces (USB port, Parallel port, Serial Port etc.) The secure keys are never exchanged or transmitted and are thus impervious to sniffing across the wireless network.
As seen in FIG. 3 , the Subnet Box comprises two Ethernet ports. The first Ethernet port ( 305 ) is attached to the Ethernet cable ( 150 ) that is connected to the Access Point ( 140 ) in FIG. 2 . The Ethernet port is identified by its MAC Address ( 300 ), a 48-bit hardware address whose function is well understood by one of ordinary skill in the art. Similarly, a second Ethernet port ( 315 ) is found on the Subnet Box that is attached to the Wired Ethernet Network (LAN, 190 ) in FIG. 2 . Packets input on the Ethernet port ( 305 ) must be processed internally within the Subnet Box ( 160 ) before appearing on port ( 315 ) and then going onto the network ( 190 ).
The Subnet Box further contains a KEY DATABASE ( 340 ) that is uploaded securely by a Key Management Program. The KEY DATABASE contains, by example, all of the SERIAL NUMBERS of authorized Client Tokens ( 125 ) and their encrypted Secret Key (NK_UIDs). Additional parameters may be stored in the Key Database ( 340 ) such as STATUS, PRIORITY etc.
The Subnet Box further maintains a table ( 330 ) containing a list of all active Client sessions. Entries in this table are made from time to time as individual Clients are authenticated in the Subnet Box. This table ( 330 ) contains the Client NIC's MAC Address( 105 ), Client Token ( 125 ) Serial Number and AES Session Key among other parameters.
Koolspan Protocol
As seen in FIG. 7 , Koolspan packets are formed by setting the TYPE field ( 530 )=“Koolspan” within the Ethernet Header ( 150 ). The next eight bytes of the data portion of the Ethernet packet are used as the Koolspan Protocol Header (KP) as seen in FIG. 7 . The Koolspan Protocol Header ( 720 ) contains various parameters ( 740 ) such as KOOLSPAN_TYPE. The setting of “KOOLSPAN_TYPE’ defines how the rest of the Ethernet packet is constructed.
There are three currently defined KoolspanTypes.
Type=KEP AES Encrypted IP data;
Type=KMP Koolspan Management Protocol; and
Type=KAP Koolspan Authentication Protocol.
Client NDIS Intermediate Driver
In a preferred embodiment, as shown in FIG. 6 , an NDIS Intermediate Driver ( 630 ) is placed in the driver stack of the operating system, e.g., Microsoft Windows Operating System. The purpose of this NDIS Intermediate Driver ( 630 ) is to intercept packets to/from the network at the appropriate level. In non-Koolspan mode, when the Client Key is NOT inserted, the NDIS Intermediate Driver ( 620 ) operates in pass-through mode ( 640 ) whereby all packet between the LAN Protocols component ( 660 ) and the NDIS Device Driver ( 620 ) are untouched.
When the Koolspan Key is first inserted, the NDIS Device Driver ( 620 ) for the wireless NIC ( 110 ) will perform an “open authentication” followed by an “association” with the Access Point as previously described. On completion of the “association”, the NDIS Device Driver ( 620 ) will trigger an event message that is passed up the stack to signify that association is complete and the Client's PC is now on the network. As the Koolspan Client Key has been inserted, the NDIS Intermediate Driver ( 630 ) is now intercepting all packets between the LAN Protocols ( 660 ) and the NDIS Device Driver ( 620 ). The NDIS Intermediate Driver ( 630 ) will now attempt to perform a Koolspan Authentication wherein a Koolspan Authentication Packet is formed by the NDIS Intermediate Driver ( 630 ). As the Access Point ( 140 ) is acting now in bridge mode, all packets received are simply passed onto the Ethernet Cable ( 150 ) where they are received first by the Subnet Box ( 160 ).
As seen in FIG. 5 , all Ethernet packets comprise a DESTINATION_MAC_ADDRESS (SIO), a SOURCE_MAC_ADDRESS ( 520 ) and a TYPE field ( 530 ) that precede the data portion of the packet ( 540 ). The MAC addresses are 48-bit fields that identify a unique hardware address of a node on the network. The TYPE field is used to determine how to process the data portion ( 540 ). Well known packet types are as follows:
TABLE 1
Ethernet Packet Types
FIG. 5
Name
Type
Description
550
ARP
0806
Address Resolution Protocol
560
RARP
8035
Reverse Address Resolution
Protocol
570
IP
0800
Normal IP Traffic
580
Koolspan
“koolspan” 1
Koolspan Packet
1 Koolspan Type to be subsequently provided by the Internet Authority Naming Association (IANA).
Koolspan uses a well-defined fourth type (type=“Koolspan”) to distinguish Koolspan packets from other well-known packets ( 550 / 560 / 570 ). In forming a Koolspan first authentication packet, the Ethernet Header Type ( 530 ) is set to Koolspan and the DESTINATION_MAC_ADDRESS ( 510 ) is set to “FF:FF:FF:FF:FF:FF”. This initial setting will ensure that the Access Point “broadcasts” this first authentication packet to all locally connected nodes attached to the Access Point. The Subnet Box will be the only device locally attached to the Access Point that will respond to a Koolspan First Authentication Packet and will respond as shown in the flow chart, FIG. 8 . When responding to the authenticating Client NIC ( 110 ), the Subnet Box will set its SOURCE_MAC_ADDRESS to that of its Access Point Ethernet Port ( 300 ) (hardware address)
The Subnet Box software is designed to intercept all packets of the Ethernet Type=“Kookspan” including “Authentication Packets”. There are several other types of Koolspan packets including “Management” and “Discovery” packets as well as “Koolspan Encryption” packets (the most common packet type for sending AES encrypted data during a session).
Subnet Box Packet Processing: Wireless Side Processing
Note the Subnet Box has two Ethernet Ports, one attached to the Access Point ( 300 ) and one attached to the LAN (wired network) side ( 310 ) as seen in FIG. 3 . The Subnet Box further has an embedded Smart Card ( 165 ) that is provisioned with three keys:
NKS—Network Send Key NKR—Network Receive Key NK_UIDs—Secret Key
The NKS key is the mirror of the Client's NKR key and the NKR key is the mirror of the Client's NKS key. In this manner, data encrypted by the Client with his “SEND” key (NKS) can be decrypted with the Subnet Box's RECEIVE key (NKR).
In the preferred embodiment of the invention, the Subnet Box processes packets of data according to the series of flowcharts seen first in FIG. 8 a.
On receipt of any wireless packet step 800 , the Subnet Box will know from the Ethernet Header ( 150 ), the SOURCE_MAC_ADDRESS ( 520 ) of the Client NIC ( 110 ). This address will be saved temporarily. The Ethernet Header ( 150 ) will be examined further to determine the packet TYPE ( 530 ) in step 810 . If the packet type is non-Koolspan (ARP (S O), RARP ( 560 ) or IP ( 570 )), the Subnet Box will check its current configuration to see if unencrypted packets are allowed to pass through, step 812 . If not, the packet will be dropped step 814 . If “pass-through” is permitted, the packet will be sent, step 816 , to the LAN via the LAN-PORT ( 165 ) of the Subnet Box.
If the Ethernet Header TYPE field ( 530 ) is set to Koolspan, the Subnet Box ( 165 ) will examine the next eight bytes as a Koolspan Protocol Header (KP) ( 720 ). Within the KP header, is a “KOOLSPAN_TYPE’ field that can have one of several values: 1. Authentication; 2. Management; and 3. Encryption.
The KOOLSPAN_TYPE field is discovered in step 825 .
Koolspan Authentication Protocol
If the KOOLSPAN-TYPE is “Authentication”, the Subnet Box ( 165 ) will examine the data portion of the Ethernet packet ( 730 ) as an “authentication packet” ( 700 ). The First Authentication Packet is generated by the Client NDIS Intermediate Driver ( 630 ) and is formed as shown in FIG. 7 . After the Ethernet Header ( 150 ), the data portion of the Ethernet packet comprises a Koolspan Protocol Header ( 720 ) whose internal structure is shown in the diagram ( 740 ). The Koolspan Protocol Header (KP) ( 720 ) is followed by a Koolspan Authentication Packet Header (KAP) ( 710 )
The KAP ( 710 ) includes several fields shown by example ( 700 ) including the authentication version, KOOLSPAN_TYPE etc. The Subnet Box ( 160 ) will process the data portion of the packet that contains the appropriate encrypted Koolspan authentication data formed by the Client NDIS Intermediate Driver ( 630 ).
The Subnet Box will begin processing the First Authentication Packet step 827 , by decrypting the authData (shown in 700 ) with the Subnet Box's NKR (Receive Key), step 860 , contained within the Subnet Box Smart Card. The structure of an Authentication Packet is shown by example in step 855 . Various checks are made to determine if the packet has been altered. In step 865 , the Serial Number of the Client's token ( 125 ) is used to retrieve the Client's Secret Key (NK_UIDs) from the Subnet Box Database ( 340 ) of previously stored Serial Numbers and matching encrypted. Secret Keys (NK_UIDs). If the serial number does not exist in the Subnet Box Database ( 340 ) an error message, step xxx, is returned to the Client. If the serial number is found in the Subnet Box Database ( 340 ), then the Client's NK-UISs is retrieved from the Subnet Box Database ( 340 ) and the hash is computed on the received data, step 868 , and compared, step 869 , against the received signature, step 862 . If the signatures do not match, an error message is returned to the Client, step 870 and further processing stops.
If the signature match, a new entry is made in the Subnet Box Client Table ( 330 ), step 880 , The entry into this table ( 330 ) contains the Client MAC Address ( 105 ) recovered from the Ethernet Header ( 520 ), the Client Token ( 125 ) Serial Number and eventually the AES Session Key when computed in step 890 .
The Subnet Box will continue processing the AuthData recovering the Random Number (R 1 ) by decrypting the internal packet data with the Client's NK_UID recovered from the Subnet Box Database ( 340 ) using the Client Key ( 125 ) Serial Number step 882 . A second random number (R 2 ) is computed, step 884 , and concatenated with R 1 and then encrypted with the Client's secret key (NK_UIDs), step 886 . The ciphertext is then encrypted this time with the Subnet Box's SEND Key (NKS) and the ciphertext is placed into the “authData” field of the Koolspan Authentication Packet ( 700 ) and the appropriate parameters are set in the Koolspan Authentication Header to indicate this is the Second Authentication Packet and the entire packet is returned to the Access Point for transmission to the Client via the Client's MAC Address, step 892 .
The Access Point, now acting as a bridge, delivers the Koolspan Second Authentication Packet to the Client, step 1105 . The construction of the packet data is shown, by example, in step 1100 , FIG. 10 . Referring to FIG. 10 , The authData of the Authentication Packet ( 700 ) is decrypted by the NDIS Intermediate Driver ( 630 ) step 1110 yielding the encrypted RI:R 2 numbers and the signature. The encrypted R 1 :R 2 numbers are then decrypted with the Client Token's ( 125 ) RECEIVE KEY (NKR), step 1130 , yielding the unencrypted R 1 :R 2 combination. A signature is computed from these two numbers, step 1140 , and compared against the received signature, step 1150 . If a match is not found, the error is reported to the user, step 1160 , and processing terminates leaving the client blocked from sending further packets through the Subnet Box.
If a match is found, then the NDIS Intermediate Driver will conclude that the Koolspan Authentication process has been successful and will compute the AES Session Key from the two random numbers R 1 , R 2 , step 1180 and save the AES Session Key for further use during the session. All further communications between the Client and the Subnet Box will subsequently be encrypted with the AES Session Key. Additionally, the Client NDIS Intermediate Driver ( 630 ) will note the SOURCE MAC ADDRESS ( 520 ) of the Subnet Box that is returned in the Ethernet Header ( 150 ) of the Second Koolspan Authentication Packet. All further Koolspan-enabled communications between the Client NDIS Intermediate Driver will be specifically addressed to the MAC Address of Subnet Box Access Point port ( 300 ).
Encryption
If, in fact, the Client has been authenticated, then when sending network traffic of any kind, the Client NDIS Intermediate Driver ( 630 ) will encapsulate all of the fields of a normal Ethernet packet (IP header, TCP header, Application Data, Ethernet trailer with the exception of the Ethernet Header) as shown in FIG. 4 , encrypting this data with the Client's AES Session Key. The Koolspan Protocol Header will set the KOOLSPAN_TYPE to Koolspan Encrypted Protocol (KEP) and the Ethernet Header Type will be set to Type=“Koolspan”.
On receipt of a type KEP Koolspan packet, processing will he directed to step 828 as shown in FIG. 8 c. The Ethernet Packet Header will reveal the SOURCE MAC ADDRESS of the Client ( 105 ). The SOURCE MAC ADDRESS will ( 520 ) will be used to see if there is an entry in the Subnet Box NETWORK TABLE ( 330 ). If there is no entry for that SOURCE MAC ADDRESS ( 520 ), step 900 , an error message will be returned to the Client NIC ( 110 ), step 910 , and the packet will be dropped, step 912 . If the SOURCE MAC ADDRESS ( 520 ) is found in the Network Table ( 330 ), it will then be used to retrieve the AES Session Key from the Network Table ( 330 ). The AES Session Key is then used to decrypt the Koolspan Data field resulting in a normal Ethernet Data Packet (non-Koolspan type). This packet is then directed appropriately to either the normal LAN port ( 310 ) or the Access Point port if the routing indicates the recipient also resides on the wireless side of the Subnet Box.
In the case of an inbound packet destined to be returned to another Koolspan-enabled Client on the wireless side of the Subnet Box, the plain-text packet, step 906 , must now be encrypted with the recipient's AES Session Key for transmission to the recipient. If the recipient is not Koolspan-enabled and “pass-through” mode is enabled, the packet is simply sent normally without encryption. If “pass-through” mode is not enabled, the packet is dropped.
Routing
All AES-encrypted Koolspan packets are directed to the Subnet Box ( 165 ) using the Subnet Box's MAC address ( 300 ). This is necessary to ensure that all packets regardless of their destination be first decrypted in the Subnet Box before they are sent to their destination.
The reason this is necessary is that if two clients attempt to communicate on the same wireless side of the Access Point, the Access Point will simply route the received communications from the sending client to the receiving client as the Access Point routing table will not forward the packets to the Ethernet Port of the Access Point but instead retransmit the packet wirelessly. By forcing all packets to go directly to the Subnet Box regardless of their ultimate destination, this ensures that proper authentication and security are always maintained.
Dual-Use
The Subnet Box ( 160 ) can be configured to allow both non Koolspan-enabled Clients to communicate as well as Koolspan-enabled Clients. This method of allowing non Koolspan-enabled Clients to communicate is known as “pass through” mode.
In “pass through” mode, the Ethernet Packet Header Type field ( 530 ) indicates a non-Koolspan TYPE. On determination that “pass through” mode is enabled, the packet is allowed to pass through. It's final destination, however, determines how the packet is transmitted in the outbound direction.
If the packet was received on the Access Point side of the Subnet Box, Ethernet Port ( 300 ), and the destination is on the LAN side ( 310 ), the packet will simply be let through the Subnet Box ( 165 ) without further processing. If however, the destination is on the same Access Point side ( 300 ) i.e., another wireless Client connected to the same Access Point, further processing is required. If the destination Client is non-Koolspan enabled and “pass through” mode is enabled, the Subnet Box will simply pass the packet through to the Access Point via the Access Point Ethernet Port ( 300 ). If the destination Client is Koolspan-enabled, the packet must be encrypted using the destination Client's AES Session Key with an appropriate Koolspan KEP header and Koolspan KP header pre-pended to the packet.
This dual-use mode allows the possibility of both Koolspan-enabled Clients and non-Koolspan-enabled Clients to communicate on a wireless network. Koolspan-enabled Clients are provided automatic AES security across the wireless link whereas non-Koolspan-enabled Clients may be either denied access entirely (pass-through mode disabled) or provided non-secure access (pass-through mode enabled).
The technology described herein provides an end-to-end security link. In the preferred embodiment, the network is wireless, but in other embodiments the end-to-end link (client-to-subnet box) might not involve any wireless components.
The present invention provides a technique for automatically detecting both non-Koolspan clients and Koolspan-enabled clients and thus providing both protected communications for Koolspan-enabled clients and normal (non secure) communications for non Koolspan-enabled users simultaneously. Wireless link security can be provided in a public hotspot by the simple addition of an inline Koolspan Subnet Box providing automatic wireless link security without affecting existing non-Koolspan-enabled users.
Other embodiments and uses of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. Although the invention has been particularly shown and described with reference to several 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 spirit and scope of the invention as defined in the appended claims.
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The invention provides an external in-line device (“Subnet Box”) placed between a network and an access point to achieve secure Wi-Fi communications without needing to modify the access point. The Subnet Box comprises an embedded token and will authenticate users based on pre-stored access rights. In at least one embodiment of the invention, the Subnet Box comprises: a first communications port for intercepting data packets communicated to and from a wired communications network; a second communications port for intercepting data packets communicated to and from a wireless access point, wherein the wireless access point is an edge device of the wired communications network; a database comprising a number of serial numbers each associated with a client token and a secret cryptographic key; and a processor for determining whether a computing device having a client token can access the wired communications network via the wireless access point. The processor establishes a secure tunnel between the computing device and the first communications port.
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RELATED APPLICATIONS
The present application is a continuation-in-part of U.S. patent application Ser. No. 14/311,980, filed Jun. 23, 2014, the disclosure of which is incorporated herein by reference in its entirety.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The field of invention relates to zeolites. More specifically, the field relates to partially collapsed zeolites for the purification of hydrocarbon based gaseous fractions such as natural gas.
2. Description of the Related Art
Almost one quarter of the total worldwide production of energy is met through natural gas production. The regulations for the transportation of natural gas that occurs mainly through pipelines vary by country. In many countries and jurisdictions, there are specific restrictions to the amounts of inert chemical species such as nitrogen (N 2 ) and carbon dioxide (CO 2 ) that may be transported. Nitrogen is typically found in wellhead gas in a concentration range of about 0.5 to 5 mole percent and may approach concentrations of up to 30 mole percent. Sub-quality natural gas is a composition that exceeds pipeline specifications for contaminants such as CO 2 , hydrogen sulfide (H 2 S) and nitrogen. For instance, sub-quality natural gas often has a nitrogen concentration exceeding 4 mole percent and a CO 2 concentration in a range of about 0.2 mole percent to about 1 mole percent with respect to the wellhead gas. Both nitrogen and CO 2 have no heating value and therefore reduce the thermal quality of the wellhead gas. In addition, CO 2 is an “acid gas” that, in the presence of water, forms carbonic acid. The resulting acid reacts rapidly with carbon steel and other metals susceptible to acidification and produces corrosion, a common problem in areas along a pipeline where pools of aqueous liquids may form.
CO 2 is normally removed during natural gas refinement and processing by the process of amine scrubbing using gas-liquid contactors operating at a temperature range of from about 323 K to about 333 K. The resulting (saturated) alkanolamine is regenerated in a temperature range of from about 383 K to about 403 K and releases the purified carbon dioxide. This energy intensive process typically involves the handling of a corrosive and toxic solvent. In addition, the removal of nitrogen from methane, the primary component in natural gas is very difficult. The only commercial process commonly used for separating nitrogen from methane is cryogenic distillation, where a turboexpander reduces the temperature of the gas to about 220 K. The nitrogen-poor product stream must be recompressed to transport it through pipelines effectively. Both turboexpansion and recompression are energy-intensive and therefore increase the costs associated with natural gas processing.
Adsorption processes using zeolites are capable of performing certain CH 4 —CO 2 and CH 4 —N 2 separations. For instance, Molecular Gate® (Engelhard Corp.; Iselin, N.J.) uses titanosilicate-based zeolites (ETS and CTS configurations) doped with transition metals that allow for the micropores of the zeolite to be adjusted based upon activation temperature. Other adsorbents include carbon based molecular sieves for CH 4 —N 2 separations. A pressure swing adsorption (PSA) system using metal-exchanged clinoptilolites, a natural zeolite largely comprised of silica and alumina, has also shown some promise for CH 4 —N 2 separation. In addition, CMS 3A (carbon molecular Sieve 3A) has been evaluated for performing CH 4 —CO 2 separation.
As a selective adsorbent of N 2 and CO 2 , zeolite-based materials are attractive candidates. Zeolite 13X, which is an aluminosilicate zeolite, has been shown to reduce carbon dioxide levels in flue gases at low temperatures. Zeolites are thermochemically stable, available in the market and their surfaces can be controlled through post-modifications such as ion-exchange. Zeolites have well-defined microporous structures with mean diameters in a range of from about 0.3 nanometers (nm) to about 1.5 nm, allowing a zeolite material to advantageously provide a molecular sieve type effect for separating certain unwanted constituents found in natural gas.
Despite the advantages of zeolites, the separation of N 2 and CO 2 from CH 4 remains challenging. For instance, the extremely small difference between the kinetic diameters of the compounds (CO 2 : 0.33 nm; N 2 : 0.36 nm; CH 4 : 0.38 nm) requires precision in forming zeolite apertures. It should be noted that the pore diameter of zeolites and similar materials is difficult to control in the ultra-small pore range (e.g. materials with mean diameters less than 0.38 nm). The attraction of a titanosilicate-type ETS-4 zeolite for small molecular separations is attributable to its pore size tuning. However, two significant problems are associated with the broad use of titanosilicate materials: 1) they have lower thermal stability, so it is more difficult to use them in processes that apply thermal cycling to promote adsorption aid desorption; and 2) these materials can be costly and not readily available. In this regard, aluminosilicate-based zeolites are advantageously more commercially available and less expensive than titanosilicate-based zeolites.
SUMMARY OF THE INVENTION
The present invention relates to amorphous adsorbent compositions capable of purifying a gaseous hydrocarbon fraction and methods for synthesizing these compositions. In some embodiments, a composition in accordance with the present invention comprises a hydrolyzed, partially collapsed Linde Type A aluminosilicate zeolite, and a plurality of pores characterized by a pore aperture size of from about 0.33 nm to about 0.38 nm. In further embodiments, the composition is characterized by a carbon dioxide/methane equilibrium selectivity factor in a range of about 3.8 to about 40. In still further embodiments, the composition has a Na/Al ratio in a range of from about 0.60 to about 1.00. In further embodiments, the composition is hydrolyzed using deionized water. In additional embodiments, the deionized water is present in a phase selected from the group consisting of liquid, saturated steam and superheated steam.
In some embodiments, the composition is decationized and calcined prior to hydrolysis. In additional embodiments, the composition is calcined at a temperature between about 473 K and about 773 K. In further embodiments, the composition is operable at a temperature in a range of between about 273 K and about 323 K and a pressure in a range of between about 1 bar and about 8 bars. In some embodiments, the composition further comprises one or more cations selected from sodium, ammonium, and combinations thereof.
In some embodiments, the invention relates to a method for synthesizing an amorphous adsorbent material capable of purifying a gas fraction comprising combining at least a stoichiometric amount of a compound comprising at least one exchangeable cation with a stoichiometric amount of a sodium Linde Type A aluminosilicate zeolite compound under temperature and pressure conditions suitable for promoting cation exchange between the compound comprising at least one exchangeable cation and the sodium Linde Type A aluminosilicate zeolite compound; isolating the Linde Type A aluminosilicate zeolite compound comprising the exchangeable cation; calcinating the Linde Type A aluminosilicate zeolite compound comprising the exchangeable cation under conditions such that the Linde Type A aluminosilicate zeolite compound undergoes at least a partial structural collapse and the exchangeable cation is removed to form a calcinated amorphous adsorbent precursor; and hydrolyzing the calcinated amorphous adsorbent precursor under conditions appropriate for forming a plurality of pores characterized by a pore aperture size of from about 0.33 nm to about 0.38 nm. In further embodiments, the compound comprising at least one exchangeable canon is ammonium nitrate. In still further embodiments, the calcination step is performed at a temperature in a range of about 473 K to about 773 K and at a pressure in a range of about 1 bar to about 8 bars, preferably at a pressure of about 1 bar.
In some embodiments, the invention relates to a method for purifying a natural gas fraction comprising the steps of introducing a natural gas traction into a vessel containing the composition of claim 1 , where the introduced natural gas is a non-upgraded natural gas comprising non-combustible gases and where the amorphous adsorbent is characterized by a carbon dioxide/methane equilibrium selectivity factor in a range of about 3.8 to about 40; contacting the natural gas fraction with the composition of claim 1 ; and maintaining the natural gas fraction in the vessel containing the composition of claim 1 for a sufficient time such that the concentrations of the non-combustible gases are reduced in the natural gas fraction. The non-upgraded natural gas fraction may refer to a natural gas traction that is previously unrefined, previously unprocessed, incompletely refined or incompletely processed.
A highly selective, ultra-small pore amorphous adsorbent composition in accordance with the present invention, is useful for upgrading a sub-quality natural gas. The amorphous adsorbent of gaseous contaminants at operating conditions selectively removes at least a portion of contaminants including but not limited to nitrogen and carbon dioxide from the natural gas introduced to it, thereby upgrading the quality of the natural gas for downstream users. The adsorbent material is amorphous and allows for higher hydrothermal stability, e.g. in systems that apply thermal cycling as part of an adsorption/desorption process. The use of repeated thermal variations over time in such processes does not modify the pore structure. The amorphous adsorbent is advantageously environmentally friendly and non-toxic, unlike many commercially available salt- and solvent-based removal systems.
BRIEF DESCRIPTION OF THE DRAWINGS
So that the manner in which the features, advantages and compositions of the invention, as well as others which will become apparent, are attained, and can be understood in more 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 that form a part of this specification. If is to be noted, however, that the drawings illustrate only a preferred embodiment of the invention and are therefore not to be considered limiting of its scope as the invention may admit to other equally effective embodiments. The present technology will be better understood on reading the toll owing detailed description of non-limiting embodiments thereof, and on examining the accompanying drawings, in which:
FIG. 1A shows X-ray diffraction (XRD) patterns for a Linde Type A zeolite (“Reference”) and Samples 1 through 5;
FIG. 1B shows X-ray diffraction (XRD) patterns for a Linde Type A zeolite (“Reference”) and Samples 6 through 10;
FIG. 2A shows CO 2 and CH 4 equilibrium gas adsorption capacity plots for a Linde Type A zeolite (“Reference”) and Samples 1 through 5 at a temperature (T) of 323 K and a pressure (P) of 8 bars;
FIG. 2B shows a CO 2 /CH 4 equilibrium selectivity factor plot for a Linde Type A zeolite (“Reference”) and Samples 1 through 5 aid the percentage of remaining CO 2 capacity for a Linde Type A zeolite (“Reference”) and Samples 1 through 5 at T=323 K and P=8 bars;
FIG. 3 shows CO 2 and CH 4 gas adsorption isotherms for a Linde Type A zeolite (“Reference”) and Samples 6 through 10;
FIG. 4A shows a graph of both the CO 2 and CH 4 equilibrium gas adsorption capacities for a Linde Type A zeolite (“Reference”) and Samples 6 through 10 at T=323 K and P=8 bars; and
FIG. 4B shows a CO 2 /CH 4 equilibrium selectivity factor plot for a Linde Type A zeolite (“Reference”) and Samples 6 through 9 and the percentage of remaining CO 2 capacity for a Linde Type A zeolite (“Reference”) and Samples 6 through 10 at T=323 K and P=8 bars.
DETAILED DESCRIPTION OF THE INVENTION
Although the following detailed description contains specific details for illustrative purposes, the skilled artisan will appreciate that many examples, variations and alterations to the following details are within the scope and spirit of the invention. Accordingly, the exemplary embodiments of the invention described herein and provided in the appended figures are set forth without any loss of generality, and without undue limitations, on the claimed invention. The referenced elements, components or steps may be present utilized or combined with other elements, components or steps not expressly referenced.
As used herein, the term “decationize” and its conjugated forms such as “decationization” refers to the process of removing an electrostatically coordinated or adventitiously associated cation from a material. While in no way limiting the context of the present invention to any particular methodology or physicochemical process, decationization may be performed using chemical and/or thermal treatment, including but not limited to solvent washing or solvation as well as heating a composition under conditions capable of thermally evolving a cation such as calcination.
As used herein, the term “operable” and its conjugated forms should be interpreted to mean fit for its proper functioning and able to be used for its intended use. The term “maintain” and its conjugated forms should be interpreted to mean conditions capable of causing or enabling a condition or situation to continue. As used herein, the term “detect” and its conjugated forms should be interpreted to mean the identification of the presence or existence of a characteristic or property. The term “determine” and its conjugated forms should be interpreted to mean the ascertainment or establishment through analysis or calculation of a characteristic or property.
Where the specification or claims provide a range of values, it is understood that the interval encompasses each intervening value between the upper limit and the lower limit as well as the upper limit and the lower limit. The invention encompasses and bounds smaller ranges of the interval subject to any specific exclusion provided. Where a method comprising two or more defined steps is referenced herein, the defined steps can be carried out in any order or simultaneously except where the context expressly excludes that possibility.
The present invention relates to a method for using the controlled structural collapse of a crystalline aluminosilicate zeolite to form a highly selective, ultra-small pore size amorphous adsorbent. In one embodiment, the aluminosilicate zeolite is a Linde Type A zeolite, and commercially-available, small-pore size (pore diameter=4 Å) sodium Linde Type A zeolites (alternatively referenced herein as “NaA”) may be used as the precursor for forming the amorphous adsorbent. NaA is known to have a high gas adsorption capacity but a low selectivity for heterogeneous gas fractions including those of 1) methane and CO 2 ; and 2) methane and N 2 .
The method for forming the amorphous adsorbent includes ion-exchange, calcination and liquid H 2 O treatment (under ambient or heated conditions) of the precursor to irreversibly transform the crystalline aluminosilicate zeolite with a small pore size into the highly selective, ultra-small pore size amorphous adsorbent. In alternative embodiments, the liquid H 2 O treatment of the precursor may be replaced with steam treatment, including superheated steam. The resulting composition can adsorb natural gas components under moderate temperature and elevated pressure conditions such that a greater-than-expected selectivity for CO 2 over methane occurs. Under similar conditions, a higher selectivity for N 2 over methane would likewise occur.
In a preferred embodiment, the starting material for the formation of the highly selective, ultra-small pore amorphous adsorbent composition of the present invention is NaA. The zeolite is typically synthesized using hydrothermal crystallization techniques from a synthesis gel composition comprising stoichiometric ratios of (3-4)Na 2 O:Al 2 O 3 :(1.8-3.0)SiO 2 :(50-200)H 2 O, where the parenthetical values represent stoichiometric ranges for each of the chemical components. The crystallization of the zeolite from the gel occurs over a time period of about 3-24 hours in a temperature range of about 353 K to about 373 K, resulting in generally cubic crystals exhibiting an average crystal diameter size of 1-3 micrometers (μm), an X-ray defection (XRD) pattern of strong reflections at d=4.107, 3.714, 3.293 and 2.987 Å, and Si/Al and Na/Al stoichiometric ratios of about 1.00.
The highly selective, ultra-small pore amorphous adsorbent composition of the present invention may be formed by initially reacting an ion-exchange material having an exchangeable cation with an aluminosilicate zeolite having a cation, for instance NaA such that the cationic exchange results in an ion-exchanged zeolite. A higher degree of (thermodynamically driven) cation exchange correlates to a greater degree of structural collapse to produce the amorphous form of the crystalline zeolite during the subsequent calcination step. The degree of cation exchange is dependent on both the temperature and the cation concentration in the ion-exchange material. The “cation/Al ratio” is the stoichiometric ratio of the exchangeable zeolite cation to aluminum in the zeolite, for instance, a sodium aluminosilicate zeolite such as NaA is expressed as a “Na/Al ratio”.
As the cation exchange progresses the ratio will be reduced as the (zeolite) cation is exchanged for the (ion-exchange material) cation. Generally, higher concentrations of the cation of the ion-exchange material result in higher cation exchange with the crystalline zeolite. However, based upon the type of ion-exchange material used and the cation exchange conditions, the resulting exchanged cation/Al ratio may be lower than expected due to factors including hut not limited to transport phenomenon effects inside the crystalline zeolite.
In some embodiments, the exchangeable cation of the ion-exchange material is an ammonium (NH 4 + ) ion. In reacting an NH 4 + containing ion-exchange material with a sodium aluminosilicate zeolite such as NaA, the Na/Al ratio will decrease with an increased degree of NH 4 + substitution for the Na + cation of the crystalline zeolite. In one embodiment, the amorphous adsorbent has a Na/Al ratio in a range of from about 0.60 to about 1.00. In further embodiments, the amorphous adsorbent has a Na/Al ratio in a range of from about 0.60 to about 0.77.
The method of forming the highly selective, ultra-small pore amorphous adsorbent composition of the present invention includes calcinating the ion-exchanged zeolite at a calcination temperature such that the ion-exchanged zeolite partially collapses and forms a decationized adsorbent. The steps of cation exchange and subsequent calcination such that at least some of the positive ion is removed from the ion-exchanged zeolite are collectively referred to as the “decationization” of the zeolite. Decationization is characterized by the partial collapse of the crystalline zeolite into an amorphous, unstructured material. The structural portions of the amorphous adsorbent composition where the cation exchange occurs are irreversibly degraded.
In some instances, the cation-exchanged zeolite may begin collapsing at temperatures greater than about 373 K. In some embodiments, the calcination temperature is in a range of from about 473 K to about 773 K, for instance about 673 K. Alternatively, thermally collapsing a sodium aluminosilicate zeolite such as NaA in the absence of cation exchange requires high calcination temperatures, for example temperatures greater than about 973 K. However, the resulting collapsed zeolite structure is non-porous and therefore unsuitable for performing molecular separations.
In some embodiments, the cation used in the ion-exchange material is an ammonium ion (NH 4 + ). While not limited the present invention to any particular theory, it is believed that calcination of the ion-exchanged zeolite causes the NH 4 + ion to thermally degrade into ammonia (NH 3 ) and a hydrogen ion (H + ). The resulting ammonia evolves from the collapsing zeolite, while the hydrogen ion is integrated into the partially-collapsed zeolite structure. The degree of structural collapse during decationization correlates to the degree of cation exchange that occurs.
In some embodiments, a method for forming a highly selective, ultra-small pore amorphous adsorbent composition of the present invention includes introducing water to the decationized adsorbent such that the decationized adsorbent collapses to form the composition. Treatment of the decationized adsorbent with water (H 2 O) having no significant mineral, salt or free ion content was found to enhance the structural collapse of the decationized adsorbent by degradation of the silicon/aluminum based structure, while the cation exchange and the calcination steps remove residual (non-ammonium) cations with large atomic radii in the crystalline zeolite material.
The introduction of water following calcination results in the hydrolysis of destabilized Si—O—Al bonds that are present in the decationized adsorbent. The hydrolysis of susceptible Si—O—Al bonds may lead to additional pore size narrowing for enhancing the selectivity properties of the amorphous adsorbent composition without adversely impacting the adsorption capacity of the material.
As used herein, the term “Si/Al ratio” refers to the molecular ratio of silicon to aluminum in compositions such as zeolites and compositions of the present invention. For instance, the Si/Al ratio in the original zeolite is about 1.00. In certain embodiments, the Si/Al ratio of the amorphous adsorbent composition of the present, invention is in a range of from about 1.00 to about 1.03.
Following the decationization and post-calcination water treatment of the precursor material, the original crystalline zeolite framework collapses and forms an amorphous adsorbent composition in accordance with the present invention. The degree of structural collapse can be controlled at each step by the degree of cation exchange in the crystalline zeolite, the extent of decationization during calcination, and the hydrolysis of susceptible silicon-aluminum bonds.
The methods described herein transform cation-bearing aluminosilicate zeolites such as sodium aluminosilicate zeolites with small pores apertures (less than 4 Å), into aluminosilicate based materials characterized by enhanced density and increased amorphous domains. The resulting dense, amorphous structure advantageously restricts diffusion to molecules with small diameters, including but not limited to H 2 (2.89 Å), H 2 O (2.7 Å), CO 2 (3.3 Å), O 2 (3.46 Å), N 2 (3.64 Å), Ar (3.3 Å) and CH 4 (3.8 Å). The pore aperture size of the claimed composition allows the adsorption of contaminant gases while restricting the adsorption of methane. In some embodiments, a highly selective, ultra-small pore amorphous adsorbent composition in accordance with the present invention has a pore aperture size in a range of from about 0.33 nm to about 0.38 nm. In further embodiments, the composition has carbon dioxide/methane equilibrium selectivity factor in a range of from about 3.8 to about 40 at a temperature of about 323 K and a pressure of about 8 bars.
In preferred embodiments, the amorphous adsorbent cannot revert back to a Linde Type A structure. For instance, the structural configuration of titanium-based zeolites like ETS-1 and CTS-1 can rearrange with temperature and/or pressure variations and alter the adsorption properties of these zeolites drastically and unpredictably. In contrast, the amorphous adsorbent compositions of the present invention advantageously retain their adsorptive properties under the variable and wide ranging temperatures and pressures that often characterize chemical separation processes, including conditions associated with gas adsorption/desorption systems.
In certain embodiments, the present invention relates to methods for improving the quality of a natural gas fraction or stream comprising introducing the natural gas fraction or stream into a vessel comprising a highly selective, ultra-small pore amorphous adsorbent composition such as those described herein. The method includes maintaining the natural gas fraction or stream in the vessel for a sufficient amount of time such that the natural gas contacts the amorphous adsorbent to produce a purified natural gas. The natural gas fraction or stream may or may not be previously refined or purified.
In some embodiments, the natural gas fraction or stream is a non-upgraded natural gas comprising a first mole percent of carbon dioxide that, in certain embodiments, are converted in an upgraded natural gas traction or stream with a second mole percent of carbon dioxide using the methods described herein. In some embodiments, the first mole percent of carbon dioxide is greater than the second mole percent of carbon dioxide. In further embodiments, the methods for improving the quality of a natural gas fraction or stream are characterized by a residence time in a range of about two minutes to about 30 minutes.
EXAMPLES
The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventors to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.
Samples 1 through 5 are decationized materials that have been treated using ion-exchange and calcination procedures, while Samples 6 through 10 are five ultra-small pore amorphous adsorbents that have been treated with water following calcination. The Reference Sample (described as “Reference” in FIGS. 1A through 4B ) is the zeolite precursor material used to synthesize Samples 1 through 10. The samples were synthesized using the same procedure for each of Samples 1 through 10 except for variations in the concentrations of ammonium nitrate (NH 4 NO 3 ). Each sample was synthesized by initially suspending 1 gram of the sodium Linde Type A (NaA) zeolite in 20 mL of NH 4 NO 3 solution at the various molar concentrations given in Table 1. The resulting suspension was stirred for six hours at room temperature to form ion-exchanged zeolite precursors, where the ammonium (NH 4 + ) ion substitutes for the sodium (Na + ) ion to varying degrees based upon the ammonium nitrate concentration. The precursors are collected by filtration, washed with deionized water followed by acetone, and dried at 333 K for 24 hours. The dried, ion-exchanged zeolite precursors am then calcined in a plug-flow reactor under flowing dry air (25 mL/minute) at 673 K (temperature ramp: 1 K/minute) for 2 hours to produce Samples 1 through 5. An additional fraction of 1 gram calcined precursors were stirred in 300 mL room temperature water (H 2 O) for 6 hours, collected by filtration, washed with deionized water and dried at 373 K for 24 hours to produce Samples 6 through 10.
Elemental analyses were performed on the Reference Sample and Samples 1 through 10 using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The compositional results for Samples 1-5 were, within standard error, the same as those of Samples 6-10. For instance, the Si/Al ratio of the (10) samples were all very close to 1.00, which is the Si/Al ratio of starting zeolite material. The ratio of Si/Al and Na/Al did not change significantly during the calcination and the post-calcination water treatment procedures.
The Na/Al ratio gradually decreases as the degree of NH 4 + ion-exchange increases because of the removal of Na + cation during the decationization procedure. In addition, powder X-ray diffraction (XRD) patterns were recorded for the Reference Sample and Samples 1 through 10 using a D2-phaser (Bruker) equipped with Cu radiation (30 kV, 10 mA) and a LYNXEYE detector. The resulting diffraction patterns for Samples 1-5 are shown in FIG. 1A , while the patterns for Samples 6-10 are given in FIG. 1B . Each trace has been off-set by a fixed intensity value for the purposes of clarity of the drawing and has the same original value at 2θ=5. The XRD patterns for Samples 1-5 revealed that the spectral intensities of the characteristic NaA peaks were mostly intact even after significant decationization. However, the XRD analysis for Samples 6-10 revealed that the intensities of the characteristic NaA zeolite peaks significantly decreased and became broader as the degree of decationization increased, indicating that Linde Type A (LTA) zeolites gradually loses their crystallinity (i.e., their long-range structural ordering) during decationization and subsequent water treatment procedures and their structural framework appears to resemble that of amorphitized aluminosilicate.
TABLE 1
Ammonium nitrate concentrations used for the synthesis of and the
resulting elemental analysis ratios for the Reference Sample and
Samples 1 through 10 as determined via ICP-AES.
NH 4 NO 3
Example
Concentration (M)
Na/Al ratio
Si/Al ratio
Reference Sample
—
1.00
1.00
Sample 1
0.14
0.77
1.03
Sample 6
Sample 2
0.21
0.71
1.02
Sample 7
Sample 3
0.28
0.65
1.03
Sample 8
Sample 4
0.35
0.63
1.01
Sample 9
Sample 5
0.42
0.60
1.01
Sample 10
FIG. 2A shows CO 2 and CH 4 equilibrium gas adsorption capacity isotherms for the Reference Sample (“Reference”) and Samples 1-5 at a temperature of 323 K and a pressure of 8 bars. The observed CO 2 and the CH 4 gas adsorption capacities did not significantly change despite extensive decationization. This result indicates that, while NH 4 + exchange followed by calcination can lead to the decationization of the zeolite precursors, the resulting pore structure collapse and pore size narrowing are not significant.
FIG. 2B shows both the CO 2 /CH 4 equilibrium selectivity factors for the Reference Sample (“Reference”) and Samples 1-5 at a temperature of 323 K and a pressure of 8 bars and the percentage of remaining CO 2 capacity for the Reference Sample (“Reference”) and Samples 1-5 at T=323 K and P=8 bars. The values used to calculate the selectivity factor values for CO 2 to CH 4 at P=8 bars were determined using the gas adsorption capacity values for CO 2 and CH 4 in FIG. 2A . The results indicate that Samples 1-5 exhibit very low selectivity enhancement, and that the decationization of the zeolite precursor does not show significant narrowing with respect to pore size.
The gas adsorption capacity of Samples 1 through 10 was tested using a volumetric adsorption unit (Micromeritics ASAP2050) at a temperature of 323 K and a pressure range from 0 to 8 bars. The resulting CO 2 and CH 4 gas adsorption isotherms for the Reference Sample (“Reference”) and those of Samples 6-10 are presented in FIG. 3 . An absorptive equilibrium was assumed to have been reached when a pressure change of less than 0.01% over a 30 second interval was observed. The Reference Sample demonstrated the highest adsorption volume for CO 2 , but it similarly exhibited the highest adsorption for CH 4 . Samples 6-10 demonstrated decreasing amounts of gas adsorption (both CO 2 and CH 4 ) which correlates to decreases in each sample's Na/Al ratio while inversely correlating to the NH 4 NO 3 concentration used to manufacture Samples 6-10 (Table 1).
The observed gas adsorption decreases may be attributable to the structural transformation of the crystalline zeolite precursor into the amorphous adsorbent composition during the decationization and water treatment procedures. In this regard, the decationized adsorbent did not exhibit a significant decrease in CO 2 and CH 4 gas adsorption capacity for samples where the Na/Al ratio is in a range of from about 0.60 to about 1.00, and the CO 2 /CH 4 equilibrium selectivity factor of the decationized adsorbent was not significantly enhanced at T=323 K and P=8 bars.
FIG. 4A shows a graph of both the CO 2 and CH 4 equilibrium gas adsorption capacities for the Reference Sample (“Reference”) and Samples 1 through 10 at a temperature of 323 K and a pressure of 8 bars. The gas adsorption capacity for carbon dioxide and methane at a pressure of 8 bars was determined using the values provided in FIG. 3 . The results herein demonstrate that CO 2 and the CH 4 adsorption capacities decrease as the zeolite structural collapse becomes more extensive with the corresponding increase in ammonium nitrate (NH 4 NO 3 ) concentration in the ion-exchange material. For instance. Sample 10 was synthesized using the highest concentration of NH 4 NO 3 (0.42 M) and did not demonstrate any significant methane adsorption.
A comparison of the separation between the CO 2 and CH 4 equilibrium gas adsorption in FIG. 4A suggests that CH 4 adsorption capacity decreases more rapidly than that observed for CO 2 . These results suggest that in view of the kinetic diameter of CH 4 being greater than that of CO 2 , CH 4 will be excluded more readily upon a narrowing of the pore size daring the controlled collapse of the zeolite based precursor.
FIG. 4B shows CO 2 /CH 4 equilibrium selectivity factors for the Reference Sample (“Reference”) and Samples 6 through 10 as well as the percentage of remaining CO 2 capacity for the Reference Sample (“Reference”) and Samples 6 through 10 at a temperature of 323 K and a pressure of 8 bars. The values used to calculate the selectivity factors for CO 2 and CH 4 at the disclosed pressure were determined using the gas adsorption capacity values for both carbon dioxide and methane in FIG. 4A . As described above, Sample 10 does not demonstrate any significant methane adsorption, and consequently demonstrated an undefined (infinite) CO 2 /CH 4 equilibrium selectivity factor.
As shown in FIG. 4B , the Reference Sample—a Linde Type A zeolite—demonstrates an equilibrium selectivity factor of only about three times greater selectivity for CO 2 than for CH 4 at T=323 K and P=8 bars, while Samples 6-9 exhibit CO 2 /CH 4 equilibrium selectivity factors greater than 3.0. Sample 6 produced a CO 2 /CH 4 equilibrium selectivity factor in a range of about 3.8 to about 10 with a CO 2 gas adsorption capacity. In addition, Sample 6 exhibited about 90% to about 95% of the adsorption value produced by the Reference Sample. Samples 7 and 8 demonstrated equilibrium selectivity factors in a range of about 10 to about 20. Sample 8 exhibited significant CO 2 gas adsorption capacity (equilibrium selectivity factor of about 50 to about 60) in comparison with the Reference Sample. In addition, Sample 9 produced a CO 2 /CH 4 equilibrium selectivity factor of about 35 to about 40 and a CO 2 gas adsorption capacity in a range of from about 15% to about 20% of the Reference Sample's capacity.
In some embodiments, the amorphous adsorbent advantageously is characterized by an equilibrium selectivity factor of CO 2 /CH 4 in a range of from about 3.8 to about 40, preferably in a range of from about 10 to about 40. In further embodiments, the amorphous adsorbent exhibits a CO 2 gas adsorption capacity in a range of from about 15% to about 95% of the capacity of the aluminosilicate zeolite used to form the amorphous adsorbent, preferably in a range of about 15% to about 45%.
Although the present invention has been described in detail, it should be understood that various changes, substitutions, and alterations can be made hereupon without departing from the principle and scope of the invention. Accordingly, the scope of the present invention should be determined by the following claims and then appropriate legal equivalents.
The singular forms “a”, “an” and “the” include plural references, unless the context clearly dictates otherwise.
“Optional” or “optionally” means that the subsequently described component may or may not be present or the event or circumstances may or may not occur. The description includes instances where the component is present and instances where it is not present, and instances where the event or circumstance occurs and instances where it does not occur.
Ranges may be expressed herein as from about one particular value, and/or to about another particular value. When such a range is expressed, it is to be understood that another embodiment is from the one particular value and/or to the other particular value, along with all combinations within said range.
Throughout this application, where patents or publications are referenced, the disclosures of these references in their entireties are intended to be incorporated by reference into this application, in order to more fully describe the state of the art to which the invention pertains, except when these references contradict the statements made herein.
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The present invention relates to an amorphous adsorbent composition capable of purifying a gaseous hydrocarbon fraction and methods for synthesizing the composition. The composition is advantageously capable of filtering non-combustible contaminants for increasing the quality and heating value of a gaseous hydrocarbon such as methane. The composition comprises a zeolite based framework that is at least partially collapsed and capable of selectively adsorbing and desorbing gaseous components such as methane and carbon dioxide for purifying the gaseous hydrocarbon fraction.
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FIELD OF THE INVENTION
This invention relates to exercise devices and methods performed by an exercise apparatuses, and particularly but not exclusively to exercise devices with treadles.
BACKGROUND OF THE INVENTION
Conventional exercise apparatuses, such as stair climbers and steppers, serve to assist the user in performing a desired motion. For example, the exercise apparatuses allow for the proper positioning of the user and proper completion of the user's motion so as to isolate work-out of the desired muscles. Further, such machines serve to support the user to a certain degree to minimize impact during use.
Some exercise apparatuses include air compression systems that utilize conduits to transfer air between bellows (e.g., from a first support bellow to a second air bellow). That is, movement of a treadle of an apparatus compresses air in a first bellow. The latter then forces air into a second bellow that applies a reciprocal force to a second treadle, to provide support or resistance to the user at a second treadle.
Conventional air compression systems, however, provide minimal operational improvement over the mechanical based support systems within other exercise apparatuses. Generally, such air compression systems merely facilitate up and down motion of a user.
An object of the invention is to overcome these problems
SUMMARY OF EMBODIMENTS OF THE INVENTION
An embodiment of the invention involves an exercise resistance device with depresser plates angled to receive a user's appendages at targeted angles.
A more specific embodiment involves a targeted air support or resistance stepper system with angled treadles that compress bellows connected by air passages.
The various features of novelty that characterize the invention are pointed out in the claims appended to and forming a part of this specification. Other objects and advantages of the invention will become evident from the detailed description when read in light of the following drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
A further understanding of the present invention and the objectives other than those set forth above can be obtained by reference to the various implementations set forth in the illustrations of the accompanying figures. Although the shown implementations illustrate certain aspects of the present invention, the apparatus and method of use of the invention, in general, together with further objectives and advantages thereof, may be more easily understood by reference to the drawings, examples, and the following description. The examples and figures are not intended to limit the scope of this invention, which is set forth with particularity in the claims as appended or as subsequently amended, but merely to clarify and exemplify the invention. The detailed description makes reference to the accompanying figures wherein:
FIG. 1 is a perspective view of an exercise apparatus having an air support system.
FIG. 2 is a top view of the exercise apparatus having an air support system.
FIG. 3 is a front view of the exercise apparatus having an air support system.
FIG. 4 is a side view of the exercise apparatus having an air support system.
FIG. 5 is a schematic diagram of an air support system.
FIG. 6 is a schematic diagram of an air support system having multiple support portions.
FIG. 7 is a side view of an exercise apparatus having multiple support bellows.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Overview
An embodiment of the exercise apparatus takes the form of a climbing or stepping apparatus, which employs a targeted air support or resistance system. In some implementations, the exercise apparatus includes an air support system configured to provide two-dimensional supporting or resistance forces during use of the exercise apparatus.
Depending on the particular embodiment disclosed, a single bellow configured to support a single treadle of the exercise apparatus is positioned and/or attached at various angles. Such configuration serves to facilitate the application of two-dimensional forces to the treadles.
In alternate embodiments, two or more bellows configured to support treadles of the exercise apparatus are positioned and/or attached to the treadles. The bellows may be attached next to one another at one section of a treadle, and/or may be attached next to one another along the length of the treadle. This facilitates the application of two-dimensional forces to the treadles.
Thus, the present apparatus or device described herein provides targeted support to a user of an exercise apparatus. Such targeted support offers improved or enhanced support to the user during exercise, to assist in exercising certain muscle groups, to adjust or modify a workout.
A detailed description of the aforementioned embodiments of the present invention is disclosed herein. However, techniques of manufacture and resulting structures in accordance with the present invention may be embodied in a wide variety of forms and modes, some of which may be quite different from those in the disclosed embodiment. Consequently, the specific structural details disclosed herein are merely representative, yet in that regard, they are deemed to represent suitable implementations for purposes of disclosure and to provide a basis for the claims herein, which define the scope of the present invention. The following presents a detailed description of several examples of the present invention.
Moreover, well known methods, procedures, and substances for both carrying out the objectives of the present invention and illustrating the preferred embodiment are incorporated herein but have not been described in detail as not to unnecessarily obscure novel aspects of the present invention.
The Exercise Apparatus
FIGS. 1 to 4 depict an embodiment of an exercise apparatus 100 , such as a stair climber or stepper, having an air support system to assist fluid stepping motion performed by a user. The exercise apparatus 100 includes a housing 110 , one or more treadles 120 , one or more pivots 130 , one or more bellows 140 , one or more knobs 150 , and one or more displays 160 . The housing 110 includes a front section 112 , a back section 116 , and a middle section 114 located between the front section 112 and the back section 116 . The back section 116 contains or partially contains an air support system and/or components of the air support system, such as bellows 140 . Bellows 140 include a top portion 142 and a bottom portion 144 . In the present embodiment of the invention, the back section 116 of the housing 110 is coupled to bottom portion 144 of bellows 140 .
In use the bellows 140 deliver pressurized air, or an alternate fluid such as a gas, in a controlled quantity from an air transport pathway to the treadles 120 . In the present embodiment, the bellow 140 includes a deformable container and a nozzle or outlet located at the top portion of the bellow 140 . When a force is applied to a top portion 142 of the bellow 140 , via the vertical motion of the user applied to a treadle 120 , the size of the bellow 140 decreases and air escapes through the outlet. Thereafter the outlet closes, and air transfers between bellows as the user steps on alternate bellows 140 . This fluid transfer provides a supporting force to the treadles 120 attached to the bellow 140 . An inlet is located at a bottom portion 144 of the bellow 140 and coupled to an air transport pathway to facilitate the intake of air into the bellow 140 . The bellows 140 is part of an air support system at least partially contained by the housing 110 . This air transport system is discussed in greater detail herein.
The front section 112 of housing 110 contains or partially contains pivots 130 . In the present example, the front portion 112 of the housing 110 serves to couple to pivots 130 to allow for the clockwise and counterclockwise movement of pivots through a predetermined range. This desired movement facilitates a substantially vertical movement of treadles 120 , which are coupled to the pivots 130 .
Furthermore, the housing 110 includes and/or contains one or more knobs, such as the knob 150 . Knob 150 serves to allow the apparatus user to adjust and control a valve or valves within the bellows 140 transfer components of the air support system contained, at least in part, within the housing 110 .
As shown, the treadles 120 are attached to the pivots 130 . The treadles 120 are configured to receive an appendage of user, in this case a foot, and may be sized or shaped accordingly. In some examples, the treadles include various tread patterns and/or are sized or shaped to accommodate a foot, such as the right foot or left foot of a user of the exercise apparatus 100 . While the present embodiment serves to receive a foot of a user, one of ordinary skill in the art will readily recognize the application of the present invention for use with a hand of a user. In the present embodiment, the treadles 120 include back portions configured to attach to top portions of bellows 140 and front portions configured to attach to pivots 130 or other mechanisms that facilitate a rotation or lateral movement of the treadles 120 .
In the present embodiment, the treadles 120 are attached to the pivots 130 and/or the bellows 140 such that they provide an angled reception surface for a foot of the user when the apparatus is in resting position. The angled attachment may be modified by the user based on the desired comfort angle. In one embodiment, the treadles 120 are angled toward the front section 112 of housing 110 , with the rear of treadles 120 at a higher elevation than the front of treadles 120 . According to various embodiments this angled surface is accomplished by attaching treadles 120 to angled pivots 130 , angled bellows 140 , or multiple bellows 140 , or by pressurization of bellows 140 .
FIG. 2 illustrates a top view of the exercise apparatus 100 having an air support system. As appears in FIG. 1 , the exercise apparatus 100 includes a housing 110 , one or more treadles 120 , one or more pivots 130 , one or more bellows 140 , one or more knobs 150 , and one or more displays 160 .
The housing 110 , comprised of front section 112 , a back section 116 , and a middle section 114 , contains a knob 150 or other control mechanism(s), electronic or manual, that control, adjust, modify, and/or otherwise operate one or more valves within an air support system contained within the housing 110 . Knob 150 serves to facilitate controlling a valve to increase an amount of air taken in by a bellow 140 , to decrease an amount of air taken in by a bellow 140 , and to modulate between the two. As shown, knob 150 includes predefined setting increments 200 for establishing a certain pressure calibrated to a desired resistance. While four predefined settings are apparent in the present embodiment, one of ordinary skill in the art will readily recognized that any series of control mechanisms may be employed through a range for a myriad of resistance settings as is known in the art.
The housing 110 contains a display 160 , such as a digital display 208 that provides information and/or data about an exercise workout sequence performed by a user with the exercise apparatus 100 . The display 160 , and associated computing system, is capable of tracking and presenting information associated with a number of steps taken during a workout, a duration of a workout, a number of calories burned during a workout, an estimated distance traveled during a workout, a range of values associated with a degree of difficulty of a workout, and so on. Display 160 further includes a status button 202 , including an indicator light. Status button 202 serves to perform multiple functions such as the ability to reset the computing system, enter user data, etc. One of ordinary skill in the art will appreciate that the exercise apparatus may include other components and/or devices not shown in the present embodiment, such as a body cord attachment component that facilitates attachment of a body cord to the housing 110 . Such body cord attachment, may also allow the transmission of data related to the user exercise regimen to monitor the exercise workout, store data related to the exercise workout, etc.
As shown in FIG. 2 , each treadle 120 includes an upper reception pedal 206 and a lower support pedal 204 both attached to the pivot 130 for vertical movement of the treadle. In each treadle 120 the upper reception pedal 126 lies in one plane and the lower support pedal 124 lies in a plane substantially parallel to the plane of the upper reception pedal. In each treadle 120 one of upper reception pedal 206 and lower support pedal 204 is fixed and the other one of upper reception pedal 206 and lower support pedal 204 is rotatable, relative to the pivot 130 , in its own horizontal or near-horizontal plane. This allows the pedals 204 and 206 to move substantially lateral to each other. In the embodiment shown of FIG. 2 , the upper reception pedal 206 of a treadle 120 is fixed and the lower support pedal 204 of the same treadle 120 is movable to the right. In another embodiment the upper reception pedal 206 of a treadle 120 is movable and the lower support pedal of the same treadle 120 is fixed. Such substantially horizontal movement of the reception pedals 206 or substantially horizontal movement of the support pedals 204 permits the back ends 124 in each treadle 120 to separate and come together rotationally and thereby to allow for a narrow user stance or a broad user stance as desired by the user for the user's comfort. Further, such horizontal lateral movement between upper reception pedal 206 and lower support pedal 204 facilitates alternate muscle toning capabilities for the user.
FIG. 3 is a front view of the exercise apparatus 100 having an air support system and uses the same reference numerals as in FIG. 1 . In FIG. 3 the exercise apparatus 100 includes a housing 110 , one or more treadles 120 , one or more pivots 130 , one or more bellows 140 one or more knobs (not shown), and one or more displays 160 . In the present embodiment, the housing 110 is manufactured of substantially rigid material to sustain the forces applied by a user of various weight ranges. Further, the housing 110 is substantially weighted to control movement of the exercise apparatus 100 while in use. As one of ordinary skill in the art will readily recognize, a workout regimen by a user of a “stepping device” places substantial forces at various angles and such a device must be able to withstand such applied forces, and to some degree counter such forces, while minimizing the travel of the housing 110 on the surface on which the exercise apparatus 100 stands. In addition to substantial weighting of the exercise apparatus 100 , an embodiment of the invention involves using appliqués on the bottom of the housing 110 for use on a rough flooring such as a carpeted flooring, and another embodiment involves attaching suctioning devices to the bottom of the housing for use on a smooth surface flooring such as a wooden floor, to increase the static friction of the exercise apparatus 100 depending on the surface on which the exercise apparatus 100 stands.
FIG. 4 depicts a side view of the exercise apparatus 100 having an air support system. In the present embodiment, exercise apparatus 100 is shown in an “active state”. Here a first force 410 is applied to a treadle 406 (corresponding to a treadle 120 ) connected to the pivot 130 , for example by a user's foot (not shown). This force compresses bellow 408 (corresponding to a bellow 140 ) and forces fluid transfer of air through an air support system. The transfer of air from bellow 408 results in an increased pressure in bellow 404 (also corresponding to a bellow 140 ) and produces an upward force, or support force, to raise a treadle 402 (also corresponding to a treadle 120 ) connected to the pivot 130 . This effectively creates an upward force on the user's other foot (not shown). In turn, once a user of exercise apparatus 100 applies a downward force to treadle 402 , bellow 404 will compress and transfer air through the air support system to bellow 408 thereby raising treadle 406 . Such transfer of force mimics the repetitious “stepping” action desired.
While two bellows integrated as part of an air compression system are disclosed, it is readily apparent that independent bellows may be employed.
The Air Support System
Further detail of the air support system of the exercise apparatus appears in FIG. 5 . This figure shows a schematic diagram of an air support system 500 having angled support bellows. The air support system 500 includes bellows 140 having top portions attached to treadles 120 of an exercise apparatus and bottom portions attached to the housing 110 of the exercise apparatus 100 . The air support system 500 supports movement of treadles 120 of the exercise apparatus, providing a one- or two-dimensional support force to a treadle as the treadle moves down towards the housing 110 of the exercise apparatus. That is, the air support system may receive a force at a first treadle of the exercise apparatus; and transfer the received force to a second treadle of the exercise apparatus, such as via an angled bellow or multiple bellows, thereby facilitating application of a targeted and/or two-dimensional force on a treadle moving downwards or upwards during operation of the exercise apparatus. The air support system 500 also includes a sealed air transfer pathway, conduit, or component 510 that contains air 525 and a valve 520 that controls the flow of air within the air transfer pathway 510 .
In the present embodiment, the air transfer pathway 510 is coupled to an inlet component of a bellow 140 , which facilitates the input of air 525 from the air transfer pathway 510 to the bellow 140 . In some embodiments, the air pressure within the bellows 140 and/or air transfer pathway 510 are controlled by the valve 520 , which is connected to a knob to regulate resistance and calibrate the exercise apparatus, or other component of the housing 110 . This enables a user to adjust the valve 520 and the air pressure within the bellows 140 .
In the present embodiment, the air transfer pathway 510 facilitates the transfer of forces between treadles 120 , such as between a right treadle and a left treadle. That is, a downward force received at a right treadle, such as a force caused by a foot of a user stepping down on the right treadle, may cause air 525 to leave an associate bellow 140 , travel through the air transfer pathway 510 , and apply a support force, such as a two-dimensional force, to the left treadle.
In some embodiments, the bellows 140 are configured and/or positioned at an angle θ i with respect to a vertical axis V of the housing 110 of the exercise apparatus. That is, a bellow or bellows 140 are positioned such that an angle θ formed between a longitudinal axis L of a bellow 140 and the plane of the housing 110 of the exercise apparatus 100 is less than 90 degrees. In some cases, the angle θ is an acute angle, such as an angle between 90 and 60 degrees.
In these embodiments, the bellows 140 are configured such that a longitudinal axis L of the right bellow and a longitudinal axis L of the left bellow intersect one another. In one embodiment of the present invention, the intersection of inner angle θ i is 45 degrees or less.
The angled bellows 140 provide various targeted support forces to treadles 120 , such as support forces having vertical and horizontal components. For example, an angled bellow facilitates application of a first dimensional component of a support force and a second dimensional component of the support force to a treadle, among other things.
Although shown in FIG. 5 as being at a fixed angle, according to an embodiment, the angle of attachment of the bellows 140 is adjustable. For example, the treadle 120 includes a coupling component that facilitates user adjustment of the angle θ of one or both bellows 140 . Thus, a user may wish to make adjustments during a workout, by changing the angle of one or both bellows 140 to enhance comfort, target certain muscles.
Additionally and/or alternatively, in some embodiments the air support system may support treadles of an exercise apparatus via two or more bellows, such as bellows 140 .
FIG. 6 is a schematic diagram of an air support system 600 having multiple support bellows. The air support system 600 includes outer bellows 610 coupled to outer portions of treadles 120 and inner bellows 620 coupled to inner portions of the treadles 120 . The outer bellows 610 are coupled to a first air transfer pathway 630 that contains a valve 632 and compressed air 635 . Similarly, the inner bellows 620 are coupled to a second air transfer pathway 640 that contains a valve 642 and compressed air 645 .
In an embodiment, the outer bellows 610 are taller and expand to a greater degree than the inner bellows 620 . This allows an attached treadle 120 to provide an angled support surface, among other benefits. In some embodiments, the first air transfer pathway 630 is set at a higher pressure than the second air transfer pathway 640 . In some embodiments, the first air transfer pathway 630 is set at a lower pressure than the second air transfer pathway 640 . A knob of the housing 110 controls valve 635 and/or valve 645 , in order to adjust the air pressure within one or both air transfer pathways 630 , 640 .
Thus, in alternate embodiments, use of two or more bellows 610 , 620 facilitates the application of targeted support forces, such as a first force at an outer portion of a treadle and a second, optionally different, force at an inner portion of the treadle. These targeted support forces provide enhanced support and/or comfort for a user of an exercise apparatus, and provide a modified or targeted workout, among other benefits.
In some embodiments, two or more bellows are positioned to provide support at various locations along a treadle. FIG. 7 shows a side view of an exercise apparatus 700 having multiple support bellows. The exercise apparatus 700 includes a back bellow 710 located at a back portion 116 of a housing 110 and a middle bellow 720 located at a middle portion 114 of the housing 110 . As discussed with the air support system 600 , the exercise apparatus 700 may include two or more air transfer pathways, each associated with a set of bellows, such as back bellows 710 and/or middle bellows 720 .
During use of the exercise apparatus 700 , the back bellows 710 provide a first support force to treadles, and the middle bellows 720 provide a second, and different, support force to the treadles. For example, the back bellows 710 may provide a support force that is lower than a support force provided by the middle bellows 720 . The variable support forces may provide enhanced comfort to a user, may provide a workout targeted to specific muscle groups, such as muscle groups within a user's legs, among other benefits.
In some embodiments, an exercise apparatus, such as exercise apparatus 100 or 700 , utilizes a support system that relies on fluids other than air to provide support to a user of the exercise apparatus. In one embodiment a fluid support system includes a hydraulic fluid and/or other compressible or incompressible fluids.
Various embodiments of an exercise apparatus having an air support system are described. In some embodiments, the exercise apparatus provides targeted support to a user of the exercise apparatus via angled bellows and/or multiple bellows, among other things.
While certain aspects of the device are presented below in certain claim forms, the inventor contemplates the various aspects of the system in any number of claim forms. Accordingly, the inventor reserves the right to add additional claims after filing the application to pursue such additional claim forms for other aspects of the system.
Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise,” “comprising,” and the like are to be construed in an inclusive sense, as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to.” As used herein, the terms “connected,” “coupled,” or any variant thereof, means any connection or coupling, either direct or indirect, between two or more elements; the coupling of connection between the elements can be physical, logical, or a combination thereof. Additionally, the words “herein,” “above,” “below,” and words of similar import, when used in this application, shall refer to this application as a whole and not to any particular portions of this application. Where the context permits, words in the Detailed Description using the singular or plural number may also include the plural or singular number respectively. The word “or,” in reference to a list of two or more items, covers all of the following interpretations of the word: any of the items in the list, all of the items in the list, and any combination of the items in the list. The term “air” as used herein is intended to include not just air but any gas.
Thus, there has been summarized and outlined, generally in broad form, a plurality of the most important features of the present invention. While this summary is presented so that the novelty of the present contribution to the related art may be better appreciated, it will further be apparent that additional features of the invention described hereinafter (which will form the subject matter of the claims appended hereto) will further define the scope, novelty, and in certain instances the improvements upon any existing art. The following description provides specific details for a thorough understanding of, and enabling description for, various examples of the technology. One skilled in the art will understand that the technology may be practiced without many of these details and it is to be readily understood that the invention presented herein 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 various figures integrated and categorized herein. For example, in some instances, well-known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the examples of the technology. It is intended that the terminology used in the description presented below be interpreted in its broadest reasonable manner, even though it is being used in conjunction with a detailed description of certain examples of the technology. Although certain terms may be emphasized below, any terminology intended to be interpreted in any restricted manner will be overtly and specifically defined as such in this Detailed Description section. Those skilled in the art will appreciate that the disclosure of the present invention may readily be utilized as a basis for forming other similar structures, methods and systems for carrying out the various purposes and objectives of the present invention. Thus, the claims as set forth shall allow for such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention as described herein.
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An exercise stepper with a fluid resistance system guides stepper treadles angularly downward and outward from the center of the stepper. According to an embodiment bellows that support treadles angle downward and outward.
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BACKGROUND OF THE INVENTION
The present invention relates to an apparatus for preventing troublesome load change shocks caused by a combustion engine used to propel a vehicle, whereby control commands for a power control element delivered by an accelerator pedal are transmitted with a time delay. An apparatus constructed in such a fashion is described in EP No. 0,155,993 F 02 D 11/10. By delaying the transmission of the control commands, a flattening or lengthening of the rise and fall times occurs.
It is known that in the case of automobiles with internal combustion engines, a so-called load change shock occurs during a change in load, i.e., on transition from engine braking to traction. Such a shock possibly leads to longitudinal vibrations of the vehicle otherwise known as jerking. This often occurs at low speeds of the internal combustion engine This phenomenon is determined essentially by the kinetic energy of the combustion engine and the drive train which, due to elasticities and clearances in the drive train, is set free and is partially transmitted to the vehicle's body during the load change. Therefore, the undesirable load change phenomena can be largely prevented if the kinetic energy built up during the load change is reduced to a minimum This occurs also in accordance with the state of the art cited, whereby the delayed transmission of the control command delivered by the accelerator pedal to the control element, e.g., a throttle valve or a control rod of an injection device, is limited to approximately 50% of the control range so that the operator, if necessary, can undertake a rapid acceleration of the vehicle.
From this would follow that the delay per se in the transmission of the accelerator pedal command would be undesirable. However, according to the state of the art it must be accepted within a relatively large control range in order to avoid or diminish to a tolerable measure the even more undesirable longitudinal dynamic instabilities of the vehicle.
SUMMARY OF THE INVENTION
It is the object of the present invention to provide a method and an apparatus which reduce the undesirable load change phenomena to an extent which is at least not troublesome, without the need to accept as a consequence disturbing delays in the transmission of the accelerator pedal commands to the power control element.
Accordingly, the time delay in the transmission of the accelerator pedal command to the power control element is limited to a very narrow region of the course in time of the torque gradient of the internal combustion engine, which takes into account the fact that essentially only the inversion in the sign of the torque on transition from engine braking to traction and vice versa is responsible for the load change shock.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be more fully explained in the following description of the preferred embodiment, as represented in the accompanying drawings, in which:
FIG. 1 is a circuit diagram for the preferred embodiment of the apparatus pursuant to the present invention; and
FIGS. 2-5 are diagrams showing torque gradients and their application according to the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The apparatus for preventing troublesome load change shocks illustrated in FIG. 1 is designed with an accelerator pedal 1 which acts on a potentiometer 2 which delivers an electric accelerator pedal signal g corresponding to the position of the accelerator pedal 1 to the coupling element 3. The signal g* produced by the coupling element 3, and to be described below, reaches a device 4 which, on the one hand, converts the electric signal g* into an actuating signal for a power control element of the internal combusion engine, e.g., a throttle valve or a control device of a fuel injection system, and, on the other hand, delivers by means of a position sensor on the power control element, a position signal x.
Both the position signal x and engine speed signal n, produced by means of an engine speed sensor 5 which measures the number of revolutions of the internal combusion engine, and possibly also an ignition angle signal, actuate the performance characteristic storage 6 in which is stored the gradient of the torque M d of the combustion engine as a function of the aforementioned quantities. The torque signal M d , thus called up, arrives at the amplitude window circuit 7, which is designed in such a manner that it permits only torque signals M d * to reach a time delay signal generator 8. The torque signals occupy a very narrow region of the torque gradient of the combustion engine where torque passage is zero. For example, this region, which represents the amplitude window produced by the device 7, may be limited on the positive side and on the negative side by the torque signal for one tenth of the maximum torque of the combustion engine. Only if the torque signal M d is placed between these limit values will the amplitude window circuit 7 deliver a signal M d * triggering the time delay signal generator 8, whereafter the device 8, which contains a differentiating device, will deliver a time delay signal v to the coupling element 3. The time delay signal can be dimensioned advantageously in such a manner that in the case of torque signals within the amplitude window, i.e., in the direct vicinity of the torque gradient where torque pasage is zero, the increase in the control command of the accelerator pedal 1 is flattened within a small region and thereby lengthened by 0.03 to 0.5 seconds. Accordingly, the full effect of the accelerator pedal g is delayed. These "rise-extended" accelerator pedal signals are indicated in FIG. 1 by g*. As will be explained by the additional figures, the time delay within the aforementioned amplitude window can be imparted a non-linear course in time by simple means.
Viewing the further figures, we find that FIG. 2 shows the course of the accelerator pedal signal g over the time t with g max indicating the full kick-down position of the accelerator pedal. We can see that very rapid accelerator pedal actuation is assumed here which results in a practically rectangular course, over time, for the signal g.
In FIGS. 3, 4 and 5 it has been assumed that the accelerator pedal actuation described with reference to FIG. 2 serves the transition from engine braking (with negative values of the torque M d ) to normal traction of the internal combustion engine (with positive torque values). The method according to the present invention operates such that a time delay signal is generated only in the immediate vicinity of the torque gradient where torque passage is zero. Therefore, as the torque increases, only a very small (short-time) time delay region V is present in the torque increase. Directly after the vicinity where torque passage is zero, the torque gradient rises very steeply and corresponds to the steep rise of the gas pedal signal g.
The curves in FIGS. 3, 4 and 5 differ with respect to the gradient of the torque curve within the time delay region V. FIG. 3 illustrates a gradient combined of two straight lines with different rises. In FIG. 4, said gradient follows a straight line. On depression of the accelerator pedal, there initially occurs in both embodiments, a steep torque increase to a value directly below zero, which is initially maintained in FIG. 3. In FIG. 4 this is directly followed by a linear increase with a very small rise.
In the embodiment as per FIG. 5, the torque increase occurs within the region V in a non-linear manner, initially with a relatively large rise which decreases increasingly. In this case, too, it is ensured that directly following transit through the vicinity where torque passage is zero, the torque gradient assumes a steep rise.
In FIGS. 3, 4 and 5 it is assumed that the corresponding time delay regions V' are passed during the transition from traction to engine braking. These regions are mirror images of the rise regions V so that they need not be further discussed. Evidently, it is also possible to render the torque gradient within the regions V and V' different for each case.
All of the described embodiments offer the advantage that the time delays or flattenings of the torque increase, which serves the elimination or considerable reduction of load change phenomena, are limited to that region of the torque gradient of the internal combustion engine which is responsible for the phenomena. Outside this very narrow time range, transmission of the accelerator pedal command to the pertinent output control element occurs without delay.
While the invention has been illustrated and described as embodied in an apparatus for preventing troublesome load change shocks caused by a combustion engine, 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.
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 method and apparatus for preventing troublesome load change shocks caused by a combustion engine having a time delay in the transmission of the accelerator pedal commands to the output control element. In order to exclude undesirable influences on operation due to the time delay, the time delay is limited to a very narrow region around the location zero of the torque gradient in relation to time.
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This application claims priority to U.S. Provisional Patent Application Ser. No. 60/121,339, filed Feb. 24, 1999.
TECHNICAL FIELD
The present invention generally relates to the use of drugs for the treatment of mental disorders. More specifically, the invention describes methods for the treatment and prevention of Impulse Control Disorders (ICD's) by administering sulfamate derivatives.
BACKGROUND OF THE INVENTION
Sulfamate derivatives having useful pharmaceutical activity in the areas of epilepsy, glaucoma, peptic ulcers and male infertility are disclosed in U.S. Pat. Nos. 4,075,351, 4,513,006, 4,591,601, 4,792,569, and 5,760,007. One of these compounds 2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate known as topiramate has been demonstrated in clinical trials of human epilepsy to be effective as adjunctive therapy or as monotherapy in treating simple and complex partial seizures and secondarily generalized seizures and is currently marketed for the treatment of simple and complex partial seizure epilepsy with or without secondary generalized seizures.
Binge eating disorder (BED) is characterized by discrete periods of binge eating during which large amounts of food are consumed in a discrete period of time and a sense of control over eating is absent. Persons with bulimia nervosa have been reported to have electroencephalographic abnormalities and to display reduced binge eating in response to the anti-epileptic drug phenytoin. Also, in controlled trials in patients with epilepsy, topiramate was associated with suppression of appetite and weight loss unreleated to binge eating.
Binge eating disorder is a subset of a larger classification of mental disorders broadly defined as Impulse Control Disorders (ICDs) characterized by harmful behaviors performed in response to irresistible impulses. It has been suggested that ICDs may be related to obsessive-compulsive disorder or similarly, maybe forms of obsessive-complusive disorders. It has also been hypothesized that ICDs may be related to mood disorder or may be forms of affective spectrum disorder, a hypothesized family of disorders sharing at least one common physiologic abnormality with major depression. In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), the essential feature of an ICD is the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or to others. For most ICDs, the individual feels an increasing sense of tension or arousal before committing the act, and then experiences pleasure, gratification, or release at the time of committing the act. After the act is performed, there may or may not be regret or guilt. ICDs are listed in a residual category, the ICDs Not Elsewhere Classified, which includes intermittent explosive disorder (IED), kleptomania, pathological gambling, pyromania, trichotillomania, and ICD not otherwise specified (NOS). Examples of ICDs NOS are compulsive buying or shopping, repetitive self-mutilation, nonparaphilic sexual addictions, severe nail biting, compulsive skin picking, personality disorders with impulsive features, attention deficit/hyperactivity disorder, eating disorders characterized by binge eating, and substance use disorders.
SUMMARY OF THE INVENTION
It is an object of the present invention to describe the use of sulfamate derivatives for the treatment of Impulse Control Disorders.
The present invention comprises methods for the treatment or prevention of Impulse Control Disorders using the compounds of formula (I), pharmaceutical compositions containing one or more of the compounds of formula (I), or pharmaceutical compositions containing one or more of the compounds of formula (I) in addition to a safe and effective amount of one or more additional agents to treat related symptoms and conditions.
DETAILED DESCRIPTION OF THE INVENTION
The sulfamates of use in the present invention are of the following formula (I):
wherein
X is CH 2 or oxygen;
R 1 is hydrogen or alkyl; and R 2 , R 3 , R 4 and R 5 are independently hydrogen or lower alkyl and, when X is CH 2 , R 4 and R 5 may be alkene groups joined to form a benzene ring and, when X is oxygen, R 2 and R 3 and/or R 4 and R 5 together may be a methylenedioxy group of the following formula (II):
wherein
R 6 and R 7 are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring. R 1 in particular is hydrogen or alkyl of about 1 to 4 carbons, such as methyl, ethyl and iso-propyl. Alkyl throughout this specification includes straight and branched chain alkyl. Alkyl groups for R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are of about 1 to 3 carbons and include methyl, ethyl, iso-propyl and n-propyl. When X is CH 2 , R 4 and R 5 may combine to form a benzene ring fused to the 6-membered X-containing ring, i.e., R 4 and R 5 are defined by the alkatrienyl group ═C—CH═CH—CH═.
A particular group of compounds of formula (I) is that wherein X is oxygen and both R 2 and R 3 and R 4 and R 5 together are methylenedioxy groups of the formula (II), wherein R 6 and R 7 are both hydrogen, both alkyl or combine to form a spiro cyclopentyl or cyclohexyl ring, in particular where R 6 and R 7 are both alkyl such as methyl. A second group of compounds is that wherein X is CH 2 and R 4 and R 5 are joined to form a benzene ring. A third group of compounds of formula (I) is that wherein both R 2 and R 3 are hydrogen.
The compounds of formula I: may be made by the processes disclosed in U.S. Pat. Nos. 4,075,351, 4,513,006, 4,591,601, 4,792,569, 5,242,942, 5,387,700, which are incorporated in their entirety herein by reference.
The compounds of formula I include the various individual isomers as well as the racemates thereof. For treating ICDs, a compound of formula (I) may be employed at a daily dosage in the range of about 15 to 1400 mg administered orally, for an average adult human.
To prepare the pharmaceutical compositions of this invention, one or more sulfamate compounds of formula (I) are intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques, which carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral, by suppository, or parenteral. In preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed. Thus, for liquid oral preparations, such as for example, suspensions, elixirs and solutions, suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like; for solid oral preparations such as, for example, powders, capsules and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar coated or enteric coated by standard techniques. Suppositories may be prepared, in which case cocoa butter could be used as the carrier. For parenterals, the carrier will usually comprise sterile water, though other ingredients, for example, for purposes such as aiding solubility or for preservation, may be included. Injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed. Topiramate is currently available for oral administration in round tablets containing 25 mg, 100 mg or 200 mg of active agent. The tablets contain the following inactive ingredients: lactose hydrous, pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, purified water, carnauba wax, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol, synthetic iron oxide, and polysorbate 80 .
The pharmaceutical compositions herein will contain, per dosage unit, e.g., tablet, capsule, powder injection, teaspoonful, suppository and the like from about 5 to about 1000 mg of the active ingredient.
The activity of the compounds of formula I in treating ICD's was first evidenced in clinical studies conducted to evaluate the efficacy of topiramate in treating mood disorders. Several patients who coincidentally had binge eating disorder reported that there was a marked reduction in their binging and a concurrent loss in weight.
Examples of specific compounds of formula (I) are:
2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose sulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-L-fructopyranose sulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose methylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose butylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose ethylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose octylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose 2-propenylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose phenylmethylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose cyclopropylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose cyclobutylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose (2,2,2-trifluoroethyl)sulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose dimethylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose diethylsulfamate;
2,3-O-(1-methylethylidene)-4,5-O-sulfonyl-beta-D-fructopyranose azidosulfamate;
(S)-2,3-O-(1-methylethylidene)-4,5-O-sulfinyl-beta-D-fructopyranose sulfamate;
(R)-2,3-O-(1-methylethylidene)-4,5-O-sulfinyl-beta-D-fructopyranose sulfamate;
2,3-O-(1-ethylpropylidene)-4,5-O-sulfonyl-beta-D-fructopyranose sulfamate;
2,3-O-(1-methylethylidene)-4,5-O-[N-(4-methylbenzenesulfonyl)imidosulfinyl]-beta-D-fructopyranose sulfamate;
2,3-O-(1-methylethylidene)-4,5-O-[N-(4-methylbenzenesulfonyl)imidosulfonyl]-beta-D-fructopyranose sulfamate;
2,3-O-(cyclohexylidene)-4,5-O-sulfonyl-beta-D-fructopyranose sulfamate;
(S)-4,5-O-[N-(1,1-dimethylethoxycarbonyl)imidosulfinyl]-2,3-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate;
and the pharmaceutically acceptable salts thereof
Included within the scope of this invention are the various individual anomers, diastereomers and enantiomers as well as mixtures thereof. Such compounds are included within the definition of formula (I). In addition, the compounds of this invention also include any pharmaceutically acceptable salts, for example: alkali metal salts, such as sodium and potassium; ammonium salts; monoalkylammonium salts; dialkylammonium salts; trialkylammonium salts; tetraalkylammonium salts; and tromethamine salts. Hydrates and other solvates of the compound of the formula (I) are included within the scope of this invention.
Pharmaceutically acceptable salts of the compounds of formula (I) can be prepared by reacting the sulfamate of formula (I) with the appropriate base and recovering the salt.
The sulfamate derivatives may be used in conjunction with one or more other drug compound and used according to the methods of the present invention so long as the pharmaceutical agent has a use that is also effective in treating ICD's and/or concurrent illnesses. Pharmaceutical agents include the following categories and specific examples. It is not intended that the category be limited by the specific examples. Those of ordinary skill in the art will be able to identify readily those pharmaceutical agents that have utility with the present invention. Those of ordinary skill in the art will recognize also numerous other compounds that fall within the categories and that are useful according to the invention.
Adrenergic: Adrenalone; Amidephrine Mesylate; Apraclonidine Hydrochloride; Brimonidine Tartrate; Dapiprazole Hydrochloride; Deterenol Hydrochloride; Dipivefrin; Dopamine Hydrochloride; Ephedrine Sulfate; Epinephrine; Epinephrine Bitartrate; Epinephryl Borate; Esproquin Hydrochloride; Etafedrine Hydrochloride; Hydroxyamphetamine Hydrobromide; Levonordefrin; Mephentermine Sulfate; Metaraminol Bitartrate; Metizoline Hydrochloride; Naphazoline Hydrochloride; Norepinephrine Bitartrate; Oxidopamine; Oxymetazoline Hydrochloride; Phenylephrine Hydrochloride; Phenylpropanolamine Hydrochloride; Phenylpropanolamine Polistirex; Prenalterol Hydrochloride; Propylhexedrine; Pseudoephedrine Hydrochloride; Tetrahydrozoline Hydrochloride; Tramazoline Hydrochloride; Xylometazoline Hydrochloride.
Adrenocortical steroid: Ciprocinonide; Desoxycorticosterone Acetate; Desoxycorticosterone Pivalate; Dexamethasone Acetate; Fludrocortisone Acetate; Flumoxonide; Hydrocortisone Hemisuccinate; Methylprednisolone Hemisuccinate; Naflocort; Procinonide; Timobesone Acetate; Tipredane.
Adrenocortical suppressant: Aminoglutethimide; Trilostane.
Alcohol deterrent: Disulfiram.
Aldosterone antagonist: Canrenoate Potassium; Canrenone; Dicirenone; Mexrenoate Potassium; Prorenoate Potassium; Spironolactone.
Amino acid: Alanine; Aspartic Acid; Cysteine Hydrochloride; Cystine; Histidine; Isoleucine; Leucine; Lysine; Lysine Acetate; Lysine Hydrochloride; Methionine; Phenylalanine; Proline; Serine; Threonine; Tryptophan; Tyrosine; Valine.
Analeptic: Modafinil.
Analgesic: Acetaminophen; Alfentanil Hydrochloride; Aminobenzoate Potassium; Aminobenzoate Sodium; Anidoxime; Anileridine; Anileridine Hydrochloride; Anilopam Hydrochloride; Anirolac; Antipyrine; Aspirin; Benoxaprofen; Benzydamine Hydrochloride; Bicifadine Hydrochloride; Brifentanil Hydrochloride; Bromadoline Maleate; Bromfenac Sodium; Buprenorphine Hydrochloride; Butacetin; Butixirate; Butorphanol; Butorphanol Tartrate; Carbamazepine; Carbaspirin Calcium; Carbiphene Hydrochloride; Carfentanil Citrate; Ciprefadol Succinate; Ciramadol; Ciramadol Hydrochloride; Clonixeril; Clonixin; Codeine; Codeine Phosphate; Codeine Sulfate; Conorphone Hydrochloride; Cyclazocine; Dexoxadrol Hydrochloride; Dexpemedolac; Dezocine; Diflunisal; Dihydrocodeine Bitartrate; Dimefadane; Dipyrone; Doxpicomine Hydrochloride; Drinidene; Enadoline Hydrochloride; Epirizole; Ergotamine Tartrate; Ethoxazene Hydrochloride; Etofenamate; Eugenol; Fenoprofen; Fenoprofen Calcium; Fentanyl Citrate; Floctafenine; Flufenisal; Flunixin; Flunixin Meglumine; Flupirtine Maleate; Fluproquazone; Fluradoline Hydrochloride; Flurbiprofen; Hydromorphone Hydrochloride; Ibufenac; Indoprofen; Ketazocine; Ketorfanol; Ketorolac Tromethamine; Letimide Hydrochloride; Levomethadyl Acetate; Levomethadyl Acetate Hydrochloride; Levonantradol Hydrochloride; Levorphanol Tartrate; Lofemizole Hydrochloride; Lofentanil Oxalate; Lorcinadol; Lomoxicam; Magnesium Salicylate; Mefenamic Acid; Menabitan Hydrochloride; Meperidine Hydrochloride; Meptazinol Hydrochloride; Methadone Hydrochloride; Methadyl Acetate; Methopholine; Methotrimeprazine; Metkephamid Acetate; Mimbane Hydrochloride; Mirfentanil Hydrochloride; Molinazone; Morphine Sulfate; Moxazocine; Nabitan Hydrochloride; Nalbuphine Hydrochloride; Nalmexone Hydrochloride; Namoxyrate; Nantradol Hydrochloride; Naproxen; Naproxen Sodium; Naproxol; Nefopam Hydrochloride; Nexeridine Hydrochloride; Noracymethadol Hydrochloride; Ocfentanil Hydrochloride; Octazamide; Olvanil; Oxetorone Fumarate; Oxycodone; Oxycodone Hydrochloride; Oxycodone Terephthalate; Oxymorphone Hydrochloride; Pemedolac; Pentamorphone; Pentazocine; Pentazocine Hydrochloride; Pentazocine Lactate; Phenazopyridine Hydrochloride; Phenyramidol Hydrochloride; Picenadol Hydrochloride; Pinadoline; Pirfenidone; Piroxicam Olamine; Pravadoline Maleate; Prodilidine Hydrochloride; Profadol Hydrochloride; Propirarn Fumarate; Propoxyphene Hydrochloride; Propoxyphene Napsylate; Proxazole; Proxazole Citrate; Proxorphan Tartrate; Pyrroliphene Hydrochloride; Remifentanil Hydrochloride; Salcolex; Salethamide Maleate; Salicylamide; Salicylate Meglumine; Salsalate; Sodium Salicylate; Spiradoline Mesylate; Sufentanil; Sufentanil Citrate; Talmetacin; Talniflumate; Talosalate; Tazadolene Succinate; Tebufelone; Tetrydamine; Tifurac Sodium; Tilidine Hydrochloride; Tiopinac; Tonazocine Mesylate; Tramadol Hydrochloride; Trefentanil Hydrochloride; Trolamine; Veradoline Hydrochloride; Verilopam Hydrochloride; Volazocine; Xorphanol Mesylate; Xylazine Hydrochloride; Zenazocine Mesylate; Zomepirac Sodium; Zucapsaicin.
Anorectic compounds including dexfenfluramine.
Anorexic: Aminorex; Amphecloral; Chlorphentermine Hydrochloride; Clominorex; Clortennine Hydrochloride; Diethylpropion Hydrochloride; Fenfluramine Hydrochloride; Fenisorex; Fludorex; Fluminorex; Levamfetamine Succinate; Mazindol; Mefenorex Hydrochloride; Phenmetrazine Hydrochloride; Phentermine; Sibutramine Hydrochloride.
Anti-anxiety agent: Adatanserin Hydrochloride; Alpidem; Binospirone Mesylate; Bretazenil; Glemanserin; Ipsapirone Hydrochloride; Mirisetron Maleate; Ocinaplon; Ondansetron Hydrochloride; Panadiplon; Pancopride; Pazinaclone; Serazapine Hydrochloride; Tandospirone Citrate; Zalospirone Hydrochloride.
Antidepressant: Adatanserin Hydrochloride; Adinazolam; Adinazolam Mesylate; Alaproclate; Aletamine Hydrochloride; Amedalin Hydrochloride; Amitriptyline Hydrochloride; Amoxapine; Aptazapine Maleate; Azaloxan Fumarate; Azepindole; Azipramine Hydrochloride; Bipenarnol Hydrochloride; Bupropion Hydrochloride; Butacetin; Butriptyline Hydrochloride; Caroxazone; Cartazolate; Ciclazindol; Cidoxepin Hydrochloride; Cilobamine Mesylate; Clodazon Hydrochloride; Clomipramine Hydrochloride; Cotinine Fumarate; Cyclindole; Cypenamine Hydrochloride; Cyprolidol Hydrochloride; Cyproximide; Daledalin Tosylate; Dapoxetine Hydrochloride; Dazadrol Maleate; Dazepinil Hydrochloride; Desipramine Hydrochloride; Dexamisole; Deximafen; Dibenzepin Hydrochloride; Dioxadrol Hydrochloride; Dothiepin Hydrochloride; Doxepin Hydrochloride; Duloxetine Hydrochloride; Eclanamine Maleate; Encyprate; Etoperidone Hydrochloride; Fantridone Hydrochloride; Fehmetozole Hydrochloride; Fenmetramide; Fezolamine Fumarate; Fluotracen Hydrochloride; Fluoxetine; Fluoxetine Hydrochloride; Fluparoxan Hydrochloride; Gamfexine; Guanoxyfen Sulfate; Imafen Hydrochloride; Imiloxan Hydrochloride; Imipramine Hydrochloride; Indeloxazine Hydrochloride; Intriptyline Hydrochloride; Iprindole; Isocarboxazid; Ketipramine Fumarate; Lofepramine Hydrochloride; Lortalamine; Maprotiline; Maprotiline Hydrochloride; Melitracen Hydrochloride; Milacemide Hydrochloride; Minaprine Hydrochloride; Mirtazapine; Moclobemide; Modaline Sulfate; Napactadine Hydrochloride; Napamezole Hydrochloride; Nefazodone Hydrochloride; Nisoxetine; Nitrafudam Hydrochloride; Nomifensine Maleate; Nortriptyline Hydrochloride; Octriptyline Phosphate; Opipramol Hydrochloride; Oxaprotiline Hydrochloride; Oxypertine; Paroxetine; Phenelzine Sulfate; Pirandamine Hydrochloride; Pizotyline; Pridefine Hydrochloride; Prolintane Hydrochloride; Protriptyline Hydrochloride; Quipazine Maleate; Rolicyprine; Seproxetine Hydrochloride; Sertraline Hydrochloride; Sibutramine Hydrochloride; Sulpiride; Suritozole; Tametraline Hydrochloride; Tampramine Fumarate; Tandamine Hydrochloride; Thiazesim Hydrochloride; Thozalinone; Tomoxetine Hydrochloride; Trazodone Hydrochloride; Trebenzomine Hydrochloride; Trimipramine; Trimipramine Maleate; Venlafaxine Hydrochloride; Viloxazine Hydrochloride; Zimeldine Hydrochloride; Zometapine.
Antihypertensive: Aflyzosin Hydrochloride; Alipamide; Althiazide; Amiquinsin Hydrochloride; Amlodipine Besylate; Amlodipine Maleate; Anaritide Acetate; Atiprosin Maleate; Belfosdil; Bemitradine; Bendacalol Mesylate; Bendroflumethiazide; Benzthiazide; Betaxolol Hydrochloride; Bethanidine Sulfate; Bevantolol Hydrochloride; Biclodil Hydrochloride; Bisoprolol; Bisoprolol Fumarate; Bucindolol Hydrochloride; Bupicomide; Buthiazide: Candoxatril; Candoxatrilat; Captopril; Carvedilol; Ceronapril; Chlorothiazide Sodium; Cicletanine; Cilazapril; Clonidine; Clonidine Hydrochloride; Clopamide; Cyclopenthiazide; Cyclothiazide; Darodipine; Debrisoquin Sulfate; Delapril Hydrochloride; Diapamide; Diazoxide; Dilevalol Hydrochloride; Diltiazem Malate; Ditekiren; Doxazosin Mesylate; Ecadotril; Enalapril Maleate; Enalaprilat; Enalkiren; Endralazine Mesylate; Epithiazide; Eprosartan; Eprosartan Mesylate; Fenoldopam Mesylate; Flavodilol Maleate; Flordipine; Flosequinan; Fosinopril Sodium; Fosinoprilat; Guanabenz; Guanabenz Acetate; Guanacline Sulfate; Guanadrel Sulfate; Guancydine; Guanethidine Monosulfate; Guanethidine Sulfate; Guanfacine Hydrochloride; Guanisoquin Sulfate; Guanoclor Sulfate; Guanoctine Hydrochloride; Guanoxabenz; Guanoxan Sulfate; Guanoxyfen Sulfate; Hydralazine Hydrochloride; Hydralazine Polistirex; Hydroflumethiazide; Indacrinone; Indapamide; Indolaprif Hydrochloride; Indoramin; Indoramin Hydrochloride; Indorenate Hydrochloride; Lacidipine; Leniquinsin; Levcromakalim; Lisinopril; Lofexidine Hydrochloride; Losartan Potassium; Losulazine Hydrochloride; Mebutamate; Mecamylamine Hydrochloride; Medroxalol; Medroxalol Hydrochloride; Methalthiazide; Methyclothiazide; Methyldopa; Methyldopate Hydrochloride; Metipranolol; Metolazone; Metoprolol Fumarate; Metoprolol Succinate; Metyrosine; Minoxidil ; Monatepil Maleate; Muzolimine; Nebivolol; Nitrendipine; Ofornine; Pargyline Hydrochloride; Pazoxide; Pelanserin Hydrochloride; Perindopril Erbumine; Phenoxybenzamine Hydrochloride; Pinacidil; Pivopril; Polythiazide; Prazosin Hydrochloride; Primidolol; Prizidilol Hydrochloride; Quinapril Hydrochloride; Quinaprilat; Quinazosin Hydrochloride; Quinelorane Hydrochloride; Quinpirole Hydrochloride; Quinuclium Bromide; Ramipril; Rauwolfia Serpentina; Reserpine; Saprisartan Potassium; Saralasin Acetate; Sodium Nitroprusside; Sulfinalol Hydrochloride; Tasosartan; Teludipine Hydrochloride; Temocapril Hydrochloride; Terazosin Hydrochloride; Terlakiren; Tiamenidine; Tiamenidine Hydrochloride; Ticrynafen; Tinabinol; Tiodazosin; Tipentosin Hydrochloride; Trichlormethiazide; Trimazosin Hydrochloride; Trimethaphan Camsylate; Trimoxamine Hydrochloride; Tripamide; Xipamide; Zankiren Hydrochloride; Zofenoprilat Arginine.
Anti-inflammatory: Alclofenac; Alclometasone Dipropionate; Algestone Acetonide; Alpha Amylase; Amcinafal; Amcinafide; Amfenac Sodium; Amiprilose Hydrochloride; Anakinra; Anirolac; Anitrazafen; Apazone; Balsalazide Disodium; Bendazac; Benoxaprofen; Benzydamine Hydrochloride; Bromelains; Broperamole; Budesonide; Carprofen; Cicloprofen; Cintazone; Cliprofen; Clobetasol Propionate; Clobetasone Butyrate; Clopirac; Cloticasone Propionate; Cormethasone Acetate; Cortodoxone; Deflazacort; Desonide; Desoximetasone; Dexamethasone Dipropionate; Diclofenac Potassium; Diclofenac Sodium; Diflorasone Diacetate; Diflumidone Sodium; Diflunisal; Difluprednate; Diftalone; Dimethyl Sulfoxide; Drocinonide; Endrysone; Enlimomab; Enolicam Sodium; Epirizole; Etodolac; Etofenamate; Felbinac; Fenamole; Fenbufen; Fenclofenac; Fenclorac; Fendosal; Fenpipalone; Fentiazac; Flazalone; Fluazacort; Flufenamic Acid; Flumizole; Flunisolide Acetate; Flunixin; Flunixin Meglumine; Fluocortin Butyl; Fluorometholone Acetate; Fluquazone; Flurbiprofen; Fluretofen; Fluticasone Propionate; Furaprofen; Furobufen; Halcinonide; Halobetasol Propionate; Halopredone Acetate; Ibufenac; Ibuprofen; Ibuprofen Aluminum; Ibuprofen Piconol; Ilonidap; Indomethacin; Indomethacin Sodium; Indoprofen; Indoxole; Intrazole; Isoflupredone Acetate; Isoxepac; Isoxicam; Ketoprofen; Lofemizole Hydrochloride; Lornoxicam; Loteprednol Etabonate; Meclofenamate Sodium; Meclofenamic Acid; Meclorisone Dibutyrate; Mefenamic Acid; Mesalamine; Meseclazone; Methylprednisolone Suleptanate; Momiflumate; Nabumetone; Naproxen; Naproxen Sodium; Naproxol; Nimazone; Olsalazine Sodium; Orgotein; Orpanoxin; Oxaprozin; Oxyphenbutazone; Paranyline Hydrochloride; Pentosan Polysulfate Sodium; Phenbutazone Sodium Glycerate; Pirfenidone; Piroxicam; Piroxicam Cinnamate; Piroxicam Olamine; Pirprofen; Prednazate; Prifelone; Prodolic Acid; Proquazone; Proxazole; Proxazole Citrate; Rimexolone; Romazarit; Salcolex; Salnacedin; Salsalate; Sanguinarium Chloride; Seclazone; Sermetacin; Sudoxicam; Sulindac; Suprofen; Talmetacin; Talniflumate; Talosalate; Tebufelone; Tenidap; Tenidap Sodium; Tenoxicam; Tesicam; Tesimide; Tetrydamine; Tiopinac; Tixocortol Pivalate; Tolmetin; Tolmetin Sodium; Triclonide; Triflumidate; Zidometacin; Zomepirac Sodium.
Antinauseant: Buclizine Hydrochloride; Cyclizine Lactate; Naboctate Hydrochloride.
Antineutropenic: Filgrastim; Lenograstim; Molgramostim; Regramostim; Sargramostim.
Antiobsessional agent: Fluvoxamine Maleate.
Antiparkinsonian: Benztropine Mesylate; Biperiden; Biperiden Hydrochloride; Biperiden Lactate; Carmantadine; Ciladopa Hydrochloride; Dopamantine; Ethopropazine Hydrochloride; Lazabemide; Levodopa; Lometraline Hydrochloride; Mofegiline Hydrochloride; Naxagolide Hydrochloride; Pareptide Sulfate; Procyclidine Hydrochloride; Quinetorane Hydrochloride; Ropinirole Hydrochloride; Selegiline Hydrochloride; Tolcapone; Trihexyphenidyl Hydrochloride. Antiperistaltic: Difenoximide Hydrochloride; Difenoxin; Diphenoxylate Hydrochloride; Fluperamide; Lidamidine Hydrochloride; Loperamide Hydrochloride; Malethamer; Nufenoxole; Paregoric.
Antipsychotic: Acetophenazine Maleate; Alentemol Hydrobromide; Alpertine; Azaperone; Batelapine Maleate; Benperidol; Benzindopyrine Hydrochloride; Brofbxine; Bromperidol; Bromperidol Decanoate; Butaclamol Hydrochloride; Butaperazine; Butaperazine Maleate; Carphenazine Maleate; Carvotroline Hydrochloride; Chlorpromazine; Chlorpromazine Hydrochloride; Chlorprothixene; Cinperene; Cintriamide; Clomacran Phosphate; Clopenthixol; Clopimozide; Clopipazan Mesylate; Cloroperone Hydrochloride; Clothiapine; Clothixamide Maleate; Clozapine; Cyclophenazine Hydrochloride; Droperidol; Etazolate Hydrochloride; Fenimide; Flucindole; Flumezapine; Fluphenazine Decanoate; Fluphenazine Enanthate; Fluphenazine Hydrochloride; Fluspiperone; Fluspirilene; Flutroline; Gevotroline Hydrochloride; Halopemide; Haloperidol; Haloperidol Decanoate; Iloperidone; Imidoline Hydrochloride; Lenperone; Mazapertine Succinate; Mesoridazine; Mesoridazine Besylate; Metiapine; Milenperone; Milipertine; Molindone Hydrochloride; Naranol Hydrochloride; Neflumozide Hydrochloride; Ocaperidone; Olanzapine; Oxiperomide; Penfluridol; Pentiapine Maleate; Perphenazine; Pimozide; Pinoxepin Hydrochloride; Pipamperone; Piperacetazine; Pipotiazine Palniitate; Piquindone Hydrochloride; Prochlorperazine Edisylate; Prochlorperazine Maleate; Promazine Hydrochloride; Remoxipride; Remoxipride Hydrochloride; Rimcazole Hydrochloride; Seperidol Hydrochloride; Sertindole; Setoperone; Spiperone; Thioridazine; Thioridazine Hydrochloride; Thiothixene; Thiothixene Hydrochloride; Tioperidone Hydrochloride; Tiospirone Hydrochloride; Trifluoperazine Hydrochloride; Trifluperidol; Triflupromazine; Triflupromazine Hydrochloride; Ziprasidone Hydrochloride.
Appetite suppressant: Dexfenfluramine Hydrochloride; Phendimetrazine Tartrate; Phentermine Hydrochloride.
Blood glucose regulators: Human insulin; Glucagon; Tolazamide; Tolbutamide; Chloropropamide; Acetohexamide and Glipizide.
Carbonic anhydrase inhibitor: Acetazolamide; Acetazolamide Sodium, Dichlorphenamide; Dorzolamide Hydrochloride; Methazolamide; Sezolarmide Hydrochloride.
Cardiac depressant: Acecainide Hydrochloride; Acetylcholine Chloride; Actisomide; Adenosine; Amiodarone; Aprindine; Aprindine Hydrochloride; Artilide Fumarate; Azimilide Dihydrochloride; Bidisomide; Bucainide Maleate; Bucromarone; Butoprozine Hydrochloride; Capobenate Sodium; Capobenic Acid; Cifenline; Cifenline Succinate; Clofilium Phosphate; Disobutamide; Disopyramide; Disopyramide Phosphate; Dofetilide; Drobuline; Edifolone Acetate; Emilium Tosylate; Encainide Hydrochloride; Flecainide Acetate; Ibutilide Fumarate; Indecainide Hydrochloride; Ipazilide Fumarate; Lorajmine Hydrochloride; Lorcainide Hydrochloride; Meobentine Sulfate; Mexiletine Hydrochloride; Modecainide; Moricizine; Oxiramide; Pirmenol Hydrochloride; Pirolazamide; Pranolium Chloride; Procainamide Hydrochloride; Propafenone Hydrochloride; Pyrinoline; Quindonium Bromide; Quinidine Gluconate; Quinidine Sulfate; Recainam Hydrochloride; Recainam Tosylate; Risotilide Hydrochloride; Ropitoin Hydrochloride; Sematilide Hydrochloride; Suricainide Maleate; Tocainide; Tocainide Hydrochloride; Transcainide.
Cardiotonic: Actodigin; Amrinone; Bemoradan; Butopamine; Carbazeran; Carsatrin Succinate; Deslanoside; Digitalis; Digitoxin; Digoxin; Dobutamine; Dobutamine Hydrochloride; Dobutamine Lactobionate; Dobutamine Tartrate; Enoximone; Imazodan Hydrochloride; Indolidan; Isomazole Hydrochloride; Levdobutamine Lactobionate; Lixazinone Sulfate; Medorinone; Milrinone; Pelrinone Hydrochloride; Pimobendan; Piroximone; Prinoxodan; Proscillaridin; Quazinone; Tazolol Hydrochloride; Vesnarinone.
Cardiovascular agent: Dopexamine; Dopexamine Hydrochloride.
Choleretic: Dehydrocholic Acid; Fencibutirol; Hymecromone; Piprozolin; Sincalide; Tocamphyl.
Cholinergic: Aceclidine; Bethanechol Chloride; Carbachol; Demecarium Bromide; Dexpanthenol; Echothiophate Iodide; Isoflurophate; Methacholine Chloride; Neostigmine Bromide; Neostigmine Methylsulfate; Physostigmine; Physostigmine Salicylate; Physostigmine Sulfate; Pilocarpine; Pilocarpine Hydrochloride; Pilocarpine Nitrate; Pyridostigmine Bromide.
Cholinergic agonist: Xanomeline; Xanomeline Tartrate.
Cholinesterase Deactivator: Obidoxime Chloride; Pralidoxime Chloride; Pralidoxime Iodide; Pralidoxime Mesylate.
Coccidiostat: Arprinocid; Narasin; Semduramicin; Semduramicin Sodium.
Cognition adjuvant: Ergoloid Mesylates; Piracetam; Pramiracetam Hydrochloride; Pramiracetam Sulfate; Tacrine Hydrochloride.
Cognition enhancer: Besipirdine Hydrochloride; Linopirdine; Sibopirdine.
Hormone: Diethylstilbestrol; Progesterone; 17 hydroxy progesterone; Medroxyprogesterone; Norgestrel; Norethynodrel; Estradiol; Megestrol (Megace); Norethindrone; Levonorgestrel; Ethyndiol; Ethinyl estradiol; Mestranol; Estrone; Equilin; 17 alpha dihydroequilin; equilenin; 17 alpha dihydroequilenin; 17 alpha estradiol; 17 beta estradiol; Leuprolide (lupron); Glucagon; Testolactone; Clomiphene; Han memopausal gonadotropins; Human chorionic gonadotropin; Urofollitropin; Bromocriptine; Gonadorelin; Luteinizing hormone releasing hormone and analogs; Gonadotropins; Danazol; Testosterone; Dehydroepiandrosterone; Androstenedione; Dihydroestosterone; Relaxin; Oxytocin; Vasopressin; Folliculostatin; Follicle regulatory protein; Gonadoctrinins; Oocyte maturation inhibitor; Insulin growth factor; Follicle Stimulating Hormone; Luteinizing hormone; Tamoxifen.; Corticorelin Ovine Triftutate; Cosyntropin; Metogest; Pituitary, Posterior; Seractide Acetate; Somalapor; Somatrem; Somatropin; Somenopor; Somidobove.
Memory adjuvant: Dimoxamine Hydrochloride; Ribaminol.
Mental performance enhancer: Aniracetam.
Mood regulator: Fengabine.
Neuroleptic: Duoperone Fumarate; Risperidone.
Neuroprotective: Dizocilpine Maleate.
Psychotropic: Minaprine.
Relaxant: Adiphenine Hydrochloride; Alcuronium Chloride; Aminophylline; Azumolene Sodium; Baclofen; Benzoctamine Hydrochloride; Carisoprodol; Chlorphenesin Carbamate; Chlorzoxazone; Cinflumide; Cinnamedrine; Clodanolene; Cyclobenzaprine Hydrochloride; Dantrolene; Dantrolene Sodium; Fenalanide; Fenyripol Hydrochloride; Fetoxylate Hydrochloride; Flavoxate Hydrochloride; Fletazepam; Flumetramide;-Flurazepam Hydrochloride; Hexafluorenium Bromide; Isomylamine Hydrochloride; Lorbamate; Mebeverine Hydrochloride; Mesuprine Hydrochloride; Metaxalone; Methocarbamol; Methixene Hydrochloride; Nafomine Malate; Nelezaprine Maleate; Papaverine Hydrochloride; Pipoxolan Hydrochloride; Quinctolate; Ritodrine; Ritodrine Hydrochloride; Rolodine; Theophylline Sodium Glycinate; Thiphenamil Hydrochloride; Xilobam.
Sedative-hypnotic: Allobarbital; Alonimid; Alprazolam; Amobarbital Sodium; Bentazepam; Brotizolam; Butabarbital; Butabarbital Sodium; Butalbital; Capuride; Carbocloral; Chloral Betaine; Chloral Hydrate; Chlordiazepoxide Hydrochloride; Cloperidone Hydrochloride; Clorethate; Cyprazepam; Dexclamol Hydrochloride; Diazepam; Dichloralphenazone; Estazolam; Ethchlorvynol; Etomidate; Fenobam; Flunitrazepam; Fosazepam; Glutethimide; Halazepam; Lormetazepam; Mecloqualone; Meprobamate; Methaqualone; Midaflur; Paraldehyde; Pentobarbital; Pentobarbital Sodium; Perlapine; Prazepam; Quazepam; Reclazepam; Roletamide; Secobarbital; Secobarbital Sodium; Suproclone; Thalidomide; Tracazolate; Trepipam Maleate; Triazolam; Tricetamide; Triclofos Sodium; Trimetozine; Uldazepam; Zaleplon; Zolazepam Hydrochloride; Zolpidem Tartrate.
Serotonin antagonist: Altanserin Tartrate; Amesergide; Ketanserin; Ritanserin.
Serotonin inhibitor: Cinanserin Hydrochloride; Fenclonine; Fonazine Mesylate; Xylamidine Tosylate.
Serotonin receptor antagonist: Tropanserin Hydrochloride.
Stimulant: Amfonelic Acid; Amphetamine Sulfate; Ampyzine Sulfate; Arbutamine Hydrochloride; Azabon; Caffeine; Ceruletide; Ceruletide Diethylamine; Cisapride; Dazopride Fumarate; Dextroamphetamine; Dextroamphetamine Sulfate; Difluanine Hydrochloride; Dimefline Hydrochloride; Doxapram Hydrochloride; Etryptamine Acetate; Ethamivan; Fenethylline Hydrochloride; Flubanilate Hydrochloride; Flurothyl; Histamine Phosphate; Indriline Hydrochloride; Mefexamide; Methamphetamine Hydrochlo ride; Methylphenidate Hydrochloride; Pemoline; Pyrovalerone Hydrochloride; Xamoterol; Xamoterol Fumarate. Synergist: Proadifen Hydrochloride.
Thyroid hormone: Levothyroxine Sodium; Liothyronine Sodium; Liotrix.
Thyroid inhibitor: Methimazole; Propyithiouracil.
Thyromimetic: Thyromedan Hydrochloride.
Cerebral ischemia agents: Dextrorphan Hydrochloride.
Vasoconstrictor: Angiotensin Amide; Felypressin; Methysergide; Methysergide Maleate.
Vasodilator: Alprostadil; Azaclorzine Hydrochloride; Bamethan Sulfate; Bepridil Hydrochloride; Buterizine; Cetiedil Citrate; Chromonar Hydrochloride; Clonitrate; Diltiazem Hydrochloride; Dipyridamole; Droprenilamine; Erythrityl Tetranitrate; Felodipine; Flunarizine Hydrochloride; Fostedil; Hexobendine; Inositol Niacinate; Iproxamine Hydrochloride; Isosorbide Dinitrate; Isosorbide Mononitrate; Isoxsuprine Hydrochloride; Lidoflazine; Mefenidil; Mefenidil Fumarate; Mibefradil Dihydrochloride; Mioflazine Hydrochloride; Mixidine; Nafronyl Oxalate; Nicardipine Hydrochloride; Nicergoline; Nicorandil; Nicotinyl Alcohol; Nifedipine; Nimodipine; Nisoldipine; Oxfenicine; Oxprenolol Hydrochloride; Pentaerythritol Tetranitrate; Pentoxifylline; Pentrinitrol; Perhexiline Maleate; Pindolol; Pirsidomine; Prenylamine; Propatyl Nitrate; Suloctidil; Terodiline Hydrochloride; Tipropidil Hydrochloride; Tolazoline Hydrochloride; Xanthinol Niacinate.
Specifically, topiramate may be administered in combination with other medications to treat certain symptoms and disorders including:
I. Treatment of Binge Eating (Binge Eating Disorder, Bulimia Nervosa, Anorexia Nervosa with Binge eating) with serotonin re-uptake inhibitors (e.g., citalopram (CELEXA), clomipramine (ANAFRANIL)), fluoxetine (PROZAC), fluvoxamine (LUVOX), venlafaxine (EFFEXOR), other antidepressants (e.g., bupropion (WELLBUTRIN) nefazodone (SERZONE), tricyclics (e.g., NORPRAMIN and PAMELOR), trazodone (DESYREL), Substance P antagonists), psychostimulants, (e.g., d-amphetamine, phentermine; and sibutramine (MERIDIA)) and orlistat.
II. Treatment of overweight/obesity condition with sibutramine (MERIDIA); psychostimulants, (e.g., d-amphetamine, phentermine) and orlistat.
III. Treatment of nicotine addiction/smoking cessation with bupropion (ZYBAN), serotonin reuptake inhibitors, nicotine patches and gun, and other antidepressants.
IV. Treatment of alcohol abuse/dependence (alcoholism) with naltrexone (REVIA), serotonin reuptake inhibitors, and other antidepressants.
V. Treatment of other impulse control disorders (behavioral addictions) with serotonin reuptake inhibitors, lithium, valproic acid or divalproex sodium (e.g., DEPAKENE or DEPAKOTE), other antidepressants, naltrexone, atypical antipsychotics, (e.g., olanzapine (ZYPREXA), quetiapine (SEROQUEL), risperidone (RISPERDAL), ziprasidone) and other mood stabilizers (e.g., carbamazepine)
VI. Treatment of paraphilias/sexual addictions with serotonin reuptake inhibitors, lithium, divalproex sodium/valproic acid, antiandrogen medications (e.g., medroxyprogesterone, gonadotropin-releasing hormone (GnRH) agonists), other antidepressants, and other mood stabilizers (e.g., carbamazepine).
When administered, the formulations of the invention are applied in pharmaceutically acceptable amounts and in pharmaceutically acceptable compositions. Such preparations may routinely contain salts, buffering agents, preservatives, compatible carriers, and optionally other therapeutic ingredients. When used in medicine the salts should be pharmaceutically acceptable, but non-pharmaceutically acceptable salts may conveniently be used to prepare pharmaceutically acceptable salts thereof and are not excluded from the scope of the invention. Such pharmacologically and pharmaceutically acceptable salts include, but are not limited to, those prepared from the following acids: hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, maleic, acetic, salicylic, p-toluene sulfonic, tartaric, citric, methane sulfonic, formic, malonic, succinic, naphthalene-2-sulfonic, and benzene sulfonic. Also, pharmaceutically acceptable salts can be prepared as alkaline metal or alkaline earth salts, such as sodium, potassium or calcium salts.
Suitable buffering agents include: acetic acid and a salt (1-2% W/V); citric acid and a salt (1-3% W/V); boric acid and a salt (0.5-2.5% W/V); and phosphoric acid and a salt (0.8-2% W/V). Suitable preservatives include benzalkonium chloride (0.003-0.03% W/V); chlorobutanol (0.3-0.9% W/V); parabens (0.01-0.25% W/V) and thimerosal (0.004-0.02% W/V).
In the present invention, the sulfamide derivatives are administered in safe and effective amounts. An effective amount means that amount necessary to delay the onset of, inhibit the progression of, halt altogether the onset or progression of or diagnose the particular condition being treated. In general, an effective amount for treating an ICD will be that amount necessary to inhibit mammalian symptoms of the particular ICD in-situ. When administered to a subject, effective amounts will depend, of course, on the particular condition being treated; the severity of the condition; individual patient parameters including age, physical condition, size and weight; concurrent treatment; frequency of treatment; and the mode of administration. These factors are well known to those of ordinary skill in the art and can be addressed with no more than routine experimentation. It is preferred generally that a minimum dose be used, that is, the lowest safe dosage that provides appropriate relief of symptoms.
Dosage may be adjusted appropriately to achieve desired drug levels, locally or systemically. Generally, daily oral doses of active compounds will be from about 0.01 mg/kg per day to 2000 mg/kg per day. It is expected that IV doses in the range of about 1 to 1000 mg/cm 3 per day will be effective. In the event that the response in a subject is insufficient at such doses, even higher doses (or effective higher doses by a different, more localized delivery route) may be employed to the extent that patient tolerance permits. Continuous IV dosing over, for example 24 hours or multiple doses per day is contemplated to achieve appropriate systemic levels of compounds.
A variety of administration routes are available. The particular mode selected will depend of course, upon the particular drug selected, the severity of the disease state(s) being treated and the dosage required for therapeutic efficacy. The methods of this invention, generally speaking, may be practiced using any mode of administration that is medically acceptable, meaning any mode that produces effective levels of the active compounds without causing clinically unacceptable adverse effects. Such modes of administration include oral, rectal, sublingual, topical, nasal, transdermal or parenteral routes. The term “parenteral” includes subcutaneous, intravenous, intramuscular, or infusion. Intravenous routes are preferred.
The compositions may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. In general, the compositions are prepared by uniformly and intimately bringing the compounds into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product.
Compositions suitable for oral administration may be presented as discrete units such as capsules, cachets, tablets, or lozenges, each containing a predetermined amount of the active compound. Other compositions include suspensions in aqueous liquors or non-aqueous liquids such as a syrup, an elixir, or an emulsion.
Other delivery systems can include time-release, delayed release or sustained release delivery systems. Such systems can avoid repeated administrations of the active compounds of the invention, increasing convenience to the subject and the physician. Many types of release delivery systems are available and known to those of ordinary skill in the art. They include polymer based systems such as polylactic and polyglycolic acid, polyanhydrides and polycaprolactone; nonpolymer systems that are lipids including sterols such as cholesterol, cholesterol esters and fatty acids or neutral fats such as mono-, di and triglycerides; hydrogel release systems; silastic systems; peptide based systems; wax coatings, compressed tablets using conventional binders and excipients, partially fused implants and the like. In addition, a pump-based hardware delivery system can be used, some of which are adapted for implantation.
A long-term sustained release implant also may be used. “Long-term” release, as used herein, means that the implant is constructed and arranged to deliver therapeutic levels of the active ingredient for at least 30 days, and preferably 60 days. Long-term sustained release implants are well known to those of ordinary skill in the art and include some of the release systems described above.
EXAMPLES
In the examples, patients were treated with open-label topiramate starting at 25 mg/qHS and the dosage increased by the patient in 25 mg increments as tolerated by the subjects until a response is seen up to a maximum of 1200 mg.
TABLE 1
Patients with Binge Eating Disorder (BED) Treated Clinically with
Open-Label Topiramate (as of 12/16/98)
Reasons
Max
Pt
Topiramate
Dose
#
Pt ID
Begun
(mg/day)
Response
1
LJM
BD
1200
Remission of BD
(BED)
Remission of BED
(Obesity)
Loss of 107 lbs.
2
CEJ
BD
150
Mild improvement of BD,
BED
Moderate decrease of BED,
Overweight
Loss of 5 lbs.
Discontinued due to sedation,
cognitive dulling
3
JAC
BD
1200
Moderate improvement of BD.
BED
Remission of BED
Obesity
Loss of 50.5 lbs
4
JEB
BD
900
Moderate improvement of BD,
BED
Marked improvement of BED,
Overweight
Loss of 30.5 lbs.
5
KCW
BED
100
First trial: No response of BED,
Obesity
discontinued due to GI distress
Compulsive
Buying
(BD, in
100
remission)
Second Trial: Worsening of BD
Remission of BED
Loss of 11 lbs.
Remission of Compulsive
Buying
6
JB
BED
100
No response of BED
Overweight
No weight change
Key: BD = Bipolar Disorder; BED = Binge Eating Disorder; Pt. = patient; D/C = topiramate treatment discontinued; Cont.= topiramate treatment continued; GI = gastrointestinal
TABLE 2
Patients with Overeating, Overweight, and Obesity Treated Clinically with
Topiramate (as of 12/16/98)
Reasons
Max
Pt
Topiramate
dose
#
Pt ID
Begun
(mg/day)
Response
1
BAA
BD
700
No response of BD
Obesity
Loss of 9 lbs. (293-284)
(BED, in
remission)
2
HTB
BD
300
Remission of BD
Overeating
Remission of overeating
Overweight
Loss of 16 lbs. (248-232)
Discontinued 2° illness in
remission
3
ADJ
BD
400
Moderate improvement
of BD
Overeating,
Moderate improvement of
overeating
Overweight
Loss of 7 lbs. (239-232)
4
TK
BD
350
No response of BD
Overeating
Mild improvement in overeating
Overweight
Loss of 5 lbs. (238-233)
5
JCJ
BD
1. 250
First Trial: Worsening of BD
Overeating
2. 200
Mild decrease of overeating
Overweight
Loss of 7 lbs. (152-145)
Second Trial Mild improvement of
BD
Mild decrease of overeating
Gain of 1 lb. (154-155 lbs.)
6
KDC
Overeating
800
Worsening of BD
Overweight
Loss of 9 lbs. (208-199 lbs)
(BD, in
remission)
7
NLR
BD
300
Worsening of BD
Overweight
Loss of 46 lbs. (196-150 lbs.)
Discontinued due to anorexia
8
PR
BD
700
Moderate improvement of BD
Overeating
Marked improvement in overeating
Overweight
Loss of 19 lbs. (185-166)
Discontinued due to
G.I. Distress
Key: Pt. = patient; BD = Bipolar Disorder; BED = Binge Eating Disorder; D/C = topiramate treatment discontinued; cont = topiramate treatment continued; GI = gastrointestinal
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Impulse Control Disorders (ICD's) are characterized by harmful behaviors performed in response to irresistible impulses. The essential feature of an ICD is the failure to resist an impulse, drive, or temptation and to perform an act that is harmful to the person or to others. The present invention comprises methods for the treatment or prevention of ICD's using a class of sulfamates of the following formula:
wherein X is CH 2 or oxygen, and R 1 , R 2 , R 3 , R 4 and R 5 are as herein defined. Further, pharmaceutical compositions containing a compound of formula (I) as well as methods for their use and intermediates form part of the present invention are also disclosed.
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This application is a continuation of application Ser. No. 10/016,353, filed Dec. 10, 2001 now U.S. Pat. No. 6,830,599.
BACKGROUND OF THE INVENTION
This invention relates generally to vacuum type cleaning machines and more particularly concerns back-flow valves and valve triggers facilitating cyclical washing of the cleaning machine filters.
Back flow valves typically employ gates which are directly mechanically or electrically driven. Consequently, the speed of movement of the gate is governed throughout its range of motion. The result is a response time that is detrimental to the smooth operation of the machine, the filtering action being blocked for unnecessarily long intervals because of the slow response of the back-flow valve. Furthermore, these mechanical and electronic systems are extremely complex and expensive and available only on the most expensive cleaning machines. For lower priced equipment, down time for filter replacement or cleaning is required.
In one valve system disclosed in U.S. Pat. No. 4,618,352 to Nelson, cams within the system air ducts rotate in direct physical contact with their valve gates, holding the gates in horizontal planes until notches in the cams allow them to rotate into diagonal planes. This system has serious power and efficiency problems. First of all, the cams are disposed on a common shaft. The common shaft arrangement of the cams requires side-by-side alignment of the system ducts transverse to the common shaft. This adds to duct length and imposes location requirements which increase system losses and structural complexity. Second, the notches are angularly displaced on the cams to synchronize the operation of the gates. Since the gates are in direct contact with the cams, the notches must be relatively wide in order for the gates to open for a sufficient interval. This imposes limitations on the blower to vacuum time ratios which greatly reduce the efficiency of the system. Third, in the horizontal condition the gates completely seal the openings to the blower ducts. However, in the diagonal condition only the free ends of the gates engage the vacuum ducts, so that there is no seal and air loss occurs. Fourth, since the cam notches receive the gates, the cam diameters must be greater than the ducts the gates close. Consequently, for the gates and cams to maintain physical contact, the ducts must be slotted to receive the cams. Therefore, special housings are required to prevent further air losses in the system. Fifth, the cams are constantly driven so that the back-flow cycle occurs throughout the cleaning process, reducing the normal operating efficiency of the system. Sixth, because there is no seal during the vacuum process, the speed of operation of the gate is left essentially to an initial push by the blower and the force of gravity rather than taking advantage of the vacuum to help slam the gate home. Seventh, the blower and the vacuum share a common shaft, so the blower is operating unnecessarily throughout the vacuum process. The composite result of these individual problems is that the system is ineffective for cleaning at any appreciable distance from the machine.
It is, therefore, an object of this invention to provide a back-flow valve and valve trigger which facilitate cyclical washing of the cleaning machine filters. Another object of this invention is to provide a back-flow valve and valve trigger which have a rapid response time so as to limit the duration of the back flow interval. A further object of this invention is to provide a back-flow valve and valve trigger using a gate which is air-flow biased by both a blower and a vacuum source toward a back-flow condition. Yet another object of this invention is to provide a back-flow valve and valve trigger using a gate which is not mechanically controlled during its transition from normal operation to back-flow operation. It is also an object of this invention to provide a back-flow valve and valve trigger using a gate which is not electrically controlled during its transition from normal operation to a back-flow operation. Still another object of this invention is to provide a back-flow valve and valve trigger using a gate which is not governed during its transition from normal operation to back-flow operation. Another object of this invention is to provide a back-flow valve and valve trigger which do not unnecessarily increase the length of the internal duct system. Another object of this invention is to provide a back-flow valve and valve trigger which eliminate openings and gaps which would cause pressure losses in the system. Still another object of this invention is to provide a back-flow valve and valve trigger in which an external valve trigger controls an internal valve gate. Still another object of this invention is to provide a back-flow valve and valve trigger which provide a relatively short back-flow interval during each filter cycle. Another object of this invention is to provide a back-flow valve and valve trigger which require only intermittent use of the back-flow system during the normal vacuuming process. An additional object of this invention is to provide a back-flow valve and valve trigger which are relatively simple and inexpensive. And it is an object of this invention to provide a back-flow valve and valve trigger which require operation of the blower only during the back-flow process.
SUMMARY OF THE INVENTION
A valve and a valve trigger are provided which cyclically connect a vacuum and a blower to a filter. The valve has a box with three openings. The first opening is connectable to the vacuum. The second opening is connectable to the blower. The third opening is connectable to the filter. A gate within the box is adapted to be biased by the blower and the vacuum to close the first opening. The gate is held against the bias by the external trigger to close the second opening. The external trigger is intermittently operated and is adapted to intervally release the internal gate to the bias to close the first opening and open the second opening. The preferred gate is a flapper hinged for angular motion between the first and second openings. The preferred trigger is a rotating cam with a follower fixed to the flapper. The cam operation is controlled by a timer. As the cam perimeter remains engaged with the follower, the flapper is held against the bias to close the second opening. An irregularity in the perimeter of the cam intermittently disengages the cam from the follower and releases the flapper to the bias of the air flow, allowing the flapper to slam against and close the first opening and open the second opening. The blower is energized in response to the timer so that it operates only when the cam is rotating.
A plurality of valves can be combined with a single trigger in a system for cyclically connecting a plurality of filters to the vacuum and the blower. In the preferred system, a plurality of cam followers are equally angularly displaced along the perimeter of a circular cam. The cam irregularity is shaped to release each gate for approximately 1/12 rotation of the cam and intervally releases the gates to the bias to sequentially close their first openings.
BRIEF DESCRIPTION OF THE DRAWINGS
Other objects and advantages of the invention will become apparent upon reading the following detailed description and upon reference to the drawings in which:
FIG. 1 is a mechanical schematic drawing of a three filter cleaning machine employing three back-flow valves and a single valve trigger;
FIG. 2 is a perspective assembly view of the back-flow valves and valve trigger of FIG. 1 ;
FIG. 3 is a perspective view of the assembled back-flow valve and valve trigger of FIG. 1 ;
FIG. 4 is a perspective assembly view of a preferred embodiment of the valves of FIG. 1 ;
FIG. 5 is a top perspective view of the assembled valve of FIG. 4 ;
FIG. 6 is a bottom perspective view of the assembled valve of FIG. 4 ; and
FIG. 7 is an electrical schematic drawing of the machine of FIG. 1 .
While the invention will be described in connection with a preferred embodiment, it will be understood that it is not intended to limit the invention to that embodiment. On the contrary, it is intended to cover all alternatives, modifications and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.
DETAILED DESCRIPTION
Turning first to FIG. 1 , a three-filter cleaning machine employing three back-flow valves and a single valve trigger is illustrated. During normal operation, a vacuum source S connected through valve V 1 , V 2 or V 3 pulls air contaminated with undesirable particles into three filters F 1 , F 2 and F 3 which remove the undesirable particles. While most of the accumulated particles are discharged into a filter pan, some of the particles amass on and clog the filter walls, diminishing the efficiency of the system. For back-flow operation, a blower B is connected to push air through the valves V 1 , V 2 and V 3 to their respective filters F 1 , F 2 and F 3 to dislodge the clogging particles from the filter walls. Each of the valves V 1 , V 2 and V 3 has a gate G 1 , G 2 and G 3 , respectively, which seals off flow from the blower B into the valves V 1 , V 2 or V 3 and permits the vacuum source S to draw contaminated air into the filters F 1 , F 2 and F 3 during the normal vacuuming process. The gates G 1 and G 2 and G 3 are mechanically held in place against the bias created by the blower B and the vacuum source S during the normal vacuuming process by a trigger T. The trigger T cyclically sequentially releases the gates G 1 , G 2 and G 3 to the bias of the blower B and the vacuum source S to cause them to seal off the suction of the vacuum source S and allow air pushed by the blower B to blast into the filters F 1 , F 2 and F 3 . The trigger T is external to the valves V 1 , V 2 and V 3 . In switching to the back-flow process, the trigger T completely disengages mechanical connection to the gates G 1 , G 2 and G 3 so that the bias afforded by the blower B and vacuum source S causes the gates G 1 , G 2 and G 3 to rapidly slam from the vacuum to the back-flow condition.
Looking now at FIGS. 2 and 3 , the valve deck 10 is illustrated in greater detail. Valves V 1 , V 2 and V 3 are mounted on a base 11 . For the three-filter machine illustrated, the base 11 has three passages 12 , 13 and 14 which are equidistantly spaced from a center point 15 on axes 16 , 17 and 18 and are equally angularly displaced from each other. The filters F 1 , F 2 and F 3 are mounted below the plate 11 and aligned with the passages 12 , 13 and 14 , respectively, as best seen in FIG. 1 . The valves V 1 , V 2 and V 3 are secured to the top face of the base 11 by mounting plates 21 which receive bolts 22 extending upwardly from the base 11 .
The valves V 1 , V 2 and V 3 are illustrated in greater detail in FIGS. 4–6 . The mounting plates 21 have openings 23 which align with the passages 12 , 13 and 14 through the base 11 . A hub 24 at the center of each opening 23 allows the filter F 1 , F 2 or F 3 to be engaged beneath its respective opening 23 . Each of the valves V 1 , V 2 and V 3 has sidewalls 25 , 26 , 27 and 28 and a cover 29 which, in cooperation with the mounting plate 21 , defines the valve box. Two of the walls 25 and 28 have ports 31 and 32 . Adapters 33 and 34 , respectively, are secured at the ports 31 and 32 to facilitate connection of system ducts, seen in FIG. 1 , to the valve box. As shown, the ports 31 and 32 are in adjacent orthogonal sidewalls 25 and 28 . A clapper 35 , such as an approximately square sheet of metal stock, has circular disks 36 and 37 of compressible material attached to its opposite faces. The adapters 33 and 34 have circumferences within the valve boxes to provide a suitable sealing surface and the disks 36 and 37 are sized and textured to cooperate with the adapters 33 and 34 to seal the passages 31 and 32 . One edge of the clapper 35 abuts and is fixed to a shaft 38 which extends above and below the upper and lower edges of the clapper 35 . A brass bushing 42 is fitted into an aperture 41 in the corner of the cover 29 at the junction point of the sidewalls 25 and 28 . Another brass bushing 44 is fitted into another aperture 43 in the mounting plate 21 which is vertically aligned with the aperture 41 in the cover 29 . The upper and lower ends of the flapper shaft 38 are journaled for rotation in the bushings 42 and 44 so that the flapper 35 can rotate between a first position in which one of the disks 36 seals one of the ports 31 and a second position in which the other of the disks 37 seals the other of the ports 32 . The upper end 45 of the shaft 38 further extends through its bushing 42 upwardly beyond the top of the cover 29 for engagement with one end of a follower arm 46 . The arm 46 is secured proximate one of its ends to the top end of the shaft 45 . A threaded screw 47 through a split in the arm 46 tightens the aperture 48 into which the end 45 of the shaft is inserted. The arm 46 extends radially outwardly from the shaft 38 to a cam follower 51 which is journaled for rotation using a washer 52 on a post 53 extending upwardly from the arm 46 . The seams of the valve box are sealed with a suitable duct sealant to insure the pneumatic integrity of the valves V 1 , V 2 and V 3 .
Returning to FIGS. 2 and 3 , a motor 54 is mounted beneath a motor mounting plate 55 with the shaft 56 of the motor 54 extending upwardly through the mounting plate 56 . The bottom face of the motor mounting plate 56 is fastened to the top faces of the valve covers 29 with the axis 57 of the motor shaft 56 in vertical alignment through the center point 15 of the symmetrical arrangement of valves V 1 , V 2 and V 3 . A circular cam 58 is concentrically mounted on the top of the motor shaft 56 by the cam hub 59 . The diameter of the cam 58 is such that its circumference engages the cam followers 51 to hold the flapper disks 36 against the valve ports 31 . This can be assured by adjustment of the angular position of the follower arms 46 in the gate shafts 38 . An irregularity 61 in the circumference of the cam 58 completely disengages the cam 58 from mechanical contact with the follower 51 so that, when the follower 51 is released, its corresponding flapper 35 is free to rotate on its shaft 38 until the other disk 37 on the flapper 35 seals the other port 32 of its respective valve V 1 , V 2 or V 3 . Looking at FIGS. 1 , 2 and 3 , a manifold 62 has outlets 63 connected by ducts 64 to their respective inlet ports 33 in the valves V 1 , V 2 and V 3 . The blower B is connected by a duct 65 to the inlet of the manifold 62 . Similarly, the vacuum source S is connected to the ports 32 of the valves V 1 , V 2 and V 3 by ducts 66 .
Looking at FIGS. 1 and 7 , the operation of the machine can be understood. The cam drive motor 54 is controlled through a switch 67 and time delay circuit 68 which are part of the trigger T. The cam 58 is normally engaged with the cam followers 51 so as to hold the flappers 35 with their disks 36 sealing the blower inlet ports 31 into the valves V 1 , V 2 and V 3 . In this position, the suction of the vacuum source S and the pressure from the blower B, the former drawing against the vacuum side disks 37 and the latter pushing against the blower side disks 36 , biases the flappers 35 to rotate from the blower inlet ports 31 toward the vacuum outlet ports 32 . However, the flappers 35 are held against the bias by the mechanical engagement of the cam 58 with the followers 51 . As the cam motor 54 rotates the cam 58 , the irregularity 61 in the cam circumference sequentially releases the cam followers 51 completely from mechanical engagement so that the gates G 1 , G 2 and G 3 are free to rotate in response to the bias to open the blower inlet ports 31 and slam the vacuum outlet ports 32 closed. Thus, air is no longer drawn by the vacuum source S into the filter F 1 , F 2 or F 3 associated with the released gate G 1 , G 2 or G 3 in the forward flow direction 71 but air is blown into the filter F 1 , F 2 or F 3 in reverse-flow direction 72 to dislodge particles collected on the filter walls during the vacuuming process. The contour of the irregularity 61 of the cam 58 is selected so as to release each cam follower 51 from mechanical engagement for approximately 1/12 of a rotation of the cam 58 . Because of the rapid response of the mechanically released gates G 1 , G 2 and G 3 , each filter F 1 , F 2 and F 3 experiences back flow for only 1/12 of a cam rotation and the entire system is experiencing back flow for only ¼ of a cam rotation. Thus, even during the back flow process, the normal vacuum process continues at 100% effectiveness for ¾ of the cam rotation. Furthermore, the timer rheostat 68 A can be adjusted by the machine operator to cause its switch 68 A to operate at any desired interval, preferably in a range of from 1.5 to 30 minutes. When the switch 67 is closed, a first relay 81 is energized, closing its normally open contacts 81 A to energize the vacuum source S. The timer 68 is energized simultaneously through normally closed contacts 84 A. As long as the timer 68 is energized, it will cause its switch 68 B to operate at the intervals set by the timer rheostat 68 A. Assuming, for example, a selected interval of twenty minutes, the timer switch 6 B will close twenty minutes after the switch 67 is turned “ON” and every twenty minutes thereafter. This will energize a second relay 83 which closes two of its normally open contacts 83 A and 83 B to engage the blower B and the cam motor 54 , respectively, and third normally open contacts 83 C in the circuit of a third relay 84 . The third relay 84 controls the normally closed contacts 84 A which control the timer 68 . The energized cam motor 54 causes the cam 58 to rotate. A post 85 A fixed to and rotating with the cam 58 activates a proximity switch 85 in the circuit of the third relay 84 . The proximity switch is normally open. If the blower B and cam motor 54 are energized, the second relay contacts 83 C are closed. When the proximity switch 85 closes, the third relay 84 opens the contacts 84 A to de-energize the timer 68 , opening the timer switch 68 B and de-energizing the second relay 83 to shut off the blower B and cam motor 54 and reset the system which will repeat itself when the selected time interval of twenty minutes has elapsed. The proximity switch 85 is operated after one revolution of the cam 58 . Therefore, each of the filters F 1 , F 2 and F 3 will receive one blast of blower air every twenty minutes and the blower B and cam motor 54 are energized for only one rotation of the cam 58 every twenty minutes. If, for example, the cam motor 64 drives the cam 58 at one (1) rpm, the back-flow process is in operation for only 1/20 of the vacuuming process and each filter will sequentially receive one five second blast of blower air during the one minute back-flow interval. In this manner, the back-flow process can be used to eliminate down time to replace or clean filters without any significant reduction in the power and efficiency of the vacuum process, even while back-flow is occurring. While the invention has been described in relation to a three-valve system, any number of valves and filters can be used applying the principles of the invention.
Thus, it is apparent that there has been provided, in accordance with the invention, a back flow valve and valve trigger for a cleaning machine that fully satisfies the objects, aims and advantages set forth above. While the 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 and in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, modifications and variations as fall within the spirit of the appended claims.
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A valve and trigger cyclically connect a vacuum and a blower to a filter. The valve box has three openings, the first connectable to the vacuum, the second connectable to the blower and the third connectable to the filter. A gate inside the box, biased by the blower and the vacuum toward closing the first opening, is held against the bias by a trigger outside the box to close the second opening. The external trigger intervally operates to release the interior gate to close the first opening and open the second opening. The blower operates only if the trigger is operating. The gate is released once for approximately 1/12 of a cycle interval during each trigger operating interval. A plurality of valves can be combined in a system with one trigger for cyclically sequentially connecting a plurality of filters to the vacuum and the blower.
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FIELD OF THE INVENTION
This invention relates to a system for securely storing and selectively transmitting sensitive information. More particularly, the invention relates to a system incorporated into a conventional data or voice transmission network that includes a secure repository for storing the sensitive information and means to selectively deliver the information from the repository to an authorized caller.
DESCRIPTION OF THE PRIOR ART
Storing and transmitting information electronically has become an accepted mode of operating for both the business and private sector. On-line public databases exist which are accessed through conventional telephone lines.
In addition means have been developed for releasing stored information only after appropriate identification has been produced. Typically, when telephone lines are used to access databases a billing or identification number must be inserted, usually by DTMF tones, to access the information in the data base.
Thus there is available in the prior art large capacity storage devices to maintain and accumulate data, transmission networks to deliver the information from the database to a subscriber and means for releasing the information only after appropriate identification has been provided.
In addition conventional means exist for encrypting information before storing the information and for decrypting the information after releasing the information from storage.
SUMMARY OF THE INVENTION
The subject invention provides a system for storing and securing sensitive and confidential information.
The system also provides means for only authorized individuals to access the information. Further, the system provides means to secure the sensitive and confidential information at a plurality of discrete levels, each level being accessible by an individual depending on his/her level of authorization.
The system includes a computer connected within the telephone transmission network. The computer interfaces with the network through standard telephone switching means that enable access to information in the computer upon entry of the proper identification code. The system is programmed to recognize a plurality of levels of authorization. Identification code is provided respectively for marginally sensitive information, sensitive information and highly confidential information. The program releases information from the computer as a function of the authorization code.
The sensitive information and highly confidential information is stored in an encrypted format for security purposes, while the marginally sensitive information is stored in the usual fashion. The sensitive information is decrypted prior to transmission to the authorized caller, but the highly confidential information is delivered to the user in the same encrypted form as it is stored, thereby enabling only a telephone receiver equipped with the required decoding means to be able to convert the information to understandable and usable form.
DESCRIPTION OF THE DRAWINGS
The system of the present invention will be better understood when considered with the following drawings wherein:
FIG. 1 is the overall schematic of the system.
FIG. 2 is a flow chart of the software that controls the delivery of securely stored information to an authorized caller.
FIG. 3 is a flow chart of a program for decoding highly confidential information delivered to a caller in encrypted form.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention has application in the storage in a database and transmission upon authorized request of sensitive information. Individual, personal, medical, financial, legal and personal information that must be maintained and periodically provided that serve the individuals are illustrations of records that have particular application in the system.
As seen in FIG. 1, an existing conventional telephone network 10 such as the AT&T network is provided with a high capacity secure storage computer 12 and means 14 to interface between the network 10 and the computer 12. In addition, a decrypting means 15 is provided at the appropriate user's location (e.g. installed in his/her phone set) to decode information provided to the caller in encrypted form.
The particularly suitable repository 12 is a NCR 3000 gigabyte computer. The interface means 14 is a 4ESS switch programmed to respond to requests from the conventional network receiver such as telephones 16 or facsimile machines 18.
The computer 12 is illustrated in FIG. 1 as having three discrete data bases 20, 22 and 24 for storing information and data having varying degrees of confidential sensitivity. These databases need not necessarily reside on separate computers or storage devices but may be integrated on one device.
Basic to the invention is the capability of the system to enable selective access to the information stored in the data bases 20, 22 and 24. Illustratively, when the system is employed to store and transmit medical records, data base 20 will store the regular formal information pertaining to a patient such as birth date, insurance carrier, etc., which is desired to be marginally sensitive. Data base 22 will store more sensitive information such as the test ordered and the duties performed. Data base 24 will store the highly confidential information such as the diagnostic results or interpretation by physicians. The selection of which level of security the particular information is stored is a function of the subscriber's requirements.
The control programs for the computer 12 will allow access to the information in data base 20 to anyone having a Security Category 1 identification number that can be entered into the telephone network by depressing the touch tone keypad, which transmits conventional DTMF tones. Only information stored in data base 20 will be transmitted in response to an inquiry entering a Security Category 1 identification number. The information is not stored in encrypted format and will be transmitted in uncoded usable form.
The control program for the system will allow access to the information in data base 22 only to persons having a Security Category 2 identification number that can be entered into the network by conventional DTMF tones. The information in data base 22 is stored in encrypted form but is delivered to the caller with Security Category 2 identification in uncoded usable form. The delivery of information from data base 22 will always carry the patient's information stored in data base 20.
The control program for the system will allow access to the information in data base 24 only to persons having a Security Category 3 identification number that can be entered into the network by conventional DTMF tones. The information in data base 24 is highly confidential and is stored and also transmitted in encrypted form. The information from data base 24 reaches the caller in encrypted form and must be decoded at the caller's facility for use. The patient information stored in data bases 20 and 22 are always provided with the information from data base 24.
The decrypting means 15, which is used only to decode highly confidential information sent in encrypted form to the authorized user, may be an integral part of the user's telephone set. Optionally, decrypting means 15 may be a separate "blackbox" add on component.
As seen in FIG. 2, the flow chart for verification of the validity of the caller and transmission of the proper data in response to the particular Security Category identification number proceeds from entry of an identification number to either termination of a call or delivery of selected information.
The decryption of a Security Category 3 message is performed in the BIC decoder 15. A suitable program provided for decryption is the AT&T BIC program shown in FIG. 3.
The database 24 will also maintain record of successful as well as unsuccessful attempts on a given information. The record will consist of caller ID, time and date. This record will be available to the depositer of the information on demand or automatically. The system administrator can also request information for security reason but only of unsuccessful attempts.
An example of the use of the system of the invention to access information is as follows:
Dr. A has determined that it is necessary for him to have the case history of patient B.
Dr. A's secretary will dial 800-222-3333 (her identification number) from a standard conventional telephone to access the data stored in AT&T Network by computer 12. She obtained by on-line transmission the summary of all the test results received to that day because she has clearance to access Security Category 1 data.
Dr. A will dial in with his AT&T security device after reviewing the report from the secretary. The call will be secured and the information will be transmitted after verification of identity. The information will be encrypted until it reaches Dr. A's handset. The decoding will take place based on the key and algorithm. The data transmitted is of the Security Category 3.
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A secure information retrieval system comprising three levels of confidential access to a database, wherein the first level is stored and transmitted in an unencrypted form, the second level is stored in an encrypted form but transmitted in an unencrypted form, and the third level is stored and transmitted in an encrypted form.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This is a Continuation Application of U.S. application Ser. No. 10/778,139 filed on Feb. 17, 2004, which is a Continuation-In-Part of U.S. application Ser. No. 10/302,668, filed on Nov. 23, 2002, now issued U.S. Pat. No. 7,152,958 all of which is herein incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a thermal ink jet printhead, to a printer system incorporating such a printhead, and to a method of ejecting a liquid drop (such as an ink drop) using such a printhead.
BACKGROUND TO THE INVENTION
[0003] The present invention involves the ejection of ink drops by way of forming gas or vapor bubbles in a bubble forming liquid. This principle is generally described in U.S. Pat. No. 3,747,120 (Stemme).
[0004] There are various known types of thermal ink jet (bubblejet) printhead devices. Two typical devices of this type, one made by Hewlett Packard and the other by Canon, have ink ejection nozzles and chambers for storing ink adjacent the nozzles. Each chamber is covered by a so-called nozzle plate, which is a separately fabricated item and which is mechanically secured to the walls of the chamber. In certain prior art devices, the top plate is made of Kapton™ which is a Dupont trade name for a polyimide film, which has been laser-drilled to form the nozzles. These devices also include heater elements in thermal contact with ink that is disposed adjacent the nozzles, for heating the ink thereby forming gas bubbles in the ink. The gas bubbles generate pressures in the ink causing ink drops to be ejected through the nozzles.
[0005] It is an object of the present invention to provide a useful alternative to the known printheads, printer systems, or methods of ejecting drops of ink and other related liquids, which have advantages as described herein.
SUMMARY OF THE INVENTION
[0006] Accordingly the present invention provides a method of producing an ink jet printhead comprising:
a structure with a plurality of nozzles, the structure formed on an underlying substrate having at least one heater element corresponding to each of the nozzles respectively; the heater elements being configured for thermal contact with a bubble forming liquid for heating at least part of the bubble forming liquid to a temperature above its boiling point to form a gas bubble therein to eject a drop of the liquid through the nozzle corresponding to the heater elements; wherein the method of production comprises the step of: forming the structure in-situ on the substrate. By forming the nozzle plate in-situ on the wafer substrate, there is no need to assemble the plate and the etched wafer. Such assembly involves a precision alignment of the nozzle plate using custom equipment.
[0010] As will be understood by those skilled in the art, the ejection of a drop of the ejectable liquid as described herein, is caused by the generation of a vapor bubble in a bubble forming liquid, which, in embodiments, is the same body of liquid as the ejectable liquid. The generated bubble causes an increase in pressure in ejectable liquid, which forces the drop through the relevant nozzle. The bubble is generated by Joule heating of a heater element which is in thermal contact with the ink. The electrical pulse applied to the heater is of brief duration, typically less than 2 microseconds. Due to stored heat in the liquid, the bubble expands for a few microseconds after the heater pulse is turned off. As the vapor cools, it recondenses, resulting in bubble collapse. The bubble collapses to a point determined by the dynamic interplay of inertia and surface tension of the ink. In this specification, such a point is referred to as the “point of collapse” of the bubble.
[0011] The printhead according to the invention comprises a plurality of nozzles, as well as a chamber and one or more heater elements corresponding to each nozzle. Each portion of the printhead pertaining to a single nozzle, its chamber and its one or more elements, is referred to herein as a “unit cell”.
[0012] In this specification, where reference is made to parts being in thermal contact with each other, this means that they are positioned relative to each other such that, when one of the parts is heated, it is capable of heating the other part, even though the parts, themselves, might not be in physical contact with each other.
[0013] Also, the term “ink” is used to signify any ejectable liquid, and is not limited to conventional inks containing colored dyes. Examples of non-colored inks include fixatives, infra-red absorber inks, functionalized chemicals, adhesives, biological fluids, water and other solvents, and so on. The ink or ejectable liquid also need not necessarily be a strictly a liquid, and may contain a suspension of solid particles or be solid at room temperature and liquid at the ejection temperature.
[0014] In this specification, the term “periodic element” refers to an element of a type reflected in the periodic table of elements.
DETAILED DESCRIPTION OF THE DRAWINGS
[0015] Preferred embodiments of the invention will now be described, by way of example only, with reference to the accompanying representations. The drawings are described as follows.
[0016] FIG. 1 is a schematic cross-sectional view through an ink chamber of a unit cell of a printhead according to an embodiment of the invention, at a particular stage of operation.
[0017] FIG. 2 is a schematic cross-sectional view through the ink chamber FIG. 1 , at another stage of operation.
[0018] FIG. 3 is a schematic cross-sectional view through the ink chamber FIG. 1 , at yet another stage of operation.
[0019] FIG. 4 is a schematic cross-sectional view through the ink chamber FIG. 1 , at yet a further stage of operation.
[0020] FIG. 5 is a diagrammatic cross-sectional view through a unit cell of a printhead in accordance with the an embodiment of the invention showing the collapse of a vapor bubble.
[0021] FIGS. 6, 8 , 10 , 11 , 13 , 14 , 16 , 18 , 19 , 21 , 23 , 24 , 26 , 28 and 30 are schematic perspective views ( FIG. 30 being partly cut away) of a unit cell of a printhead in accordance with an embodiment of the invention, at various successive stages in the production process of the printhead.
[0022] FIGS. 7, 9 , 12 , 15 , 17 , 20 , 22 , 25 , 27 , 29 and 31 are each schematic plan views of a mask suitable for use in performing the production stage for the printhead, as represented in the respective immediately preceding figures.
[0023] FIG. 32 is a further schematic perspective view of the unit cell of FIG. 30 shown with the nozzle plate omitted.
[0024] FIG. 33 is a schematic perspective view, partly cut away, of a unit cell of a printhead according to the invention having another particular embodiment of heater element.
[0025] FIG. 34 is a schematic plan view of a mask suitable for use in performing the production stage for the printhead of FIG. 33 for forming the heater element thereof.
[0026] FIG. 35 is a schematic perspective view, partly cut away, of a unit cell of a printhead according to the invention having a further particular embodiment of heater element.
[0027] FIG. 36 is a schematic plan view of a mask suitable for use in performing the production stage for the printhead of FIG. 35 for forming the heater element thereof.
[0028] FIG. 37 is a further schematic perspective view of the unit cell of FIG. 35 shown with the nozzle plate omitted.
[0029] FIG. 38 is a schematic perspective view, partly cut away, of a unit cell of a printhead according to the invention having a further particular embodiment of heater element.
[0030] FIG. 39 is a schematic plan view of a mask suitable for use in performing the production stage for the printhead of FIG. 38 for forming the heater element thereof.
[0031] FIG. 40 is a further schematic perspective view of the unit cell of FIG. 38 shown with the nozzle plate omitted.
[0032] FIG. 41 is a schematic section through a nozzle chamber of a printhead according to an embodiment of the invention showing a suspended beam heater element immersed in a bubble forming liquid.
[0033] FIG. 42 is schematic section through a nozzle chamber of a printhead according to an embodiment of the invention showing a suspended beam heater element suspended at the top of a body of a bubble forming liquid.
[0034] FIG. 43 is a diagrammatic plan view of a unit cell of a printhead according to an embodiment of the invention showing a nozzle.
[0035] FIG. 44 is a diagrammatic plan view of a plurality of unit cells of a printhead according to an embodiment of the invention showing a plurality of nozzles.
[0036] FIG. 45 is a diagrammatic section through a nozzle chamber not in accordance with the invention showing a heater element embedded in a substrate.
[0037] FIG. 46 is a diagrammatic section through a nozzle chamber in accordance with an embodiment of the invention showing a heater element in the form of a suspended beam.
[0038] FIG. 47 is a diagrammatic section through a nozzle chamber of a prior art printhead showing a heater element embedded in a substrate.
[0039] FIG. 48 is a diagrammatic section through a nozzle chamber in accordance with an embodiment of the invention showing a heater element defining a gap between parts of the element.
[0040] FIG. 49 is a diagrammatic section through a nozzle chamber not in accordance with the invention, showing a thick nozzle plate.
[0041] FIG. 50 is a diagrammatic section through a nozzle chamber in accordance with an embodiment of the invention showing a thin nozzle plate.
[0042] FIG. 51 is a diagrammatic section through a nozzle chamber in accordance with an embodiment of the invention showing two heater elements.
[0043] FIG. 52 is a diagrammatic section through a nozzle chamber of a prior art printhead showing two heater elements.
[0044] FIG. 53 is a diagrammatic section through a pair of adjacent unit cells of a printhead according to an embodiment of the invention, showing two different nozzles after drops having different volumes have been ejected therethrough.
[0045] FIGS. 54 and 55 are diagrammatic sections through a heater element of a prior art printhead.
[0046] FIG. 56 is a diagrammatic section through a conformally coated heater element according to an embodiment of the invention.
[0047] FIG. 57 is a diagrammatic elevational view of a heater element, connected to electrodes, of a printhead according to an embodiment of the invention.
[0048] FIG. 58 is a schematic exploded perspective view of a printhead module of a printhead according to an embodiment of the invention.
[0049] FIG. 59 is a schematic perspective view the printhead module of FIG. 58 shown unexploded.
[0050] FIG. 60 is a schematic side view, shown partly in section, of the printhead module of FIG. 58 .
[0051] FIG. 61 is a schematic plan view of the printhead module of FIG. 58 .
[0052] FIG. 62 is a schematic exploded perspective view of a printhead according to an embodiment of the invention.
[0053] FIG. 63 is a schematic further perspective view of the printhead of FIG. 62 shown unexploded.
[0054] FIG. 64 is a schematic front view of the printhead of FIG. 62 .
[0055] FIG. 65 is a schematic rear view of the printhead of FIG. 62 .
[0056] FIG. 66 is a schematic bottom view of the printhead of FIG. 62 .
[0057] FIG. 67 is a schematic plan view of the printhead of FIG. 62 .
[0058] FIG. 68 is a schematic perspective view of the printhead as shown in FIG. 62 , but shown unexploded.
[0059] FIG. 69 is a schematic longitudinal section through the printhead of FIG. 62 .
[0060] FIG. 70 is a block diagram of a printer system according to an embodiment of the invention.
DETAILED DESCRIPTION
[0061] In the description than follows, corresponding reference numerals, or corresponding prefixes of reference numerals (i.e. the parts of the reference numerals appearing before a point mark) which are used in different figures relate to corresponding parts. Where there are corresponding prefixes and differing suffixes to the reference numerals, these indicate different specific embodiments of corresponding parts.
[0000] Overview of the Invention and General Discussion of Operation
[0062] With reference to FIGS. 1 to 4 , the unit cell 1 of a printhead according to an embodiment of the invention comprises a nozzle plate 2 with nozzles 3 therein, the nozzles having nozzle rims 4 , and apertures 5 extending through the nozzle plate. The nozzle plate 2 is plasma etched from a silicon nitride structure which is deposited, by way of chemical vapor deposition (CVD), over a sacrificial material which is subsequently etched.
[0063] The printhead also includes, with respect to each nozzle 3 , side walls 6 on which the nozzle plate is supported, a chamber 7 defined by the walls and the nozzle plate 2 , a multi-layer substrate 8 and an inlet passage 9 extending through the multi-layer substrate to the far side (not shown) of the substrate. A looped, elongate heater element 10 is suspended within the chamber 7 , so that the element is in the form of a suspended beam. The printhead as shown is a microelectromechanical system (MEMS) structure, which is formed by a lithographic process which is described in more detail below.
[0064] When the printhead is in use, ink 11 from a reservoir (not shown) enters the chamber 7 via the inlet passage 9 , so that the chamber fills to the level as shown in FIG. 1 . Thereafter, the heater element 10 is heated for somewhat less than 1 micro second, so that the heating is in the form of a thermal pulse. It will be appreciated that the heater element 10 is in thermal contact with the ink 11 in the chamber 7 so that when the element is heated, this causes the generation of vapor bubbles 12 in the ink. Accordingly, the ink 11 constitutes a bubble forming liquid. FIG. 1 shows the formation of a bubble 12 approximately 1 microsecond after generation of the thermal pulse, that is, when the bubble has just nucleated on the heater elements 10 . It will be appreciated that, as the heat is applied in the form of a pulse, all the energy necessary to generate the bubble 12 is to be supplied within that short time.
[0065] Turning briefly to FIG. 34 , there is shown a mask 13 for forming a heater 14 of the printhead (which heater includes the element 10 referred to above), during a lithographic process, as described in more detail below. As the mask 13 is used to form the heater 14 , the shape of various of its parts correspond to the shape of the element 10 . The mask 13 therefore provides a useful reference by which to identify various parts of the heater 14 . The heater 14 has electrodes 15 corresponding to the parts designated 15 . 34 of the mask 13 and a heater element 10 corresponding to the parts designated 10 . 34 of the mask. In operation, voltage is applied across the electrodes 15 to cause current to flow through the element 10 . The electrodes 15 are much thicker than the element 10 so that most of the electrical resistance is provided by the element. Thus, nearly all of the power consumed in operating the heater 14 is dissipated via the element 10 , in creating the thermal pulse referred to above.
[0066] When the element 10 is heated as described above, the bubble 12 forms along the length of the element, this bubble appearing, in the cross-sectional view of FIG. 1 , as four bubble portions, one for each of the element portions shown in cross section.
[0067] The bubble 12 , once generated, causes an increase in pressure within the chamber 7 , which in turn causes the ejection of a drop 16 of the ink 11 through the nozzle 3 . The rim 4 assists in directing the drop 16 as it is ejected, so as to minimize the chance of a drop misdirection.
[0068] The reason that there is only one nozzle 3 and chamber 7 per inlet passage 9 is so that the pressure wave generated within the chamber, on heating of the element 10 and forming of a bubble 12 , does not effect adjacent chambers and their corresponding nozzles.
[0069] The advantages of the heater element 10 being suspended rather than being embedded in any solid material, is discussed below.
[0070] FIGS. 2 and 3 show the unit cell 1 at two successive later stages of operation of the printhead. It can be seen that the bubble 12 generates further, and hence grows, with the resultant advancement of ink 11 through the nozzle 3 . The shape of the bubble 12 as it grows, as shown in FIG. 3 , is determined by a combination of the inertial dynamics and the surface tension of the ink 11 . The surface tension tends to minimize the surface area of the bubble 12 so that, by the time a certain amount of liquid has evaporated, the bubble is essentially disk-shaped.
[0071] The increase in pressure within the chamber 7 not only pushes ink 11 out through the nozzle 3 , but also pushes some ink back through the inlet passage 9 . However, the inlet passage 9 is approximately 200 to 300 microns in length, and is only approximately 16 microns in diameter. Hence there is a substantial viscous drag. As a result, the predominant effect of the pressure rise in the chamber 7 is to force ink out through the nozzle 3 as an ejected drop 16 , rather than back through the inlet passage 9 .
[0072] Turning now to FIG. 4 , the printhead is shown at a still further successive stage of operation, in which the ink drop 16 that is being ejected is shown during its “necking phase” before the drop breaks off. At this stage, the bubble 12 has already reached its maximum size and has then begun to collapse towards the point of collapse 17 , as reflected in more detail in FIG. 5 .
[0073] The collapsing of the bubble 12 towards the point of collapse 17 causes some ink 111 to be drawn from within the nozzle 3 (from the sides 18 of the drop), and some to be drawn from the inlet passage 9 , towards the point of collapse. Most of the ink 11 drawn in this manner is drawn from the nozzle 3 , forming an annular neck 19 at the base of the drop 16 prior to its breaking off.
[0074] The drop 16 requires a certain amount of momentum to overcome surface tension forces, in order to break off. As ink 11 is drawn from the nozzle 3 by the collapse of the bubble 12 , the diameter of the neck 19 reduces thereby reducing the amount of total surface tension holding the drop, so that the momentum of the drop as it is ejected out of the nozzle is sufficient to allow the drop to break off.
[0075] When the drop 16 breaks off, cavitation forces are caused as reflected by the arrows 20 , as the bubble 12 collapses to the point of collapse 17 . It will be noted that there are no solid surfaces in the vicinity of the point of collapse 17 on which the cavitation can have an effect.
[0000] Manufacturing Process
[0076] Relevant parts of the manufacturing process of a printhead according to embodiments of the invention are now described with reference to FIGS. 6 to 29 .
[0077] Referring to FIG. 6 , there is shown a cross-section through a silicon substrate portion 21 , being a portion of a Memjet printhead, at an intermediate stage in the production process thereof. This figure relates to that portion of the printhead corresponding to a unit cell 1 . The description of the manufacturing process that follows will be in relation to a unit cell 1 , although it will be appreciated that the process will be applied to a multitude of adjacent unit cells of which the whole printhead is composed.
[0078] FIG. 6 represents the next successive step, during the manufacturing process, after the completion of a standard CMOS fabrication process, including the fabrication of CMOS drive transistors (not shown) in the region 22 in the substrate portion 21 , and the completion of standard CMOS interconnect layers 23 and passivation layer 24 . Wiring indicated by the dashed lines 25 electrically interconnects the transistors and other drive circuitry (also not shown) and the heater element corresponding to the nozzle.
[0079] Guard rings 26 are formed in the metallization of the interconnect layers 23 to prevent ink 11 from diffusing from the region, designated 27 , where the nozzle of the unit cell 1 will be formed, through the substrate portion 21 to the region containing the wiring 25 , and corroding the CMOS circuitry disposed in the region designated 22 .
[0080] The first stage after the completion of the CMOS fabrication process consists of etching a portion of the passivation layer 24 to form the passivation recesses 29 .
[0081] FIG. 8 shows the stage of production after the etching of the interconnect layers 23 , to form an opening 30 . The opening 30 is to constitute the ink inlet passage to the chamber that will be formed later in the process.
[0082] FIG. 10 shows the stage of production after the etching of a hole 31 in the substrate portion 21 at a position where the nozzle 3 is to be formed. Later in the production process, a further hole (indicated by the dashed line 32 ) will be etched from the other side (not shown) of the substrate portion 21 to join up with the hole 31 , to complete the inlet passage to the chamber. Thus, the hole 32 will not have to be etched all the way from the other side of the substrate portion 21 to the level of the interconnect layers 23 .
[0083] If, instead, the hole 32 were to be etched all the way to the interconnect layers 23 , then to avoid the hole 32 being etched so as to destroy the transistors in the region 22 , the hole 32 would have to be etched a greater distance away from that region so as to leave a suitable margin (indicated by the arrow 34 ) for etching inaccuracies. But the etching of the hole 31 from the top of the substrate portion 21 , and the resultant shortened depth of the hole 32 , means that a lesser margin 34 need be left, and that a substantially higher packing density of nozzles can thus be achieved.
[0084] FIG. 11 shows the stage of production after a four micron thick layer 35 of a sacrificial resist has been deposited on the layer 24 . This layer 35 fills the hole 31 and now forms part of the structure of the printhead. The resist layer 35 is then exposed with certain patterns (as represented by the mask shown in FIG. 12 ) to form recesses 36 and a slot 37 . This provides for the formation of contacts for the electrodes 15 of the heater element to be formed later in the production process. The slot 37 will provide, later in the process, for the formation of the nozzle walls 6 , that will define part of the chamber 7 .
[0085] FIG. 13 shows the stage of production after the deposition, on the layer 35 , of a 0.25 micron thick layer 38 of heater material, which, in the present embodiment, is of titanium nitride.
[0086] FIG. 14 shows the stage of production after patterning and etching of the heater layer 38 to form the heater 14 , including the heater element 10 and electrodes 15 .
[0087] FIG. 16 shows the stage of production after another sacrificial resist layer 39 , about 1 micron thick, has been added.
[0088] FIG. 18 shows the stage of production after a second layer 40 of heater material has been deposited. In a preferred embodiment, this layer 40 , like the first heater layer 38 , is of 0.25 micron thick titanium nitride.
[0089] FIG. 19 then shows this second layer 40 of heater material after it has been etched to form the pattern as shown, indicated by reference numeral 41 . In this illustration, this patterned layer does not include a heater layer element 10 , and in this sense has no heater functionality. However, this layer of heater material does assist in reducing the resistance of the electrodes 15 of the heater 14 so that, in operation, less energy is consumed by the electrodes which allows greater energy consumption by, and therefore greater effectiveness of, the heater elements 10 . In the dual heater embodiment illustrated in FIG. 38 , the corresponding layer 40 does contain a heater 14 .
[0090] FIG. 21 shows the stage of production after a third layer 42 , of sacrificial resist, has been deposited. As the uppermost level of this layer will constitute the inner surface of the nozzle plate 2 to be formed later, and hence the inner extent of the nozzle aperture 5 , the height of this layer 42 must be sufficient to allow for the formation of a bubble 12 in the region designated 43 during operation of the printhead.
[0091] FIG. 23 shows the stage of production after the roof layer 44 has been deposited, that is, the layer which will constitute the nozzle plate 2 . Instead of being formed from 100 micron thick polyimide film, the nozzle plate 2 is formed of silicon nitride, just 2 microns thick.
[0092] FIG. 24 shows the stage of production after the chemical vapor deposition (CVD) of silicon nitride forming the layer 44 , has been partly etched at the position designated 45 , so as to form the outside part of the nozzle rim 4 , this outside part being designated 4 . 1
[0093] FIG. 26 shows the stage of production after the CVD of silicon nitride has been etched all the way through at 46 , to complete the formation of the nozzle rim 4 and to form the nozzle aperture 5 , and after the CVD silicon nitride has been removed at the position designated 47 where it is not required.
[0094] FIG. 28 shows the stage of production after a protective layer 48 of resist has been applied. After this stage, the substrate portion 21 is then ground from its other side (not shown) to reduce the substrate portion from its nominal thickness of about 800 microns to about 200 microns, and then, as foreshadowed above, to etch the hole 32 . The hole 32 is etched to a depth such that it meets the hole 31 .
[0095] Then, the sacrificial resist of each of the resist layers 35 , 39 , 42 and 48 , is removed using oxygen plasma, to form the structure shown in FIG. 30 , with walls 6 and nozzle plate 2 which together define the chamber 7 (part of the walls and nozzle plate being shown cut-away). It will be noted that this also serves to remove the resist filling the hole 31 so that this hole, together with the hole 32 (not shown in FIG. 30 ), define a passage extending from the lower side of the substrate portion 21 to the nozzle 3 , this passage serving as the ink inlet passage, generally designated 9 , to the chamber 7 .
[0096] While the above production process is used to produce the embodiment of the printhead shown in FIG. 30 , further printhead embodiments, having different heater structures, are shown in FIG. 33 , FIGS. 35 and 37 , and FIGS. 38 and 40 .
[0000] Control of Ink Drop Ejection
[0097] Referring once again to FIG. 30 , the unit cell 1 shown, as mentioned above, is shown with part of the walls 6 and nozzle plate 2 cut-away, which reveals the interior of the chamber 7 . The heater 14 is not shown cut away, so that both halves of the heater element 10 can be seen.
[0098] In operation, ink 11 passes through the ink inlet passage 9 (see FIG. 28 ) to fill the chamber 7 . Then a voltage is applied across the electrodes 15 to establish a flow of electric current through the heater element 10 . This heats the element 10 , as described above in relation to FIG. 1 , to form a vapor bubble in the ink within the chamber 7 .
[0099] The various possible structures for the heater 14 , some of which are shown in FIGS. 33, 35 and 37 , and 38 , can result in there being many variations in the ratio of length to width of the heater elements 10 . Such variations (even though the surface area of the elements 10 may be the same) may have significant effects on the electrical resistance of the elements, and therefore on the balance between the voltage and current to achieve a certain power of the element.
[0100] Modern drive electronic components tend to require lower drive voltages than earlier versions, with lower resistances of drive transistors in their “on” state. Thus, in such drive transistors, for a given transistor area, there is a tendency to higher current capability and lower voltage tolerance in each process generation.
[0101] FIG. 36 , referred to above, shows the shape, in plan view, of a mask for forming the heater structure of the embodiment of the printhead shown in FIG. 35 . Accordingly, as FIG. 36 represents the shape of the heater element 10 of that embodiment, it is now referred to in discussing that heater element. During operation, current flows vertically into the electrodes 15 (represented by the parts designated 15 . 36 ), so that the current flow area of the electrodes is relatively large, which, in turn, results in there being a low electrical resistance. By contrast, the element 10 , represented in FIG. 36 by the part designated 10 . 36 , is long and thin, with the width of the element in this embodiment being 1 micron and the thickness being 0.25 microns.
[0102] It will be noted that the heater 14 shown in FIG. 33 has a significantly smaller element 10 than the element 10 shown in FIG. 35 , and has just a single loop 36 . Accordingly, the element 10 of FIG. 33 will have a much lower electrical resistance, and will permit a higher current flow, than the element 10 of FIG. 35 . It therefore requires a lower drive voltage to deliver a given energy to the heater 14 in a given time.
[0103] In FIG. 38 , on the other hand, the embodiment shown includes a heater 14 having two heater elements 10 . 1 and 10 . 2 corresponding to the same unit cell 1 . One of these elements 10 . 2 is twice the width as the other element 10 . 1 , with a correspondingly larger surface area. The various paths of the lower element 10 . 2 are 2 microns in width, while those of the upper element 10 . 1 are 1 micron in width. Thus the energy applied to ink in the chamber 7 by the lower element 10 . 2 is twice that applied by the upper element 10 . 1 at a given drive voltage and pulse duration. This permits a regulating of the size of vapor bubbles and hence of the size of ink drop ejected due to the bubbles.
[0104] Assuming that the energy applied to the ink by the upper element 10 . 1 is X, it will be appreciated that the energy applied by the lower element 10 . 2 is about 2X, and the energy applied by the two elements together is about 3X. Of course, the energy applied when neither element is operational, is zero. Thus, in effect, two bits of information can be printed with the one nozzle 3 .
[0105] As the above factors of energy output may not be achieved exactly in practice, some “fine tuning” of the exact sizing of the elements 10 . 1 and 10 . 2 , or of the drive voltages that are applied to them, may be required.
[0106] It will also be noted that the upper element 10 . 1 is rotated through 180° about a vertical axis relative to the lower element 10 . 2 . This is so that their electrodes 15 are not coincident, allowing independent connection to separate drive circuits.
[0000] Features and Advantages of Particular Embodiments
[0107] Discussed below, under appropriate headings, are certain specific features of embodiments of the invention, and the advantages of these features. The features are to be considered in relation to all of the drawings pertaining to the present invention unless the context specifically excludes certain drawings, and relates to those drawings specifically referred to.
[0000] Suspended Beam Heater
[0108] With reference to FIG. 1 , and as mentioned above, the heater element 10 is in the form of a suspended beam, and this is suspended over at least a portion (designated 11 . 1 ) of the ink 11 (bubble forming liquid). The element 10 is configured in this way rather than forming part of, or being embedded in, a substrate as is the case in existing printhead systems made by various manufacturers such as Hewlett Packard, Canon and Lexmark. This constitutes a significant difference between embodiments of the present invention and the prior ink jet technologies.
[0109] The main advantage of this feature is that a higher efficiency can be achieved by avoiding the unnecessary heating of the solid material that surrounds the heater elements 10 (for example the solid material forming the chamber walls 6 , and surrounding the inlet passage 9 ) which takes place in the prior art devices. The heating of such solid material does not contribute to the formation of vapor bubbles 12 , so that the heating of such material involves the wastage of energy. The only energy which contributes in any significant sense to the generation of the bubbles 12 is that which is applied directly into the liquid which is to be heated, which liquid is typically the ink 11 .
[0110] In one preferred embodiment, as illustrated in FIG. 1 , the heater element 10 is suspended within the ink 11 (bubble forming liquid), so that this liquid surrounds the element. This is further illustrated in FIG. 41 . In another possible embodiment, as illustrated in FIG. 42 , the heater element 10 beam is suspended at the surface of the ink (bubble forming liquid) 11 , so that this liquid is only below the element rather than surrounding it, and there is air on the upper side of the element. The embodiment described in relation to FIG. 41 is preferred as the bubble 12 will form all around the element 10 unlike in the embodiment described in relation to FIG. 42 where the bubble will only form below the element. Thus the embodiment of FIG. 41 is likely to provide a more efficient operation.
[0111] As can be seen in, for example, with reference to FIGS. 30 and 31 , the heater element 10 beam is supported only on one side and is free at its opposite side, so that it constitutes a cantilever.
[0000] Efficiency of the Printhead
[0112] The feature presently under consideration is that the heater element 10 is configured such that an energy of less than 500 nanojoules (nJ) is required to be applied to the element to heat it sufficiently to form a bubble 12 in the ink 11 , so as to eject a drop 16 of ink through a nozzle 3 . In one preferred embodiment, the required energy is less that 300 nJ, while in a further embodiment, the energy is less than 120 nJ.
[0113] It will be appreciated by those skilled in the art that prior art devices generally require over 5 microjoules to heat the element sufficiently to generate a vapor bubble 12 to eject an ink drop 16 . Thus, the energy requirements of the present invention are an order of magnitude lower than that of known thermal ink jet systems. This lower energy consumption allows lower operating costs, smaller power supplies, and so on, but also dramatically simplifies printhead cooling, allows higher densities of nozzles 3 , and permits printing at higher resolutions.
[0114] These advantages of the present invention are especially significant in embodiments where the individual ejected ink drops 16 , themselves, constitute the major cooling mechanism of the printhead, as described further below.
[0000] Self-Cooling of the Printhead
[0115] This feature of the invention provides that the energy applied to a heater element 10 to form a vapor bubble 12 so as to eject a drop 16 of ink 11 is removed from the printhead by a combination of the heat removed by the ejected drop itself, and the ink that is taken into the printhead from the ink reservoir (not shown). The result of this is that the net “movement” of heat will be outwards from the printhead, to provide for automatic cooling. Under these circumstances, the printhead does not require any other cooling systems.
[0116] As the ink drop 16 ejected and the amount of ink 11 drawn into the printhead to replace the ejected drop are constituted by the same type of liquid, and will essentially be of the same mass, it is convenient to express the net movement of energy as, on the one hand, the energy added by the heating of the element 10 , and on the other hand, the net removal of heat energy that results from ejecting the ink drop 16 and the intake of the replacement quantity of ink 11 . Assuming that the replacement quantity of ink 11 is at ambient temperature, the change in energy due to net movement of the ejected and replacement quantities of ink can conveniently be expressed as the heat that would be required to raise the temperature of the ejected drop 16 , if it were at ambient temperature, to the actual temperature of the drop as it is ejected.
[0117] It will be appreciated that a determination of whether the above criteria are met depends on what constitutes the ambient temperature. In the present case, the temperature that is taken to be the ambient temperature is the temperature at which ink 11 enters the printhead from the ink storage reservoir (not shown) which is connected, in fluid flow communication, to the inlet passages 9 of the printhead. Typically the ambient temperature will be the room ambient temperature, which is usually roughly 20 degrees C. (Celsius).
[0118] However, the ambient temperature may be less, if for example, the room temperature is lower, or if the ink 11 entering the printhead is refrigerated.
[0119] In one preferred embodiment, the printhead is designed to achieve complete self-cooling (i.e. where the outgoing heat energy due to the net effect of the ejected and replacement quantities of ink 11 is equal to the heat energy added by the heater element 10 ).
[0120] By way of example, assuming that the ink 11 is the bubble forming liquid and is water based, thus having a boiling point of approximately 100 degrees C., and if the ambient temperature is 40 degrees C., then there is a maximum of 60 degrees C. from the ambient temperature to the ink boiling temperature and that is the maximum temperature rise that the printhead could undergo.
[0121] It is desirable to avoid having ink temperatures within the printhead (other than at time of ink drop 16 ejection) which are very close to the boiling point of the ink 11 . If the ink 11 were at such a temperature, then temperature variations between parts of the printhead could result in some regions being above boiling point, with the unintended, and therefore undesirable, formation of vapor bubbles 12 . Accordingly, a preferred embodiment of the invention is configured such that complete self-cooling, as described above, can be achieved when the maximum temperature of the ink 11 (bubble forming liquid) in a particular nozzle chamber 7 is 10 degrees C. below its boiling point when the heating element 10 is not active.
[0122] The main advantage of the feature presently under discussion, and its various embodiments, is that it allows for a high nozzle density and for a high speed of printhead operation without requiring elaborate cooling methods for preventing undesired boiling in nozzles 3 adjacent to nozzles from which ink drops 16 are being ejected. This can allow as much as a hundred-fold increase in nozzle packing density than would be the case if such a feature, and the temperature criteria mentioned, were not present.
[0000] Areal Density of Nozzles
[0123] This feature of the invention relates to the density, by area, of the nozzles 3 on the printhead. With reference to FIG. 1 , the nozzle plate 2 has an upper surface 50 , and the present aspect of the invention relates to the packing density of nozzles 3 on that surface. More specifically, the areal density of the nozzles 3 on that surface 50 is over 10,000 nozzles per square cm of surface area.
[0124] In one preferred embodiment, the areal density exceeds 20,000 nozzles 3 per square cm of surface 50 area, while in another preferred embodiment, the areal density exceeds 40,000 nozzles 3 per square cm. In a preferred embodiment, the areal density is 48 828 nozzles 3 per square cm.
[0125] When referring to the areal density, each nozzle 3 is taken to include the drive-circuitry corresponding to the nozzle, which consists, typically, of a drive transistor, a shift register, an enable gate and clock regeneration circuitry (this circuitry not being specifically identified).
[0126] With reference to FIG. 43 in which a single unit cell 1 is shown, the dimensions of the unit cell are shown as being 32 microns in width by 64 microns in length. The nozzle 3 of the next successive row of nozzles (not shown) immediately juxtaposes this nozzle, so that, as a result of the dimension of the outer periphery of the printhead chip, there are 48,828 nozzles 3 per square cm. This is about 85 times the nozzle areal density of a typical thermal ink jet printhead, and roughly 400 times the nozzle areal density of a piezoelectric printhead.
[0127] The main advantage of a high areal density is low manufacturing cost, as the devices are batch fabricated on silicon wafers of a particular size.
[0128] The more nozzles 3 that can be accommodated in a square cm of substrate, the more nozzles can be fabricated in a single batch, which typically consists of one wafer. The cost of manufacturing a CMOS plus MEMS wafer of the type used in the printhead of the present invention is, to a some extent, independent of the nature of patterns that are formed on it. Therefore if the patterns are relatively small, a relatively large number of nozzles 3 can be included. This allows more nozzles 3 and more printheads to be manufactured for the same cost than in a cases where the nozzles had a lower areal density. The cost is directly proportional to the area taken by the nozzles 3 .
[0000] Bubble Formation on Opposite Sides of Heater Element
[0129] According to the present feature, the heater 14 is configured so that when a bubble 12 forms in the ink 11 (bubble forming liquid), it forms on both sides of the heater element 10 . Preferably, it forms so as to surround the heater element 10 where the element is in the form of a suspended beam.
[0130] The formation of a bubble 12 on both sides of the heater element 10 as opposed to on one side only, can be understood with reference to FIGS. 45 and 46 . In the first of these figures, the heater element 10 is adapted for the bubble 12 to be formed only on one side as, while in the second of these figures, the element is adapted for the bubble 12 to be formed on both sides, as shown.
[0131] In a configuration such as that of FIG. 45 , the reason that the bubble 12 forms on only one side of the heater element 10 is because the element is embedded in a substrate 51 , so that the bubble cannot be formed on the particular side corresponding to the substrate. By contrast, the bubble 12 can form on both sides in the configuration of FIG. 46 as the heater element 10 here is suspended.
[0132] Of course where the heater element 10 is in the form of a suspended beam as described above in relation to FIG. 1 , the bubble 12 is allowed to form so as to surround the suspended beam element.
[0133] The advantage of the bubble 12 forming on both sides is the higher efficiency that is achievable. This is due to a reduction in heat that is wasted in heating solid materials in the vicinity of the heater element 10 , which do not contribute to formation of a bubble 12 . This is illustrated in FIG. 45 , where the arrows 52 indicate the movements of heat into the solid substrate 51 . The amount of heat lost to the substrate 51 depends on the thermal conductivity of the solid materials of the substrate relative to that of the ink 11 , which may be water based. As the thermal conductivity of water is relatively low, more than half of the heat can be expected to be absorbed by the substrate 51 rather than by the ink 11 .
[0000] Prevention of Cavitation
[0134] As described above, after a bubble 12 has been formed in a printhead according to an embodiment of the present invention, the bubble collapses towards a point of collapse 17 . According to the feature presently being addressed, the heater elements 10 are configured to form the bubbles 12 so that the points of collapse 17 towards which the bubbles collapse, are at positions spaced from the heater elements. Preferably, the printhead is configured so that there is no solid material at such points of collapse 17 . In this way cavitation, being a major problem in prior art thermal ink jet devices, is largely eliminated.
[0135] Referring to FIG. 48 , in a preferred embodiment, the heater elements 10 are configured to have parts 53 which define gaps (represented by the arrow 54 ), and to form the bubbles 12 so that the points of collapse 17 to which the bubbles collapse are located at such gaps. The advantage of this feature is that it substantially avoids cavitation damage to the heater elements 10 and other solid material.
[0136] In a standard prior art system as shown schematically in FIG. 47 , the heater element 10 is embedded in a substrate 55 , with an insulating layer 56 over the element, and a protective layer 57 over the insulating layer. When a bubble 12 is formed by the element 10 , it is formed on top of the element. When the bubble 12 collapses, as shown by the arrows 58 , all of the energy of the bubble collapse is focussed onto a very small point of collapse 17 . If the protective layer 57 were absent, then the mechanical forces due to the cavitation that would result from the focussing of this energy to the point of collapse 17 , could chip away or erode the heater element 10 . However, this is prevented by the protective layer 57 .
[0137] Typically, such a protective layer 57 is of tantalum, which oxidizes to form a very hard layer of tantalum pentoxide (Ta 2 O 5 ). Although no known materials can fully resist the effects of cavitation, if the tantalum pentoxide should be chipped away due to the cavitation, then oxidation will again occur at the underlying tantalum metal, so as to effectively repair the tantalum pentoxide layer.
[0138] Although the tantalum pentoxide functions relatively well in this regard in known thermal ink jet systems, it has certain disadvantages. One significant disadvantage is that, in effect, virtually the whole protective layer 57 (having a thickness indicated by the reference numeral 59 ) must be heated in order to transfer the required energy into the ink 11 , to heat it so as to form a bubble 12 . This layer 57 has a high thermal mass due to the very high atomic weight of the tantalum, and this reduces the efficiency of the heat transfer. Not only does this increase the amount of heat which is required at the level designated 59 to raise the temperature at the level designated 60 sufficiently to heat the ink 11 , but it also results in a substantial thermal loss to take place in the directions indicated by the arrows 61 . These disadvantage would not be present if the heater element 10 was merely supported on a surface and was not covered by the protective layer 57 .
[0139] According to the feature presently under discussion, the need for a protective layer 57 , as described above, is avoided by generating the bubble 12 so that it collapses, as illustrated in FIG. 48 , towards a point of collapse 17 at which there is no solid material, and more particularly where there is the gap 54 between parts 53 of the heater element 10 . As there is merely the ink 11 itself in this location (prior to bubble generation), there is no material that can be eroded here by the effects of cavitation. The temperature at the point of collapse 17 may reach many thousands of degrees C., as is demonstrated by the phenomenon of sonoluminesence. This will break down the ink components at that point. However, the volume of extreme temperature at the point of collapse 17 is so small that the destruction of ink components in this volume is not significant.
[0140] The generation of the bubble 12 so that it collapses towards a point of collapse 17 where there is no solid material can be achieved using heater elements 10 corresponding to that represented by the part 10 . 34 of the mask shown in FIG. 34 . The element represented is symmetrical, and has a hole represented by the reference numeral 63 at its center. When the element is heated, the bubble forms around the element (as indicated by the dashed line 64 ) and then grows so that, instead of being of annular (doughnut) shape as illustrated by the dashed lines 64 and 65 ) it spans the element including the hole 63 , the hole then being filled with the vapor that forms the bubble. The bubble 12 is thus substantially disc-shaped. When it collapses, the collapse is directed so as to minimize the surface tension surrounding the bubble 12 . This involves the bubble shape moving towards a spherical shape as far as is permitted by the dynamics that are involved. This, in turn, results in the point of collapse being in the region of the hole 63 at the center of the heater element 10 , where there is no solid material.
[0141] The heater element 10 represented by the part 10 . 31 of the mask shown in FIG. 31 is configured to achieve a similar result, with the bubble generating as indicated by the dashed line 66 , and the point of collapse to which the bubble collapses being in the hole 67 at the center of the element.
[0142] The heater element 10 represented as the part 10 . 36 of the mask shown in FIG. 36 is also configured to achieve a similar result. Where the element 10 . 36 is dimensioned such that the hole 68 is small, manufacturing inaccuracies of the heater element may affect the extent to which a bubble can be formed such that its point of collapse is in the region defined by the hole. For example, the hole may be as little as a few microns across. Where high levels of accuracy in the element 10 . 36 cannot be achieved, this may result in bubbles represented as 12 . 36 that are somewhat lopsided, so that they cannot be directed towards a point of collapse within such a small region. In such a case, with regard to the heater element represented in FIG. 36 , the central loop 49 of the element can simply be omitted, thereby increasing the size of the region in which the point of collapse of the bubble is to fall.
[0000] Chemical Vapor Deposited Nozzle Plate, and Thin Nozzle Plates
[0143] The nozzle aperture 5 of each unit cell 1 extends through the nozzle plate 2 , the nozzle plate thus constituting a structure which is formed by chemical vapor deposition (CVD). In various preferred embodiments, the CVD is of silicon nitride, silicon dioxide or oxi-nitride.
[0144] The advantage of the nozzle plate 2 being formed by CVD is that it is formed in place without the requirement for assembling the nozzle plate to other components such as the walls 6 of the unit cell 1 . This is an important advantage because the assembly of the nozzle plate 2 that would otherwise be required can be difficult to effect and can involve potentially complex issues. Such issues include the potential mismatch of thermal expansion between the nozzle plate 2 and the parts to which it would be assembled, the difficulty of successfully keeping components aligned to each other, keeping them planar, and so on, during the curing process of the adhesive which bonds the nozzle plate 2 to the other parts.
[0145] The issue of thermal expansion is a significant factor in the prior art, which limits the size of ink jets that can be manufactured. This is because the difference in the coefficient of thermal expansion between, for example, a nickel nozzle plate and a substrate to which the nozzle plate is connected, where this substrate is of silicon, is quite substantial. Consequently, over as small a distance as that occupied by, say, 1000 nozzles, the relative thermal expansion that occurs between the respective parts, in being heated from the ambient temperature to the curing temperature required for bonding the parts together, can cause a dimension mismatch of significantly greater than a whole nozzle length. This would be significantly detrimental for such devices.
[0146] Another problem addressed by the features of the invention presently under discussion, at least in embodiments thereof, is that, in prior art devices, nozzle plates that need to be assembled are generally laminated onto the remainder of the printhead under conditions of relatively high stress. This can result in breakages or undesirable deformations of the devices. Also, by forming the nozzle plate in-situ on the wafer substrate, there is no need to assemble the plate and the etched wafer. Such assembly involves a precision alignment of the nozzle plate using custom equipment. The depositing of the nozzle plate 2 by CVD in embodiments of the present invention avoids this.
[0147] A further advantage of the present features of the invention, at least in embodiments thereof, is their compatibility with existing semiconductor manufacturing processes. Depositing a nozzle plate 2 by CVD allows the nozzle plate to be included in the printhead at the scale of normal silicon wafer production, using processes normally used for semi-conductor manufacture. Standard lithographic equipment used in the modern semiconductor industry provides a high throughput as well as a high degree of accuracy.
[0148] Existing thermal ink jet or bubble jet systems experience pressure transients, during the bubble generation phase, of up to 100 atmospheres. If the nozzle plates 2 in such devices were applied by CVD, then to withstand such pressure transients, a substantial thickness of CVD nozzle plate would be required. As would be understood by those skilled in the art, such thicknesses of deposited nozzle plates would give rise certain problems as discussed below.
[0149] For example, the thickness of nitride sufficient to withstand a 100 atmosphere pressure in the nozzle chamber 7 may be, say, 10 microns. With reference to FIG. 49 , which shows a unit cell 1 that is not in accordance with the present invention, and which has such a thick nozzle plate 2 , it will be appreciated that such a thickness can result in problems relating to drop ejection. In this case, due to the thickness of nozzle plate 2 , the fluidic drag exerted by the nozzle 3 as the ink 11 is ejected therethrough results in significant losses in the efficiency of the device.
[0150] Another problem that would exist in the case of such a thick nozzle plate 2 , relates to the actual etching process. This is assuming that the nozzle 3 is etched, as shown, perpendicular to the wafer 8 of the substrate portion, for example using a standard plasma etching. This would typically require more than 10 microns of resist 69 to be applied. To expose that thickness of resist 69 , the required level of resolution becomes difficult to achieve, as the focal depth of the stepper that is used to expose the resist is relatively small. Although it would be possible to expose this relevant depth of resist 69 using x-rays, this would be a relatively costly process.
[0151] A further problem that would exist with such a thick nozzle plate 2 in a case where a 10 micron thick layer of nitride were CVD deposited on a silicon substrate wafer, is that, because of the difference in thermal expansion between the CVD layer and the substrate, as well as the inherent stress of within thick deposited layer, the wafer could be caused to bow to such a degree that further steps in the lithographic process would become impractical. Thus, a layer for the nozzle plate 2 as thick as 10 microns (unlike in the present invention), while possible, is disadvantageous.
[0152] With reference to FIG. 50 , in a Memjet thermal ink ejection device according to an embodiment of the present invention, the CVD nitride nozzle plate layer 2 is only 2 microns thick. Therefore the fluidic drag through the nozzle 3 is not particularly significant and is therefore not a major cause of loss.
[0153] Furthermore, the etch time, and the resist thickness required to etch nozzles 3 in such a nozzle plate 2 , and the stress on the substrate wafer 8 , will not be excessive.
[0154] The relatively thin nozzle plate 2 in this invention is enabled as the pressure generated in the chamber 7 is only approximately 1 atmosphere and not 100 atmospheres as in prior art devices, as mentioned above.
[0155] There are many factors which contribute to the significant reduction in pressure transient required to eject drops 16 in this system. These include:
[0000] 1. small size of chamber 7 ;
[0000] 2. accurate fabrication of nozzle 3 and chamber 7 ;
[0000] 3. stability of drop ejection at low drop velocities;
[0000] 4. very low fluidic and thermal crosstalk between nozzles 3 ;
[0000] 5. optimum nozzle size to bubble area;
[0000] 6. low fluidic drag through thin (2 micron) nozzle 3 ;
[0000] 7. low pressure loss due to ink ejection through the inlet 9 ;
[0000] 8. self-cooling operation.
[0156] As mentioned above in relation the process described in terms of FIGS. 6 to 31 , the etching of the 2-micron thick nozzle plate layer 2 involves two relevant stages. One such stage involves the etching of the region designated 45 in FIGS. 24 and 50 , to form a recess outside of what will become the nozzle rim 4 . The other such stage involves a further etch, in the region designated 46 in FIGS. 26 and 50 , which actually forms the nozzle aperture 5 and finishes the rim 4 .
[0000] Nozzle Plate Thicknesses
[0157] As addressed above in relation to the formation of the nozzle plate 2 by CVD, and with the advantages described in that regard, the nozzle plates in the present invention are thinner than in the prior art. More particularly, the nozzle plates 2 are less than 10 microns thick. In one preferred embodiment, the nozzle plate 2 of each unit cell 1 is less than 5 microns thick, while in another preferred embodiment, it is less than 2.5 microns thick. Indeed, a preferred thickness for the nozzle plate 2 is 2 microns thick.
[0000] Heater Elements Formed in Different Layers
[0158] According to the present feature, there are a plurality of heater elements 10 disposed within the chamber 7 of each unit cell 1 . The elements 10 , which are formed by the lithographic process as described above in relation to FIG. 6 to 31 , are formed in respective layers.
[0159] In preferred embodiments, as shown in FIGS. 38, 40 and 51 , the heater elements 10 . 1 and 10 . 2 in the chamber 7 , are of different sizes relative to each other.
[0160] Also as will be appreciated with reference to the above description of the lithographic process, each heater element 10 . 1 , 10 . 2 is formed by at least one step of that process, the lithographic steps relating to each one of the elements 10 . 1 being distinct from those relating to the other element 10 . 2 .
[0161] The elements 10 . 1 , 10 . 2 are preferably sized relative to each other, as reflected schematically in the diagram of FIG. 51 , such that they can achieve binary weighted ink drop volumes, that is, so that they can cause ink drops 16 having different, binary weighted volumes to be ejected through the nozzle 3 of the particular unit cell 1 . The achievement of the binary weighting of the volumes of the ink drops 16 is determined by the relative sizes of the elements 10 . 1 and 10 . 2 . In FIG. 51 , the area of the bottom heater element 10 . 2 in contact with the ink 11 is twice that of top heater element 10 . 1 .
[0162] One known prior art device, patented by Canon, and illustrated schematically in FIG. 52 , also has two heater elements 10 . 1 and 10 . 2 for each nozzle, and these are also sized on a binary basis (i.e. to produce drops 16 with binary weighted volumes). These elements 10 . 1 , 10 . 2 are formed in a single layer, adjacent to each other in the nozzle chamber 7 . It will be appreciated that the bubble 12 . 1 formed by the small element 10 . 1 , only, is relatively small, while that 12.2 formed by the large element 10 . 2 , only, is relatively large. The bubble generated by the combined effects of the two elements, when they are actuated simultaneously, is designated 12 . 3 . Three differently sized ink drops 16 will be caused to be ejected by the three respective bubbles 12 . 1 , 12 . 2 and 12 . 3 .
[0163] It will be appreciated that the size of the elements 10 . 1 and 10 . 2 themselves are not required to be binary weighted to cause the ejection of drops 16 having different sizes or the ejection of useful combinations of drops. Indeed, the binary weighting may well not be represented precisely by the area of the elements 10 . 1 , 10 . 2 themselves. In sizing the elements 10 . 1 , 10 . 2 to achieve binary weighted drop volumes, the fluidic characteristics surrounding the generation of bubbles 12 , the drop dynamics characteristics, the quantity of liquid that is drawing back into the chamber 7 from the nozzle 3 once a drop 16 has broken off, and so forth, must be considered. Accordingly, the actual ratio of the surface areas of the elements 10 . 1 , 10 . 2 , or the performance of the two heaters, needs to be adjusted in practice to achieve the desired binary weighted drop volumes.
[0164] Where the size of the heater elements 10 . 1 , 10 . 2 is fixed and where the ratio of their surface areas is therefore fixed, the relative sizes of ejected drops 16 may be adjusted by adjusting the supply voltages to the two elements. This can also be achieved by adjusting the duration of the operation pulses of the elements 10 . 1 , 10 . 2 —i.e. their pulse widths. However, the pulse widths cannot exceed a certain amount of time, because once a bubble 12 has nucleated on the surface of an element 10 . 1 , 10 . 2 , then any duration of pulse width after that time will be of little or no effect.
[0165] On the other hand, the low thermal mass of the heater elements 10 . 1 , 10 . 2 allows them to be heated to reach, very quickly, the temperature at which bubbles 12 are formed and at which drops 16 are ejected. While the maximum effective pulse width is limited, by the onset of bubble nucleation, typically to around 0.5 microseconds, the minimum pulse width is limited only by the available current drive and the current density that can be tolerated by the heater elements 10 . 1 , 10 . 2 .
[0166] As shown in FIG. 51 , the two heaters elements 10 . 1 , 10 . 2 are connected to two respective drive circuits 70 . Although these circuits 70 may be identical to each other, a further adjustment can be effected by way of these circuits, for example by sizing the drive transistor (not shown) connected to the lower element 10 . 2 , which is the high current element, larger than that connected to the upper element 10 . 1 . If, for example, the relative currents provided to the respective elements 10 . 1 , 10 . 2 are in the ratio 2:1, the drive transistor of the circuit 70 connected to the lower element 10 . 2 would typically be twice the width of the drive transistor (also no shown) of the circuit 70 connected to the other element 10 . 1 .
[0167] In the prior art described in relation to FIG. 52 , the heater elements 10 . 1 , 10 . 2 , which are in the same layer, are produced simultaneously in the same step of the lithographic manufacturing process. In the embodiment of the present invention illustrated in FIG. 51 , the two heaters elements 10 . 1 , 10 . 2 , as mentioned above, are formed one after the other. Indeed, as described in the process illustrated with reference to FIGS. 6 to 31 , the material to form the element 10 . 2 is deposited and is then etched in the lithographic process, whereafter a sacrificial layer 39 is deposited on top of that element, and then the material for the other element 10 . 1 is deposited so that the sacrificial layer is between the two heater element layers. The layer of the second element 10 . 1 is etched by a second lithographic step, and the sacrificial layer 39 is removed.
[0168] Referring once again to the different sizes of the heater elements 10 . 1 and 10 . 2 , as mentioned above, this has the advantage that it enables the elements to be sized so as to achieve multiple, binary weighted drop volumes from one nozzle 3 .
[0169] It will be appreciated that, where multiple drop volumes can be achieved, and especially if they are binary weighted, then photographic quality can be obtained while using fewer printed dots, and at a lower print resolution.
[0170] Furthermore, under the same circumstances, higher speed printing can be achieved. That is, instead of just ejecting one drop 14 and then waiting for the nozzle 3 to refill, the equivalent of one, two, or three drops might be ejected. Assuming that the available refill speed of the nozzle 3 is not a limiting factor, ink ejection, and hence printing, up to three times faster, may be achieved. In practice, however, the nozzle refill time will typically be a limiting factor. In this case, the nozzle 3 will take slightly longer to refill when a triple volume of drop 16 (relative to the minimum size drop) has been ejected than when only a minimum volume drop has been ejected. However, in practice it will not take as much as three times as long to refill. This is due to the inertial dynamics and the surface tension of the ink 11 .
[0171] Referring to FIG. 53 , there is shown, schematically, a pair of adjacent unit cells 1 . 1 and 1 . 2 , the cell on the left 1 . 1 representing the nozzle 3 after a larger volume of drop 16 has been ejected, and that on the right 1 . 2 , after a drop of smaller volume has been ejected. In the case of the larger drop 16 , the curvature of the air bubble 71 that has formed inside the partially emptied nozzle 3 . 1 is larger than in the case of air bubble 72 that has formed after the smaller volume drop has been ejected from the nozzle 3 . 2 of the other unit cell 1 . 2 .
[0172] The higher curvature of the air bubble 71 in the unit cell 1 . 1 results in a greater surface tension force which tends to draw the ink 11 , from the refill passage 9 towards the nozzle 3 and into the chamber 7 . 1 , as indicated by the arrow 73 . This gives rise to a shorter refilling time. As the chamber 7 . 1 refills, it reaches a stage, designated 74 , where the condition is similar to that in the adjacent unit cell 1 . 2 . In this condition, the chamber 7 . 1 of the unit cell 1 . 1 is partially refilled and the surface tension force has therefore reduced. This results in the refill speed slowing down even though, at this stage, when this condition is reached in that unit cell 1 . 1 , a flow of liquid into the chamber 7 . 1 , with its associated momentum, has been established. The overall effect of this is that, although it takes longer to completely fill the chamber 7 . 1 and nozzle 3 . 1 from a time when the air bubble 71 is present than from when the condition 74 is present, even if the volume to be refilled is three times larger, it does not take as much as three times longer to refill the chamber 7 . 1 and nozzle 3 . 1 .
[0000] Heater Elements Formed from Materials Constituted by Elements with Low Atomic-Numbers
[0173] This feature involves the heater elements 10 being formed of solid material, at least 90% of which, by weight, is constituted by one or more periodic elements having an atomic number below 50. In a preferred embodiment the atomic weight is below 30, while in another embodiment the atomic weight is below 23.
[0174] The advantage of a low atomic number is that the atoms of that material have a lower mass, and therefore less energy is required to raise the temperature of the heater elements 10 . This is because, as will be understood by those skilled in the art, the temperature of an article is essentially related to the state of movement of the nuclei of the atoms. Accordingly, it will require more energy to raise the temperature, and thereby induce such a nucleus movement, in a material with atoms having heavier nuclei that in a material having atoms with lighter nuclei.
[0175] Materials currently used for the heater elements of thermal ink jet systems include tantalum aluminum alloy (for example used by Hewlett Packard), and hafnium boride (for example used by Canon). Tantalum and hafnium have atomic numbers 73 and 72, respectively, while the material used in the Memjet heater elements 10 of the present invention is titanium nitride. Titanium has an atomic number of 22 and nitrogen has an atomic number of 7 , these materials therefore being significantly lighter than those of the relevant prior art device materials.
[0176] Boron and aluminum, which form part of hafnium boride and tantalum aluminum, respectively, like nitrogen, are relatively light materials. However, the density of tantalum nitride is 16.3 g/cm 3 , while that of titanium nitride (which includes titanium in place of tantalum) is 5.22 g/cm 3 . Thus, because tantalum nitride has a density of approximately three times that of the titanium nitride, titanium nitride will require approximately three time less energy to heat than tantalum nitride. As will be understood by a person skilled in the art, the difference in energy in a material at two different temperatures is represented by the following equation:
E=ΔT×C p ×VOL×ρ,
where ΔT represents the temperature difference, C p is the specific heat capacity, VOL is the volume, and ρ is the density of the material. Although the density is not determined only by the atomic numbers as it is also a function of the lattice constants, the density is strongly influenced by the atomic numbers of the materials involved, and hence is a key aspect of the feature under discussion.
Low Heater Mass
[0177] This feature involves the heater elements 10 being configured such that the mass of solid material of each heater element that is heated above the boiling point of the bubble forming liquid (i.e. the ink 11 in this embodiment) to heat the ink so as to generate bubbles 12 therein to cause an ink drop 16 to be ejected, is less than 10 nanograms.
[0178] In one preferred embodiment, the mass is less that 2 nanograms, in another embodiment the mass is less than 500 picograms, and in yet another embodiment the mass is less than 250 picograms.
[0179] The above feature constitutes a significant advantage over prior art inkjet systems, as it results in an increased efficiency as a result of the reduction in energy lost in heating the solid materials of the heater elements 10 . This feature is enabled due to the use of heater element materials having low densities, due to the relatively small size of the elements 10 , and due to the heater elements being in the form of suspended beams which are not embedded in other materials, as illustrated, for example, in FIG. 1 .
[0180] FIG. 34 shows the shape, in plan view, of a mask for forming the heater structure of the embodiment of the printhead shown in FIG. 33 . Accordingly, as FIG. 34 represents the shape of the heater element 10 of that embodiment, it is now referred to in discussing that heater element. The heater element as represented by reference numeral 10 . 34 in FIG. 34 has just a single loop 49 which is 2 microns wide and 0.25 microns thick. It has a 6 micron outer radius and a 4 micron inner radius. The total heater mass is 82 picograms. The corresponding element 10 . 2 similarly represented by reference numeral 10 . 39 in FIG. 39 has a mass of 229.6 picograms and that 10 represented by reference numeral 10 . 36 in FIG. 36 has a mass of 225.5 picograms.
[0181] When the elements 10 , 102 represented in FIGS. 34, 39 and 36 , for example, are used in practice, the total mass of material of each such element which is in thermal contact with the ink 11 (being the bubble forming liquid in this embodiment) that is raised to a temperature above that of the boiling point of the ink, will be slightly higher than these masses as the elements will be coated with an electrically insulating, chemically inert, thermally conductive material. This coating increases, to some extent, the total mass of material raised to the higher temperature.
[0000] Conformally Coated Heater Element
[0182] This feature involves each element 10 being covered by a conformal protective coating, this coating having been applied to all sides of the element simultaneously so that the coating is seamless. The coating 10 , preferably, is electrically non-conductive, is chemically inert and has a high thermal conductivity. In one preferred embodiment, the coating is of aluminum nitride, in another embodiment it is of diamond-like carbon (DLC), and in yet another embodiment it is of boron nitride.
[0183] Referring to FIGS. 54 and 55 , there are shown schematic representations of a prior art heater element 10 that is not conformally coated as discussed above, but which has been deposited on a substrate 78 and which, in the typical manner, has then been conformally coated on one side with a CVD material, designated 76 . In contrast, the coating referred to above in the present instance, as reflected schematically in FIG. 56 , this coating being designated 77 , involves conformally coating the element on all sides simultaneously. However, this conformal coating 77 on all sides can only be achieved if the element 10 , when being so coated, is a structure isolated from other structures—i.e. in the form of a suspended beam, so that there is access to all of the sides of the element.
[0184] It is to be understood that when reference is made to conformally coating the element 10 on all sides, this excludes the ends of the element (suspended beam) which are joined to the electrodes 15 as indicated diagrammatically in FIG. 57 . In other words, what is meant by conformally coating the element 10 on all sides is, essentially, that the element is fully surrounded by the conformal coating along the length of the element.
[0185] The primary advantage of conformally coating the heater element 10 may be understood with reference, once again, to FIGS. 54 and 55 . As can be seen, when the conformal coating 76 is applied, the substrate 78 on which the heater element 10 was deposited (i.e. formed) effectively constitutes the coating for the element on the side opposite the conformally applied coating. The depositing of the conformal coating 76 on the heater element 10 which is, in turn, supported on the substrate 78 , results in a seam 79 being formed. This seam 79 may constitute a weak point, where oxides and other undesirable products might form, or where delamination may occur.
[0186] Indeed, in the case of the heater element 10 of FIGS. 54 and 55 , where etching is conducted to separate the heater element and its coating 76 from the substrate 78 below, so as to render the element in the form of a suspended beam, ingress of liquid or hydroxyl ions may result, even though such materials could not penetrate the actual material of the coating 76 , or of the substrate 78 .
[0187] The materials mentioned above (i.e. aluminum nitride or diamond-like carbon (DLC)) are suitable for use in the conformal coating 77 of the present invention as illustrated in FIG. 56 due to their desirably high thermal conductivities, their high level of chemical inertness, and the fact that they are electrically non-conductive. Another suitable material, for these purposes, is boron nitride, also referred to above. Although the choice of material used for the coating 77 is important in relation to achieving the desired performance characteristics, materials other than those mentioned, where they have suitable characteristics, may be used instead.
[0000] Example Printer in which the Printhead is Used
[0188] The components described above form part of a printhead assembly which, in turn, is used in a printer system. The printhead assembly, itself, includes a number of printhead modules 80 . These aspects are described below.
[0189] Referring briefly to FIG. 44 , the array of nozzles 3 shown is disposed on the printhead chip (not shown), with drive transistors, drive shift registers, and so on (not shown), included on the same chip, which reduces the number of connections required on the chip.
[0190] With reference to FIGS. 58 and 59 , there is shown, in an exploded view and a non-exploded view, respectively, a printhead module assembly 80 which includes a MEMS printhead chip assembly 81 (also referred to below as a chip). On a typical chip assembly 81 such as that shown, there are 7680 nozzles, which are spaced so as to be capable of printing with a resolution of 1600 dots per inch. The chip 81 is also configured to eject 6 different colors or types of ink 11 .
[0191] A flexible printed circuit board (PCB) 82 is electrically connected to the chip 81 , for supplying both power and data to the chip. The chip 81 is bonded onto a stainless-steel upper layer sheet 83 , so as to overlie an array of holes 84 etched in this sheet. The chip 81 itself is a multi-layer stack of silicon which has ink channels (not shown) in the bottom layer of silicon 85 , these channels being aligned with the holes 84 .
[0192] The chip 81 is approximately 1 mm in width and 21 mm in length. This length is determined by the width of the field of the stepper that is used to fabricate the chip 81 . The sheet 83 has channels 86 (only some of which are shown as hidden detail) which are etched on the underside of the sheet as shown in FIG. 58 . The channels 86 extend as shown so that their ends align with holes 87 in a mid-layer 88 . Different ones of the channels 86 align with different ones of the holes 87 . The holes 87 , in turn, align with channels 89 in a lower layer 90 . Each channel 89 carries a different respective color of ink, except for the last channel, designated 91 . This last channel 91 is an air channel and is aligned with further holes 92 in the mid-layer 88 , which in turn are aligned with further holes 93 in the upper layer sheet 83 . These holes 93 are aligned with the inner parts 94 of slots 95 in a top channel layer 96 , so that these inner parts are aligned with, and therefore in fluid-flow communication with, the air channel 91 , as indicated by the dashed line 97 .
[0193] The lower layer 90 has holes 98 opening into the channels 89 and channel 91 . Compressed filtered air from an air source (not shown) enters the channel 91 through the relevant hole 98 , and then passes through the holes 92 and 93 and slots 95 , in the mid layer 88 , the sheet 83 and the top channel layer 96 , respectively, and is then blown into the side 99 of the chip assembly 81 , from where it is forced out, at 100 , through a nozzle guard 101 which covers the nozzles, to keep the nozzles clear of paper dust. Differently colored inks 11 (not shown) pass through the holes 98 of the lower layer 90 , into the channels 89 , and then through respective holes 87 , then along respective channels 86 in the underside of the upper layer sheet 83 , through respective holes 84 of that sheet, and then through the slots 95 , to the chip 81 . It will be noted that there are just seven of the holes 98 in the lower layer 90 (one for each color of ink and one for the compressed air) via which the ink and air is passed to the chip 81 , the ink being directed to the 7680 nozzles on the chip.
[0194] FIG. 60 , in which a side view of the printhead module assembly 80 of FIGS. 58 and 59 is schematically shown, is now referred to. The center layer 102 of the chip assembly is the layer where the 7680 nozzles and their associated drive circuitry is disposed. The top layer of the chip assembly, which constitutes the nozzle guard 101 , enables the filtered compressed air to be directed so as to keep the nozzle guard holes 104 (which are represented schematically by dashed lines) clear of paper dust.
[0195] The lower layer 105 is of silicon and has ink channels etched in it. These ink channels are aligned with the holes 84 in the stainless steel upper layer sheet 83 . The sheet 83 receives ink and compressed air from the lower layer 90 as described above, and then directs the ink and air to the chip 81 . The need to funnel the ink and air from where it is received by the lower layer 90 , via the mid-layer 88 and upper layer 83 to the chip assembly 81 , is because it would otherwise be impractical to align the large number (7680) of very small nozzles 3 with the larger, less accurate holes 98 in the lower layer 90 .
[0196] The flex PCB 82 is connected to the shift registers and other circuitry (not shown) located on the layer 102 of chip assembly 81 . The chip assembly 81 is bonded by wires 106 onto the PCB flex and these wires are then encapsulated in an epoxy 107 . To effect this encapsulating, a dam 108 is provided. This allows the epoxy 107 to be applied to fill the space between the dam 108 and the chip assembly 81 so that the wires 106 are embedded in the epoxy. Once the epoxy 107 has hardened, it protects the wire bonding structure from contamination by paper and dust, and from mechanical contact.
[0197] Referring to FIG. 62 , there is shown schematically, in an exploded view, a printhead assembly 19 , which includes, among other components, printhead module assemblies 80 as described above. The printhead assembly 19 is configured for a page-width printer, suitable for A4 or US letter type paper.
[0198] The printhead assembly 19 includes eleven of the printhead modules assemblies 80 , which are glued onto a substrate channel 110 in the form of a bent metal plate. A series of groups of seven holes each, designated by the reference numerals 111 , are provided to supply the 6 different colors of ink and the compressed air to the chip assemblies 81 . An extruded flexible ink hose 112 is glued into place in the channel 110 . It will be noted that the hose 112 includes holes 113 therein. These holes 113 are not present when the hose 112 is first connected to the channel 110 , but are formed thereafter by way of melting, by forcing a hot wire structure (not shown) through the holes 111 , which holes then serve as guides to fix the positions at which the holes 113 are melted. The holes 113 , when the printhead assembly 19 is assembled, are in fluid-flow communication, via holes 114 (which make up the groups 111 in the channel 110 ), with the holes 98 in the lower layer 90 of each printhead module assembly 80 .
[0199] The hose 112 defines parallel channels 1 . 15 which extend the length of the hose. At one end 116 , the hose 112 is connected to ink containers (not shown), and at the opposite end 117 , there is provided a channel extrusion cap 118 , which serves to plug, and thereby close, that end of the hose.
[0200] A metal top support plate 119 supports and locates the channel 110 and hose 112 , and serves as a back plate for these. The channel 110 and hose 112 , in turn, exert pressure onto an assembly 120 which includes flex printed circuits. The plate 119 has tabs 121 which extend through notches 122 in the downwardly extending wall 123 of the channel 110 , to locate the channel and plate with respect to each other.
[0201] An extrusion 124 is provided to locate copper bus bars 125 . Although the energy required to operate a printhead according to the present invention is an order of magnitude lower than that of known thermal ink jet printers, there are a total of about 88,000 nozzles 3 in the printhead array, and this is approximately 160 times the number of nozzles that are typically found in typical printheads. As the nozzles 3 in the present invention may be operational (i.e. may fire) on a continuous basis during operation, the total power consumption will be an order of magnitude higher than that in such known printheads, and the current requirements will, accordingly, be high, even though the power consumption per nozzle will be an order of magnitude lower than that in the known printheads. The busbars 125 are suitable for providing for such power requirements, and have power leads 126 soldered to them.
[0202] Compressible conductive strips 127 are provided to abut with contacts 128 on the upperside, as shown, of the lower parts of the flex PCBs 82 of the printhead module assemblies 80 . The PCBs 82 extend from the chip assemblies 81 , around the channel 110 , the support plate 119 , the extrusion 124 and busbars 126 , to a position below the strips 127 so that the contacts 128 are positioned below, and in contact with, the strips 127 . Each PCB 82 is double-sided and plated-through. Data connections 129 (indicated schematically by dashed lines), which are located on the outer surface of the PCB 82 abut with contact spots 130 (only some of which are shown schematically) on a flex PCB 131 which, in turn, includes a data bus and edge connectors 132 which are formed as part of the flex itself. Data is fed to the PCBs 131 via the edge connectors 132 .
[0203] A metal plate 133 is provided so that it, together with the channel 110 , can keep all of the components of the printhead assembly 19 together. In this regard, the channel 110 includes twist tabs 134 which extend through slots 135 in the plate 133 when the assembly 19 is put together, and are then twisted through approximately 45 degrees to prevent them from being withdrawn through the slots.
[0204] By way of summary, with reference to FIG. 68 , the printhead assembly 19 is shown in an assembled state. Ink and compressed air are supplied via the hose 112 at 136 , power is supplied via the leads 126 , and data is provided to the printhead chip assemblies 81 via the edge connectors 132 . The printhead chip assemblies 81 are located on the eleven printhead module assemblies 80 , which include the PCBs 82 .
[0205] Mounting holes 137 are provided for mounting the printhead assembly 19 in place in a printer (not shown). The effective length of the printhead assembly 19 , represented by the distance 138 , is just over the width of an A4 page (that is, about 8.5 inches).
[0206] Referring to FIG. 69 , there is shown, schematically, a cross-section through the assembled printhead 19 . From this, the position of a silicon stack forming a chip assembly 81 can clearly be seen, as can a longitudinal section through the ink and air supply hose 112 . Also clear to see is the abutment of the compressible strip 127 which makes contact above with the busbars 125 , and below with the lower part of a flex PCB 82 extending from a the chip assembly 81 . The twist tabs 134 which extend through the slots 135 in the metal plate 133 can also be seen, including their twisted configuration, represented by the dashed line 139 .
[0000] Printer System
[0207] Referring to FIG. 70 , there is shown a block diagram illustrating a printhead system 140 according to an embodiment of the invention.
[0208] Shown in the block diagram is the printhead (represented by the arrow) 141 , a power supply 142 to the printhead, an ink supply 143 , and print data 144 which is fed to the printhead as it ejects ink, at 145 , onto print media in the form, for example, of paper 146 .
[0209] Media transport rollers 147 are provided to transport the paper 146 past the printhead 141 . A media pick up mechanism 148 is configured to withdraw a sheet of paper 146 from a media tray 149 .
[0210] The power supply 142 is for providing DC voltage which is a standard type of supply in printer devices.
[0211] The ink supply 143 is from ink cartridges (not shown) and, typically various types of information will be provided, at 150 , about the ink supply, such as the amount of ink remaining. This information is provided via a system controller 151 which is connected to a user interface 152 . The interface 152 typically consists of a number of buttons (not shown), such as a “print” button, “page advance” button, an so on. The system controller 151 also controls a motor 153 that is provided for driving the media pick up mechanism 148 and a motor 154 for driving the media transport rollers 147 .
[0212] It is necessary for the system controller 151 to identify when a sheet of paper 146 is moving past the printhead 141 , so that printing can be effected at the correct time. This time can be related to a specific time that has elapsed after the media pick up mechanism 148 has picked up the sheet of paper 146 . Preferably, however, a paper sensor (not shown) is provided, which is connected to the system controller 151 so that when the sheet of paper 146 reaches a certain position relative to the printhead 141 , the system controller can effect printing. Printing is effected by triggering a print data formatter 155 which provides the print data 144 to the printhead 141 . It will therefore be appreciated that the system controller 151 must also interact with the print data formatter 155 .
[0213] The print data 144 emanates from an external computer (not shown) connected at 156 , and may be transmitted via any of a number of different connection means, such as a USB connection, an ETHERNET connection, a IEEE1394 connection otherwise known as firewire, or a parallel connection. A data communications module 157 provides this data to the print data formatter 155 and provides control information to the system controller 151 .
[0214] Although the invention is described above with reference to specific embodiments, it will be understood by those skilled in the art that the invention may be embodied in many other forms. For example, although the above embodiments refer to the heater elements being electrically actuated, non-electrically actuated elements may also be used in embodiments, where appropriate.
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A method of producing a pagewidth inkjet printhead to have structures of a plurality of nozzle openings defined through a single surface layer is provided In the method, the structures are formed in-situ on a substrate having heater elements for heating ink so that the surface layer has a thickness of ten microns or less and so that each nozzle opening is defined as a hole through the surface layer in association with at least one of the heater elements, and the structures are arranged to extend across a pagewidth. The nozzle openings are formed so that gas bubbles in the ink formed by the heating causes ejection of drops of the ink through the nozzle openings in a predetermined direction with respect to the pagewidth.
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BACKGROUND OF THE INVENTION
This invention concerns sulfur plasticizing compositions which comprise both an aromatic polysulfide and a linear aliphatic polysulfide. In particular, this invention concerns the use of olefinic-type unsaturated carboxylic acids to moderate hydrogen sulfide evolution during the reaction of sulfur with sulfur plasticizing compositions comprising both an aromatic and a linear aliphatic polysulfide.
Elemental sulfur has been proposed for use in a variety of applications such as coatings, foams, adhesives, and the like, but the development of many of these applications has been hindered by the propensity of sulfur to revert rapidly to its crystalline form. Many additives have been suggested to modify elemental sulfur to produce sulfur-based materials with "plastic" properties. Nearly all of these plasticizers are polysulfides.
The aromatic polysulfides and the linear aliphatic polysulfides are two of the most widely used classes of sulfur plasticizers. U.S. Pat. No. 4,026,719, granted May 31, 1977, describes sulfur-based compositions containing a mica filler and a plasticizing material which have been found to be unexpectedly strong. One of the recommended plasticizing materials comprises a mixture of aromatic and aliphatic polysulfides.
Aromatic polysulfide sulfur plasticizers are generally prepared by the base-catalyzed reaction of an aromatic compound and sulfur. In some instances, the reaction product is neutralized with acid, but in many cases the unneutralized product is used in combination with a linear aliphatic polysulfide. It has been found that, when a sulfur-plasticizing composition comprising an unneutralized aromatic polysulfide prepared by base catalysis and a linear aliphatic polysulfide are contacted with molten elemental sulfur, hydrogen sulfide gas is evolved at such an extremely rapid rate that conventional gas scrubbers cannot function satisfactorily and some noxious fumes are liberated to the atmosphere.
The evolution of hydrogen sulfide gas, which occurs when the plasticizer composition is contacted with molten sulfur, significantly limits the manufacture of plasticizer compositions comprising an aromatic polysulfide and a linear aliphatic polysulfide.
SUMMARY OF THE INVENTION
It has been found that incorporating a small amount of an unsaturated carboxylic acid in sulfur plasticizer compositions comprising an aromatic polysulfide and a linear aliphatic polysulfide moderates the evolution of hydrogen sulfide which normally occurs when the plasticizing composition is contacted with molten sulfur. Thus, this invention encompasses sulfur plasticizing compositions comprising from about 5% by weight to about 80% by weight of an aromtic polysulfide, from about 5% by weight to about 80% by weight of a linear aliphatic polysulfide, and from about 0.1% by weight to about 10% by weight of an unsaturated carboxylic acid. Preferably the composition contains sufficient sulfur to form a solid mixture at ambient temperatures.
DETAILED DESCRIPTION OF THE INVENTION
As summarized above, the sulfur plasticizing compositions of the invention comprise three ingredients: an aromatic polysulfide, a linear aliphatic polysulfide, and an unsaturated carboxylic acid.
Aromatic polysulfides which are suitable for use in the platicizing composition include aromatic polysulfides formed by reacting one mol of an aromatic carbocyclic or heterocyclic compound, substituted by at least one functional group of the class --OH or --NHR in which R is hydrogen or lower alkyl, with at least two mols of sulfur. Suitable aromatic compounds of this type include phenol, aniline, N-methyl aniline, 3-hydroxy thiophene, 4-hydroxy pyridine, p-aminophenol, hydroxyquinone, resorcinol, meta-cresol, thymol, 4,4'-dihydroxy biphenyl, 2,2-di(p-hydroxyphenyl)propane, dianiline, and the like. The reaction can be carried out by heating the sulfur and aromatic compound at a temperature of from about 120° C. to about 170° C. for 1 hour to 12 hours in the presence of a base catalyst such as sodium hydroxide. The polysulfide product made in this way has a mol ratio of aromatic compound to sulfur of about 1:2 to 1:10, usually 1:3 to 1:7.
Linear aliphatic polysulfides which are suitable for use in the plasticizing composition, although conventionally described as linear, may have some branching, indicated as follows: ##STR1## wherein x is an integer of from about 2 to about 6 and B is hydrogen, alkyl, halogen, nitrile, or ester or amide group. Thus, the sulfur-containing chain is linear, but can have side groups. The side group can, in fact, be an aromatic. For instance, styrene can be used to form a phenyl-substituted linear aliphatic polysulfide. However, the preferred linear aliphatic polysulfides include those containing an ether linkage having the recurring unit
--S.sub.x --CH.sub.2 --CH.sub.2 --O--CH.sub.2 --O--CH.sub.2 --CH.sub.2 --S.sub.x --
wherein x is an integer having an average value of about 12. The ether moiety of these polysulfides is relatively inert. These polysulfides, called Thiokols, are commercially available from the Thiokol Corporation, e.g., Thiokol LP-3. Other commercially available unbranched linear aliphatic polysulfides have the recurring units
--S.sub.x --CH.sub.2 --yS.sub.x --
from the reaction of an alpha, omega-dihaloalkane with sodium polysulfide,
--S.sub.x --CH.sub.2 --CH.sub.2 --S--CH.sub.2 --CH.sub.2 --S.sub.x --
from the reaction of alpha, omega-dihalosulfides with sodium polysulfide, and
--S.sub.x --CH.sub.2 CH.sub.2 --O--CH.sub.2 --CH.sub.2 --S.sub.x --
from the reaction of alpha, omega-dihaloesters with sodium polysulfide; wherein x is an integer from 2 to about 5 and y is an integer from 2 to about 10.
Unsaturated carboxylic acids which are suitable for use in the plasticizing composition are those mono- and di-carboxylic acids having olefinic-type unsaturation. For instance, suitable unsaturated mono-carboxylic acids have the formula
R.sub.2 C═CR--R.sup.1 --.sub.x COOH
wherein each R is independently hydrogen, alkyl, or aryl; R 1 is alkylene or arylene and x is either 0 or 1. Thus, alkenyl-substituted benzoic acids are suitable. However, aliphatic acids are preferred, and alpha, beta-unsaturated aliphatic carboxylic acids are particularly preferred. It is also preferable to use low-molecular-weight acids containing from 3 to about 10 carbon atoms. Accordingly, acrylic acid is an especially preferred acid. Other specific acids which are suitable include, for example, crotonic acid, angelic acid, tiglic acid, undecylenic acid, alpha-methylacrylic acid, p-allyl benzoic acid, and cinnamic acid. Suitable dicarboxylic acids include maleic acid and fumaric acid.
The sulfur plasticizing composition is prepared by contacting the three ingredients in a suitable vessel. Since unreacted sulfur is usually present in both the aromatic and aliphatic polysulfides, it is a preferred practice to add the unsaturated acid to one or the other of the polysulfide ingredients before combining the polysulfides. The relative weight ratios of ingredients are not particularly critical, although it is preferable to use at least two equivalents of acid per mol of base catalyst used in the aromatic polysulfide preparation. In general, the plasticizing composition comprises from about 5% to 80%, by weight, of aromatic polysulfide, from about 5% to 80% by weight, of aliphatic polysulfide, and from about 0.1% to 10%, by weight, of unsaturated acid. Preferably the composition comprises from about 30% to 70%, by weight, of aromatic polysulfide, from about 5% to 60%, by weight, aliphatic polysulfide, and from 0.5% to 5%, by weight, of unsaturated acid. A particularly preferred composition comprises about 66%, by weight, of aromatic polysulfide, about 33%, by weight, of aliphatic polysulfide, and about 1%, by weight, of unsaturated acid.
The plasticizing composition may also comprise up to as much as about 90%, by weight, of various optional ingredients. For instance, the composition may comprise a substantial weight percent of sulfur; filler such as asbestos, talc, clay, fiberglass, or mica; pigment; viscosity modifier; or the like. In a preferred embodiment, the plasticizing composition is intended as a concentrate for use in the preparation of a sulfur-based coating composition. Accordingly, in addition to the three principal ingredients, the composition comprises elemental sulfur and a filler. For instance, the plasticizing composition may comprise from about 30% to 80%, by weight, of sulfur and from about 10% to 30%, by weight, of filler. When preparing an embodiment comprising substantial amounts of elemental sulfur, it is usually desirable to heat the sulfur above its melting point while adding the principal ingredients. In this way, the plasticizers combine with the sulfur, and when cooled form a solid material. The solid can be pulverized or broken into smaller lumps for use as a concentrate which when further diluted with additional sulfur forms a sulfur-based composition.
Among other factors, the present invention is based upon the discovery that a sulfur plasticizing composition comprising both an aromatic and aliphatic polysulfide is stabilized against the vigorous evolution of hydrogen sulfide gas by including an unsaturated acid in the composition. As an additional benefit, it has been found that the acid prevents fragmentation of the linear aliphatic polysulfide and has plasticizing properties of its own. While the actual mechanisms of the reactions have not been identified, it appears that hydrogen sulfide is produced by the reaction of sulfur with the end-groups of the aliphatic polysulfide and by the base catalyzed fragmentation of the linear aliphatic polysulfides. As a result, many available hydrogen atoms combine with sulfur to evolve hydrogen sulfide gas. An unsaturated acid, such as acrylic acid, will combine with sulfur to form a plasticized sulfur-bridged polysulfide: ##STR2##
In addition, the acrylic acid neutralizes any base present in the system, further inhibiting the polysulfide fragmentation.
EXAMPLES
The following examples illustrate the preparation and use of specific embodiments of the composition of this invention. The examples are not intended to limit the scope of the invention, as other embodiments will be suggested by them.
EXAMPLE 1
The aromatic polysulfide, PSA, which was used as an ingredient in the following composition was prepared by the reaction of sulfur with phenol in the presence of a sodium hydroxide catalyst, as thoroughly discussed in U.S. Pat. No. 3,892,686, granted July 1, 1975 (see Example 1 at Cols. 13-14).
The aliphatic polysulfide, LP-3, which was used as an ingredient was commercially available from the Thiokol Corporation as Thiokol LP-3.
The composition was prepared by mixing elemental sulfur and PSA at 140° C.-145° C., acrylic acid was then added, and the mixture was allowed to react 60 to 90 minutes. LP-3 was added over a 20- to 30-minute period and allowed to react 30 minutes. The hydrogen sulfide gas was evolved slowly throughout the reaction. The composition was cast into 0.5- to 0.75-inch-thick layers and solidified in 3 to 4 hours.
______________________________________Plasticizing CompositionIngredients Total Weight Weight %______________________________________(1) Sulfur 1200 lbs 54.3(2) PSA 800 lbs 36.2(3) LP-3 200 lbs 9.0(4) Acrylic acid 10 lbs 0.5 2210 lbs 100.0%______________________________________
The procedure of Example 1 was repeated except that there was no acrylic acid in the composition. After addition of the LP-3, an extremely vigorous reaction occurred and the resulting evolution of hydrogen sulfide gases was so violent that a portion of the reaction contents was blown out of the reactor.
At a later data, 5.5 parts of the plasticizing composition prepared with acrylic acid was added to 77.5 parts of sulfur and 17 parts of mica, and the resulting mixture was heated at 130°-150° C. for 30 minutes. The product was an excellent cement coating composition.
EXAMPLE 2
In this example, the aromatic polysulfide, PSA, was prepared as in Example 1 using a 30:70 phenol to sulfur weight ratio.
The composition was prepared by charging molten sulfur at 130° C. to a reaction vessel, adding PSA and acrylic acid, adding LP-3, holding at 120° C., adding mica, and allowing the composition to cool.
______________________________________Plasticizing Composition Ingredients Weight %______________________________________(1) Sulfur 49.7(2) PSA 20.0(3) Mica 20.0(4) LP-3 10.0(5) Acrylic acid 0.3 100.0%______________________________________
A portion of the sulfur plasticizing composition was used to prepare a sulfur-based coating by adding additional sulfur and mica to the plasticizing composition, which was heated to its molten state.
______________________________________CoatingIngredients Weight %______________________________________(1) Sulfur 74(2) Mica 16(3) Plasticizing Composition 10 100%______________________________________
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A sulfur plasticizing composition comprising an aromatic polymeric polysulfide, a linear aliphatic polysulfide and an olefinic-type unsaturated carboxylic acid. The presence of unsaturated acid moderates the evolution of hydrogen sulfide when the plasticizing composition is reacted with sulfur, thereby preventing a rapid, uncontrolled degassing of the reaction mixture.
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BACKGROUND OF THE INVENTION
The invention relates to an apparatus for dispensing fluent matter, and more particularly, to a hopper and vehicle having a hydraulically driven apparatus to dispense fluent matter from the vehicle into individual receptacles.
Deformable receptacles containing fluent matter have been found to be effective in the formation of permanent or temporary barricades for preventing the passage of liquid therethrough. In particular, bags filled with sand or other substantially fluent material are used extensively to obstruct the flow of water and thereby protect property from potential water damage during a flood. Sandbags may also be used for a number of other applications, including for barricades at construction sites, for riot control, and for military fortification.
Filling such receptacles manually, however, is slow and difficult work, and is generally accomplished by one person holding a receptacle in an open position while a second person repeatedly shovels or otherwise carries fluent matter from a bulk source through the opening of the receptacle until the receptacle is appropriately filled. Relatively efficient two-person teams generally require about twenty to thirty seconds using such manual techniques to fill a single bag with approximately thirty pounds of fluent matter. Sandbags, however, are often demanded in large quantities and in emergency situations where time is of the essence. Thus, it is desirable to expedite the preparation and delivery of sandbags in such situations.
The problem facing providers of sandbags is the prompt and efficient delivery of sandbags to the application site. Obviously, a bulk source of fluent matter must be present at the site where the sandbags are to be filled. Thus, the sandbags must either be filled at a location remote from where the sandbags are to be applied or a bulk source of fluent matter must be transported to the application site. There are numerous advantages of the latter method with respect to the former. First, it is generally not known prior to arriving at the application site how many sandbags will be required. Thus, if one is required to remotely fill the sandbags, then it is likely that either too many or too few sandbags will be prepared. Obviously, if too many sandbags are prepared, one risks that the additional time required to prepare the extra sandbags will permit an emergency situation to worsen. Alternatively, if too few sandbags are prepared, one risks not being able to adequately address the emergency situation.
Another disadvantage of preparing sandbags at a location remote from the application site is that, once prepared, the sandbags must be transported to the application site. It generally requires considerable manpower to load and unload vehicles for transporting sandbags from a remote location to an application site. Thus, in order to reduce required manpower, it is desirable to fill the required sandbags very proximately to, or preferably at, the application site.
The difficulty with on-site filling is that it is usually manually performed and very arduous. Furthermore, one must transport a bulk quantity of fluent matter to the application site. In order to fill bags mechanically on-site, one must provide power to operate the filling apparatus. This has proven to be very difficult.
U.S. Pat. No. 5,417,261, issued to Kanzler et al., discloses a stand-alone filling apparatus designed to reduce the manpower needed to fill sandbags. A difficulty with such an apparatus, however, is that it would be difficult to transport it to an application site, particularly if heavy bulk fluent matter were already contained in the apparatus. Thus, such an apparatus is likely to be subject to all the remote-filling disadvantages discussed above. Furthermore, manufacturing the disclosed sandbag-filling apparatus would be quite expensive.
Others have made efforts at transportable sandbag-filling apparatus, but these efforts also have had significant disadvantages. Specifically, U.S. Pat. No. 3,552,346, issued to Garden, teaches a bagging attachment for the rear of a dump truck. The Garden patent requires the use of a hydraulic lift for raising the dump truck onto an angle so that the fluent matter therein may be received into a vibrating hopper. The disclosure of the power sources for the lift and vibrator is limited, however, and the patent indicates that multiple external power sources, such as air-cooled engines, could be needed. Furthermore, using such apparatus it would be difficult to closely regulate the amount of matter being vibrated into the bags.
U.S. Pat. No. 4,044,921, issued to Caverly, employs an external power plant comprising an internal combustion engine connected to an appropriate transmission to drive a power shaft that is mounted on appropriately located bearings attached to a support stand, and an electrically actuated drive clutch is mounted to the power shaft for driving a canvas belt. It is believed that such a means for powering a sandbag-filling apparatus is completely impractical and would be prohibitively expensive, both to construct and to maintain with proper fuel. Furthermore, it is believed that the canvas belt would be likely to become jammed by larger particulates within the fluent matter.
SUMMARY OF THE INVENTION
In accordance with the invention there is provided a vehicle comprising a motor for providing drive power to the vehicle, a hydraulic system powered by the motor, a container for containing a bulk quantity of fluent matter, and matter dispensing apparatus comprising a hopper for receiving fluent matter from the container, a selectively operable transfer mechanism for transferring fluent matter from the container to the hopper, and an actuator disposed proximately to the hopper, the actuator being operatively associated with the transfer mechanism by the hydraulic system such that the transference of fluent matter from the container to the hopper is controlled by the actuator.
The inventive vehicle enables prompt and efficient delivery of sandbags at the application site, and has significant advantages over the devices described above. First, the inventive vehicle carries a bulk quantity of fluent matter in a container to the application site rather than pre-filling an indeterminate number of bags. By filling the bags at the application site, the above-described disadvantages of remote-filling are avoided. Furthermore, if there are multiple application points at a given site, filled bags need not be carried from point to point. Rather, the vehicle may simply be driven from point to point so that the bags can be filled at the specific locations where they are to be applied.
Second, the inventive sandbag-filling apparatus can be used to fill sandbags much more quickly than by conventional means. Rather than requiring two operators approximately twenty to thirty seconds to fill one thirty pound bag, a preferred embodiment of the inventive apparatus can be used by a single operator to fill a thirty pound bag in approximately three seconds. Given that it generally requires approximately another three seconds to prepare a new bag for filling, the preferred embodiment of the inventive sandbag-filling apparatus can generally be used to fill ten bags per minute with one operator at the site of application, rather than remotely filling two bags per minute with two operators using conventional means.
Third, unlike prior art apparatus described above, the inventive sandbag-filling apparatus has an efficient power source. By drawing power into a hydraulic circuit directly from the motor of the vehicle, significant cost savings can be realized. External power systems, such as those disclosed in the '346 patent to Garden and the '921 patent to Caverly, are typically more expensive to build, buy, and operate than is the hydraulic system of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevational view of a vehicle in accordance with the invention.
FIG. 2 is a perspective view of the rear portion of the vehicle shown in FIG. 1.
FIG. 3 is a perspective view of part of the rear portion of the vehicle shown in FIG. 1, particularly showing the transfer mechanism thereof.
FIG. 4 is a rear elevational view of the vehicle shown in FIG. 1.
FIG. 5 is a perspective view of part of the rear portion of the vehicle shown in FIG. 1, particularly showing the hopper thereof.
FIG. 6 is a perspective view of the front side of the hopper removed from the vehicle shown in FIG. 1.
FIG. 7 is a schematic view of a hydraulic system in accordance with the invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
The preferred embodiment of the invention is a truck 10, shown primarily in broken lines in FIG. 1 to permit viewing of some interior components, the truck 10 having a cab 12 disposed in front of a container 14. At the front of the cab 12, housed under the hood 16, is a motor 20 for providing drive power to the truck 10 through a drive train and for providing power to a hydraulic pump 22 which is also housed under the hood 16 and disposed proximately to the motor 20.
As seen in FIGS. 2, 3, and 4, the container 14 is preferably a standard V-box type container such that it generally tapers inwardly toward the bottom of the container 14. Thus, as gravity pulls fluent matter 60 downwardly within the container 14, the V-shaped cross-section guides the fluent matter 60 onto a conveyor bed 44 which extends longitudinally along the bottom of the container 14. Extra support is preferably provided to the sidewalls of the container 14 by triangular container support ribs 40. There is also a gate 42 on the rear wall 15 of the container 14. The gate 42 can be vertically adjusted between a closed position and a continuum of open positions by rotating crank arm 43.
As seen particularly in FIG. 3, the conveyor bed 44 is longitudinally supported by guide rails 45 on both sides of the bed 44. A linked conveyor belt 46, comprising a series of individual conveyor slats 47 extending transversely across the bed 44 from one guide rail 45 to the other, encircles the bed 44 and is supported by the guide rail 45 and by a pair of sprockets connected by an axle at each longitudinal end of the conveyor bed 44. At least one axle and corresponding pair of sprockets is in rotational communication with a conveyor motor 48 which is selectively operable and driven by the hydraulic system. Activation of the conveyor motor 48 forces rotation of the axle and sprockets on one end of the conveyor bed 44, preferably the end at the rear of the truck 10 proximate to the motor 48, thereby driving the belt 46 around the conveyor bed 44 and pushing fluent matter 60 lying atop the bed 44 toward the gate 42 at the rear wall 15 of the container 14. When it is desired to operate the sandbag-filling apparatus, the gate 42 is opened with crank arm 43, thereby permitting fluent matter 60 to escape the container 14 through the gate 42. The conveyor belt 46 is then selectively operated to push fluent matter 60 through the gate 42, where it falls into a hopper 50.
As seen in FIG. 5, the hopper 50 preferably has four substantially trapezoidal sidewalls, including a front side wall 62, and a restricted neck portion 64 beneath and connecting the four sidewalls. The neck portion may be of rectangular cross-section, as seen in the figures, or may be substantially circular, or of any other appropriate shape. The sidewalls may be substantially vertical, but preferably at least one sidewall angles downwardly and inwardly to reduce the vertical cross-sectional area through which the fluent matter 60 falls. The narrowing produces a funneling effect and facilitates filling a receptacle held beneath the neck portion 64 with minimal spillage of fluent matter 60. The hopper 50 is supported behind the rear wall 15 of the container 14, and descends from cantilevered beams 51 of the conveyor guide rails 45. Additional support is provided to the cantilevered beams 51 by triangular stress plates 52.
The preferred disposition of the hydraulic system is shown in FIG. 1, and, for clarity, the preferred hydraulic system is shown schematically in FIG. 7. The system has a hydraulic pump 22 having an input line known as a feed line (or tank line) 24 and an output line called a pressure line 26. The pump 22 is disposed proximately to and is powered by the motor 20. The feed line 24 comes from a fluid reserve tank 28 preferably disposed along side the container 14, and the hydraulic fluid passes through a filter 30 on its way from the tank 28 to the pump 22.
The pressure line 26 preferably extends from the pump 22 into the operator chamber 18 of the cab 12. In the cab 12, there is apparatus for driving the truck 10, such as an accelerator, gear shift, steering wheel, etc. In the operator chamber 18, there is also preferably a valve body 32 in the pressure line 26. The valve body 32 can be adjusted by the truck operator to control the hydraulic pressure into the pressure line 26. From the valve body 32, the pressure line 26 extends through the back of the cab 12 and under the container 14 to the front side wall 62 of the hopper 50.
As seen in FIGS. 5 and 6, at the hopper 50, the pressure line 26 is in communication with a pressure end 59a of a valve body 58, preferably an electrical solenoid valve body. From the valve body 58, the pressure line 26 extends to a hydraulic fluid input 49a for the conveyor motor 48. The conveyor motor 48 also has a hydraulic fluid output 49b from where the hydraulic fluid exits the motor 48 and begins its return cycle. Thus, hydraulic return line 38 extends from the conveyor motor output 49b to the front side wall 62 of said hopper 50 where it is in communication with a return end 59b of the valve body 58. From the hopper 50, the return line 38 extends back to the fluid reserve tank 28 so that the fluid can be recycled. The vehicle may also include a second pressure line extending from said pump. In the preferred embodiment of the invention, the second pressure line is directed back into the reserve tank such that there is no significant pressure loss in the pressure line 26.
The valve body 58 is normally in an open state, permitting fluid flow therethrough. Thus, in its normal state, the valve body 58 acts as a short circuit between the pressure line 26 and the return line 38 because the fluid, primarily choosing the path of least resistance, flows through the valve body 58, into the return line 38, and back to the reserve tank 28 rather than the more resistive path of flowing through the conveyor motor 48 prior to recycling through the return line 38. Therefore, when the valve is in its normal open state, virtually no hydraulic fluid is flowing into the conveyor motor 48, and the conveyor belt 46 therefore is motionless.
In order to selectively operate the conveyor motor 48, the valve body 58 must be closed, thereby forcing the fluid through the conveyor motor 48 and back through the return line 38. The electrically operated solenoid valve body 58 is preferably activated through electrical communication 57 with microswitch 56 on the front side wall 62 of the hopper 50. Preferably, the microswitch 56 is toggled by depressing and releasing a button 55 on the perimeter of the microswitch 56.
To facilitate filling receptacles with minimal spillage of fluent material 60, the neck portion 64 of the hopper 50 is preferably restricted so that a receptacle can be held beneath the hopper 50 to receive the fluent matter 60 falling therethrough. To facilitate operation of the sandbag-filling apparatus by a single individual, an actuator ring 53 is preferably disposed to substantially encircle the neck portion 64 of the hopper 50 such that it is manually accessible to an individual who is holding a receptacle in place beneath the hopper 50. A substantially round actuator rod 54 having a cammed surface thereon supports the actuator ring 53 on the front side wall 62 of the hopper 50. The cammed surface of the rod 54 provides clearance for the microswitch button 55 so that the button 55 is ordinarily not depressed. By pressing downwardly on the actuator ring 53, however, the actuator ring 53 and actuator rod 54 are rotated so that the cammed surface of the rod 54 is angularly displaced such that the more radially outward portion of the cammed surface depresses the button 55 of the microswitch 56. In an alternative embodiment, the actuator may have a plurality or continuum of states to control the speed of the conveyor.
Thus, by pressing downwardly on the actuator ring 53 when holding a bag in place under the neck portion 64 of the hopper 50, the microswitch button 55 is depressed, thereby electrically activating the solenoid valve body 58 and obstructing the short circuit between the pressure line 26 and the return line 38 so that the hydraulic fluid is forced through conveyor motor 48. FIG. 7 illustrates the hydraulic system as described wherein the short circuit at valve body 58 is obstructed (represented by an open switch). Activation of the conveyor motor 48 rotates the slatted conveyor belt 46 around the conveyor bed 44 to force fluent matter 60 through the open gate 42, through the hopper 50, and finally into the bag.
From the foregoing it will be appreciated that the invention provides a novel hopper and vehicle for filling receptacles with fluent matter. The invention is not limited to the embodiment described herein, or to any particular embodiment.
Specific examples of alternative embodiments considered to be within the scope of the invention include embodiments where the hopper is disposed on the side wall of the container rather than on the rear wall, or where there may be more than one hopper, such as where one hopper is disposed on each sidewall. It is also considered within the scope of the invention to provide an embodiment using one or more augers, rather than, or in addition to one or more conveyors, to displace fluent matter toward a hopper. Another example of an alternative embodiment specifically considered to be within the scope of the invention is one wherein a foot pedal is disposed proximately to the hopper and is used instead of the above-described actuator ring to toggle the switch and valve body. Other modifications to the preferred embodiment may also be made within the scope of the invention.
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A vehicle comprising a motor for providing drive power to the vehicle, a hydraulic system powered by the motor, a container for containing a bulk quantity of fluent matter, and matter-dispensing apparatus comprising the hopper for receiving fluent matter from the container, a selectively operable transfer mechanism for transferring fluent matter from the container to the hopper, and an actuator disposed proximately to the hopper, the actuator being operatively associated with the transfer mechanism by the hydraulic system such that the transference of fluent matter from the container to the hopper is controlled by the actuator.
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CROSS-REFERENCE TO RELATED APPLICATION
This application claims priority to Serial No. 60/153,576, filed Sep. 13, 1999. Serial No. 60/153,576 is incorporated by reference herein.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
This invention was made with United States government support awarded by the following agencies: NIH GM57322. The United States has certain rights in this invention.
BACKGROUND OF THE INVENTION
Rhodospirillum rubrum is a facultatively phototrophic purple nonsulfur bacterium. Under reduced oxygen concentration, this organism forms an intracytoplasmic membrane (ICM) that is the site of the photosynthetic apparatus (Collins, M. L. P., and C. C. Remsen, The purple phototrophic bacteria , p. 49-77, In J. F. Stolz (ed.), Structure of Phototrophic Procaryotes. CRC Press, Boca Raton Fla., 1990; Crook, S. M., et al., J. Bacteriol . 167:89-95, 1986; Hessner, M. J., et al., J. Bacteriol . 173:5712-5722, 1991). This apparatus consists of the light-harvesting antenna (LH) and the photochemical reaction center (RC). The pigment-binding proteins, the LH α and β and the RC-L and -M, are encoded by the puf operon while RC-H is encoded by puhA. The nucleotide sequences of puhA and the puf operon have been determined in R. rubrum (Bélanger, G., et al., J. Biol. Chem . 263:7632-7638, 1988; Bérard, J., et al., J. Biol. Chem . 261:82-87, 1986; Bérard, J., and G. Gingras, Biochem. Cell Biol . 69:122-131, 1991) and related bacteria (Donohue, T. J., et al., J. Bacteriol . 168:953-961, 1986; Kiley, P. J., et al., J. Bacteriol . 169:742-750, 1987; Michel, H., et al., EMBO J . 5:1149-1158, 1986; Michel, H., et al., EMBO J . 4:1667-1672, 1985; Weissner, C., et al., J. Bacteriol . 172:2877-2887, 1990; Williams, J. C., et al., Proc. Natl. Acad. Sci . 81:7303-7307, 1984; Williams, J. C., et al., Proc. Natl. Acad. Sci . 80:6505-6509, 1983; Youvan, D. C., et al., Proc. Natl. Acad. Sci . 81:189-192, 1984; Youvan, D. C., et al., Cell 37:949-957, 1984).
R. rubrum may grow phototrophically under anaerobic light conditions or by respiration under aerobic or anaerobic conditions in the dark. Because R. rubrum is capable of growth under conditions for which the photosynthetic apparatus is not required, and because the photosynthetic apparatus and the ICM may be induced by laboratory manipulation of oxygen concentration, this is an excellent organism in which to study membrane formation (Collins, M. L. P., and C. C. Remsen, supra, 1990; Crook, S. M., et al., supra, 1986).
In previous studies, the puf region was cloned and interposon mutations within this region were constructed (Hessner, M. J., et al., supra, 1991). R. rubrum P5, in which most of the puf genes were deleted, was shown to be incapable of phototrophic growth and ICM formation. P5 was restored to phototrophic growth and ICM formation by complementation with puf in trans (Hessner, M. J., et al., supra, 1991; Lee, I. Y., and M. L. P. Collins, Curr. Microbiol . 27:85-90, 1993). These results imply that in R. rubrum the puf gene products are required for ICM formation. These results differ from those obtained with a puf interposon mutant of Rhodobacter sphaeroides (Davis, J., et al., J. Bacteriol . 170:320-329, 1988) which was phototrophically incompetent but was still capable of ICM formation (Kiley, P. J., and S. Kaplan, Microbiol. Rev . 52:50-69, 1988). In the case of R. sphaeroides , the formation of ICM in the absence of the puf products may be attributable to the presence of an accessory light-harvesting component (LHII) encoded by puc (Hunter, C. N., et al., Biochem . 27:3459-3467, 1988). This implies that R. rubrum is a simpler model for studies of membrane formation.
Because the puf-encoded proteins are required for ICM formation in R. rubrum and because the RC is assembled from puf and puhA products, it is important to evaluate the role of puhA-encoded RC-H in RC assembly and ICM formation in R. rubrum.
Cheng, et al., J. Bacteriol . 182(5):1200-1207, 2000 and Yongjian S. Cheng, “Molecular Analysis of Biochemical Intracytoplasmic Membrane Proteins,” PhD thesis, UW-Milwaukee, August, 1998 describe the cloning, mutation, and complementation of the puhA region of R. rubrum . (Both of these documents are incorporated herein by reference.) The present application proposes a model for the preparation of proteins, preferably membrane proteins.
SUMMARY OF THE INVENTION
In one embodiment, the present invention is a method of expressing protein comprising the steps of placing a DNA sequence encoding a protein or peptide in an expression vector that contains a regulatable promoter expressible in Rhodospirillum rubrum and expressing the protein within a bacterial host, wherein the host has extra capacity for membrane formation and wherein the host is a member of the genus Rhodospirillum.
In a preferred embodiment of the present invention, the protein or peptide is a membrane protein or peptide and/or the protein or peptide is a heterologous protein or peptide.
In another preferred form of the present invention, the host is Rhodospirillum rubrum.
In another embodiment, the present invention is a protein expression system. In one embodiment, the protein expression system encompasses a vector comprising a DNA molecule encoding the protein or peptide in an expression vector containing a regulatable promoter expressible in R. rubrum . The vector is contained within a host, preferably R. rubrum with extra capacity for membrane formation.
Other objects, advantages and features of the present invention will become apparent to one of skill in the art after review of the specification, claims and drawings.
DETAILED DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
FIG. 1 is a diagram illustrating the construction of the expression cassettes and the DNA sequence of the cassette of pREX1 (SEQ ID NO:1). The PS fragment extends from position 92-429 and the T fragment extends from position 469-671. The multiple cloning site is from position 430-468. Sequences from position 1-91 and 672-857 are those of the vector. PM, PL and PG are not shown and include additional upstream sequences. The exact lengths and positions of PS/PM, PL and PG are specified by the sequences of the primers reported herein and in Cheng thesis, supra.
FIG. 2 diagrams the construction of various expression vectors. PCR products PS, PM, PL and PG (not shown) from the various puh regions are shown in position and size relative to the map of puh and flanking ORFs.
FIG. 3 is a diagram of modular cloning of pPSpuhT or pPMpuhT. PCR primers incorporated appropriate restriction sites to facilitate cloning of pPSpuhT or pPMpuhT. The promoter and terminator sequences were placed at the ends of the multiple cloning site to allow flexibility in designing PCR primers for cloning genes inserted between the promoter and terminator. Mutated bases are indicated by the dotted boxes.
FIG. 4 is a set of absorbance spectra of R. rubrum H15 complemented with pPSpuhT and pPMpuhT. Cells were grown phototropically (top of spectra) or semi-aerobically (bottom of spectra).
DESCRIPTION OF THE INVENTION
In one embodiment, the present invention is a host/vector system for expression of proteins. In preferable embodiments of the present invention, the protein is a heterologous protein and/or a membrane protein. While numerous expression vector systems are commercially available, these vector systems generally cannot be applied to membrane proteins. Over-expression of membrane proteins is often toxic for the cell or results in the production of inclusion bodies in which the protein is in a non-native structure.
By “membrane proteins” we mean proteins normally or naturally located in the cell membrane. Such proteins generally have one or more membrane-spanning domains.
A host designed for the expression of membrane proteins in the present invention should have extra capacity to proliferate membranes to accommodate the expressed protein. Extra capacity would avoid problems with formation of inclusion bodies or lethality associated with over-expressed membrane proteins. By “extra capacity” we mean that the host organism has the ability to make an intracytoplasmic membrane (ICM) but has a reduced ability to produce native membrane proteins.
The ability of a bacterium to make an ICM can be determined (assayed) by examining a sample with the electron microscope. ICM is known to be made ordinarily by only three known groups of bacteria—phototrophs (such as R. rubrum ), methanotrophs and ammonia-oxidizers. The latter two (especially ammonia-oxidizers) are not preferred for molecular biology applications because of their growth requirements.
The extra capacity for ICM formation by the mutants described herein is due to mutation in the genes encoding the major membrane proteins—i.e., the proteins of the photochemical complexes. Because the bacteria retain the capacity to make ICM, they have “extra capacity.”
The host is a member of the genus Rhodospirillum and most preferably one of several mutants of Rhodospirillum rubrum . Preferably, the mutant hosts are defective in the production of puhA-encoded RC-H ( Rhodospirillum rubrum H15) or puhA-encoded RC-H and puf-encoded LH-α, LH-β, RC-L and RC-M ( Rhodospirillum rubrum H1). A puf knock-out mutant ( Rhodospirillum rubrum P5 or P4) would also be suitable. (Note that P5 mutant has a puf − phenotype but still retains a partial pufB but pufALM is completely deleted.) Another puf − mutant, R. rubrum P4 (described in Jester, B., MS Thesis, University of Wisconsin at Milwaukee, May 1998, incorporated by reference herein), which is a puf knock-out but differs from P5 in that more genomic DNA is removed, is also suitable.
The basis for the mutational design described herein is that the host's ability to produce its own native major membrane proteins has been disrupted, thus providing the “extra capacity” to incorporate heterologous membrane proteins. For R. rubrum this means knocking or disrupting out puh and/or puf. For other phototrophic bacteria (e.g., Rhodobacter sphaeroides ), it would be preferable to also knock out puc which encodes an additional photochemical component that is a major membrane protein. Such an R. sphaeroides mutant has been constructed (see M. R. Jones, et al., Molec. Microb . 6:1173-1184, 1992).
While these R. rubrum mutants are impaired in ICM formation, they retain the capacity to form an intracytoplasmic membrane in response to the synthesis of membrane proteins, including heterologous membrane proteins. (Cheng, et al., supra, 2000, describes a comparison of the properties of wild-type Rhodospirillum rubrum and mutated Rhodospirillum rubrum and describes the development of a suitable host for the present invention. (This article is incorporated by reference as if fully set forth herein.) In addition, Cheng, et al., supra, 2000, reports that the puh promoter is contained within pH 3.6+. This promoter is incorporated into the expression vector described herein and is derepressed (i.e., induced) by semi-aerobic conditions.
The R. rubrum system is advantageous, in part, because R. rubrum does not infect humans or animals and grows on a simple medium. The intracytoplasmic membrane that houses the expressed protein may be separated from the other particulate cellular material.
One may most easily obtain a suitable R. rubrum host by constructing organisms analogous to P5 or H15. P5 may be reconstructed by following Hessner, et al., supra, 1991. H15 may be reconstructed by following the procedure of Cheng, et al., supra, 2000.
An expression vector of the present invention should have the following properties: (a) strong promoter; (b) regulated promoter; and (c) promoter regulated by a stimulus that is simple, inexpensive and non-toxic. The parent plasmid used to construct the expression vector must be capable of replication in a R. rubrum host. We have used IncP plasmids to construct the expression vector. However, IncQ plasmids also replicate in R. rubrum , and one preferred embodiment of the present invention would be to move the cassette into an IncQ plasmid. Because these plasmids would be compatible in the host, this will make it possible to simultaneously express two proteins. This embodiment could be applied to the synthesis of a membrane protein that is a heterodimer. Alternatively, it may be possible to use a single vector to express oligomeric proteins that are co-transcribed on a single message.
The expression vectors preferably include an R. rubrum promoter which can be induced by reduction of oxygen. In addition, to being able to replicate in the Rhodospirillum rubrum host, the expression vector must have a promoter that is expressed strongly in this host.
Our development of a suitable expression vector is based on our studies of puh expression. The expression vector pREX1 (also known as pPST) is a construct in which cloning sites are located between promoter and terminator sequences. 1 These sequences are derived from the puh region of pH 3.6+/−. The expression vectors pREX2 (also known as PPMT) and pREX3 (also known as pPLT, not yet built) contain longer portions of the R. rubrum sequence contained within pH 3.6−. The promoter can be induced by reduction of oxygen tension. When the gene encoding a desired protein, such as a membrane protein, is cloned into this expression vector and the vector is introduced into a suitable host, such as Rhodospirillum rubrum H15 or Rhodospirillum rubrum H1, this protein can be expressed by reducing the oxygen tension. This expression has been demonstrated by the expression of Escherichia coli MalF in Rhodospirillum rubrum H15, as described below in the Examples.
1 Applicants note that some nomenclature regarding expression vectors and clones has been modified between the Cheng PhD thesis (Yongjian S. Cheng, “Molecular Analysis of Biochemical Intracytoplasmic Membrane Proteins,” UW-Milwaukee, August, 1998), priority application U.S. Serial No. 60/153,576, Cheng, et al., supra, 2000 and the present application. The table below describes the relationship of this terminology.
The construct pH 3.6− has a strong promoter which results in the synthesis of mRNA encoding the abundant protein PuhA. This promoter is regulated by oxygen and it can be derepressed by simple manipulations applicable to both lab scale and production scale. This avoids the use of chemical inducers which may be costly and/or toxic.
NOMENCLATURE OF EXPRESSION VECTOR AND CLONES
This application
U.S. Ser. No. 60/153,576
Cheng thesis
pREX1, pPST
pPST
pPST
pREX2, pPMT
pPLT
pPLT
pPREX3, pPLT
—
—
pPSpuhT
pPSpuhT
pPSpuhT
pPMpuhT
pPLpuhT
pPLpuhT
pPSpuh88T
—
pPSHD1T
FIG. 1 is a diagram illustrating the construction of the expression cassettes and the DNA sequence of the cassette of pREX1. The DNA sequence includes a small portion of the vector sequence that could be used in subcloning a cassette into various vectors. The sequence of the puh region was reported in the literature. (Bérard, J., et al., J. Biol. Chem . 264:10897-10903, 1989 and Bérard, J. and Gingras, G, Biochem. Cell Biol . 69:122-131, 1991).
We envision the construction of PPLT and PPGT, alternatives with more upstream sequence, as follows:
Longer promoter fragments will be amplified using PF3EcoRI and PF4SacI. (See Table 1 below.) pRK415 will be used as a platform. The PG fragment amplified using PF4SacI contains all of the sequence upstream of puhA in pH 3.6− and extends into the additional sequence reported in Cheng, et al., supra, 2000.
TABLE 1
Amplification Primers
TFSphI
GTAATTGGGGGCATGCCACATGGATGA
(SEQ ID NO:2)
TRHindIII
CGGCGGTCAGAAGCTTGGGCAGCGGAT
(SEQ ID NO:3)
PF3EcoRI
GCAACCAAGGAATTCCCGCTGGGTCGT
(SEQ ID NO:4)
PRSacI
GAGGGTGACGAGCTCTCCTGGGAACTC
(SEQ ID NO:5)
PRSacI
ATGACCAGTTGAGCTCCCATCCAGCCGCTTGG
(SEQ ID NO:6)
pPLT will be constructed with a similar strategy for pPST and pPMT. In brief:
1. One would PCR amplify PL product with PF3EcoRI and PRSacI
2. Digest with EcoRI and SacI or Sstl
3. Digest pRK415 Eco and SacI or Sstl
4. Ligate PL fragment into digested vector to construct pPL; transform E. coli.
5. PCR amplify T fragment with TRHindIII and TFSphI
6. Digest T PCR product with SphI and HindIII
7. Digest pPL with SphI and HindIII
8. Ligate T fragment into digested pPL
The strategy for PPGT is similar:
1. PCR amplify T fragment with TR and TF
2. Digest T PCR product with SphI and HindIII
3. Digest pRK415 with SphI and HindIII
4. Ligate T fragment into digested pRK415 to form pRKT
5. PCR amplify PG product with Pf4SacI and PRSacI
15 6. Digest pRKT with SacI
7. Ligate PG fragment into SacI-digested pRKT
8. Transform E. colli and screen transformants to identify those with the PG sequence in the correct orientation.
Applicants deposited strain Rhodospirillum rubrum H1 at ATCC (10801 University Boulevard, Menassas, Virginia 20110-2209) Patent Deposit Designation PTA-5207 under the terms and conditions of the Budapest Treaty. Access to the deposit will be available during pendency of the patent application to one determined by the Commissioner to be entitled thereto under 35 U.S.C.§1.14 and 35 U.S.C. §122. Subject to 37 C.F.R. § 1.808 ( 2) (b), all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrovocably removed upon the granting of the patent.
To build a construct that expresses a desired protein, the following steps would preferably be used:
1. Amplify by PCR the structural gene encoding the protein. For this purpose, the PCR primers should incorporate a restriction site available in the polycloning site such that the amplified product can be inserted in the correct orientation. The sites must be in the multiple cloning site and not present in the parent plasmid used to construct the expression vector nor in the structural gene being cloned. The promoter/MCS/terminator sequences (FIG. 1) can be subcloned into different parent plasmids and this will affect the sites available for cloning. Primers may incorporate an optimized ribosomal binding site. To clone a partial sequence, initiation and termination codons as well as a ribosomal binding site preferably should be engineered into the primers. To clone eukaryotic proteins, the template DNA preferably should be cDNA in order to avoid introns.
2. Trim the purified PCR product with the appropriate restriction enzymes. It would be possible to use the same restriction site on both primers. However, under these conditions, this will not be “directional cloning” and it will be necessary to screen recombinants (restriction analysis) to identify those in the proper orientation.
3. Ligate the trimmed fragment into the expression vector digested with the appropriate enzymes. In addition to pJB3Cm6 (mentioned in the Examples), other vectors that could preferably be used as a platform for the expression fragment are pSUP104, pJRD215 and pKT210. (See [for pPSUP104]:
Priefer, U. B., et al., J. Bacteriol . 163:324-330, 1985; [for pJRD215]: Davison, J., et al., Gene 51:275-280, 1987; [for pKT210]: Priefer, U. B., et al., J. Bacteriol . 163:324-330, 1985.)
4. Transform a suitable E. colli strain (such as S17-1) with the construct.
5. Conjugate the construct into the R. rubrum host. Alternatively, R. rubrum can be electroporated or transformed. Select for transconjugants with the appropriate antibiotic. The appropriate antibiotic will be determined by the selection markers on the parent plasmid and the host.
6. Culture transconjugant under aerobic conditions.
7. Reduce oxygen tension to derepress cloned gene under control of puh promoter.
There are numerous potential applications for the host/vector system of the present invention. For example, biotechnology investigators could use the system in basic science applications concerning the numerous putative genes that have been identified and continue to be identified by genome sequencing. Immunological and biochemical approaches to understanding the role of these genes in healthy and diseased cells will require expression of the genes. This new host/vector system is uniquely suited for expression of membrane proteins.
Physical analysis (e.g. X-ray crystallography) requires milligram quantities of pure protein. This requirement has limited the application of this type of analysis to only a few membrane proteins, largely those that are highly expressed in their natural host. Expression of membrane proteins in the new host/vector system would extend this approach to many membrane proteins of importance. This would include, for example, receptors which play a role in intercellular communication in the immune response, neuroendocrine function, viral infection, and other important physiological activities.
Many immunoprotective antigens of viruses, bacteria and other infectious agents are membrane proteins. One of the most important potential applications of the present invention would be to produce vaccines. This host/vector system could be used for the production of new, improved or more cost-effective subunit vaccines. Among the potential advantages of this system are the following: (1) vaccine would not be infectious, (2) large scale production should be efficient, (3) proteins from difficult-to-cultivate pathogens could be expressed provided that sufficient sequence information is available to design PCR primers, and (4) the protein should be assembled in the membrane in its native (antigenic) state.
One potential obstacle is that the expressed protein would not be modified as in the native host. In the case of modification by proteolytic cleavage, this obstacle may be overcome by engineering a truncated protein. Viral proteins that are normally glycosylated would not be modified when produced in this R. rubrum host/vector system. However, non-glycosylated proteins may stimulate the production of protective antibody as has been found to be the case with the recombinant vaccine now in use for hepatitis B.
EXAMPLES
Vectors designed for the expression of membrane proteins in R. rubrum H15 were constructed. These constructs were based on pJB3Cm6 because this vector is small and fully sequenced. See, Blatny, J. M., et al., Appl. Environ. Microb . 63:370-379, 1997. Also note, the sequence of the puh region is reported in Berard, J., et al., supra, 1989 and Bérard, J. and Gingras, G, supra, 1991. Expression of cloned genes will be driven by puh expression sequences contained within pH 3.6−. Because of uncertainty in the length of sequence required for oxygen regulated expression, four putative puh promoter sequences of differing length (designated S and M done, L and G in progress) will be amplified by PCR and cloned into this vector to form pPS, pPM, pPL and pPG (FIG. 2 ). The putative puh terminator sequence was or will be cloned into each of these to form pPST, PPMT, pPLT and pPGT (FIG. 2 ). These sequences flank multiple cloning sites into which genes intended for expression may be cloned.
To test the capacity to express genes, the homologous gene puhA was used as a reporter. PuhA was amplified by PCR using primers that incorporated restriction sites for SacI and Sphl. The PCR product and the vectors were treated with these enzymes and the PCR fragments were ligated to the vectors to form pPSpuhT and pPMpuhT (FIGS. 2 and 3 ). These constructs were used to transform Escherichia coli S17-1 that was in turn conjugated to the puh knock-out strain R. rubrum H15. Both pPSpuhT and pPMpuhT restored phototrophic growth and photopigment content to H15 and the photochemical reaction center was detected by spectroscopy in cells incubated under phototrophic or semi-aerobic conditions (FIG. 4 ). The vector controls (PPST and PPMT) did not restore the phenotype. These results suggest that both expression vectors will function in R. rubrum for puhA expression.
To test the expression of a heterologous protein, MalF was amplified by PCR using total DNA from E. coli MC4100 as a template. This PCR product was cloned into pPST to form pPSMalFT (FIG. 2 ). This plasmid was transferred to R. rubrum H15 by conjugation and H15(pPSMalFT) was incubated under semi-aerobic conditions to evaluate expression of malF. Membranes were prepared from H15(pPSMalFT) and H15(pPSpuhT); the later served as a negative control. When analyzed by SDS-PAGE, MalF was not detected (not shown). When analyzed by immunoblot, MalF was detected in membranes prepared from H15(pPSMalFT) but not H15(pPSpuhT). These results indicate that while expression of MalF was achieved, hyperexpression was not.
Use of pREX to Express a Truncated Protein
The expression of puhA from pREX (aka pPST) provided the opportunity to evaluate a truncated puhA. The reverse primer 88R (below) was designed to incorporate a termination codon as well as a restriction site. The fragment amplified with HF and 88R, which encodes the first 88 amino acids of RC-H, was cloned into pREX to form pREXpuh88. The phenotype of H15 complemented with this construct was evaluated. This truncated puhA restored the photopigment content of the membrane to a level equivalent to that obtained with pREXpuh which is reflected in the spectrum. The spectrum also shows a peak at 800 nm indicative of the photochemical reaction center (RC). This RC formed with a truncated RC-H is functional because H15 (pREXpuh88) is capable of phototrophic growth. The ability to grow phototrophically was lost when H15 was cured of pREXpuh88.
primer
sequence 5-3
res. site
HF
GTTCCCAGGA gAGCtC GTCACCCTCAG
SacI
(SEQ ID NO:7)
88R
GCGCGGTGC GCaTGc C TTa GATCGCGACGGCATC 3
SphI
(SEQ ID NO:8)
restrictions sites in bold
termination codon underlined
8
1
857
DNA
Artificial Sequence
Description of Artificial Sequenceexpression
vector
1
cagctggcga aagggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc 60
cagtcacgac gttgtaaaac gacggccagt gaattcggtg ggcacgctga ccgcggcgat 120
ggcgctggcc gatgaaacgg tcagcggaat ggcgctcggc gcttggggcg ccgtgcaggc 180
caccgcgacc ggcgcggccg ttgcccttgg cggcggcttg cgcgatggcg tttcctcgtt 240
ggcggcccat ggcctgctcg gcgaggcctt aaccacggcc catacgggct atggtttcgt 300
ttatctggta gaagttgttt tgttatttac aaccttggcc atcatcggcc cgctggttcg 360
tacggccgga caccgcgcgt cccagtcttc ggaaggacgt ttcggtttgg ccgagttccc 420
aggagagctc ggtacccggg gatcctctag agtcgacctg caggcatgcc acatggatga 480
gtacgattcc gaaccgatcc gtggactgcc tgcggatctg ccgccgggcg aattcatcct 540
gtggcagggc gcgccgacac ggcgcgccct tgccctccgg gtgtttcaca ttcggctgat 600
cgcgctttat ttcgcgattc tggtggcgtg gaacgtggcc tcggctttgt atgacggcca 660
tccgctgccc aagcttggcg taatcatggt catagctgtt tcctgtgtga aattgttatc 720
cgctcacaat tccacacaac atacgagccg gaagcataaa gtgtaaagcc tggggtgcct 780
aatgagtgag ctaactcaca ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa 840
acctgtcgtg ccagctg 857
2
27
DNA
Artificial Sequence
Description of Artificial Sequence
oligonucleotide
2
gtaattgggg gcatgccaca tggatga 27
3
27
DNA
Artificial Sequence
Description of Artificial Sequence
oligonucleotide
3
cggcggtcag aagcttgggc agcggat 27
4
27
DNA
Artificial Sequence
Description of Artificial Sequence
oligonucleotide
4
gcaaccaagg aattcccgct gggtcgt 27
5
27
DNA
Artificial Sequence
Description of Artificial Sequence
oligonucleotide
5
gagggtgacg agctctcctg ggaactc 27
6
32
DNA
Artificial Sequence
Description of Artificial Sequence
oligonucleotide
6
atgaccagtt gagctcccat ccagccgctt gg 32
7
27
DNA
Artificial Sequence
Description of Artificial Sequence
oligonucleotide
7
gttcccagga gagctcgtca ccctcag 27
8
34
DNA
Artificial Sequence
Description of Artificial Sequence
oligonucleotide
8
gcgcggtgcg catgccttag atcgcgacgg catc 34
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A method of expressing proteins is disclosed. In a preferable embodiment, the method comprises placing a DNA sequence encoding a protein or peptide and expression vector containing a regulatable promoter expressible in Rhodospirillum rubrum and expressing the protein within a bacterial host, wherein the host has extra capacity for membrane formation and wherein the host is a member of the genus Rhodospirillum.
| 2
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PRIORITY CLAIM
Applicants claim the benefit of their prior Provisional Application, Ser. No. 60/727,175, filed Oct. 14, 2005, and titled IMPROVED DECK CONNECTOR.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an improved construction for deck connectors. The connectors of this invention basically comprise a metal piece that is cast into the edge of a concrete slab or tee, and a void is provided and defined by a box disposed behind the connector in the slab and communicating with a slot formed through the face of the connector. A plate dowel is movably disposed within the box, through the slot formed in the connector whereby adjacent concrete structural members may be joined by welding opposed plate dowels.
2. Description of the Prior Art
In the construction industry the use of flange connectors for the purpose of connecting adjacent concrete slabs and wall panels is certainly well-known. One early example of such prior art devices is provided in U.S. Pat. No. 3,958,954, to Ehlenbeck. According to the teaching of that patent, the connector is embedded along the edges of concrete members, and is formed of sheet metal that includes an elongated central portion which is exposed for the purpose of welding adjacent connectors on opposed panels.
Yet another form of such a connector is taught in U.S. Pat. No. 5,402,616, to Klein. Still another teaching in the patent literature is provided by U.S. Pat. No. 6,185,897, to Johnson, et al. All three of the prior art devices identified in the above patents provide a substantially flat metal surface exposed on the edge of the concrete element and a pair of angularly-extending legs into the concrete element, those legs extending back into the concrete from the exposed planar weldment face. The actual connection between adjacent slabs and connectors is performed by either welding the exposed faces to each other, or, more commonly, inserting a bar or slug between the faces and accomplishing the welding connection.
The prior art also teaches that the use of plate dowels between such concrete structures may be advantageous in that such plate dowels may be inserted into a pocket so that the slabs may move horizontally to minimize the size and number of restraint cracks. However, the prior art neither discloses nor suggests any structure whereby the utility of a plate dowel may be combined with state-of-the-art connectors.
It is therefore clear that an improved deck connector, suitable for use in combination with a form of plate dowel, would represent a significant improvement in the construction of various structures utilizing precast/prestressed slabs and wall panels. Of course, for purposes of economy and utility, any such improved connector must be suitable for installation as the slabs are formed and easily accessible as the structure is erected. For purposes of safety, the connections formed using the improved connector must satisfy all applicable codes and standards.
SUMMARY OF THE INVENTION
The present invention relates to an improved deck connector of the type used in the construction industry for joining adjacent concrete structures in an edge-to-edge or edge-to-vertical relationship. The improved connector basically comprises a bent metal anchor that is embedded into the concrete structural element as it is formed. The connector further comprises a plastic box or housing that receives a metal weld plate, preferably having a pull tab attached thereto. The invention further comprises a void former that is held over the exposed surface of the metal connector as the concrete element is formed. The void former is preferably held in place by magnets and is removed for use, as more fully set forth hereinafter.
The invention accordingly comprises the features of construction, combination of elements, and arrangement of part which will be exemplified in the construction hereinafter set forth, and the scope of the invention will be indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
For a fuller understanding of the nature and objects of the invention, reference should be had to the following detailed description taken in connection with the accompanying drawings in which:
FIG. 1 is a front elevation view of the bent metal anchoring device, with the flat metal weld plate indicated in broken lines.
FIG. 2 is a top plan view illustrating placement of the improved connector within a concrete slab and including reinforcing mesh and anchor bars.
FIG. 3 is a right side view of the improved deck connector of this invention.
FIG. 4 is a side view of a preferred embodiment for the metal weld plate.
FIG. 5 is a top plan view of the weld plate of FIG. 4 , and shows the addition of a pull tab.
FIG. 6 is as top plan view of the top half of the weld plate box or housing, depicting internal ridges in broken lines.
FIG. 7 is an inside plan view of the bottom half of the weld plate box or housing.
FIG. 8 is a front elevation of the void former.
FIG. 9 is a rear elevation of the void former.
Similar reference characters refer to similar parts throughout the several views of the drawings.
DETAILED DESCRIPTION
A preferred embodiment for the improved deck connector of this invention is shown in drawing FIGS. 1-9 . The invention basically comprises a bent metal anchoring device, generally indicated as 10 in the views of FIGS. 1-3 . A plastic box or housing, generally indicated as 12 in the views of FIGS. 2 , 6 and 7 , is provided rearwardly of the anchoring device 10 , and a flat metal weld plate, generally indicated as 14 in the views of FIGS. 4 and 5 , is mounted within box 12 . Finally, a void former, generally indicated as 16 in the views of FIGS. 2 , 8 and 9 , is removably attachable to the front of anchoring device 10 .
Attention is first invited to the view of FIG. 2 , wherein the improved deck connector of this invention is shown as it might be typically placed within a concrete slab as the slab is formed. Metal anchoring device 10 may be stamped and formed from a sheet of metal stock, preferably steel. The anchoring device 10 includes a substantially planar front face 18 having a rectangular opening 20 formed therein. On each side of front face 18 the metal stock is split to form four legs, defined by upper legs 22 and 24 and lower legs 26 and 28 . As indicated in the views of FIGS. 1 and 2 , each of the upper legs 22 and 24 are bent rearwardly from front face 18 to define an angle of about 50 degrees with respect to the plane defined by front plate front face 18 . Each of the lower legs 26 and 28 are similarly bent rearwardly, and preferably define an angle of about 95 degrees with respect to the plane defined by front face 18 . In the view of FIG. 2 one can see that all legs 22 , 24 , 26 and 28 are further formed in a wave-like manner. Finally, at the distal end of each of the legs 22 - 28 a leg aperture 30 is formed.
Both the angular orientation of legs 22 - 28 and the wave-like bending of each of those legs significantly enhance the security of anchoring device 10 within the concrete slab. Additional security of anchoring device 10 within the concrete may be accomplished by the insertion of reinforcing bars 32 through opposed leg apertures 30 in the upper legs 22 and 24 , and the opposed leg apertures 30 in each of the lower legs 26 and 28 . However, the use of reinforcing bars 32 is considered optional.
The plastic box or housing 12 is also shown in the view of FIG. 2 , and is disposed on the back side of front face 18 . Referring to the views of FIGS. 6 and 7 , it can be seen that the box 12 is preferably formed from a top half, generally indicated as 34 in the view of FIG. 6 , and a bottom half generally indicated as 36 in the view of FIG. 7 . Box 12 is preferably formed from plastic and each of the halves 34 and 36 comprise opposed, mating male tabs 38 and female receivers 40 whereby the halves 34 and 36 may be snapped together. One can also see that each of the halves 34 and 36 include a plurality of ridges 42 formed on the interior thereof. Finally, a box opening 44 is provided, and box opening 44 is in registry with rectangular opening 20 formed in front face 18 of anchoring device 10 . Attention is invited to the fact that box opening 44 is centered on the face of box 12 and is smaller than the horizontal dimension (width) defined by the interior of box 12 .
Movably mounted within box 12 is weld plate 14 . As clearly seen in the view of FIG. 5 , weld plate 14 defines a horizontal dimension (width) at its rear edge 46 that is greater than the horizontal dimension (width) defined by beveled front edge 48 . Rear edge 46 is wider than the corresponding width of box opening 44 , and beveled front edge 48 is slightly less than the corresponding dimension of box opening 44 . Thus, beveled front edge 48 of weld plate 14 may be withdrawn from box 12 , using pull tab 50 , thereby extending outwardly from box 12 and through rectangular opening 20 to position beveled front edge 48 of weld plate 14 for its intended use of connecting to an adjacent anchoring device 10 in an adjacent concrete structure. Pull tab 50 would then simply be removed.
The provision of the ridges 42 on the interior of box 12 serves as guides or runners for weld plate 14 . The substantially T-shape of weld plate 14 prevents its removal from anchoring device 10 , while still permitting adjustment of its position with respect to an adjacent anchoring device 10 in a second concrete structure to which attachment is desired. The beveled structure defined by front edge 48 of weld plate 14 further enhances the ease with which a connection can be made. It is to be understood that a welding slug or bar is not required, but may be used. It is also to be understood that, for purposes of economy, the opposed anchoring device in the second concrete structure may be constructed to define a continuous front face, having no rectangular opening 20 , no box or housing 12 , and no weld plate 14 . That second device would, however, include upper legs 22 and 24 and lower legs 26 and 28 as described above. If such a modified anchoring device were used, in the second concrete structure, weld plate 14 as described above could be welded directly to the modified front face of the modified anchoring device.
While the preferred method of connecting adjacent anchoring devices is by welding opposed weld plates 14 as described above, or by welding weld plate 14 to the modified face of the modified anchoring device, other means for accomplishing the connection are also contemplated. For example, the front edge of opposed weld plates may be modified to define correspondingly opposed relieved portions, or steps such that opposed modified weld plates would actually overlap each other when withdrawn from their respective boxes 12 for attachment. Physical attachment could then be accomplished by welding, or even by the placement of bolts through apertures formed in the opposed ledges.
Referring once again to the view of FIGS. 2 and 3 , it should be noted that leg apertures 30 are preferably of an oval configuration and that each of the upper legs 22 and 24 are preferably disposed above reinforcing mesh 52 while lower legs 26 and 28 are preferably disposed below reinforcing mesh 52 .
According to known forming techniques, it is necessary to “protect” what will be the exposed front face 18 of anchoring device 10 as the concrete is poured and allowed to set. This “protection” is accomplished by the use of void former 16 . Referring to the view of FIG. 8 , one can see that void former front face 54 comprises opposed, substantially U-shaped ridges 56 thereon. While attachment of void former 16 to anchoring device 10 may be accomplished by any suitable, standard means for removal after the structure has been formed, the preferred attachment is by placing magnets within the area defined by U-shaped ridges 56 .
Clearly, then, the improved deck connector of this invention represents a significant advance over the current state of the art. The structure of metal anchoring device 10 enhances the “capture” of the connector within the concrete structure, particularly if reinforcing bars 32 are utilized. Box or housing 12 into which the weld plate 14 is mounted is easily assembled because of its two-part, snap-together structure, and the shape of weld plate 14 literally eliminates the possibility of the plate being lost by falling out during transportation or installation. Furthermore, because weld plate 14 is free to move on the ridges 42 formed within box 12 , the connector of this invention is suitable for use across joints of from about zero (0) to about 1.5 inches in width. Even once the connection has been made, weld plate 14 may still “move” to accommodate expansion and contraction of the joined structure without transferring stress to the concrete. Finally, because the weld plate 14 does not come into contact with either surrounding concrete or anchoring device 10 , heat resulting from the welding operation more easily dissipates and is not directly transferred to the structure. This significantly reduces the likelihood of cracking or splintering during the connection process. While it may be viewed as relatively minor, the addition of the removable pull tab 50 to weld plate 14 significantly enhances the ease with which the weld plate 14 may be withdrawn for connection. Finally, the utility of the improved deck connector of this invention is enhanced by the fact that anchoring device 10 may be formed using known cutting and stamping techniques from flat stock and that box or housing 12 may be formed with extreme economy by plastic molding.
It will thus be seen that the objects set forth above, among those made apparent from the preceding description, are efficiently attained and since certain changes may be made in the above construction without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.
Now that the invention has been described,
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A deck connector that may be cast into a structural concrete element for use in joining adjacent ones of the concrete elements to each other by the use of weld plates that are movably disposed within a weld plate housing forming an element of each of the deck connectors.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. application Ser. No. 12/871,218 filed Aug. 30, 2010 that claims priority to United Kingdom Patent Application No. GB1013292.6, entitled “Low Friction Wireline Standoff,” filed on Aug. 7, 2010, the entire disclosure of each are incorporated herein by reference in their entirety.
BACKGROUND
[0002] This invention relates to a device that improves wireline cable performance during logging operations in a variety of boreholes. The use of low friction wireline standoffs ameliorates the effects of wireline cable differential sticking, wireline cable key-seating, and high cable drags by reducing or eliminating the contact of the wireline cable with the borehole wall during the logging operation.
[0003] Wireline logging is a common operation in the oil industry whereby down-hole electrical tools are conveyed on wireline (also known as “e-line” in industry parlance) to evaluate formation lithologies and fluid types in a variety of boreholes. In certain wells there is a risk of the wireline cable and/or logging tools becoming stuck in the open hole due to differential sticking or key-seating, as explained below.
[0004] Key-seating happens when the wireline cable cuts a groove into the borehole wall. This can happen in deviated or directional wells where the wireline cable may exert considerable sideways pressure at the contact points with the borehole. Since the logging tool diameter is generally much bigger than the groove cut by the wireline cable a keyseat can terminate normal ascent out of the borehole and result in a fishing job or lost tools in hole.
[0005] Differential sticking can occur when there is an overbalance between hydrostatic and formation pressures in the borehole; the severity of differential sticking is related to:
The degree of overbalance and the presence of any depleted zones in the borehole. The character and permeability of the formations bisected by the borehole. The deviation of the borehole, since the sideways component of the tool weight adds to the sticking forces. The drilling mud properties in the borehole, since the rapid formation of thick mud cakes can trap logging tools and the wireline cable against the borehole wall. The geometry of toolstring being logged on wireline. A long and large toolstring presents a larger cross sectional area and results in proportionally larger sticking forces.
[0011] Additionally, during wireline formation sampling, the logging tools and wireline may remain stationary over permeable zones for a long period of time which also increases the likelihood of differential sticking.
SUMMARY
[0012] This invention ameliorates the effects of differential sticking and key-seating of the wireline cable by reducing or eliminating direct contact of the cable to the borehole wall. This is achieved by clamping an array of low friction wireline standoffs onto the wireline cable, resulting in a lower contact area per unit length of open hole, lower applied sideways pressure of the wireline against the borehole wall, and lower cable drag when conveying the wireline in or out of the hole. The use of low area standoffs also enables more efficient use of wireline jars in the logging string since they reduce the cable friction above the jars, allowing firing at lower surface tensions and easier re-rocking of the jars in boreholes where high cable drag is a problem (absorbing the applied surface tension before it can reach the wireline cable head and jars).
[0013] The features and advantages of the present invention will be readily apparent to those skilled in the art. While numerous changes may be made by those skilled in the art, such changes are within the spirit of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] These drawings illustrate certain aspects of the present invention and should not be used to limit or define the invention.
[0015] FIG. 1 is an isometric view of the wireline standoff before being clamped onto the wireline.
[0016] FIG. 2 is an isometric view of the low friction wireline standoff clamped onto a short section of wireline.
[0017] FIG. 3 illustrates an array of low friction wireline standoffs installed on a wireline cable in the borehole during borehole logging operations. FIG. 3 a shows an example close up view of the low friction wireline standoff on the wireline cable in relation to the borehole wall.
[0018] FIG. 4 is an isometric exploded view of the low friction wireline standoff with a single wheel sub assembly and one half shell removed, to illustrate the fitting of the aluminum cable insert.
[0019] FIG. 4 a is an end view of the same components in FIG. 4 .
[0020] FIG. 5 is an exploded view of the half shells and cable inserts that make up each low friction wireline standoff assembly. The 12 wheel sub assemblies have been omitted for the sake of clarity.
[0021] FIG. 6 illustrates the use of small cap head screws to hold the cable inserts inside the half shells.
[0022] FIG. 7 illustrates a cross section of the half shell, cable inserts, cap head fixing screws and wireline cable.
[0023] FIG. 8 illustrates a cross section of the low friction wireline standoff assembly in a plane bisecting two opposing wheel sub assemblies.
DETAILED DESCRIPTION
[0024] An array of low friction wireline standoffs can be installed on the wireline cable to minimize the wireline cable contact over a selected zone(s) of the open hole section. The low friction wireline standoffs may be installed on the wireline cable to either straddle known permeable zones where differential sticking is a risk (e.g., eliminating cable contact 100%) or they can be placed at regular intervals along the wireline cable to minimize keyseating, taking into account the dog leg severity of the borehole. The higher the dogleg severity the shorter the recommended spacing between wireline standoffs installed on the wireline cable. The spacing of wireline standoffs on the cable may be from 10's of feet to 100's of feet, depending on the requirements for the particular borehole being logged.
[0025] In accordance with present embodiments, each low friction wireline standoff comprises two opposing assemblies which mate together onto the wireline cable. In an embodiment, the opposing assemblies clamp together on the wireline cable with four cap head bolts. The assemblies comprise two stainless steel half shells with exterior wheels and two disposable cable inserts on the interior. In one embodiment, the assemblies comprise twelve exterior wheels. In an exemplary embodiment, contact with the wireline cable exterior is solely with the cable inserts made from aluminum, and not the stainless steel half shells. In one embodiment, the cable inserts are designed to slightly deform around the outer wireline cable armour during installation without physically damaging the wireline cable. There are a large range of cable inserts available to fit the wireline cable, taking into account any manufacturing tolerances and varying degrees of wear or distortion along the length of the wireline cable. Therefore, for an array of low area standoffs installed on the wireline cable a range of different cable inserts may be employed to ensure a fit which does not allow slippage along the wireline cable or damage to the wireline cable when clamped. The four cap head bolts that clamp the two assemblies together are torqued to a consistently safe limit with a calibrated torque wrench.
[0026] In certain embodiments, the stainless steel half shells are vacuum hardened for improved wear resistance during use and a range of shell sizes are available for installation on the wireline, for example, from 50 mm O.D. upwards. The aluminum cable inserts are positively secured into each stainless half shell by small cap head bolts that pass through the outside of each half shell into tapped holes in the cable insert bodies. The cable inserts have zero freedom of movement inside the half shells because:
[0027] a) a central spigot eliminates rotation of the cable inserts in the half shells.
[0028] b) a central flange on the cable inserts ensures no axial movement in the half shells.
[0029] The low friction wireline standoff may further include a plurality of fins along its length. In an embodiment, the low friction wireline standoff has 12 fins cut along its length, each fin holding a wheel sub assembly. The wheels rotate in plain bearings machined in the bodies of the half shells and are clamped in position with slotted wheel retainers and cap head bolts. The wheels reduce the standoff rolling resistance which results in lower tensions and cable drags inside casing and the open borehole.
[0030] The wheels also minimize contact area of the standoff assemblies with the borehole wall and reduce the differential sticking force acted upon each wheel at the contact points with the borehole. They also allow easy rotation of the standoffs if the wireline cable rotates when it is deployed and retrieved from the borehole. Note that it is the general nature of wireline logging cable to rotate during logging operations due to the opposing lay angles of the inner and outer armours which can induce unequal torsional forces when tensions are applied. The design of the shells and wheels allows easy rotation of the wireline cable during the logging operation, avoiding the potential for damage if excessive torque was allowed to build up.
[0031] In addition, the low friction wireline standoff may further include a plurality of holes in the half shells for use in installation. In an embodiment, four holes in the standoff half shells are used to connect a lanyard during installation, to avoid dropped objects on the drill floor during installation on the wireline cable.
[0032] In accordance with certain embodiments, the maximum external diameter of the low friction wireline standoff is less than the size of overshot and drill pipe i.d. during fishing operations. In the event of a fishing job, the array of low area standoffs will safely fit inside the fishing assembly provided by the Operator, enabling the wireline cable head or tool body to be successfully engaged by the fishing overshot. The wireline cable and low friction wireline standoff array may then be safely pulled through the drill pipe all the way to surface when the cable head is released from the logging string.
[0033] The invention will now be described in detail with the aid of FIGS. 1-8 , as summarized below. Note that “low friction wireline standoff” implies the full assembly of aforementioned components i.e. the stainless steel half shells and wheel sub assemblies, the aluminum cable inserts, and the associated cap head bolts.
[0034] The low friction wireline standoff 1 as seen in FIG. 1 comprises twelve exterior wheels mounted in two stainless steel half shells 2 and two internal aluminum cable inserts 3 which clamp directly onto the wireline cable using four cap head bolts 4 . The cable inserts are secured in their half shells by two fully recessed small cap head bolts 5 . Twelve external fins 6 and wheel sub assemblies on the low friction wireline standoff aid easy passage along the borehole and casing in the well. Each fin 6 supports a wheel sub assembly comprising a high strength wheel and axle 7 , and a slotted wheel retainer 8 , secured by a pair of cap head bolts 9 . Each wheel is profiled for axial grip whilst minimizing the rolling resistance and contact area with the borehole, and also allowing for standoff rotation under the action of cable torque. The empty space between the fins and wheel sub assemblies allow for circulation of drilling mud inside drill pipe if the wireline cable and standoff assembly are fished using drill pipe. Holes across the two half shells 10 permit the fitting of a lanyard to avoid dropping them during their installation onto the wireline cable on the drill floor.
[0035] As depicted in FIG. 2 , a short section of the wireline cable 11 passes through the central bore of the cable inserts 3 in the low friction wireline standoff 1 . The wireline cable diameter may vary between 10-15 mm, depending on the logging vendor. The cable inserts are carefully matched to the diameter of the wireline cable regardless of any variations in size or profile that might occur along the length of the wireline cable. The cable inserts can be made from aluminum which is considerably softer than the armour material of the wireline cable. An accurate fit of the cable inserts on the wireline cable and the controlled torque of the four cap head bolts 4 during installation ensures that the cable inserts cannot damage the wireline cable when the bolts are tightened, pulling the two half shells 2 together.
[0036] FIG. 3 shows a generic logging operation and low friction wireline standoff deployment. An array of low friction wireline standoffs 1 is clamped onto the wireline cable 11 which is stored on the wireline drum 12 and spooled into the well by a winch driver and logging engineer in the logging unit 13 . The logging unit is fixed firmly to the drilling rig or platform 14 and the wireline is deployed through the derrick via two or three sheaves 15 and 16 to the maximum depth of the well. The logging tool connected to the end of the wireline cable 17 takes the petro-physical measurements or fluid or rock samples in the open hole section. The number of standoffs and their positions on the wireline are determined by the length of the open hole section, the location of sticky, permeable, or depleted zones, and the overall trajectory of the well, which may be deviated or directional in nature. As per the close up illustration in FIG. 3 a the low friction wireline standoff 1 can be seen in relation to the wireline cable 11 and the borehole wall 18 and the borehole 19 .
[0037] FIGS. 4 and 4 a show the low friction wireline standoff with the lower half shell 2 removed such that the upper half shell 2 with cable insert in-situ 3 can be viewed. Included is a semi-exploded view of a single wheel sub assembly that illustrates the wheel and axle 7 and slotted wheel retainer 8 , with pair of cap head bolts 9 to hold them in the half shell 2 . In FIG. 4 the four holes 20 in the upper half shell 2 allow accurate mating to the lower half shell via high strength dowel pins, eliminating any shear stress on the four cap head bolts that clamp the shells onto the wireline.
[0038] FIG. 5 shows an exploded view of the low friction wireline standoff with the main components exposed: half shells 2 , cable inserts 3 , and four clamping bolts 4 . The twelve wheel sub assemblies are not included for the sake of clarity. The cable insert flange 21 and anti-rotation spigot 22 eliminate any relative movement between the half shells and cable inserts.
[0039] FIG. 6 shows an exploded view of the cable inserts 3 with small cap head screws 5 that retain them in the half shells. The cable insert flange 21 and anti-rotation spigot 22 are clearly visible. The ends of the cable inserts are chamfered to avoid pinching the wireline cable.
[0040] FIG. 7 shows a cross section of the standoff installed on the wireline cable 11 . It includes the cable insert 3 with small cap head screws 5 that retain them in the half shells 2 . A partial view of the wheels 7 and wheel retainers 8 can also be seen in the cross section.
[0041] FIG. 8 shows a cross section of the low friction standoff installed on the wireline cable 11 , in a plane which cuts through opposing wheel sub assemblies. It includes the half shell 2 and cable insert 3 . The wheels and axles 7 are held in place with slotted wheel retainers 8 and cap head screws 9 .
[0042] Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations may be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
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The low friction wireline standoff improves wireline cable performance during borehole logging operations. The use of low friction wireline standoffs ameliorates the effects of wireline cable differential sticking, wireline cable key-seating, and high wireline cable drags, by reducing or eliminating contact of the wireline cable with the borehole wall during the logging operation. The low friction wireline standoff comprises external wheels mounted on two finned half shells that clamp onto the wireline with precision cable inserts which are manufactured to fit a wide range of logging cables. The wheels reduce the cable drag down-hole resulting in lower surface logging tensions, aiding conveyance in deep and deviated wells.
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TECHNICAL FIELD
[0001] The present disclosure relates to modifying torque limits in hybrid vehicles.
BACKGROUND
[0002] A hybrid electric vehicle utilizes both an engine and an electric machine to provide torque to the wheels. A disconnect clutch may decouple the engine from the vehicle powertrain to allow the engine to be in an off state while the electric machine is propelling the vehicle.
SUMMARY
[0003] A method of controlling a vehicle is provided. The method may include, in response to receiving a start request for an engine while an electric machine is generating torque to drive the vehicle at a torque limit of the electric machine, increasing the torque beyond the torque limit for a predefined duration of time to provide torque to start the engine.
[0004] A vehicle is provided. The vehicle includes an engine, a fraction motor, and a controller. The controller may be configured to, in response to receiving a request for additional torque to start the engine while the fraction motor is operating at a torque limit to satisfy a drive torque command, command the traction motor to increase torque output for a predefined duration of time to satisfy the request for additional torque.
[0005] A powertrain controller for a vehicle is provided. The controller may include input channels configured to receive start requests for an engine and operating condition data for an electric machine, and output channels configured to provide torque commands for the electric machine. The controller may further include control logic configured to, in response to receiving a start request for the electric machine while the operating condition data indicates that the electric machine is operating at a torque limit to drive the vehicle, generate torque commands that cause the electric machine to exceed the torque limit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1 is a schematic diagram of a hybrid electric vehicle;
[0007] FIG. 2 is a graph depicting the relationship between torque and speed during operation of a hybrid electric vehicle;
[0008] FIGS. 3A through 3C are a series of graphs depicting the relationship between speed, torque, and time during operation of a hybrid electric vehicle; and
[0009] FIG. 4 is a flow chart describing control logic for a powertrain controller of a hybrid electric vehicle.
DETAILED DESCRIPTION
[0010] Embodiments of the present disclosure are described herein. It is to be understood, however, that the disclosed embodiments are merely examples and other embodiments may take various and alternative forms. The figures are not necessarily to scale; some features could be exaggerated or minimized to show details of particular components. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the present invention. As those of ordinary skill in the art will understand, various features illustrated and described with reference to any one of the figures may be combined with features illustrated in one or more other figures to produce embodiments that are not explicitly illustrated or described. The combinations of features illustrated provide representative embodiments for typical applications. Various combinations and modifications of the features consistent with the teachings of this disclosure, however, could be desired for particular applications or implementations.
[0011] Referring to FIG. 1 , a schematic diagram of a hybrid electric vehicle (HEV) 10 is illustrated. FIG. 1 illustrates representative relationships among several vehicle components. Physical placement and orientation of the components within the vehicle 10 may vary. The vehicle 10 includes a powertrain 12 . The powertrain 12 includes an engine 14 that drives a transmission 16 . As will be described in further detail below, the transmission 16 includes an electric machine such as an electric motor/generator (M/G) 18 , an associated traction battery 20 , a torque converter 22 , and a multiple step-ratio automatic transmission, or gearbox 24 .
[0012] The engine 14 and the M/G 18 are both capable of providing motive power for the HEV 10 . The engine 14 generally represents a power source which may include an internal combustion engine such as a gasoline, diesel, or natural gas powered engine, or a fuel cell. The engine 14 generates an engine power and corresponding engine torque that is supplied to the M/G 18 when a disconnect clutch 26 between the engine 14 and the M/G 18 is at least partially engaged. The M/G 18 may be implemented by any one of a plurality of types of electric machines. For example, the M/G 18 may be a permanent magnet synchronous motor. Power electronics 28 condition direct current (DC) power provided by the battery 20 to the requirements of the M/G 18 , as will be described below. For example, power electronics may provide three phase alternating current (AC) to the M/G 18 .
[0013] The engine 14 may additionally be coupled to a turbocharger 46 to provide an air intake pressure increase, or “boost” to force a higher volume of air into a combustion chamber of the engine 14 . Related to the increased air pressure provided to the engine 14 by the turbocharger 46 , a corresponding increase in the rate of fuel combustion may be achieved. The additional air pressure boost therefore allows the engine 14 to achieve additional output power, thereby increasing engine torque.
[0014] The gearbox 24 may include gear sets (not shown) that are selectively placed in different gear ratios by selective engagement of friction elements such as clutches and brakes (not shown) to establish the desired multiple discrete or step drive ratios. The friction elements are controllable through a shift schedule that connects and disconnects certain elements of the gear sets to control the ratio between a transmission output shaft 38 and the transmission input shaft 34 . The gearbox 24 ultimately provides a powertrain output torque to output shaft 38 .
[0015] As further shown in the representative embodiment of FIG. 1 , the output shaft 38 is connected to a differential 40 . The differential 40 drives a pair of wheels 42 via respective axles 44 connected to the differential 40 . The differential transmits torque allocated to each wheel 42 while permitting slight speed differences such as when the vehicle turns a corner. Different types of differentials or similar devices may be used to distribute torque from the powertrain to one or more wheels. In some applications, torque distribution may vary depending on the particular operating mode or condition, for example.
[0016] The vehicle 10 further includes a foundation brake system 54 . The system may comprise friction brakes suitable to selectively apply pressure by way of stationary pads attached to a rotor affixed to the wheels. The applied pressure between the pads and rotors creates friction to resist rotation of the vehicle wheels 42 , and is thereby capable of slowing the speed of vehicle 10 .
[0017] When the disconnect clutch 26 is at least partially engaged, power flow from the engine 14 to the M/G 18 or from the M/G 18 to the engine 14 is possible. For example, when the disconnect clutch 26 is engaged, the M/G 18 may operate as a generator to convert rotational energy provided by a crankshaft 30 through M/G shaft 32 into electrical energy to be stored in the battery 20 . The rotational resistance imparted on the shaft through regeneration of energy may be used as a brake to decelerate the vehicle. The disconnect clutch 26 can also be disengaged to decouple the engine 14 from the remainder of the powertrain 12 such that the M/G 18 can operate as the sole drive source for the vehicle 10 .
[0018] Operation states of the powertrain 12 may be dictated by at least one controller. While illustrated by way of example as a single controller, such as a vehicle system controller (VSC) 48 , there may be a larger control system including several controllers. The individual controllers, or the control system, may be influenced by various other controllers throughout the vehicle 10 . For example controllers that may be included within representation of the VSC 48 include a transmission control module (TCM), brake system control module (BSCM), a high voltage battery energy control module (BECM), as well as other controllers in communication which are responsible for various vehicle functions. The at least one controller can collectively be referred to as a “controller” that commands various actuators in response to signals from various sensors. The VSC 48 response may serve to dictate or influence a number of vehicle functions such as starting/stopping engine 14 , operating the M/G 18 to provide wheel torque or recharge the traction battery 20 , select or schedule transmission gear shifts, etc.
[0019] The VSC 48 may further include a microprocessor or central processing unit (CPU) in communication with various types of computer readable storage devices or media. Computer readable storage devices or media may include volatile and nonvolatile storage in read-only memory (ROM), random-access memory (RAM), and keep-alive memory (KAM), for example. KAM is a persistent or non-volatile memory that may be used to store various operating variables while the CPU is powered down. Computer-readable storage devices or media may be implemented using any of a number of known memory devices such as PROMs (programmable read-only memory), EPROMs (electrically PROM), EEPROMs (electrically erasable PROM), flash memory, or any other electric, magnetic, optical, or combination memory devices capable of storing data, some of which represent executable instructions, used by the controller in controlling the engine or vehicle.
[0020] The VSC 48 communicates with various engine/vehicle sensors and actuators via an input/output (I/O) interface that may be implemented as a single integrated interface that provides various raw data or signal conditioning, processing, and/or conversion, short-circuit protection, and the like. Alternatively, one or more dedicated hardware or firmware chips may be used to condition and process particular signals before being supplied to the CPU. As generally illustrated in the representative embodiment of FIG. 1 , the VSC 48 may communicate signals to and/or from the engine 14 , the turbocharger 46 , the disconnect clutch 26 , the M/G 18 , the transmission gearbox 24 , torque converter 22 , the torque converter bypass clutch 36 , and the power electronics 28 . Although not explicitly illustrated, those of ordinary skill in the art will recognize various functions or components that may be controlled by the VSC 48 within each of the subsystems identified above. Representative examples of parameters, systems, and/or components that may be directly or indirectly actuated using control logic executed by the controller include fuel injection timing, rate, and duration, throttle valve position, spark plug ignition timing (for spark-ignition engines), intake/exhaust valve timing and duration, front-end accessory drive (FEAD) components such as an alternator, air conditioning compressor, battery charging, regenerative braking, M/G operation, clutch pressures for disconnect clutch 26 , torque converter bypass clutch 36 , and transmission gearbox 24 , and the like. Sensors communicating input through the I/O interface may be used to indicate turbocharger boost pressure, turbocharger rotation speed, crankshaft position, engine rotational speed (RPM), wheel speeds, vehicle speed, engine coolant temperature, intake manifold pressure, accelerator pedal position, ignition switch position, throttle valve position, air temperature, exhaust gas oxygen or other exhaust gas component concentration or presence, intake air flow, transmission gear, ratio, or mode, transmission oil temperature, transmission turbine speed, torque converter bypass clutch status, deceleration, or shift mode, for example.
[0021] The VSC 48 also includes a torque control logic feature. The VSC 48 is capable of interpreting driver requests based on several vehicle inputs. These inputs may include, for example, gear selection (PRNDL), accelerator pedal inputs, brake pedal input, battery temperature, voltage, current, and battery state of charge (SOC). The VSC 48 in turn may issue command signals to the transmission to control the operation of the M/G 18 .
[0022] The M/G 18 is also in connection with the torque converter 22 via shaft 32 . Therefore, the torque converter 22 is also connected to the engine 14 when the disconnect clutch 26 is at least partially engaged. The torque converter 22 includes an impeller fixed to the M/G shaft 32 and a turbine fixed to a transmission input shaft 34 . The torque converter 22 provides a hydraulic coupling between shaft 32 and transmission input shaft 34 . An internal bypass clutch 36 may also be provided such that, when engaged, clutch 36 frictionally or mechanically couples the impeller and the turbine of the torque converter 22 , permitting more efficient power transfer. The torque converter bypass clutch 36 may be operated as a launch clutch to provide smooth vehicle launch. In contrast, when the bypass clutch 36 is disengaged, the M/G 18 may be decoupled from the differential 40 and the vehicle axles 44 . For example, during deceleration the bypass clutch 36 may disengage at low vehicle speeds, providing a torque bypass, to allow the engine to idle and deliver little or no output torque to drive the wheels.
[0023] A driver of the vehicle 10 may provide input at accelerator pedal 50 and create a demanded torque, power, or drive command to propel the vehicle 10 . In general, depressing and releasing the pedal 50 generates an accelerator input signal that may be interpreted by the VSC 48 as a demand for increased power or decreased power, respectively. Based at least upon input from the pedal, the controller 48 may allocate torque commands between each of the engine 14 and/or the M/G 18 to satisfy the vehicle torque output demanded by the driver. The controller 48 may also control the timing of gear shifts within the gearbox 24 , as well as engagement or disengagement of the disconnect clutch 26 and the torque converter bypass clutch 36 . Like the disconnect clutch 26 , the torque converter bypass clutch 36 can be modulated across a range between the engaged and disengaged positions. This may produce a variable slip in the torque converter 22 in addition to the variable slip produced by the hydrodynamic coupling between the impeller and the turbine. Alternatively, the torque converter bypass clutch 36 may be operated as either locked or open without using a modulated operating mode depending on the particular application.
[0024] The driver of vehicle 10 may additionally provide input at brake pedal 52 to create a vehicle braking demand. Depressing brake pedal 52 generates a braking input signal that is interpreted by controller 48 as a command to decelerate the vehicle. The controller 48 may in turn issue commands to cause the application of negative torque to the powertrain output shaft. Additionally or in combination, the controller may issue commands to activate the brake system 54 to apply friction brake resistance to inhibit rotation of the vehicle wheels 42 . The negative torque values provided by both of the powertrain and the friction brakes may be allocated to vary the amount by which each satisfies driver braking demand.
[0025] To drive the vehicle with the engine 14 , the disconnect clutch 26 is at least partially engaged to transfer at least a portion of the engine torque through the disconnect clutch 26 to the M/G 18 , and then from the M/G 18 through the torque converter 22 and gearbox 24 . The M/G 18 may assist the engine 14 by providing additional powered torque to turn the shaft 32 . This operation mode may be referred to as a “hybrid mode.” As mentioned above, the VSC 48 may be further operable to issue commands to allocate a torque output of both the engine 14 and the M/G 18 such that the combination of both torque outputs satisfies an accelerator 50 input from the driver.
[0026] To drive the vehicle 10 with the M/G 18 as the sole power source, the power flow remains the same except the disconnect clutch 26 isolates the engine 14 from the remainder of the powertrain 12 . Combustion in the engine 14 may be disabled or otherwise OFF during this time in order to conserve fuel, for example. The traction battery 20 transmits stored electrical energy through wiring 51 to power electronics 28 that may include an inverter. The power electronics 28 convert high-voltage direct current from the battery 20 into alternating current for use by the M/G 18 . The VSC 48 may further issue commands to the power electronics 28 such that the M/G 18 is enabled to provide positive or negative torque to the shaft 32 . This operation where the M/G 18 is the sole motive source may be referred to as an “electric only” operation mode.
[0027] Therefore, it may be advantageous to operate the vehicle 10 in the “electric only” operation mode. However, during an engine restart command from the VSC 48 , drive torque from the M/G 18 may be reduced in order to supply the necessary engine torque to restart the vehicle engine 14 . In at least one embodiment, the VSC 48 may be programmed to increase torque output by the M/G 18 such that the torque output exceeds a drive torque limit of the M/G 18 to provide start torque for the engine 14 . This allows for an extended “electric only” operation mode.
[0028] Additionally, the M/G 18 may operate as a generator to convert kinetic energy from the powertrain 12 into electric energy to be stored in the battery 20 . The M/G 18 may act as a generator while the engine 14 is providing the sole propulsion power for the vehicle 10 , for example. The M/G 18 may also act as a generator during times of regenerative braking in which rotational energy from spinning of the output shaft 38 is transferred back through the gearbox 24 and is converted into electrical energy for storage in the battery 20 .
[0029] FIG. 2 is a graph of an increased torque output by the M/G 18 . FIG. 2 shows torque in Nm increasing along the y-axis and speed in RPM increasing along the x-axis. FIG. 2 depicts curves for periods of constant torque and constant power. Modifying a drive torque limit of the M/G 18 allows the M/G 18 to briefly output torque above a maximum drive torque limit. Curve 100 represents an unmodified drive torque limit for drive torque generated by the M/G 18 . The unmodified drive torque limit, as represented by curve 100 , may be a generally conservative maximum drive torque limit. The maximum drive torque limit of the M/G 18 is based on the basic design of the M/G 18 . Likewise, curve 120 represents a maximum drive torque availability for “electric only” operation mode. Curve 120 is representative of the unmodified drive torque limit of curve 100 minus an engine start torque reserved for engine starts or restarts. As depicted by curve 120 , this minimizes the availability of drive torque from the M/G 18 used during “electric only” operation mode. Increasing the maximum drive torque available during “electric only” operation mode without increasing the size of the M/G 18 improves overall fuel economy.
[0030] Curve 140 represents a modified drive torque limit for drive torque generated by the M/G 18 . Because the unmodified drive torque limit, as represented by curve 100 , is generally conservative, a modified drive torque limit, as represented by curve 140 , may be used that accounts for transient bursts of required drive torque. For example, the modified drive torque limit represented by curve 140 , may be used for engine starts and restarts that occur in less than one second. Likewise, curve 160 represents a new maximum drive torque availability for “electric only” operation mode. This is based on the modified drive torque limit, as represented by curve 140 . The new maximum drive torque availability, as represented by curve 160 , equals the modified torque limit, as represented by curve 140 , minus the torque reserved for engine starts and restarts. By increasing the unmodified, steady-state maximum torque limit of curve 100 to account for short transient bursts of required drive torque, more drive torque is available for operation within the “electric only” operation mode. This allows the M/G 18 to provide the sole motive power for a longer duration. Extending the range of the “electric only” operation mode allows for significant improvement in vehicle fuel economy.
[0031] The modified drive torque limit, as represented by curve 140 , acts as a buffer accounting for engine starts and restarts. The amount of torque required for engine starts and restarts may be pre-calculated. Therefore, the steady-state drive torque limit, as represented by curve 100 , may be raised by the pre-calculated torque necessary for engine starts and restarts for short durations. This allows for improved “electric only” operation mode capability. Further, this increases the engine off capability. Increasing the engine off capability offers the flexibility to utilize different engine brake specific fuel consumption maps. Improving the “electric only” operation mode capability and increasing the engine off capability improves fuel economy over a wide range of operating conditions.
[0032] FIGS. 3A through 3C are a series of graphs depicting the modified drive torque limit during “electric only” operation mode and “hybrid mode.” The graphs measure three different curvatures over a period of five different time intervals. The first graph measures the M/G speed and the engine speed increasing along the y-axis with the time intervals extending along the x-axis. The second graph measures M/G drive torque, engine torque, and disconnect clutch torque increasing along the y-axis with the time intervals extending along the x-axis. The third graph measures the engine torque increasing along the y-axis with the time intervals extending along the x-axis.
[0033] The first graph, referenced as graph A, measures the M/G speed as well as the engine speed over time. Specifically, the first graph compares the behavior of the M/G speed and the engine speed during the “electric only” operation mode and the “hybrid mode.” As noted in the first graph, engine speed reaches peak 200 between T 2 and T 3 . As discussed in more detail below, this peak is consistent with an engine start or restart command due to an accelerator pedal tip-in event. Further, from time interval T 3 through T 4 , the engine speed ramps up reaching peak 220 at T 4 . Peak 220 represents the point at which the disconnect clutch 26 is locked and the engine speed matches the M/G speed. Therefore, from time interval T 4 through T 5 , the engine 14 will be supplying engine torque along with the M/G 18 providing drive torque. When the engine 14 is on, the vehicle 10 will be in the “hybrid mode” operation.
[0034] The second graph, referenced as graph B, depicts torque increasing along the y-axis and time increasing along the x-axis. Dashed line 240 represents the maximum motor torque limit, as modified, to account for a transient burst of demanded torque during engine starts and restarts. Dashed line 260 represents the torque available during “electric only” operation mode. Using the modified maximum torque limit, as represented by line 240 , allows for much more M/G drive torque available during “electric only” operation mode. For example, as a vehicle driver demands impeller torque from the engine at peak 280 between time intervals T 1 and T 2 , the modified maximum motor torque limit allows the M/G 18 to provide the impeller torque demand.
[0035] Dashed line 250 represents the unmodified maximum motor torque limit. As stated above, the unmodified maximum motor torque is a generally conservative limit. This allows the M/G 18 to ramp up to the modified maximum torque limit, as represented by line 240 , for transient bursts during an engine start request. By increasing the unmodified maximum motor torque limit of line 250 to the modified maximum torque limit of line 240 , the vehicle is able to operate in “electric only” operation mode for a longer period of time.
[0036] During time interval T 2 and T 3 the M/G torque will be increased, between peaks 300 and 320 , up to the modified maximum torque limit. The M/G 18 will continue to provide drive torque at the modified maximum torque limit through a relatively small time interval. For example, in order to account for the torque demanded for engine starts and restarts, the M/G 18 will continue to provide drive torque at the modified maximum torque limit for approximately one second. Likewise, during time intervals T 2 and T 3 the disconnect clutch torque may have a complementary curvature as the M/G torque, as described above. The disconnect clutch torque will decrease by the amount of torque demanded from the modified maximum motor torque limit between peaks 380 and 400 . The disconnect clutch torque decreases due to pressure applied to the disconnect clutch in order to account for the engine start command. The additional torque load from the engine drags the disconnect clutch torque negative. This is consistent with a partially closed position of the disconnect clutch. The M/G 18 compensates for the negative torque of the disconnect clutch by applying increased positive torque. This allows the net transmission input shaft torque to remain constant. Between time intervals T 3 and T 4 the M/G 18 will ramp down at 340 and continue to provide drive torque at the maximum torque availability limit represented by dashed line 260 .
[0037] Utilizing the modified maximum torque limit to account for an increase torque demand event, such as an engine start or restart, allows for a torque buffer 360 . This allows much more drive torque available from the M/G 18 during “electric only” operation mode. Having more drive torque allows for an improved electric drive capability and improves fuel economy over a wide range of operating conditions. Further, since the additional torque is only provided within a relatively small time interval, there is little impact on the lifespan or functionality of the M/G 18 .
[0038] As the vehicle 10 begins to enter “hybrid mode” operation, between time intervals T 4 and T 5 , the drive torque produced by the M/G 18 will ramp down slope 420 . As discussed above, when the vehicle is in the “hybrid” drive mode the engine 14 is providing engine torque to the powertrain 12 . When the engine 14 is providing engine torque to the powertrain 12 , the drive torque produced by the M/G 18 will reduce to zero. Likewise, the torque produced by the disconnect clutch 26 will ramp up slope 440 until it meets the driver demanded impeller torque from the engine 14 . Slope 440 represents a slipping condition of the disconnect clutch. The slipping condition of the disconnect clutch occurs when the turbine shaft is rotating at a faster rate than the impeller shaft. Therefore, the disconnect clutch will be in a locked condition after time interval T 5 , when the impeller shaft speed of rotation meets the turbine shaft speed of rotation. This couples the engine 14 to the powertrain 12 . This increases the driver demanded torque limit at curve 460 between time intervals T 4 and T 5 . This further allows the engine 14 to have a higher driver demand torque limit and produce more output torque.
[0039] The third graph, referenced as graph C, depicts torque increasing along the y-axis and time extending along the x-axis. Line 480 depicts driver demanded impeller torque consistent with an engine start and restart event between time interval T 1 and T 5 . Line 500 represents the modified final delivered impeller torque between time interval T 1 and T 5 . As the engine starts or restarts and the vehicle begins to enter “hybrid” drive operation mode, the final delivered impeller torque peaks at 520 before reaching the demanded impeller torque. Line 510 represents the unmodified final delivered impeller torque between time interval T 1 and T 5 . Line 510 shows the final delivered impeller toque using the unmodified maximum motor torque limit. Comparing lines 500 and 510 shows the availability of more torque during “electric only” operation mode. Therefore using the modified maximum M/G torque limit, as discussed above, allows for increased capability within the “electric only” operation mode.
[0040] Referring to FIG. 4 , a flowchart depicting the control logic of the VSC 48 is shown. At 540 , the VSC 48 calculates the unmodified maximum drive torque limit. At 560 , the VSC 48 calculates the required drive torque from the M/G 18 necessary for an engine start or restart event. The VSC 48 adds the required drive torque for an engine start at 560 to the unmodified maximum drive torque limit calculated at 540 . This allows for a modified maximum drive torque limit at 560 . At 580 , the VSC 48 determines if an engine start or restart request has been made. If, at 580 , the VSC 48 determines that an engine start or restart request has not been made, then at 600 the VSC 48 may command the vehicle to drive during “electric only” operation mode using the unmodified maximum drive torque limit calculated at 540 .
[0041] Likewise, if at 580 , the VSC 48 determines that an engine start or restart request has been made, then at 620 the VSC 48 may command the vehicle to drive during “electric only” operation mode using the modified maximum drive torque limit. This allows the VSC 48 to account for the extra output torque needed in order to start or restart the vehicle engine 14 as the vehicle exits the “electric only” operation mode. Further, the VSC 48 may only command, at 600 , operation at the modified maximum torque limit for a short duration. Operating at the modified maximum torque limit for a short duration allows the VSC 48 to account for the added torque necessary for engine start or restart requests without modifying the M/G 18 . This allows for an improved fuel economy over a wide range of operating conditions as well as an improved “electric only” operation mode capability.
[0042] While exemplary embodiments are described above, it is not intended that these embodiments describe all possible forms encompassed by the claims. The words used in the specification are words of description rather than limitation, and it is understood that various changes may be made without departing from the spirit and scope of the disclosure. As previously described, the features of various embodiments may be combined to form further embodiments of the invention that may not be explicitly described or illustrated. While various embodiments could have been described as providing advantages or being preferred over other embodiments or prior art implementations with respect to one or more desired characteristics, those of ordinary skill in the art recognize that one or more features or characteristics may be compromised to achieve desired overall system attributes, which depend on the specific application and implementation. These attributes may include, but are not limited to cost, strength, durability, life cycle cost, marketability, appearance, packaging, size, serviceability, weight, manufacturability, ease of assembly, etc. As such, embodiments described as less desirable than other embodiments or prior art implementations with respect to one or more characteristics are not outside the scope of the disclosure and may be desirable for particular applications.
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A powertrain controller for a vehicle may include input channels configured to receive start requests for an engine and operating condition data for an electric machine, and output channels configured to provide torque commands for the electric machine. The powertrain controller may further include control logic configured to, in response to receiving a start request for the electric machine while the operating condition data indicates that the electric machine is operating at a torque limit to drive the vehicle, generate torque commands that cause the electric machine to exceed the torque limit.
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The present invention relates to a controllable and improved method of producing molding compounds of aldehyde condensates directly from the monomers and to the materials produced thereby.
BACKGROUND OF THE INVENTION
The condensation reactions of aldehydes, and particularly the condensation reactions of phenols and aldehydes are, or can be, quite violent, inasmuch as they generate a considerable amount of heat. Aldehyde condensate resins are relatively cheap and have been used as binders for molded articles, and foundry molds, for a long time. Aldehydes can be reacted with donors of hydrogen atoms, as for example, benzene rings containing hydroxyl groups, amines including urea, dicyandiamide, and melamine, etc., to form alkanol groups which then react with other hydrogen donors by splitting off water. These reactions liberate a considerable amount of heat and because water is also liberated, the aldehyde condensate resins are usually made in water solutions. Some control of the reaction is usually achieved by flashing water from the solutions. In addition the reactions are usually carried out in kettles containing cooling coils or jackets, so that the reactions can be stopped before the condensate resins reach a completely crosslinked and infusible state. The fusible partial condensates at this point are usually solids at room temperature and are used as binder forming materials for porous articles and electrical applicators.
The fusible B staged aldehyde condensates give off water when they react with further aldehyde to produce the infusible C-stage. When such aldehyde condensates are to be used as molding compounds, they are mixed with fillers, and are compressed between heated surfaces to cross-link the partial condensates. One of the problems with such molding compounds is that the water liberated tends to decrease the bond strength that is produced with the fillers and/or it produces porosity in the finished molded article.
Where the partial condensates are to be used to produce porous structures, such as insulation, foundry molds, etc. water escapes during molding without deliterous effects. Heretofore, aldehyde condensates, and particularly phenol formaldehyde have been limited to such useage.
Resorcinol and aldehyde have also been added to aqueous mixtures of portland cement and sand (concrete) to produce a high early strength without changing the crystal structure of the hydraulic cement (see Column 4, Collins et al. U.S. Pat. No. 3,216,966). No particular problem is produced by the heat and water liberated in concrete because the reactants comprise such a small percentage of the materials present.
In a recent U.S. Pat. No. 3,944,515 there is disclosed a process wherein the reaction of portland cement, phenol, formaldehyde, and urea is carried out in the presence of ice in a stainless steel vessel that is equipped with an agitator and an indirect heat exchanger. Even though ice is utilized, the reaction gives off so much heat that the control of the reaction requires constant attention and special equipment for removing the heat of the reaction.
An object of the present invention is the provision of a new and improved method of producing a molding compound whose binder is an aldehyde condensate resin that is so controllable that the molding compound can be made from monomers without first making a precondensate.
A further object of the present invention is the provision of a new and more controllable process for reacting phenols and aldehydes.
Further objects and advantages of the invention will become apparent from the following description of the preferred embodiments.
In order that the advantages of the present invention will be more readily apparent, an understanding of the prior art as above described should first be understood.
As used in the present specification, the term aldehydes will be used to connote materials represented by the general formula RCHO as well as polymers thereof, and will include formaldehydes, acetylaldehyde, paraformaldehyde, etc. The term phenol materials is used in the broad sense to connote all materials containing a phenolic hydroxyl group, i.e. an OH group on a benzene ring, as for example, phenol - the lower member of the group, rescorcinol, catacol, etc. which are mildly acidic in nature and have three or more labile hydrogens.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
According to the present invention, the reaction between a phenol and an aldehyde to form the binder of a molding compound is carried out in the presence of a base. Any relatively strong base can be used and the preferred bases are Ca(OH) 2 , Ba(OH) 2 and Mg(OH) 2 . This base is first reacted with the phenol material to form the phenolic salt. When portland cement is used as a filler, sufficient free calcium hydroxide exists throughout the portland cement to act as the catalyst for the reaction. In this case, the portland cement is reacted with the phenol, preferably after the portland cement has been partially hydrated, but is in a dry state. Phenol inhibits the hydration of portland cement and so by first hydrating the cement, water can be incorporated in a manner providing a dry material. The mixture of the filler, and calcium phenolate salt is then mixed with an aldehyde, preferably in the solid state, and is thoroughly mixed. A reaction proceeds without the further addition of water in a very controlled manner to a B-stage to form a molding compound. If the molding compound is in the form of thin sheets or has sufficient surface to volume ratio, the reaction will slow down after it reaches the B-stage, so that very little, if any, additional cooling is necessary to stop the reaction, when the resin is in a proper state for molding.
EXAMPLE 1
The following materials in parts by weight were mixed according to procedures which will hereinafter be designated "A" and "B" respectfully.
Procedure A
In this procedure 52.83 parts of portland cement was mixed with 7.89 parts of water and was aged 5 days to hydrate the cement. The resulting mixture was ground into a fine powder, and 8.79 parts of water was mixed therewith. This wet mixture was then introduced into 69.51 parts of melted phenol at 60° C and reacted for 30 minutes. The reaction proceeded to a dry state and the phenol cement reaction product was then ground into a fine powder and was mixed with 24 parts of paraformaldehyde. The mixture was spread out on a surface to a thickness of approximately 1/8-inch; and after a period of time, a reaction was self-initiated and a temperature of approximately 200° F developed. Thereafter, the temperature started to decrease. Portions of the molding compound so produced were then molded at 300° F and 1,000 psi for 3 minutes. The molded parts had a strength comparable to those made from the same materials, but in which a resin was first made of the phenol and paraformaldehyde to form a resole, as is done in conventional processes.
Procedure B
According to this procedure, which is not in accordance with the present invention, a portland cement, phenol and paraformaldehyde were blended together in a dry state. To this blend was added 16.68 parts of water and the resulting blend was allowed to sit at room temperature. Within 40 minutes, the mixture was boiling. At 45 minutes the boiling was vigorous and the reaction would be characterized as violent. After one hour, a viscous hot paste was obtained, and a portion thereof was used to mold parts in the same manner as described above. After approximately one hour, 15 minutes, the material had crosslinked to such a state thet it was too hard for molding.
EXAMPLE 2
In prior art processes wherein an aldehyde and phenol are first reacted to form a resole, and the resole is used as the binder forming ingredient, the water that is present in the resole must be removed during cure. The present example demonstrates that the materials can be blended together dry and a reaction initiated with the result that much less water must be removed prior to and during molding. The following materials given in parts by weight were blended together dry.
______________________________________Hydrate of cement modified phenol 100 partsParaformaldehyde 24 partsCalcium Carbonate 24 partsMica 10 partsZinc Stearate (Mold Release Agent) 3 partsChopped Glass Fiber Strand (1/2-inch lengths) 30 parts______________________________________
The hydrate of cement modified phenol was prepared in the same manner as given in Example 1 above. The material was spread onto a surface in a layer approximately 1-inch thick and was allowed to remain for approximately 1 hour. During this time, an exotherm took place following which the temperature began to drop. When the material is molded at 300° F and 1,000 pounds per square inch parts having a tensile strength of approximately 6,000 psi and a flexual strength of approximately 16,000 psi are produced.
EXAMPLE 3
A molding compound is made of the following materials:
______________________________________Material Parts by Weight______________________________________Phenol 38.2Calcium hydroxide (powdered) 10.0Ca CO.sub.3 (powdered filler) 105.0Paraformaldehyde (powdered) 18.2______________________________________
The phenol is melted and the powdered calcium hydroxide slowly added thereto with mixing. Heat is given off and a paste is formed. In some instances, the water that is in the calcium hydroxide will be sufficient for the reaction and in some instances, a few parts by weight of water may be desired to be added to speed up the reaction. The calcium phenolate salt is formed and after the material is cooled, it is pulverized to a flowable powder. The paraformaldehyde is dry blended with the CaCO 3 filler and thereafter the calcium phenolate salt is added and slowly mixed therewith. The material is then heated in a thin wall container to a temperature of 85° C and a reaction is initiated. The material is slowly mixed to control the reaction for about 10 minutes during which time the thin walled vessel is cooled to keep the temperature at approximately 110° C. After the exotherm has subsided, the material is cooled to room temperature. In those instances where the molding compound is desired to be in the form of a flowable solid, the material is then dried in a vacuum with a small amount of heat and is then pulverized as necessary for the end use.
Inorganic fibers can then be blended therewith where a fibrous reinforcement is desired. Preferably, however, the inorganic fibers are blended with the filler and paraformaldehyde before the reaction is initiated. The material when molded as given in Example 2 using 15% by weight of total solids 1/4-inch long chopped glass fibers has substantially the same properties as given in Example 2.
EXAMPLE 4
The procedure of Example 3 is repeated, excepting that Mg (OH) 2 is used in place of the calcium hydroxide. The materials produced have substantially the same properties as does the material of Example 3.
Any type filler can be used with the binder forming ingredients whether or not they absorb water, as do the wood fillers of the prior art. The present invention produces a resin insitu and permits this to be done directly from monomers by reason of the controlled reaction provided by the present invention. The water liberated during the reaction can be utilized to provide the necessary contact of the reactants spaced throughout the fillers. Unlike the prior art processes using resoles, the present invention permits molding compounds to be made from inert organic fillers which for all intent and purposes do not absorb water, so that the present invention provides molded parts that are self-extinguishing, very inexpensive, have excellent weathering properties, low water absorption rates, high densities, and a high level of strength. In general, molding compounds providing these properties can be made utilizing approximately 50% to approximately 85% of inorganic fillers including glass fiber reinforcements, and from approximately 50% to approximately 15% of the aldehyde condensate forming materials. The aldehyde and phenol should be used in a mole ratio of at least 2. Nothing is gained by using a ratio greater than 3. The ratio will usually be in the range of from 2.5 to 3.0. Any inorganic fibers can be used as reinforcements and they will preferably be used in the range of from approximately 5% to approximately 30% by weight of the total solids of the molding compound.
It will now be seen that there has been provided a new and improved procedure for producing a molding compound directly from monomers, preferably dry, and in which a phenol material is present as the phenolic salt of the catalyst that is used for the condensation reaction. The materials are preferably mixed dry, although a small amount of water may be added to initiate a reaction after the materials are blended together in the dry state. Because the reaction is so controllable, dry monomers can be utilized, and any proportion of fillers can be mixed therewith. This in turn aids in controlling the exotherm that is produced by controlling the contact of the reactants.
While the invention has been described in considerable detail, I do not wish to be limited to the particular embodiments shown and described and it is my intention to cover hereby all novel adaptations, modifications, and arrangements thereof which come within the practice of those skilled in the art to which the invention relates.
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A controlled reaction is had by reacting a phenol monomer with a basic catalyst to form a phenolate salt and the phenolate salt is then reacted with an aldehyde while dispersed throughout the inorganic filler of a molding compound. The reaction is stopped at a fusible state to produce a molding compound.
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BACKGROUND
[0001] Currently in WebSphere MQ (a family of network communication software products launched by IBM in 1992) and in other message-oriented middleware (MOM) products, a sender can send a message to a particular queue (in a point-to-point model), but the sender does not have the ability to authorize or control who can get or view the messages. Generally, MOM is a client/server infrastructure embodied by software that resides in both portions of client/server architecture and typically supports asynchronous calls between the client and server applications. However, similar arrangements can be made in a point-to-point (client-to-client) environment as well. In any environment employed, message queues provide temporary storage when the destination program is busy or not connected.
[0002] Currently, if there are two are more receivers (or “consumers”) polling on the same queue for messages, as long as the consumers have authority to access the queue itself then any of them can retrieve any message from the queue. This clearly creates problems from a security point of view, and solutions have indeed been attempted.
[0003] In one solution, the sender can set message properties on the message and send the message to the queue, while the consumer/receiver can then specify message selectors to retrieve only specific messages from the queue. However, this merely results in client-side security, meaning any malicious application need not necessarily specify a message selector and can still pull messages from queue.
[0004] In another solution, different queues can be used for different kinds of messages, or “virtual queues” can be used which point to the local queue and to users configured for those virtual queues. While this does more to address security issues, it leads to a great increase in administrative and “housekeeping” tasks, such as the need to maintain multiple queues, while an undesirable byproduct is that multiple I/O resources are consumed.
SUMMARY
[0005] Broadly contemplated herein, in accordance with at least one embodiment of the invention, is an arrangement wherein a sender tags messages with authorization information identifying those users or groups who are authorized to view or receive the messages. Thus, even if multiple users will be connected to the same queue for reading messages, only specific receivers/consumers will be able to get the messages. Not only is a comfortable degree of security ensured, but the need to waste system resources, e.g., by using multiple queues for different kinds of messages, is summarily avoided.
[0006] In summary, this disclosure describes a method comprising providing a physical computing device, providing message-oriented middleware at the physical computing device, appending a masking property to a message, sending the message to the message-oriented middleware, accepting information relating to a receiver, validating the accepted receiver information, and availing the message to the receiver upon successful validation of the receiver information.
[0007] This disclosure also described an apparatus comprising a physical computing device, the physical computing device comprising a main memory, message-oriented middleware provided at the physical computing device and being in communication with the main memory, an appender which acts to append a masking property to a message, a sender which acts to send a message to the message-oriented middleware, an accepter which accepts information relating to a receiver, a validator which validates accepted receiver information, and an availer which avails a message to a receiver upon successful validation of receiver information.
[0008] Furthermore, this disclosure additionally describes a program storage device readable by machine, tangibly embodying a program of instructions executable by the machine to perform a method comprising: providing a physical computing device, providing message-oriented middleware at the physical computing device, appending a masking property to a message, sending the message to the message-oriented middleware, accepting information relating to a receiver, validating the accepted receiver information, and availing the message to the receiver upon successful validation of the receiver information.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 schematically illustrates a computer system with which a preferred embodiment of the present invention can be used.
[0010] FIG. 2 schematically illustrates a client and server arrangement.
[0011] FIG. 3 schematically illustrates a process of masking and sending a message.
DETAILED DESCRIPTION
[0012] It will be readily understood that the embodiments of the invention, as generally described and illustrated in the Figures herein, may be arranged and designed in a wide variety of different configurations. Thus, the following more detailed description of the embodiments of the apparatus, system, and method of the embodiments of the invention, as represented in FIGS. 1-3 , is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention.
[0013] Reference throughout this specification to “one embodiment” or “an embodiment” (or the like) means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.
[0014] Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided, such as examples of programming, software modules, user selections, network transactions, database queries, database structures, hardware modules, hardware circuits, hardware chips, etc., to provide a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that embodiment of the invention can be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of embodiments of the invention.
[0015] The illustrated embodiments of the invention will be best understood by reference to the drawings, wherein like parts are designated by like numerals or other labels throughout. The following description is intended only by way of example, and simply illustrates certain selected embodiments of devices, systems, and processes.
[0016] Referring now to FIG. 1 , there is depicted a block diagram of an embodiment of a computer system 12 . The embodiment depicted in FIG. 1 may be a notebook computer system, such as one of the ThinkPad® series of personal computers previously sold by the International Business Machines Corporation of Armonk, N.Y., and now sold by Lenovo (US) Inc. of Morrisville, N.C.; however, as will become apparent from the following description, the embodiments of the invention may be applicable to any data processing system. Notebook computers, as may be generally referred to or understood herein, may also alternatively be referred to as “notebooks”, “laptops”, “laptop computers” or “mobile computers”.
[0017] As shown in FIG. 1 , computer system 12 includes at least one system processor 42 , which is coupled to a Read-Only Memory (ROM) 40 and a system memory 46 by a processor bus 44 . System processor 42 , which may comprise one of the AMD™ line of processors produced by AMD Corporation or a processor produced by Intel Corporation, is a general-purpose processor that executes boot code 41 stored within ROM 40 at power-on and thereafter processes data under the control of operating system and application software stored in system memory 46 . System processor 42 is coupled via processor bus 44 and host bridge 48 to Peripheral Component Interconnect (PCI) local bus 50 .
[0018] PCI local bus 50 supports the attachment of a number of devices, including adapters and bridges. Among these devices is network adapter 66 , which interfaces computer system 12 to a local area network (LAN), and graphics adapter 68 , which interfaces computer system 12 to display 69 . Communication on PCI local bus 50 is governed by local PCI controller 52 , which is in turn coupled to non-volatile random access memory (NVRAM) 56 via memory bus 54 . Local PCI controller 52 can be coupled to additional buses and devices via a second host bridge 60 .
[0019] Computer system 12 further includes Industry Standard Architecture (ISA) bus 62 , which is coupled to PCI local bus 50 by ISA bridge 64 . Coupled to ISA bus 62 is an input/output (I/O) controller 70 , which controls communication between computer system 12 and attached peripheral devices such as a keyboard and mouse. In addition, I/O controller 70 supports external communication by computer system 12 via serial and parallel ports, including communication over a wide area network (WAN) such as the Internet. A disk controller 72 is in communication with a disk drive 200 for accessing external memory. Of course, it should be appreciated that the system 12 may be built with different chip sets and a different bus structure, as well as with any other suitable substitute components, while providing comparable or analogous functions to those discussed above.
[0020] Reference may now be made herethroughout to FIGS. 2 and 3 . It should be understood that the arrangements and processes broadly contemplated in accordance with FIGS. 2 and 3 can be applied to a very wide range of computer systems, including that indicated at 12 in FIG. 1 .
[0021] As mentioned above, there is broadly contemplated herein, in accordance with at least one embodiment of the invention, an arrangement wherein a sender tags messages with authorization information identifying those users or groups who are authorized to view or receive the messages.
[0022] For example, in a banking environment, there can be one common queue called “Account”, where both “SavingsAccount” and “CurrentAccount” users can connect to the same queue. If it is assumed that messages for both Savings and Current account can be sent to the same queue then, in accordance with embodiments of the invention, even though SavingsAccount users and CurrentAccount users are connected to the same queue, each group user will be able to view or receive only their group specific messages, thereby reducing the overhead of maintaining multiple queues and multiple I/O resources. Accordingly, there is broadly contemplated, in accordance with embodiments of the invention, an arrangement for securing or masking a message sent by the sender so that only a specified user can view the messages.
[0023] Referring to FIG. 2 , there are shown a first user 212 and second user 214 . Either or both of the first and second users 212 / 214 may involve the use of essentially any computer system, including one configured similarly to that indicated at 12 in FIG. 1 . As is known conventionally, message-oriented middleware (MOM) may be installed in both locations 212 / 214 (as indicated at 216 a and 216 b , respectively), while locations 212 / 214 , along with their respective components of the MOM 214 a/b , are typically communicable with one another over essentially any suitable network 218 . Of course, the locations 212 / 214 may include a suitable interface via which a user may input a message for transmission to the MOM. Also, it should be understood that FIG. 2 could relate to a client/server relationship instead of a point-to-point relationship (e.g., “User 1 ” 212 could be a client while “User 2 ” 214 could be a server). Accordingly, it should be appreciated that the embodiments of the invention are applicable to a very wide variety of environments involving one or more senders and one or more receivers, and that the discussion herebelow and herethroughout should not be construed as necessarily being limited to any one such environment.
[0024] The disclosure now turns to an example of a solution in accordance with at least one embodiment of the invention. The solution may be implemented essentially on any suitable MOM arrangement, such as WebSphere MQ as the messaging provider. Reference may be made to the process flowchart in FIG. 3 .
[0025] When a sender intends to send a message authorized to a particular user or group (either or which may be regarded as “receiver”), the sender may set a property on the message specifying one or more UserID's corresponding to the intended receiver(s) ( 302 ) along with a “masking” property ( 304 ) indicating that the message is to be masked. For instance, the masking property can be embodied by “MaskMessage=true”. Accordingly, by way of an illustrative and non-restrictive example, the message may have the following parameters attached to it:
[0026] MQMD.DestinedUsers=SavingAccountUser,SavingsAccountGroup
[0027] MQMD.MaskMessage=true
[0028] The message can then be sent to the MOM (e.g., WebSphere MQ) ( 306 ). Once the message is sent, and as long as a potential receiver has not yet connected, no immediate check need be made by the MOM, and nothing more need be done with the message ( 308 , 310 ). However, when a user at the receiving end does connect to the MOM ( 308 , 312 ) to receive and/or read messages, that user (the receiver) may provide security information implicitly in the form of user-id and/or password. Before the receiver is able to read a message, UserID/Password and/or group memberships can be validated against the “DestinedUsers” property of the message ( 316 ). This validation will be primarily done by the server side part of MOM ( 308 , 312 ). If such data match, then the receiver will be able to view and/or receive the message ( 318 ).
[0029] On the other hand, should there be another user connected to the same queue and that user's UserID does not match the message parameters, then the message will not be visible to that user ( 320 ).
[0030] Generally, the sender (or sender application) need only specify the UserID or GroupID corresponding to any intended recipient(s), thereby providing the sender with complete control as to who can view or receive the message.
[0031] It is to be understood that the invention, in accordance with at least one embodiment, includes elements that may be implemented on at least one general-purpose computer running suitable software programs. These may also be implemented on at least one Integrated Circuit or part of at least one Integrated Circuit. Thus, it is to be understood that the invention may be implemented in hardware, software, or a combination of both.
[0032] Generally, embodiments may take the form of an entirely hardware embodiment, an entirely software embodiment or an embodiment containing both hardware and software elements. An embodiment that is implemented in software may include, but is not limited to, firmware, resident software, microcode, etc.
[0033] Furthermore, embodiments may take the form of a computer program product accessible from a computer-usable or computer-readable medium providing program code for use by or in connection with a computer or any instruction execution system. For the purposes of this description, a computer-usable or computer readable medium can be any apparatus that can contain, store, communicate, propagate, or transport the program for use by or in connection with the instruction execution system, apparatus, or device.
[0034] The medium can be an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, (or apparatus or device) or a propagation medium. Examples of a computer-readable medium include a semiconductor or solid state memory, magnetic tape, a removable computer diskette, a random access memory (RAM), a read-only memory (ROM), a rigid magnetic disk and an optical disk. Current examples of optical disks include compact disk-read only memory (CD-ROM), compact disk-read/write (CD-R/W) and DVD.
[0035] A data processing system suitable for storing and/or executing program code may include at least one processor coupled directly or indirectly to memory elements through a system bus. The memory elements can include local memory employed during actual execution of the program code, bulk storage, and cache memories which provide temporary storage of at least some program code in order to reduce the number of times code must be retrieved from bulk storage during execution.
[0036] Input/output or I/O devices (including but not limited to keyboards, displays, pointing devices, etc.) can be coupled to the system either directly or through intervening I/O controllers.
[0037] Network adapters may also be coupled to the system to enable the data processing system to become coupled to other data processing systems or remote printers or storage devices through intervening private or public networks. Modems, cable modems and Ethernet cards are just a few of the currently available types of network adapters.
[0038] This disclosure has been presented for purposes of illustration and description but is not intended to be exhaustive or limiting. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiments were chosen and described in order to explain principles and practical application, and to enable others of ordinary skill in the art to understand the disclosure for various embodiments with various modifications as are suited to the particular use contemplated.
[0039] Generally, although illustrative embodiments of the present invention have been described herein with reference to the accompanying drawings, it is to be understood that the invention is not limited to those precise embodiments.
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In the context of middleware products, an arrangement wherein a sender tags messages with authorization information identifying those users or groups who are authorized to view or receive the messages. Thus, even if multiple users will be connected to the same queue for reading messages, only specific receivers/consumers will be able to get the messages. Not only is a comfortable degree of security ensured, but the need to waste system resources, e.g., by using multiple queues for different kinds of messages, is summarily avoided.
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Pursuant to 37 C.F.R. § 1.78(a)(4), this application claims the benefit of and priority to prior filed co-pending Provisional Application Ser. No. 60/347,449, filed Nov. 1, 2001, which is expressly incorporated herein by reference.
FIELD OF THE INVENTION
This invention relates to the packaging of compressible spring assemblies used in the manufacture of mattresses and the like, and is more particularly directed to an apparatus for packaging such compressible spring assemblies into a roll.
BACKGROUND OF THE INVENTION
A large majority of mattresses are manufactured with inner spring assemblies. These inner spring assemblies are comprised of a multitude of interconnected coil springs arranged in a matrix of rows and columns of springs. The inner spring assemblies are most often shipped in a stacked and compressed condition. It has been found that such inner spring assemblies and the finished mattresses made from the spring assemblies can be compressed and packaged into a roll, providing improvements in efficiency of storing and shipping the mattresses and spring assemblies. Roll packing generally involves winding up spring assemblies or mattresses to form a roll and then securing the roll to prevent uncoiling during handling and storage. In many applications it is desired to incorporate a packing material into the wound roll such that the packing material is positioned between successive layers of the roll to keep each layer separate and to aid in the removal of individual spring assemblies or mattresses from the roll. U.S. Pat. No. 2,114,008 to Wunderlich discloses a machine for packaging spring assemblies into a roll.
Roll packing machines of the prior art are generally very labor intensive, requiring the close attention of an operator at various stages of the roll packing process. For example, in the apparatus disclosed by Wunderlich, an operator must manually start the feeding of packing material to a mandrel for winding the spring assemblies into a roll. Operators must also manually feed the compressible spring assemblies to the mandrel and manually cut and secure the packing material at the end of a roll to prevent premature uncoiling of the roll packed assemblies. When a roll of spring assemblies is complete, the operator must remove the mandrel from the machine and manually collapse the mandrel to remove the finished roll.
Another drawback of prior roll packing machines is that operators must manually change out rolls of packing material to switch to a new type of material or to replace a spent roll. These labor intensive operations consume a considerable amount of time, often during which time the roll packing machine may not be operated. Labor intensive operations also increase the possibility for human error which lead to inconsistent quality of roll packed material. For at least the reasons discussed above, a need exists for a roll packing machine which reduces labor intensive operations and improves efficiency and ergonomics of roll packing spring assemblies to provide roll packed units of consistent quality in shorter cycle times.
SUMMARY OF THE INVENTION
The present invention provides an improved machine for roll packing mattress spring assemblies. The machine is fully automated to permit efficient roll packing of spring assemblies of consistent quality. To this end and in accordance with the present invention, an apparatus is provided having a radially collapsible mandrel for winding in-fed spring assemblies into a roll. The mandrel is mounted to an arm that can be pivoted about an axis of the arm to move the mandrel toward and away from a fixed compression roller, whereby the in-fed spring assemblies are compressed in a controllable manner as they are wound upon the mandrel.
The apparatus also includes an automated feeding system which includes rollers to precompress in-fed spring assemblies and a moving guide system for controlling the spacing of the spring assemblies. Packing material is automatically fed to the spring assemblies as they are rolled on the mandrel, and a cutting and gluing unit automatically cuts the packing material and applies an adhesive to a final layer of packing material to secure the finished roll.
A roll pusher removes finished rolls of spring assemblies from the collapsed mandrel and a finished roll manipulator places the finished rolls on an automated palletizer which wraps pallets of finished rolls for shipping and storage. The apparatus further includes a controller and power supply which control the operation of the apparatus and provide power to various driving systems of the apparatus.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with a general description of the invention given above, and the detailed description given below, serve to explain the invention.
FIG. 1 is an elevational view of a roll packing apparatus according to the principles of the present invention;
FIG. 2 is an elevational view of the roll packing apparatus of FIG. 1 depicting a spring assembly being fed between precompression rollers and directed to the mandrel;
FIG. 3 is an elevational view of the roll packing apparatus of FIG. 1 depicting a fully wound roll of spring assemblies on the mandrel;
FIG. 4 is an elevational view of the roll packing apparatus of FIG. 1 depicting a finished roll of spring assemblies in position against the fixed compression roller after a gluing step;
FIG. 5 is a plan view of the roll packing apparatus of the present invention, further including a finished roll manipulator, a pallet magazine, and a finished roll palletizer.
DETAILED DESCRIPTION
An apparatus is provided for fully automated roll packing of spring assemblies which reduces labor intensive operations and provides faster cycle times. The present invention may be described and understood by a description of an exemplary apparatus.
With reference to FIG. 1 , there is shown an illustration of one embodiment of a roll packing apparatus 10 incorporating the principles of the present invention. The apparatus 10 includes a radially collapsible mandrel 12 for receiving in-fed spring assemblies 14 and winding them into a roll. Collapsible mandrel 12 is attached to a pivot arm 16 having pivot axis 18 . The collapsible mandrel 12 has a rotational axis 20 which is substantially parallel to the pivot axis 18 . A fixed compression roller 22 is located proximate the mandrel 12 and has a rotational axis 24 substantially parallel to the rotational axis 20 of the mandrel 12 .
Pivot arm 16 pivots about pivot axis 18 to position the mandrel 12 relative to the fixed compression roller 22 to compress in-fed spring assemblies 14 in a controllable manner as they are wound upon the mandrel 12 . The apparatus 10 further includes a precompression guide roller 26 upstream of the mandrel 12 for receiving in-fed spring assemblies 14 and directing them toward the mandrel 12 and fixed compression roller 22 . The precompression guide roller 26 provides a gradual initial compression of the spring assemblies 14 prior to being further compressed between the mandrel 12 and fixed compression roller 22 . Advantageously, the precompression guide roller 26 provides precompression to spring assemblies 14 having tall or small diameter springs which are susceptible to shifting that would otherwise occur if they were subjected to rapid compression by being directed to the fixed compression roller 22 and mandrel 12 without any precompression.
A feed table 28 upstream of the precompression guide roller 26 supports in-fed spring assemblies 14 and directs them toward the precompression guide roller 26 . The feed table 28 includes a plurality of rollers 30 disposed on a support surface 32 of the feed table 28 to transport spring assemblies 14 toward the precompression guide roller 26 . The feed table 28 further includes a precompression conveyer 34 which operates in conjunction with the precompression guide roller 26 to precompress spring assemblies 14 and automatically feed the spring assemblies 14 between the mandrel 12 and fixed compression roller 22 . Moving side guides 36 on the feed table 28 aid in automatically in-feeding the spring assemblies 14 and ensure proper spacing between the in-fed spring assemblies 14 . The feed table 28 includes a frame 38 having casters 40 located at the bottom of the frame 38 to allow movement of the feed table 28 toward and away from the precompression guide roller 26 . The casters 40 are positioned on guide rails 42 which control the path of the feed table 28 . Drive motors 44 , 46 , 48 , 50 coupled to the feed table frame 38 , the feed table rollers 30 , the side guides 36 , and the precompression conveyor 34 provide the motive forces to move spring assemblies 14 along the feed table 28 and between the precompression roller 26 and conveyor 34 to be directed to the mandrel 12 for winding.
The apparatus 10 includes one or more packing material dispensers 52 positioned near the mandrel 12 for receiving and dispensing packing material 54 , such as paper, foil, or various fabric materials, to the in-fed spring assemblies 14 as they are being wound upon the mandrel 12 . Each packing material dispenser 52 has associated packing material feed rollers 56 and a tension compensator 58 for feeding and directing packing material 54 from the dispenser 52 toward the mandrel 12 and fixed compression roller 22 . The packing material feed rollers may be supported on pneumatic cylinders whereby the position of the feed rollers may be adjusted. As spring assemblies 14 are directed through the precompression guide roller 26 toward the mandrel 12 and fixed compression roller 22 , packing material 54 is pushed toward the mandrel 12 by the spring assemblies 14 . The mandrel 12 includes a vacuum system which draws the packing material 54 toward a surface 60 of the mandrel 12 so that it is wound tightly upon the mandrel 12 prior to compressing and winding of spring assemblies 14 upon the mandrel 12 . Referring further to FIG. 2 , as spring assemblies 14 are wound upon the mandrel 12 , pivot arm 16 pivots about pivot axis 18 to move the mandrel 12 away from the fixed compression roller 22 in a controlled manner so that successive spring assemblies 14 are uniformly compressed and rolled upon the mandrel 12 .
The apparatus 10 further includes an automated cutting and gluing unit 62 in line between the packing material dispensers 52 and the mandrel 12 . The cutting and gluing unit 62 automatically cuts the packing material 54 near the end of a finished roll 64 of compressed spring assemblies 14 and applies adhesive to a final layer of packing material 54 , which is wound to secure the finished roll 64 . Referring to FIG. 3 , pivot arm 16 holds the finished roll 64 , still on the mandrel 12 , against the fixed compression roller 22 to provide pressure to the end of the final layer of packing material 54 until the adhesive has cured and the finished roll 64 may be removed from the mandrel 12 . Referring to FIG. 4 , pivot arm 16 rotates to move the finished roll 64 away from the fixed compression roller 22 and places the finished roll 64 on a finished roll support 66 . At this point, the mandrel 12 may be collapsed radially inward to release the finished roll 64 and a roll pusher 68 is activated to push the finished roll 64 off the mandrel 12 along the finished roll support 66 .
Referring to FIG. 5 , the apparatus 10 further includes a controller 70 connected to the various drive motors and to sensors positioned at various locations on the apparatus 10 for controlling the automated roll packing of spring assemblies 14 , as described above. The controller 70 is also configured to count the number of spring assemblies 14 that have been wound upon the mandrel 12 . A power supply 72 provides electrical current to the apparatus 10 and its components. While the apparatus 10 is designed for completely automated roll packing of spring assemblies, it can also be used without an automated feed table 28 when manual feeding of spring assemblies 14 is desired. As more clearly shown in FIG. 1 , the roll packing apparatus 10 includes a frame structure 74 for supporting the components described above. The frame structure 74 may be configured to have a modular design, wherein various sections of the apparatus 10 may be separately assembled and disassembled to facilitate transportation and assembly of the apparatus 10 .
Referring to FIG. 5 , an automated system 80 for providing roll packed spring assemblies 14 includes a roll packing apparatus 10 , as described above, and further includes a finished roll manipulator 82 which receives finished rolls 64 of spring assemblies 14 from the finished roll support 66 and moves them to a finished roll palletizer 84 . The finished roll palletizer 84 includes a pallet magazine 86 , a roll wrapping machine 88 for wrapping finished rolls 64 for shipment and storage, and a conveyor 90 .
In one exemplary embodiment, a roll packing apparatus 10 according to the principles of the present invention has a radially collapsible mandrel 12 having a diameter of about 300 mm. The exemplary apparatus 10 can receive rolls of packing material 54 up to about 2100 mm in width and about 1000 mm in diameter, and can accommodate spring assemblies 14 up to about 200-mm wide and about 240-mm high. The exemplary apparatus 10 can produce finished rolls 64 of spring assemblies 14 of up to about 650 mm in diameter, each roll containing 10-12 spring assemblies 14 , at a rate of about 12-20 rolls per hour.
While the present invention has been illustrated by the description of an embodiment thereof, and while the embodiment has been described in considerable detail, it is not intended to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in the art. The invention in its broader aspects is therefore not limited to the specific details, representative apparatus and method and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the scope or spirit of Applicant's general inventive concept.
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An apparatus for fully automated roll packing of compressible mattress spring assemblies, including a radially collapsible mandrel for easy removal of finished rolls. In-fed spring assemblies are precompressed prior to winding on the mandrel, which is mounted to a pivotable arm to permit controlled compression of the spring assemblies against a fixed compression roller. The apparatus further includes devices for placing the finished rolls on pallets and wrapping pallets for shipping and storage.
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RELATED APPLICATION
[0001] This application claims priority from provisional application Ser. No. 60/225,153, filed Aug. 14, 2000.
BACKGROUND OF THE INVENTION
[0002] The present invention generally relates to chafing pans, tables and burners used in the restaurant and catering businesses. More particularly, the present invention relates to a chafing system which can accommodate multiple chafing pans during use as well as being portable and collapsible so as to be used by as few as one worker.
[0003] Traditionally, the way food is cooked, warmed or served at most catered events (i.e., weddings, banquets, film and television location shoots, etc.) is by setting chafing dishes on tabletops of typically six foot or four foot banquet tables. The chafing pan is suspended in a wire frame above a heat source, such as gas hotplates or liquid fuel wick burners known as sterno.
[0004] This set up often requires two or more people to bring in and set up the tables, the chafing pans and the fuel. In addition to being labor intensive and time consuming, this method seldom utilizes good economy of space. It can also be hazardous to safety, as the heat source is often in close proximity to wooden table tops, and wind can spill the liquid fuel onto flammable surfaces. This becomes especially evident at large events where there is a high volume of food being served and quick recovery is a premium.
[0005] One existing alternative is a rigid steam table or cooking system that does not break down for transport. Such fixed steam tables are suitable perhaps to temporarily expand the capacity in a permanent facility such as a hotel, restaurant, banquet facility, etc., but the size and weight of such devices preclude portability, even when including castors.
[0006] Accordingly, what is needed is a system which allows as few as one worker to set up the necessary chafing pans and fuel. What is also needed is such a chafing system which is portable. What is further needed is a chafing system which is collapsible so as to occupy little storage space and facilitate transportation. The present invention fulfils these needs and provides other related advantages.
SUMMARY OF THE INVENTION
[0007] The present invention resides in a portable and collapsible chafing system. This system generally comprises a cart for cooking, warming and serving food. The chafing system includes a frame forming wells configured to hold a chafing container and having a working surface adjacent to the wells. Underlying the frame is a heating device holder, which is typically comprised of a platform. The platform is pivotally connected to the frame and has an aperture that can be used as a handle.
[0008] The chafing system also includes legs pivotally connected to the frame for movement between a first collapsed position and a second position in which the legs extend from and elevate the frame. The legs of the chafing system include two pairs of legs, each pair having first and second supports pivotally attached to one another intermediate ends thereof, and each pivotally attached to the frame at an upper end thereof. Each pair of legs also includes a spring interconnected between the first and second supports, which facilitates the raising and collapsing of the system.
[0009] Wheels are associated with each pair of legs to provide mobility to the chafing system. In a particularly preferred embodiment, wheel-bearing axles extend between each pair of legs.
[0010] The chafing system also includes side and front panels which are pivotally attached to an edge of the frame so as to be movable between an open and closed position.
[0011] Other features and advantages of the present invention will become apparent from the following more detailed description, taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The accompanying drawings illustrate the invention. In such drawings:
[0013] [0013]FIG. 1 is a partially exploded perspective view of a chafing system embodying the present invention and accessories therewith;
[0014] [0014]FIG. 2 is a perspective view of the chafing system of FIG. 1;
[0015] [0015]FIG. 3 is a perspective view of the chafing system of FIG. 2 showing its panels in the closed and partially closed position;
[0016] [0016]FIG. 4 is a perspective view of the chafing system of FIG. 2 in its collapsed position;
[0017] [0017]FIG. 5 is an enlarged fragmented perspective view of area “ 5 ” of FIG. 2, illustrating the connection between a frame and a second support of the chafing system; and
[0018] [0018]FIG. 6 is an enlarged fragmented perspective view of area “ 6 ” of FIG. 2, illustrating a spring interconnecting first and second supports of a pair of legs of the chafing system.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0019] As shown in the drawings for purposes of illustration, the present invention is concerned with a portable and collapsible chafing system generally illustrated in FIGS. 1 - 4 and referred to by the reference number 10 .
[0020] With reference to FIG. 1, the chafing system 10 of the present invention is a cart for cooking, warming and serving catered foods. The chafing system is comprised of a frame 12 that has a plurality of wells 14 configured to receive a pan 16 with accompanying lid 18 or a quarter pan or cutting board/work surface area 20 , and can be used with propane hot plate burners or sterno wick burners 22 . The frame 12 preferably has four wells 14 and is rectangular, such as 22″ wide by 49″ long, and made of metal, such as 18-gauge (0.049) 1″×1″ OD stainless steel orflatstock. As illustrated in FIG. 4, the entire chafing system 10 collapses to a compact and portable unit.
[0021] Referring now to FIGS. 2 , the chafing system 10 has first and second pairs of legs 24 and 24 ′, each having a first support 26 and a second support 28 . The supports 26 and 28 of the first pair of legs 24 are substantially equal to the supports 26 and 28 of the second pair of legs 24 ′. The first supports 26 are pivotally attached to the frame 12 through an axle (not shown), which is connected to the frame 12 through brackets 30 and 30 ′ configured to pivotally hold the axle. The second supports 28 are pivotally attached to the frame 12 and are also attached to the first supports 26 intermediate ends thereof via an axle bolt 32 . In a particularly preferred embodiment, the supports 26 and 28 are 1″×1″ OD 18-gauge stainless steel and the first supports 26 are approximately 58″ long while the second supports 28 are approximately 59″ long.
[0022] Referring now to FIG. 5, the top 34 of the second supports 28 are notched and beveled, and have holes 36 for the insertion of a pin 38 , such as a cotterless hitchpin. The second supports 28 are attached to the frame 12 by inserting the cotterless hitchpins 38 into the holes 36 of the second supports 28 and then through frame holes 40 thereby assembling the chafing system 10 . The supports 28 can also be designed to flex around the frame and automatically lock in place followed by the insertion of a pin 38 for safety purposes. The frame 12 may have multiple holes 40 whereby the second supports 28 can be attached nearer or further from the end of the frame 12 , allowing the chafing system 10 to be assembled to different heights.
[0023] Referring now to FIGS. 3 and 6, each pair of legs 24 and 24 ′ has a spring 42 which connects the first and second supports 26 and 28 at points below the axle bolt 32 . The length and placement of the spring is such that the spring applies a contracting force between the supports 26 and 28 . The force applied by the springs 42 assists in the assembly of the chafing system 10 by pulling the lower half of the first and second supports 26 and 28 together. The spring 42 is preferably 12″ long and made from heavy-duty galvanized steel.
[0024] As shown in FIGS. 1 - 4 , each of the supports 26 and 28 has a wheel 44 associated therewith. Axles 46 and 46 ′ are interconnected between lower ends of supports 26 and 28 . The axles 46 and 46 ′ are preferably covered with a ¾″ OD plastic sleeve and are 29″ long. Additionally, the pairs of legs 24 and 24 ′ could be reinforced by interconnecting the pairs of legs 24 and 24 ′ with an X-brace or the like.
[0025] Referring back to FIGS. 1 - 2 , a heating device holder 48 is comprised of four platform supports 50 and a platform 52 , which is preferably made of a 22-gauge galvanized flashing sheet. The platform supports 50 pivotally connect to the platform 52 through axles 54 attached to the ends thereof. The upper end of platform supports 50 are pivotally connected to an end of the frame 12 through the axle attached to the brackets 30 and 30 ′. Another end of the platform 52 is pivotally connected to the frame 12 through a similar axle configuration. Such a configuration allows the heating device holder 48 to fold flat when the chafing system 10 is collapsed. The platform 52 preferably includes a cutout 56 which acts as a handle when the chafing system 10 is in the folded position.
[0026] Referring to FIGS. 2 - 3 , a front panel 58 and two side panels 60 cover the front and sides of the chafing system 10 to provide aesthetic appeal and which can also serve to cover wells 14 . The panels 58 and 60 connect to the frame 12 through hinges 62 . The panels 58 and 60 are preferably made of 22-gauge quilted stainless steel and welded to the piano hinges 62 which are preferably riveted to the frame 12 . To allow the front panel 58 enough distance from the structural hardware to hang vertically when assembled, the front panel 58 is connected at its top to a strip 64 , which is riveted or otherwise connected to the frame 12 . While specific dimensions and material specifications have been given to describe the preferred embodiment, the present invention contemplates using different dimensions and materials.
[0027] [0027]FIG. 1 shows the chafing system 10 in its fully erected state in use. To disassemble the chafing system 10 , the pans 16 , lids 18 , and heating devices 22 are removed. The panels 52 and 54 are then closed by folding them over on top of the frame 12 as shown in FIG. 3. The chafing system 10 is unlocked from its erect position by removing the cotterless hitchpins 38 from the second supports 28 . While the cotterless hitchpins 38 are removed, the chafing system 10 can be held up with an assembly handle 66 . The assembly handle 66 is attached to the second supports 28 via cables 68 and can be used to raise or lower the chafing system 10 . Other configurations, such as hinged flatstak, can also be employed to create the handle 66 . Once the chafing device 10 is lowered to its completely collapsed position, the cofterless hitchpins 38 are again placed through the supports 28 to lock the chafing system 10 in its collapsed position, as shown in FIG. 4. In the particularly preferred embodiment, the fully collapsed chafing system 10 is approximately 2½″ high by 22″ wide by 58″ long, and 65 lbs. It is contemplated that the frame 12 include opposing apertures so that a dolly nose plate and wheel (not shown) can be removably attached to the collapsed system 10 to act as a two-hand dolly for facile transport of pans, etc.
[0028] The chafing system 10 is erected by unlocking the second supports 28 and pulling on the assembly handle 66 until the chafing system 10 is in an upright position whereupon the second supports 28 are locked in place.
[0029] The chafing system 10 of the present invention is a safe, efficient, and portable device for heating and warming foods at catering events. Use of the chafing system 10 is advantageous because it only requires one person to transport, assemble, and position it in its required place. The same worker, or more if necessary, can then place the necessary heating devices 22 , pans 16 of food, and lids 18 to provide the desired service. The compactness of the chafing system 10 in its collapsed state also provides the benefit of saving storage space and making transport easier.
[0030] Although an embodiment has been described in detail for purposes of illustration, various modifications may be made without departing from the scope and spirit of the invention. Accordingly, the invention is not to be limited, except as by the appended claims.
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A portable and collapsible chafing system includes a frame forming a well configured to hold a chafing container. Underlying the frame is a heating device holder in the form of a platform pivotally connected to the frame. The chafing system includes legs pivotally connected to the frame for movement between a first collapsed position and a second position in which legs extend from and elevate the frame. Wheels are associated with each leg to render the system mobile.
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PRIORITY
[0001] This application is a continuation of U.S. patent application Ser. No. 14/732,531, filed Jun. 5, 2016, for “Minimizing Oil Leakage From Rocking Journal Bearings Of Two-Stroke Cycle Engines”.
RELATED APPLICATIONS
[0002] This application contains subject matter related to the subject matter of commonly-owned U.S. patent application Ser. No. 13/776,656, filed Feb. 25, 2013, titled “Rocking Journal Bearings for Two-Stroke Cycle Engines”. published as US 2014/0238360 A1 on Aug. 28, 2014.
FIELD OF THE DISCLOSURE
[0003] The field is rocking journal bearings. More specifically, the field concerns rocking journal bearings that are incorporated into the piston coupling mechanisms of two-stroke cycle engines, for example, opposed-piston engines.
BACKGROUND OF THE DISCLOSURE
[0004] Due to the nature of the two-stroke cycle, a load reversal on a journal bearing of a two-stroke engine such as a wristpin may never occur during the normal speed and load range operation of the engine, or the duration of a load reversal might be relatively short. In these circumstances, it is difficult to replenish the bearings with lubricating oil (“oil”). Furthermore, given limited angular oscillation of the bearing, oil introduced between the bearing surfaces does not completely fill the bearing. Eventually the bearing begins to operate in a boundary layer lubrication mode (also called “boundary lubrication mode”), which leads to excess friction, wear, and then bearing failure.
[0005] A representative two-stroke cycle engine is embodied in the opposed-piston engine 8 of FIG. 1 . The engine 8 includes one or more cylinders such as the cylinder 10 . The cylinder 10 is constituted of a liner (sometimes called a “sleeve”) retained in a cylinder tunnel formed in a cylinder block. The liner includes a bore 12 and longitudinally displaced intake and exhaust ports 14 and 16 , machined or formed in the liner near respective ends thereof. Each of the intake and exhaust ports includes one or more circumferential arrays of openings in which adjacent openings are separated by a solid portion of the cylinder wall (also called a “bridge”).
[0006] One or more injection nozzles 17 are secured in threaded holes that open through the sidewall of the liner, between the intake and exhaust ports. Two pistons 20 , 22 are disposed in the bore 12 of the cylinder liner with their end surfaces 20 e, 22 e in opposition to each other. For convenience, the piston 20 is referred to as the “intake” piston because of its proximity to, and control of, the intake port 14 . Similarly, the piston 22 is referred to as the “exhaust” piston because of its proximity to, and control of, the exhaust port 16 . The engine includes two rotatable crankshafts 30 and 32 that are disposed in a generally parallel relationship and positioned outside of respective intake and exhaust ends of the cylinder. The intake piston 20 is coupled to the crankshaft 30 (referred to as the “intake crankshaft”), which is disposed along an intake end of the engine 8 where cylinder intake ports are positioned; and, the exhaust piston 22 is coupled to the crankshaft 32 (referred to as the “exhaust crankshaft”), which is disposed along an exhaust end of the engine 8 where cylinder exhaust ports are positioned.
[0007] Operation of a two-stroke cycle, opposed-piston engine with one or more cylinders is well understood. Using the engine 8 as an example, each of the pistons 20 , 22 reciprocates in the bore 12 between a bottom center (BC) position near a respective end of the liner 10 where the piston is at its outermost position with respect to the cylinder, and a top center (TC) position where the piston is at its innermost position with respect to the cylinder. At BC, the piston's end surface 20 e, 22 e is positioned between a respective end of the cylinder, and its associated port, which opens the port for the passage of gas. As the piston moves away from BC, toward TC, the port is closed. During a compression stroke each piston moves into the bore 12 , away from BC, toward its TC position. As the pistons approach their TC positions, air is compressed between their end surfaces. Fuel is injected into the compressed air. In response to the pressure and temperature of the compressed air, the fuel ignites and combustion follows, driving the pistons apart in a power stroke. During a power stroke, the opposed pistons move away from their respective TC positions. While moving from TC, the pistons keep their associated ports closed until they approach their respective BC positions. In some instances, the pistons may move in phase so that the intake and exhaust ports 14 , 16 open and close in unison, Alternatively, one piston may lead the other in phase, in which case the intake and exhaust ports have different opening and closing times.
[0008] In FIG. 1 , the pistons 20 and 22 are connected to the crankshafts 30 and 32 by respective coupling mechanisms 40 including journal bearings 42 . The journal bearings 42 are continuously subjected to non-reversing, compressive loads during operation of the engine 8 . Related U.S. patent application Ser. No. 13/776,656 describes and illustrates a solution to the problem of non-reversing compressive loads for two-stroke cycle, opposed-piston engines. The solution includes a rocking journal bearing (also called a “rocking bearing” or a “biaxial bearing”), which is incorporated into the engine 8 of FIG. 1 . Each journal bearing 42 of each coupling mechanism 40 of the engine 8 is constructed as a rocking journal bearing. Referring to FIGS. 1 and 2 , a coupling mechanism 40 supports a piston 20 or 22 by means of a rocking journal bearing 42 including a bearing sleeve 46 having a bearing surface 47 , and a wristpin 48 . The wristpin 48 is retained on the small end 49 of a connecting rod 50 for rocking oscillation on the bearing surface of the sleeve by threaded fasteners 51 received in threaded holes 52 . The large end 53 of the connecting rod 50 is secured to an associated crankpin 54 of a respective one of the crankshafts 30 , 32 by conventional fasteners (not shown).
[0009] As seen in FIG. 3 , the wristpin 48 is a cylindrical piece that comprises a plurality of axially-spaced, eccentrically-disposed journal segments. A first journal segment J 1 comprises an annular bearing journal surface formed in an intermediate portion of the wristpin, between two journal segments J 2 . The two journal segments J 2 comprise respective annular bearing journal surfaces formed on opposite ends of the wristpin, on respective sides of the journal segment J 1 . The journal segment J 1 has a centerline A. The journal segments J 2 share a centerline B that is offset from the centerline A of journal segment J 1 . As seen in FIG. 3 , the sleeve 46 is a semi-cylindrically shaped piece with a bearing surface that includes a plurality of axially-spaced, eccentrically-disposed surface segments. A first surface segment J 1 ′ comprises an arcuately-shaped bearing surface formed in an intermediate portion of the sleeve, between two surface segments J 2 ′. The two surface segments J 2 ′ comprise arcuately-shaped bearing surfaces formed at opposite ends of the sleeve, on respective sides of the surface segment J 1 ′. The surface segment J 1 ′ has a centerline A′. The wristpin 48 is mounted to the small end 49 of the connecting rod 50 and the sleeve is mounted to an internal structure of the piston (not shown), such that corresponding bearing segment sets J 1 -J 1 ′ and J 2 -J 2 ′ are in opposing contact. Thus disposed, the opposing corresponding segment sets J 1 -J 1 ′ and J 2 -J 2 ′ may also be called “bearing interfaces”.
[0010] In operation, as the piston to which they are mounted reciprocates between TC and BC positions, oscillatory rocking motion between the wristpin 48 and the sleeve 46 causes the bearing interfaces J 1 -J 1 ′ and J 2 -J 2 ′ to alternately receive the compressive load. The bearing surface segments receiving the load come together and the bearing surface segments being unloaded separate. Separation enables a film of oil to enter space between the separating bearing surfaces. The point at which the compressive load is shifted from one to the other set of bearing segments is referred to as a “load transfer point.” During one full cycle of the two-stroke cycle engine, this point is traversed twice by each piston, once when the piston moves from TC to BC (that is to say, during the power stroke), and again when the piston moves from BC to TC (during the compression stroke). For illustration and as an aid in visualization, but without limiting the following disclosure, the load transfer points of the pistons may occur at or near crankshaft positions of 0° (when the pistons pass through their respective TC locations) and 180° (when the pistons pass through their respective BC locations).
[0011] With reference to FIGS. 1 and 2 , the rocking journal bearings are constructed to enable provisioning and distribution of oil at pressures adequate to lubricate the rocking bearing interfaces with a continuous oil film thick and widespread enough to support heavy loading, thereby enhancing the durability of the bearing. The construction of the wristpin 48 includes a gallery 60 which receives and distributes oil for lubricating the bearing interfaces (J 1 -J 1 ′ and J 2 -J 2 ′). The gallery 60 is fed pressurized oil from a pumped oil source. The wristpin 48 includes an oil inlet into, and multiple oil outlets from, the gallery 60 . The gallery 60 receives the pressurized oil through an inlet opening 62 that opens through a portion of the wristpin surface that is out of contact with the sleeve surface segments. The pressurized oil is delivered via a high-pressure oil passage 64 in the connecting rod. Pressurized oil is provided to the bearing interfaces (J 1 -J 1 ′ and J 2 -J 2 ′) from the gallery 60 through outlets that act through a portion of the wristpin surface in contact with the sleeve's bearing surface during oscillation of the bearing. An influx of pressurized oil into the gallery 60 provides a continuous supply of pressurized oil to the bearing during operation of the engine.
[0012] As seen in FIG. 4 , oil is circulated to the bearing interfaces via a network of oil grooves formed in the bearing surface 47 of the sleeve 46 for transporting oil to the bearing surface. The network includes circumferential oil grooves 70 for transporting oil in a circumferential direction of the bearing surface. The circumferential oil grooves 70 are formed in the bearing surface at the borders between the central surface segment J 1 ′ and the lateral surface segments J 2 ′. The network further includes circumferentially-spaced, axial oil grooves 72 and 73 , each for transporting oil in an axial direction of the bearing surface. The axial oil grooves are formed in the bearing surface transversely to and intersecting with the circumferential oil grooves 70 . Each of the axial oil grooves 72 and 73 runs across the central surface segment J 1 ′ and extends at least partially into each of the lateral surface segments J 2 ′. Chamfers 74 may be formed along opposing lateral peripheries of the bearing surface 47 . FIGS. 5A-5C show a prior art rocking journal wristpin constructed to deliver oil to the sleeve's bearing surface 47 .
[0013] FIGS. 5A-5C show a rocking journal wristpin 80 with an outer surface 82 having journal segments J 1 and J 2 that contact surface segments J 1 ′ and J 2 ′ of the sleeve bearing surface 47 during oscillation of the bearing. The journal segments J 1 and J 2 are separated by circumferential grooves 85 in the wristpin outer surface 82 . Outlet passages formed in the wristpin provide pressurized oil to the sets of surface segments during relative oscillatory motion between the sleeve and wristpin. First oil outlet passages 86 for delivering pressurized oil are formed in the contacting portion of the outer surface 82 and extend through the sidewall of the wristpin in the circumferential grooves 85 in a radial direction of the journal segment J 1 and open into an oil gallery 88 . An oil inlet 90 to the oil gallery 88 and the first oil outlet passages 86 are axially spaced, in diametrical opposition. Second oil outlet passages 92 are formed through the sidewall of the wristpin, outside of the circumferential grooves 85 , and open into the oil gallery 88 . The second oil outlet passages 92 are arranged in an axial array such that there is at least one second oil outlet passage located in each journal segment J 1 and J 2 . The wristpin 80 is assembled to the sleeve 46 of FIG. 4 with the journal segments J 1 -J 2 in opposition to the surface segments J 1 ′-J 2 ′ and the circumferential grooves 85 of the wristpin aligned with the circumferential grooves 70 of the sleeve. As per FIGS. 4 and 5A , during operation of the engine, the first oil outlet passages 86 continuously supply pressurized oil to the network comprising circumferential oil grooves 70 , which flows to the axial oil grooves 72 and 73 and the oil grooves 74 . As relative oscillation occurs between the wristpin 80 and the sleeve 46 , pressurized oil flows to the space between the separated segments continuously from the oil grooves 70 , 72 , and 73 and intermittently from the second oil outlet passages 92 as the journal segments in which they are located separate from their opposing surface segments of the sleeve.
[0014] Thus, the prior art wristpin oil delivery construction provides a constant supply of pressurized oil to the oil grooves 70 , 72 and 73 in the sleeve surface; and, the oil grooves continuously transport oil to the journal segments. However, a continuous supply of pressurized oil results in a high level of oil flow from the ends of the circumferential grooves 70 . This excess oil is detrimental to the performance of the engine for at least two reasons. First, the continuous provision of pressurized oil requires pumping work to supply the oil to the grooves, which reduces the engine's efficiency. Second, the oil comes in contact with the rotating and reciprocating machinery while returning to an engine oil sump. Extra parasitic drag caused by oil returning to the sump and interacting with a swirling cloud of air in the crankcase of the engine created by the high-speed rotation of the crankshafts, (“windage”), results in frictional losses. At 3,000 RPM, for example, each crankshaft must rotate 50 times per second. As the crankpins and counterweights rotate at such high speeds, they create a swirling cloud of air around them. As a result windage friction losses occur when excess oil is caught up in this turbulent air, drawing energy from the engine to spin the oil mist. Windage may also inhibit the migration of oil into the sump and back to the oil pump, creating lubrication problems. It is therefore desirable to minimize the amount of excess pressurized oil that flows through the rocking bearing journals of an engine.
SUMMARY OF THE DISCLOSURE
[0015] Lubricating oil flow through the rocking journal bearing is minimized by limiting provision of pressurized oil from the wristpin to the network of oil grooves in the sleeve to portions of a bearing operating cycle when one or the other of the sets of bearing surfaces receives the compressive load. Excess flow of oil through the rocking journal bearing is minimized by providing pressurized oil to the network intermittently during relative movement between the sleeve and the wristpin.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 is a schematic representation of a two-stroke cycle, opposed-piston engine, and is properly labeled “Prior Art”.
[0017] FIG. 2 is an exploded perspective view of a piston coupling mechanism including a rocking journal bearing, and is properly labeled “Prior Art”.
[0018] FIG. 3 is a schematic diagram illustrating the bearing surfaces of the rocking journal of FIG. 2 , and is properly labeled “Prior Art”.
[0019] FIG. 4 is a perspective view showing a bearing surface of a rocking journal sleeve.
[0020] FIGS. 5A-5C show a rocking journal wristpin constructed to provide oil for lubricating a rocking journal bearing comprising the sleeve of FIG. 4 , and are properly labeled “Prior Art”.
[0021] FIG. 6 is a perspective view of a rocking journal wris pin according to this disclosure.
[0022] FIG. 7 is an end elevation view of a rocking journal bearing according to this disclosure comprising the sleeve of FIG. 4 and the wristpin of FIG. 6 .
[0023] FIG. 8A is a side elevation view and FIGS. 8B-8D are cross-sectional views of the rocking journal bearing of FIG. 7 showing details of bearing lubrication at a load transfer point of the bearing.
[0024] FIG. 9A is a side elevation view and FIGS. 9B-9D are cross-sectional views of the rocking journal bearing of FIG. 7 showing details of bearing lubrication at a first loading point of the bearing.
[0025] FIG. 10A is a side elevation view and FIGS. 10B-10D are cross-sectional views of the rocking journal bearing of FIG. 7 showing details of bearing lubrication at a second loading point of the bearing.
[0026] FIG. 11 is a graph showing an operational cycle of the rocking journal bearing of FIG. 7 .
[0027] FIGS. 12A-12C illustrate flow paths of pressurized oil delivered to the rocking journal bearing of FIG. 7 at respective points in the operational cycle of the bearing shown in FIG. 11 .
DETAILED DESCRIPTION
[0028] FIG. 6 shows a wristpin 100 according to this disclosure that is combined with the sleeve 46 of FIG. 4 to form a rocking journal bearing 200 as shown in FIG. 7 in which the flow of excess pressurized oil from the bearing 200 is reduced throughout its operational cycle. In this regard, pressurized oil is provided intermittently instead of continuously to the network of oil grooves in the bearing surface of the sleeve. The view in FIG. 6 is toward a contacting portion 102 of the wristpin outer surface 103 that is in contact with the sleeve bearing surface 47 during oscillation of the bearing. The wristpin is constructed with axially-offset surface segments J 1 and J 2 as per FIG. 3 . As best seen in FIG. 8C , an oil inlet passage 105 is formed in the non-contacting portion of the J 1 segment of the wristpin. As per FIG. 6 , at least one oil outlet passage 107 is formed in the contacting portion of the J 1 journal segment. At least one oil outlet passage 109 is formed in the contacting portions of each of the J 2 journal segments. The oil outlet passages 107 and 109 open through the wristpin sidewall to oil gallery space 111 within the wristpin, and are offset along the wristpin's longitudinal axis 113 relative to the circumferential grooves 115 that separate the segments J 1 and J 2 . There are no oil outlet passages along either of the circumferential grooves 115 . The wristpin 100 is assembled to the sleeve 46 with the journal segments J 1 -J 2 in engagement with the surface segments J 1 ′-J 2 ′ and the circumferential grooves 115 of the wristpin 100 aligned with the circumferential grooves 70 of the bearing surface 47 . As relative oscillation occurs between the wristpin 100 and the sleeve 46 , pressurized oil flows to the space between the separated segments from the oil grooves 70 , 72 , and 115 and from the outlet passages 107 and 109 located in the separated journal segments of the wristpin.
[0029] With reference to FIGS. 6 and 8C , to carry out the purposes of a rocking journal bearing construction according to this disclosure, the positioning of the oil outlet passage 107 locates the oil outlet passage in the J 1 journal segment at a first arcuate distance D 1 from one side of a cut plane P containing the longitudinal axis 113 of the wristpin and a radius 117 forming the axis of the oil inlet passage 105 . The positioning of the oil outlet passages 109 locates these oil outlet passages in respective J 2 journal segments at a second arcuate distance D 2 from the opposite side of the cut plane P. Thus, as the rocking journal 200 is viewed as per FIGS. 8A-8D , in which the rotational position of the wristpin 100 relative to the sleeve 47 is 0°, as would occur when the load transfer point of the bearing 200 is traversed, the oil outlet passages 107 and 109 are positioned between the axial oil grooves 72 and 73 of the sleeve 46 , with the oil outlet passage 107 relatively nearer (for example, adjacent) to the axial oil groove 72 and the oil outlet passages 109 relatively nearer (for example, adjacent) to the axial oil groove 73 . In this relative rotational position, the bearing interfaces J 1 -J 1 ′ and J 2 -J 2 ′ are equally loaded.
[0030] With reference to FIGS. 9A-9D , presume that the wristpin 100 revolves in the CCW direction from the 0° position relative to the sleeve 46 to a point where the segments J 1 -J 1 ′ are fully loaded, while the segments J 2 -J 2 ′ are separated. As a result of movement in this direction, the oil outlet passage 107 moves across the axial oil groove 72 , which enables a pulse of pressurized oil to enter the oil groove from the oil outlet passage, while the separation between the segments J 2 -J 2 ′ allows the oil outlet passages 109 to deliver pressurized oil to the space therebetween.
[0031] With reference to FIGS. 10A-10D , presume that the wristpin 100 revolves in the CW direction from the 0° position relative to the sleeve 46 to a point where the segments J 2 -J 2 ′ are fully loaded, while the segments J 1 -J 1 ′ are separated. As a result of movement in this direction, the oil outlet passages 109 cross the axial oil groove 73 , which enables a pulse of pressurized oil to enter the oil groove from each of the oil outlet passages, while the separation between the segments J 1 -J 1 ′ allows the oil outlet passage 107 to deliver pressurized oil to the space therebetween.
[0032] FIG. 11 is a graph showing an exemplary operational cycle of a rocking journal bearing as may be observed when the bearing is incorporated into the piston coupling mechanisms of a two-stroke cycle opposed-piston engine such as the engine 8 of FIG. 1 . The graph shows wristpin-to-sleeve clearance for the J 1 -J 1 ′ interface and J 2 -J 2 ′ interfaces as a function of the crank angle position (in degrees) of the one of the crankshafts to which the coupling mechanism connects its associated piston. The graph shows a full cycle of crankshaft operation, with the understanding that this represents the operational cycles of each of the two crankshafts seen in FIG. 1 (with or without a phase difference). Further, the graph is representative of the two-stroke cycle operation of the opposed-piston engine of FIG. 1 . This graph is based upon load transfer occurring at 0° (TC) and 180° (BC), although this condition should not be considered to be limiting. At a crank angle of 0°, with the piston at TC, the compressive load is about equally divided between the J 1 -J 1 ′ and J 2 -JZ interfaces, as the crank angle advances, the load is increasingly received by the J 1 -J 1 ′ interface while the J 2 -J 2 ′ segments begin to separate. At a crank angle of 90° the compressive load is maximally borne by the J 1 -J 1 ′ interface, while the J 2 -J 2 ′ segments are maximally separated. At this point, the compressive load begins shifting from the J 1 -J 1 ′ interface to the J 2 -J 2 ′ interface and the J 2 -J 2 ′ surface segments begin to close. At 180°, with the piston at BC, the compressive load is about equally divided between the J 1 -J 1 ′ and J 2 -J 2 ′ interfaces. As the crank angle advances the load is increasingly received by the J 2 -J 2 ′ interface while the J 1 -J 1 ′ segments begin to separate. At a crank angle of 270 ° the compressive load is maximally borne by the J 2 -J 2 ′ interface, while the J 1 -J 1 ′ segments are maximally separated. At this point, the compressive load begins shifting to the J 1 -J 1 ′ interface from the J 2 -J 2 ′ interface and the J 1 -J 1 ′ segments begin to close. At 360°, the compressive load is about equally divided between the J 1 -J 1 ′ and J 2 -J 2 ′ interfaces, and the cycle repeats.
[0033] FIGS. 12A-12C show the pressurized oil flow patterns through the sleeve oil grooves 70 , 72 , and 73 for load transfer points (0° and 180°), for maximum J 1 loading, and maximum J 2 loading during an engine operating cycle shown in FIGS. 11 . At 0° and 180° oscillation, no oil outlet passages align with the sleeve axial grooves 72 and 73 , and since all three interfaces are equally loaded, no significant oil is added to the interfaces. At the maximum J 1 loading point (90°), the J 1 oil outlet passage 107 is aligned with the axial oil groove 72 and oil flows freely through the oil grooves 70 , 72 , and 73 to fill the J 2 lifted segment areas. At the maximum J 2 loading point (90°), the two J 2 oil outlet passages 109 align with the axial oil groove 73 and oil freely flows into the oil grooves 70 , 72 , and 73 to fill the J 1 lifted segment area.
[0034] The column of oil in the piston connecting rod oil passage 64 applies peak positive and negative pressures to the volume of oil in the wristpin gallery when at TC and BC piston positions, respectively. By using the intermittent alignment system described and illustrated above, and in the absence of oil outlet passages positioned in alignment with the circumferential grooves, the only path for oil to flow through during these peak pressure events is between the equally-loaded J 1 -J 1 ′ and J 2 -J 2 ′ surface segments, which is quite restrictive. As a result, this construction has the additional benefit of reducing the system sensitivity to oil pressure fluctuations in the wristpin gallery.
[0035] Although this disclosure describes particular embodiments for minimizing oil leakage from journal wristpins in two-stroke cycle, opposed-piston engines, these embodiments are set forth merely as examples of underlying principles of this disclosure. Thus, the embodiments are not to be considered in any limiting sense.
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A rocking journal bearing is provided in a piston coupling mechanism of a two-stroke cycle engine. The bearing includes a sleeve and a wristpin constructed with two sets of eccentrically-disposed bearing surfaces which alternate in accepting a compressive load during an operational cycle of the bearing. The sleeve includes a network of grooves to transport oil to the bearing surfaces. Lubricating oil flow through the bearing is minimized by limiting provision of pressurized oil from the wristpin to the network of grooves to portions of the cycle when one or the other of the sets of bearing surfaces receives the compressive load.
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RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 61/730,704, filed on Nov. 28, 2012, the entire contents of which are incorporated herein by reference.
BACKGROUND
[0002] The present invention relates to a mechanical spacer with built in, non-spring electrical contacts to be placed in a multiple printed circuit board (PCB) assembly to create an electrical connection between circuit paths of upper and lower circuit boards. Alternatively, one or both of the upper and lower circuit boards could be replaced with another circuit-based construction (e.g., LTCC, MID, etc.).
[0003] A conventional PCB includes a plurality of electronic components, and is generally formed with a plurality of circuit paths for establishing electrical connection among the electronic components. The maximum number of circuit paths is proportional to the overall surface area of the printed circuit board. Printed circuit boards are often designed in multi-layered forms, thereby increasing the total surface area for forming circuit paths and for assembling the electronic components thereon.
[0004] A plurality of spacer contact posts are conventionally sandwiched between the upper and lower circuit boards to create connection of the circuit paths of the circuit boards with each other and to facilitate heat-dissipation.
SUMMARY OF THE INVENTION
[0005] In one embodiment, a spacer and electrical connector assembly for printed circuit boards is provided. The assembly includes a first member configured to be placed between two of the printed circuit boards to provide a required spacing between the printed circuit boards; at least one second member disposed adjacent to the first member, the second member extending along a length of the first member and at least partially bracketing an upper surface and a lower surface of the first member, thereby providing an electrical connection between the printed circuit boards. The assembly also includes a plurality of contact portions disposed on at least one of the upper and lower surfaces.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1A is a cross-sectional view of a spacer assembly according to an embodiment of the invention.
[0007] FIG. 1B is an exploded view of FIG. 1A .
[0008] FIG. 2A is a perspective view of the spacer assembly of FIG. 1 .
[0009] FIG. 2B is a perspective view of an alternative spacer assembly
[0010] FIG. 3 is a plan view of an alternative embodiment of a spacer assembly.
[0011] FIG. 4 is a plan view of spacers distributed on a printed circuit board.
[0012] Before any embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways.
DETAILED DESCRIPTION
[0013] The present invention includes a mechanical spacer 1 that holds two printed circuit boards 10 , 20 (hereinafter “PCB” or “PCBs”) at a set distance from each other. The spacer 1 works in conjunction with an electrical connector 40 to provide an electrical connection between the two PCBs 10 , 20 without the use of spring contacts (such as Pogo pins, leaf springs, or bare springs) in order to reduce cost and complexity, while providing a reliable mechanical and electrical connection.
[0014] As shown in FIG. 1A , the upper PCB 10 may be mechanically connected to the lower PCB 20 through a bushing and screw combination 30 . The bushing 31 may be formed of a metal such as brass or aluminum or may be a plastic component molded directly on a product housing 61 ( FIG. 3 ) so as not to be a separate component. In FIG. 1A , a securing member or screw 32 is inserted through the lower PCB 20 and is secured within a concavity of the bushing 31 . The bushing 31 and screw 32 may optionally include male and female threads to form a secure connection, or may be otherwise joined together as known in the art. The compression load to establish the electrical connection between the PCBs 10 , 20 is provided by the bushing and screw combination 30 , as shown by the arrows 33 .
[0015] With continuing reference to FIG. 1A , the spacer 1 may include a terminal 40 that has a bracket shape (C-shape) and extends along the vertical length of the spacer 1 and at least partially brackets the upper 2 and lower 3 surfaces of the spacer. However, other shapes for the terminal 40 could be used. The terminal 40 removes the need of expensive Pogo Pins and provides a more cost-effective solution to provide an electrical connection between the upper 10 and lower 20 PCBs. The terminal 40 may be in the form of a wire and may be raised above the upper surface 2 of the spacer 1 and raised below the lower surface 3 of the spacer 1 to ensure proper contact with the respective PCB 10 , 20 . As best shown in FIG. 1B , upper 41 or lower 42 surfaces of the terminal 40 may be respectively soldered to the upper PCB 10 or the lower PCB 20 . Alternatively, the terminal 40 may not be soldered to either PCB 10 , 20 and thus be a loose and easily removable piece. The upper 41 or lower 42 surface of the terminal 40 may also include a “bump” protrusion 43 . The terminal 40 may be over-molded or stitched/inserted onto the spacer 40 using conventional methods.
[0016] The assembly formed by the spacer 1 and terminal 40 can be a separate piece from either of the PCBs 10 , 20 , and thus be a “pick and place” component that can be reflowed on one of the PCBs to reduce final manufacturing/assembly line steps. Additionally, when the spacer assembly is a separate piece, an electrically conductive adhesive or glue may be used in addition to the bushing and screw combination 30 to increase the reliability of the electrical and mechanical connections. Alternatively or additionally, a non-conductive adhesive can be used to secure the PCBs 10 , 20 together to provide increased mechanical stability/resistance.
[0017] FIG. 2A shows a perspective view of a spacer 1 according to an embodiment of the invention. The spacer 1 may be formed of a plastic material and may have a generally L-shape with a plurality of locating pins or contacts 4 along an upper surface 2 thereof. The contacts 4 extend from the upper surface 2 to the lower surface 3 . A terminal 4 may respectively be secured in one or more of the contacts 4 . The contacts 4 may be flush with the surfaces 2 , 3 or may be raised therefrom. A 5-contact spacer 1 is shown in FIG. 2 , with the contacts 4 allowing the spacer to equally distribute a compression load among the five contacts 4 distributed along the upper surface 2 of the spacer 1 . However, additional or fewer contacts 4 are possible. The spacer can also have alignment posts 5 on the upper surface 2 and the lower surface 3 that fit into a corresponding hole in the PCB 10 , 20 to align the upper 2 and lower 3 surfaces with the respective PCB 10 , 20 . The spacer 1 may include alternate geometries or sizes to provide additional surface area 6 for contacts 4 . The inside surface of the spacer 1 can have a circular opening 7 , in order to fit around the bushing 31 in between the upper 10 and lower 20 PCBs. The circular opening 7 in the spacer 1 can be used in conjunction with the pin 5 to provide alignment and prevent rotation of the spacer 1 .
[0018] In an alternative embodiment as shown in FIG. 2B , the spacer 100 may be fully circular so that it surrounds the bushing between the PCBs ( FIG. 3 ). The spacer 100 shown in FIG. 2B is otherwise similar to the spacer 1 of FIG. 1 , and includes an upper surface 102 , a lower surface 103 opposite the upper surface, pins 104 and a fully-enclosed center 107 .
[0019] In an alternative embodiment shown in FIG. 3 , the terminal 40 may be replaced with a molded interconnect device (MID) 50 . As is known in the art, a MID 50 is an injection-molded thermoplastic part with integrated electronic circuit traces printed on the thermoplastic material. As discussed above with respect to the terminal 40 , the MID 50 has a bracket shape (C-shape) and extends along the vertical length of the spacer 100 and brackets the upper 102 and lower 103 surfaces of the spacer. The MID 50 may be partially spaced from the spacer 100 to ensure proper contact with the PCBs 10 , 20 . The upper 102 or lower surface of the MID 50 may also be respectively soldered to the upper PCB 10 or the lower PCB 20 . Alternatively, the MID 50 may not be soldered to either PCB 10 , 20 , and thus be a loose piece. As discussed above, a conductive or non-conductive adhesive may be used to strengthen the connection when the MID 50 is a separate piece. The upper or lower surface of the MID 50 may also include a “bump” protrusion. As shown in FIG. 3 , the upper and/or lower surfaces of the MID may also include a pad, for example made of gold.
[0020] With continued reference to FIG. 3 , the bushing and screw combination 30 may be replaced with a self-tapping screw 60 that fits into a bushing 61 . The bushing 61 is shown molded together with the PCB housing 61 , but may also be separate from the housing.
[0021] FIG. 4 shows a plan view of two spacers 1 resting on diagonally opposite ends of a PCB 20 , providing ten total contact pins. As shown, the spacers 1 are spaced apart such that a circuit component 70 , such as a sensor, can be placed on the PCB 20 so as to avoid interference from the compression load 33 undertaken by the spacers 1 .
[0022] While embodiments of the invention disclosed herein describe mechanical spacers for multiple printed circuit boards, one skilled in art should recognize that alternative configurations may be employed without deviating from the scope of the invention.
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A spacer and electrical connector assembly for printed circuit boards includes a first member to be placed between two of the printed circuit boards to provide a required spacing between the printed circuit boards. The assembly also includes at least one second member disposed adjacent to the first member, the second member extending along a length of the first member and at least partially bracketing an upper surface and a lower surface of the first member, thereby providing an electrical connection between the printed circuit boards. A plurality of contact portions that respectively receive the second member may be disposed on at least one of the upper and lower surfaces.
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a divisional of copending patent application Ser. No. 13/047,164, filed Mar. 14, 2011; the application also claims the priority, under 35 U.S.C. §119, of German patent application No. DE 10 2010 011 249.6, filed Mar. 12, 2010; the prior applications are herewith incorporated by reference in their entirety.
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to a method for producing a structured surface which makes contact with printing material, in which a structured coating which has microparticles is produced on a substrate. The invention also relates to a method for the self-repair of a structured surface which makes contact with printing material, in which a structured coating is disposed on a substrate. Furthermore, the present invention relates to a structured surface which makes contact with printing material, having a structured coating on a substrate, in which the coating has microparticles. The invention further relates to a machine which processes printing material, for example a printing press, in particular a sheet-processing rotary printing press for lithographic offset printing or, for example, a machine for further print processing. The invention additionally relates to a use of agglomerates for the self-repair of structured surfaces which make contact with printing material.
In machines of the so-called graphics industry (prepress stage, print production and further print processing), printing materials, for example paper, cardboard or film, are conveyed and processed. The printing materials can be conveyed in printing presses by using rotating cylinders which, for that purpose, have surfaces which make contact with printing material, preferably in the form of changeable cylinder covers (“jackets”). The surfaces are, as a rule, equipped with two properties: firstly they are antiadhesive (they repel ink, varnish and dirt) and secondly they are wear resistant due to the usually very hard materials which are used. Furthermore, the surfaces as a rule have a usually microscopic structure, that is to say they are not configured to be smooth, but rather (micro-) rough. That roughness reduces a contact area for the printing material and therefore the possibility of ink being deposited on the surface. For example, thermally sprayed (and therefore microrough), ceramic coatings with sealings having a low surface energy, such as silicone, have been used for some years (such as the “PerfectJacket” product from Heidelberger Druckmaschinen AG).
German Published Patent Application DE 10 2005 060 734 A1, corresponding to U.S. Pat. No. 7,651,560, discloses an antiadhesive layer including crosslinked nanoparticles, for example polyorganosiloxanes, for cylinder covers. They are crosslinked three-dimensionally and applied by using the sol-gel process. In addition, hard particles (diameter from 0.1 to 0.5 micrometer), for example diamond powder or boron nitride, can be added. The layer which is formed therefrom has uniformly distributed particles. It is not disclosed whether the layer which is produced in that way has its own structure or is applied to a separate structural layer.
Japanese Published Patent Application JP 11-165399 A has disclosed a transport roll for printing materials with a structural coating. A two step coating process for producing a roll of that type includes firstly spraying on ceramic particles with a diameter of from 5 to 60 micrometers and secondly spraying on silicone (and subsequent drying as a third step). A rough surface structure is formed, there being more particles in structural elevations than in structural troughs.
The surfaces which are disclosed in the prior art can at the same time have two disadvantages: firstly, as a result of the unavoidable wear, the covers can lose their roughness, if it exists, and secondly they can lose their antiadhesivity which is necessary for the self-cleaning effect.
One further concept which has not been pursued, however, by the invention could be seen in removing the worn covers from the machine and subjecting them to a repair process, for example by recoating. However, a process of that type would presumably be very time-consuming and expensive.
A similar repair process which is carried out in a machine is described, for example, in German Published Patent Application DE 102 27 758 A1. In that case, however, only nanoparticles (using the sol-gel process) are used and not microparticles. It is not disclosed whether the layer which is repaired in that way has its own structure or is applied to a separate structural layer.
Furthermore, German Published Patent Application DE 199 57 325 A1 has disclosed a coating composition for producing abrasion resistant anticorrosion layers for metals, with an antiadhesive sol-gel matrix being produced. A disadvantage of the described layer is the possible loss of the antiadhesive action during mechanical loading, such as abrasion.
SUMMARY OF THE INVENTION
It is accordingly an object of the invention to provide a method for producing a structured surface contacting printing material, a structured surface, a machine and a method for self-repair of structured surfaces, which overcome the hereinafore-mentioned disadvantages of the heretofore-known methods, products and devices of this general type. In particular, it is an object of the present invention to provide a method which makes the production of antiadhesive and wear resistant and/or self-repairing surfaces possible, or makes their self-repair possible. Moreover, it is a further or alternative object of the present invention to provide a surface which makes contact with printing material and has antiadhesive and wear resistant and/or self-repairing properties which are maintained even in the case of mechanical loading, such as abrasion. In addition, it is an object of the present invention to provide a cost-reducing method of using agglomerated particles.
With the foregoing and other objects in view there is provided, in accordance with the invention, a method for producing a structured surface for contacting printing material. The method comprises producing a structured coating having microparticles on a substrate, antiadhesively encasing and agglomerating the microparticles by adsorption of nanoparticles to produce agglomerates, and fixing the agglomerates in a sol-gel matrix.
The invention advantageously makes it possible to produce antiadhesive and wear resistant and/or self-repairing properties with few steps and, in particular, with only one coating step.
In accordance with another mode of the method of the invention, the microparticles have a size of from approximately 1 to approximately 5 micrometers and agglomerates with a size of from approximately 10 to approximately 50 micrometers are produced from them.
In accordance with a further mode of the method of the invention, structural elevations of the coating are formed substantially by the agglomerates.
With the objects of the invention in view, there is also provided a method for the self-repair of a structured surface for contacting printing material. The method comprises producing a structured coating on a substrate, providing the coating with structural elevations containing microparticles having antiadhesive casings formed by adsorption of nanoparticles, and exposing the microparticles together with their respective antiadhesive casings by abrasion of peaks of the structural elevations.
The invention advantageously makes it possible to produce self-repairing properties and, based on this, a self-repair function.
With the objects of the invention in view, there is furthermore provided a structured surface for contacting printing material. The structured surface comprises a substrate, and a structured coating disposed on the substrate, the structured coating having agglomerates fixed in a sol-gel matrix and microparticles encased antiadhesively by adsorption of nanoparticles.
The invention advantageously makes it possible to produce a surface with antiadhesive and wear resistant and/or self-repairing properties.
In accordance with another feature of the surface of the invention, the microparticles have a size of from approximately 1 to approximately 5 micrometers and the agglomerates have a size of from approximately 10 to approximately 50 micrometers.
In accordance with a further feature of the surface of the invention, structural elevations of the coating are formed substantially by the agglomerates.
In accordance with an added feature of the surface of the invention, the microparticles have silicon carbide.
With the objects of the invention in view, there is additionally provided a use of agglomerates which are fixed in a sol-gel matrix and include microparticles which are encased antiadhesively by adsorption of nanoparticles, for the self-repair of structured surfaces which make contact with printing material.
With the objects of the invention in view, there is concomitantly provided a printing material processing machine, for example a printing press, in particular a sheet-fed rotary printing press for lithographic offset printing or, for example, a machine for further print processing, comprising at least one structured surface according to the invention for making contact with printing material.
The invention which is described and the advantageous developments of the invention which are described also represent, in combination with one another, advantageous developments of the invention. A coating according to the invention, for example, is particularly preferred with agglomerated and encased microparticles of a size of from approximately 1 to approximately 5 micrometers and agglomerates of a size of from approximately 10 to approximately 50 micrometers, with structural elevations of the coating being formed substantially by the agglomerates.
Other features which are considered as characteristic for the invention are set forth in the appended claims.
Although the invention is illustrated and described herein as embodied in a method for producing a structured surface contacting printing material, a structured surface, a machine and a method for self-repair of structured surfaces, it is nevertheless not intended to be limited to the details shown, since various modifications and structural changes may be made therein without departing from the spirit of the invention and within the scope and range of equivalents of the claims.
The construction and method of operation of the invention, however, 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 SEVERAL VIEWS OF THE DRAWING
FIG. 1A is a diagrammatic, sectional view of a preferred exemplary embodiment of a cylinder cover according to the invention;
FIG. 1B is a further diagrammatic, sectional view of a preferred exemplary embodiment of a cylinder cover according to the invention;
FIG. 2 is an enlarged, fragmentary view of a portion II of FIGS. 1A and 1B ; and
FIG. 3 is a flow chart of a preferred exemplary embodiment of a method according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
Referring now to the figures of the drawings in detail and first, particularly, to FIG. 1A thereof, there is seen a diagrammatic, sectional view of a preferred exemplary embodiment of a cylinder cover 1 according to the invention. The cover has a substrate 2 , preferably made from stainless steel and, as an alternative, from aluminum, titanium, steel or plastic, and a wear resistant and antiadhesive coating 3 . The coating 3 includes a sol-gel matrix 4 a including crosslinked nanoparticles with microparticles 5 which are incorporated into the matrix 4 a.
The sol-gel matrix per se can be produced or built up in a conventional manner, preferably in accordance with the matrix which is disclosed in German Published Patent Application DE 199 57 325 A1. A product “H 5055” from the company FEW Chemicals GmbH in Bitterfeld-Wolfen, Germany is preferably used for the nanosol. However, during the production according to the invention, in a deviation from the known method, the above-mentioned microparticles 5 or corresponding starting material for the microparticles 5 are additionally dispersed. In a deviation from the known layer, the layer which is produced according to the invention has the above-mentioned microparticles incorporated into the matrix.
The microparticles 5 which are incorporated into the matrix 4 a and are fixed by the matrix are preferably made from silicon carbide (SiC) or, as an alternative, from silicon, aluminum oxide (Al 2 O 3 ), glass or ceramic. The silicon carbide which is preferably used can be purchased as a powder, for example, from the producer H. C. Starck in Goslar, Germany under the identifier “Type 25.”
In addition, it can be seen in FIG. 1 A that the microparticle s 5 are provided in each case with an antiadhesive casing 6 including nanoparticles 4 b which are adsorbed on the microparticle surface. The respective antiadhesive casings 6 have a thickness of from approximately 0.5 to approximately 5 micrometers. The microparticles 5 therefore have their own sol-gel casings and are therefore antiadhesively coated themselves. According to the invention, this results in the advantage shown in the enlarged portion II in FIG. 2 , which is that as the wear increases, although the microparticles 5 can be exposed by abrasion of peaks 7 of structural elevations 8 , they maintain the antiadhesivity of the layer 3 and the cover 1 over an extended time period due to their own antiadhesivity.
FIG. 1B shows a further diagrammatic sectional view of a preferred exemplary embodiment of a cylinder cover 1 according to the invention. In this case, the matrix 4 a between agglomerates 9 is substantially free of microparticles 5 , with the result that structural troughs are formed substantially only by the matrix 4 a . Although non-agglomerated microparticles 5 can also be present in places, they do not make a substantial contribution to the structure. The structure of the cover 1 is therefore formed substantially from the structural peaks including the agglomerates 9 and the structural troughs including the matrix 4 a.
FIG. 3 shows a flow chart of a preferred exemplary embodiment of a method according to the invention. In a first step A (mixing), a starting material for the above-mentioned microparticles 5 is added to the nanosol (preferably in accordance with German Published Patent Application DE 199 57 325 A1). The starting material includes so-called primary particles in powder form, that is to say particles which are agglomerated only to a small extent or loosely, with a size of from 1 to approximately 50 micrometers, preferably with a size of from 10 to approximately 30 micrometers. In one successful experiment, approximately 200 grams of primary particles were added to approximately 3 liters of sol.
In a second method step B (comminuting and encasing), the sol is stirred together with the primary particles and a dispersion is produced. In the successful experiment, dispersing was carried out for approximately 30 minutes at from approximately 10,000 to approximately 20,000 revolutions per minute.
Due to the stirring and, in particular, if a stirring device is used which acts mechanically on the primary particles, for example a stirring-machine mill, the primary particles are comminuted to a size of from approximately 1 to approximately 5 micrometers, preferably to a size of from approximately 2 to approximately 3 micrometers and particularly preferably to a size of approximately 2.5 micrometers. The microparticles 5 are produced from the primary particles in this way. At the same time, nanoparticles 4 b of the sol adsorb at the surface of the microparticles 5 and form the above-mentioned casings 6 of the microparticles 5 .
A dispersion 4 which is produced in this way is applied to the substrate 2 in a third method step C (applying), preferably by spraying onto the substrate 2 (successfully, for example, by way of a so-called High Volume Low Pressure (HVLP)-Spray pistol from the company SATA GmbH & Co. KG in Kornwestheim, Germany). A first agglomeration of the microparticles 5 already occurs during the spraying-on process.
In a following fourth step D (crosslinking and agglomerating), the applied layer 3 is treated thermally, that is to say crosslinked and cured. In one successful experiment, the crosslinking was carried out at approximately 150° C. In this case, the solvent of the dispersion evaporates and a further agglomeration of the microparticles 5 and the formation of the structure of the surface occur, with structural elevations being formed predominantly by the agglomerates 9 (see FIGS. 1A and 1B ). In this way, layers 3 can be produced with Rz values of from approximately 10 to approximately 50 micrometers, preferably with Rz values of from 20 to approximately 40 micrometers.
One advantage of the invention is to be seen in the fact that a structured and antiadhesive surface can be produced with only one coating step (method step C). It is therefore not required according to the invention, for example, to first of all apply a structural layer and then separately an antiadhesive layer. The production process according to the invention can be carried out less expensively due to that second coating step being omitted.
A further advantage results from the effect of the agglomerated and in each case encased microparticles 5 . The structural elevations 8 and the agglomerates 9 are extremely wear resistant, since even an abrasion of the structural peaks 7 does not lead to a complete loss of the necessary antiadhesivity. In other words: the structure has a self-repair function which is based on the structurally internal, antiadhesive casings of the structural particles 5 .
As an alternative to the above-described comminution of the primary particles, sufficiently small primary particles can also be admixed and encased without substantial comminution in method step B. However, the use of primary particles to be comminuted as described above is preferred, since they can be obtained less expensively and the comminution process assists the encasing according to the invention with nanoparticles.
The cylinder covers according to the invention can preferably be used on transfer cylinders, turner cylinders and impression cylinders, both in small formats (so-called 5 format and smaller) and also in large formats (so-called 6 , 7 and 8 formats, or all formats which are larger than 890×1,260 millimeters).
The following is a preferred example for the combination according to the invention of classic sol-gel chemistry with the abrasion/wear resistance of mineral microparticles as filler in layer compositions according to method step A:
a) from 5 to 40% of one or a mixture of a plurality of metal or semimetal alkoxides of the general formula M(O—R1)n(M=B, Al, Si, Ti ; R1=alkyl, aryl, acyl, alkoxyalkyl), b) from 30 to 70% of one or a mixture of a plurality of functionalized or nonfunctionalized organosilanes of the general formula R2×Si(R3)4-x (R2=alkyl C1-C20, alkenyl C1-C20, aryl, 3-aminopropyl, 3-glycidoxypropyl, 3-methacryloxypropyl, aminoethyl aminopropyl, 3-mercaptopropyl; R3=alkoxy, aryloxy, Cl) and mixtures of hydrolysis and condensation products of different organosilanes of this type, the organic radicals of which can react with one another, c) from 0 to 10% of one or more fluorinated polyethers, the polymer chain of which is constructed from tetrafluoroethylene oxide or heptafluoroethylene oxide chains and which has at least one hydrolyzable silyl radical which is bonded through a pure carbon chain or from 0 to 10% of one or more organosilanes with a fluorine-containing side chain, and d) from 20 to 70% of a pulverulent, scratch resistant pigment (primary particles), for example with a Mohs hardness of >7.
All solvents which can be mixed with water and the starting compounds being used can be used as solvent. In the case of components (a) and (b), they are normally ketones and alcohols, such as acetone, butanone, ethanol, n-propanol, iso-propanol, n-butanol, pentanol, 1-methoxy-2-propanol and mixtures thereof. Lower alcohols, such as methanol and ethanol, have proven particularly advantageous due to the compatibility, in particular, with components (d).
For the hydrolysis of the alkoxides and the organosilanes, water is added in an at least semistoichiometric amount in relation to hydrolyzable groups, but is preferably added in a stoichiometric or superstoichiometric amount, in order to ensure complete hydrolysis. All customary bases and acids which are soluble in the system can be used as catalysts for the hydrolysis and condensation. Acid catalysis is preferred.
Tetraalkoxysilanes and, in particular, tetraethyl orthosilicate (TEOS) are preferably used as metal or semimetal alkoxides. Alkylsilanes and arylsilanes without further functional groups are particularly suitable as organosilanes, but organosilanes with functional groups can also be used, such as epoxy, amino and perfluorine groups. Mineral pigments with a Mohs hardness of ≧7 are suitable as scratch resistant particles, such as quartz (hardness 7), corundum (hardness 9), silicon carbide (hardness 9.5) and diamond (hardness 10).
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A method for producing a structured surface making contact with printing material, preferably a cylinder cover, includes producing a structured coating having microparticles on a substrate, preferably a stainless steel plate. The microparticles are encased antiadhesively and agglomerated by adsorption of nanoparticles, and the agglomerates being produced are fixed in a sol-gel matrix. A surface produced in this way has a structured coating on a substrate and the coating has microparticles. The coating has agglomerates fixed in a sol-gel matrix and including microparticles encased antiadhesively by adsorption of nanoparticles and preferably formed of silicon carbide. The surfaces advantageously have a self-repair function since, in the case of abrasion of structural elevations, the antiadhesive casings of the microparticles are exposed and the antiadhesive property of the coating is maintained.
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CROSS REFERENCE TO RELATED APPLICATIONS
The present application is a continuation of application Ser. No. 10/764,072 filed Jan. 23, 2004 now U.S. Pat. No. 7,152,863.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the field of entertainment and games, and more particularly, to the field of games of chance. The present invention is relevant more specifically to the field of casino games and parlor games.
2. Background of the Related Art
Games incorporating elements of chance are well known. These games are known both in the context of casino games as well as parlor games. Games of chance generally revolve around the outcome or outcomes of some random or quasi-random event or events. These events have a limited set of possible outcomes, although the set of possible outcomes may be very large. Generally, game players attempt to predict the outcome of one or more events prior to their occurrence. Game winners may be determined by correctly predicting all or part of the outcome of the event or events.
Games of chance have particular application in the field of casino gaming. Casino gaming as used herein is understood to include gambling applications outside of actual casinos, for example, in locations such as bars, airports and the like which may have gambling. It is understood that casino gaming may include both table-based gaming, as well as machine-based gaming, including, for example, mechanical slot machine gaming and computer controlled machine gaming.
Well known casino games include craps, roulette, blackjack, pai gow poker, pai gow, the wheel of fortune, slot machines, video poker, keno, baccarat, mini-baccarat, Spanish-21, casino war, and poker. Also well know are games such as state lotteries and daily numbers drawings
The principal goal of games of chance are to provide entertainment. In the casino and gambling context, successful games attract and maintain the interest of players, thereby generating income for the casino or other game host. These games of chance ideally provide action and excitement for players, have relatively easy to learn rules which do not use complicated rankings of various outcomes (e.g., poker hand valuations), and permit a variety of different wagers to keep players' interest.
In order to create a sense of competition, and therefore excitement and interest, certain presently known games of chance determine winners by comparing the outcome of a player's event (such as the roll of one or more dice) against the results of a similar event of a “dealer” or other player.
One example of such a game of chance applicable in the casino setting is disclosed in U.S. Pat. No. 5,413,351, which discloses a dice game involving wagering on the outcome of a roll of three dice. One or more players place wagers and then roll dice against a dealer. Game results depend on the occurrence of a predefined set of outcomes and/or the relative values of the player's and dealer's outcomes.
U.S. Pat. No. 5,513,850 discloses a game in which a player and a dealer develop “hands” based on the outcome of one or more rolls of several dice by both the dealer and player. Game results depend on the value of the dealer's hand relative to the player's hand according to a predefined set of relatively complex rules.
U.S. Pat. No. 6,062,563 discloses a game in which a player and a dealer each rolls a set of dice. Wagers are made on the relative outcome of the two rolls. The player's dice ad dealer's dice may be differentiated from one another by color so as to avoid confusion upon each rolling his respective dice.
U.S. Pat. No. 5,695,193 discloses a game in which players play against one another or against a dealer. Game results are based on predefined combinations of dice outcomes Outcome combinations are compared to that of each player in turn and the combination with the highest value according to a pre-defined point values assigned to each possible outcome is deemed the winner.
Many players, however, seek to avoid confrontation and so disfavor games involving such inter-personal competition, even when such competition is against a casino as personified by a dealer.
Other presently known games attempt to create excitement by providing multiple wagering stages during the course of a single game. U.S. Pat. No. 5,513,851, for example, discloses a dice-based game requiring players to place at least one additional wager on at least one additional roll of several dice after successfully wagering on the outcome of a first roll of the several dice.
Still other presently known games attempt to attract players by providing a limited set of wagers which players may learn quickly. One such game is disclosed in U.S. Pat. No. 5,732,948, which discloses a dice-based game having a small set of available wagers. The outcome of the game is dependent on no more than two rolls of a pair of dice. The game may be terminated upon the occurrence of a pre-defined outcome during a first roll of dice, or upon the occurrence of certain outcomes of a second roll of dice relative to the outcome of the first roll the dice.
Similarly, U.S. Pat. No. 6,234,482 discloses a multiple dice game wherein players' wager relate to the outcome of a roll of three dice without differentiation of three dice. Wagers are limited to wagers regarding the total of the three dice and/or the existence of two or three identical numbers being rolled.
U.S. Pat. No. 6,508,469 discloses a multiple-dice game wherein players wager on the sum of the outcome of two rolls of three dice each and/or on poker-like outcomes (e.g., three-of-a-kind, straights, etc.) without differentiation of the dice. Wagers may be made before the first roll and/or between the first and second rolls.
U.S. Pat. No. 6,209,874 discloses a three-dice game having dice of three different colors. Players are limited to six types of wagers on the result of rolling three dice. A first type of wager is on the face-up sides of a selected two of the dice being equal both to each other and to a number selected by the player. A second type of wager is on the face-up side of a selected one of the dice indicating a selected number. A third type of wager is on the face-up side of a selected one of the dice indicating a number that is alternatively higher or lower than numbers indicated by the other two dice. A fourth type of wager is on the face up sides of the dice each being equal to each other and to a number selected by the player. A fifth type of wager is on the face-up sides of the dice indicating numbers having a sum which is a selected total number. A sixth type of wager is on the sum of numbers indicated by the face-up sides of the three dice being alternatively an odd number or an even number.
Due to the limited scope of available wagers, however, these games may not adequately maintain the interest of players. Certain presently known games address this issue by providing more complicated rules. One example is U.S. Pat. No. 5,350,175, which discloses a dice-based game wherein players wager on the outcomes of successive rolls of several dice. The game terminates upon the happening of certain pre-defined combinations of outcomes of the several rolls of the dice. Similarly, U.S. Pat. No. 6,070,872 discloses a combination card and dice-based game which proceeds through three distinct phases of random card and dice events. These games, however, may present rules which are too complicated for a number of typical players to comfortably learn or understand.
Finally, several currently known games involve game play which does not adequately develop excitement for players.
U.S. Pat. No. 5,806,847 discloses a game wherein players wager on the outcome of a single event such as the roll of a pair of dice. Several pre-defined wagers are disclosed, such as the outcome of the event being included in one or more predefined sets of outcomes. The single event results in a final and unequivocal outcome of all wagers, and so players are required to re-wager after each event, and no wager relies on the outcome of more than a single event.
U.S. Pat. No. 6,378,869 discloses a dice-based game wherein players wager on the outcome of rolls of two dice followed by the roll of a third die. Disclosed wagers include individual wagers for each possible sum of the dice values as rolled, hi/lo outcome sets (i.e., wagers that the sum of the values rolled will fall within 4 to 10 inclusive or 11 to 17 inclusive) and odd/even outcomes.
Games of chance in the parlor game context may include simulations of casino gaming, as well as point driven and other games not directly related to gambling.
With these considerations in mind, it is desirable to have a game which provides action and excitement for players, has relatively easy to learn rules which do not use complicated rankings of various outcomes, permits a variety of wagers to keep players' interest and builds excitement throughout each game.
SUMMARY OF THE INVENTION
The subject invention is directed to a new and useful game of chance particularly well suited for casino and parlor play. The present invention has the advantages of providing a variety of different wagers to players, both easy to learn as well as more complicated. Additionally, the present invention includes multi-staged play which builds excitement for players without forcing players to make multi-tiered wagers.
A method of playing a game of chance is disclosed, one preferred embodiment having the steps of defining a set of wagers on the outcome of a plurality of differentiable random events, the random events defining an aggregate event; defining a set of payout odds associated with the wagers, accepting at least one player wager for at least one wager in the set of wagers, generating the plurality of differentiable random events, and paying winning wagers according to the payout odds.
Also disclosed is a preferred embodiment of the present invention in the form of a method of playing a game of chance having the steps of: selecting a wager from a pre-defined set of wagers on the outcome of a plurality of differentiable random events, the random events defining an aggregate event and the pre-defined set of wagers having a pre-defined set of payout odds associated therewith, awaiting the outcome of the plurality of differentiable random events, and collecting payment for winning wagers according to the payout odds.
Finally, a preferred embodiment is disclosed in the form of a game of chance having a wager area for accepting wagers, the wager area having set of wagers on the outcome of a plurality of differentiable random events, the random events defining an aggregate event, a set of payout odds associated with the wagers and a random event generator for generating the plurality of differentiable random events, wherein winning wagers accepted in the wager area are paid in accordance with the payout odds.
The set of wagers may include a plurality of wager groups, the wager groups including a first wager group having single, double and trifecta wagers and a second wager group having wagers on the aggregate event. The plurality of differentiable random events may include a first, second, third and fourth random event, and the first wager group may include a single wager on the first random event, a double wager on the first and second random events, and a trifecta wager on the first, second and third random events.
The aforementioned first wager group further may include a single wager on the second random event, a double wager on the second and third random event, and a trifecta wager on the second, third and fourth random events.
The further step of generating a bonus random event may be included and the wager groups may then include a third wager group having wagers on the bonus random event.
The third wager group may include a single wager on the third random event, a double wager on the third and fourth random events, and a trifecta wager on the third, fourth and bonus random events. Additionally, the third wager group may include a single wager on the fourth random event and a double wager on the fourth and bonus random events.
The plurality of differentiable random events may include a first, second, third and fourth random event and the second wager group may include a plurality of wagers on aggregate values of the first, second, third and fourth random events. The second wager group may include an over-under wager.
The further step of generating a bonus random event may be included, and the wager groups may then include a third wager group having wagers on the bonus random event.
The third wager group may include a wager on a combination of an over-under and the bonus random event. Additionally, the second wager group may include one or more block wagers.
The aforementioned block wagers may have at least one of the group of: (a) wagers on blocks of two aggregate values of the first, second, third and fourth random events, (b) wagers on blocks of three aggregate values of the first, second, third and fourth random events, (c) wagers on blocks of four aggregate values of the first, second, third and fourth random events, (d) wagers on blocks of five aggregate values of the first, second, third and fourth random events, and (e) wagers on blocks of six aggregate values of the first, second, third and fourth random events.
In the foregoing embodiments, the second wager group may have at least one wager selected from the group of: four deuces, aces over any pair, any three of a kind, any four of a kind, 4-or-24, triple threes, big 6, any result over 20, all odd, all even, any straight, any two pair, and any result under 10.
The plurality of differentiable random events may be generated by random event generators having at least one of the group of: (a) one or more dice, (b) one or more prize wheels, (c) one or more roulette type wheels, (d) one or more air mix type random number generators, (e) one or more gravity fed random number generators, and (f) one or more pseudo random number generators.
These and other aspects of the subject invention will become more readily apparent to those having ordinary skill in the art from the following detailed description of the invention taken in conjunction with the drawings described herein.
BRIEF DESCRIPTION OF THE DRAWINGS
So that those having ordinary skill in the art to which the subject invention pertains will more readily understand how to make and use the subject invention, preferred embodiments thereof will be described in detail herein with reference to the drawings.
FIG. 1 is a depiction of dice utilized in a preferred embodiment of the present invention.
FIG. 2 is a playing board having several wager groups in accordance with a preferred embodiment of the present invention.
FIG. 3 is a wager group of a preferred embodiment of the present invention.
FIG. 4 is another wager group of a preferred embodiment of the present invention.
FIG. 5 is another wager group of a preferred embodiment of the present invention.
FIG. 6 is another wager group of a preferred embodiment of the present invention.
FIG. 7 is another wager group of a preferred embodiment of the present invention.
FIG. 8 is a flow chart showing the steps of game play in a preferred embodiment of the present invention.
FIG. 9 depicts random event generators in the form of prize wheels.
FIG. 10 is a schematic depiction of a computer based machine embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now in detail to the drawings wherein like reference numerals identify similar structural features of the several embodiments of the subject invention, there is illustrated in FIG. 1 a set of dice for use in a preferred embodiment of the present invention. Each of the numbered dice, 1 - 4 , includes six faces with representations of the numbers 1 through 6 , although other symbols may be used for each face of a die, for example, horse names, shapes, letters or other symbols. In such cases, certain wagers based on mathematical calculations of results may not be directly applicable. If such calculation based wagers were desired in such cases, numeric values may be assigned to the various shapes, symbols, etc.
The numbered dice are color coded so as to differentiate themselves from one another. In one preferred embodiment, die 1 is colored red, die 2 is colored white, die 3 is colored blue and die 4 is colored white with red and blue stripes. Other differentiation schemes may be utilized to differentiate the dice, for example, dice may be of differing sizes, contained in color coded, named, or otherwise differentiable containers and the like.
The numbered dice 1 - 4 are rolled during game play to generate random events, and players may place one or more wagers on the outcome of the rolls of the numbered dice 1 - 4 , alone or in combination, as discussed in further detail below.
“Bonus die” 5 is a six-sided die having only three different indicia; that is, each indicia is repeated on two different faces of the die. In one preferred embodiment of the present invention, the indicia of the bonus die are colors; that is, two sides are red, two sides are white, and two sides are blue. Any other distinguishable indicia may also be utilized. The bonus die is rolled during game play to generate a bonus event and players may place one or more wagers on the outcome of the roll of the bonus die either alone or in combination with other dice.
Players may place wagers by placing money, chips, chits or other indicators on a wagering surface demarcated with wager areas. A preferred embodiment of a playing surface of the present invention is shown in FIG. 2 . Wager areas 14 are delineated by lines 11 drawn on the wagering surface. Wager indicators 12 contained within each wager area indicate the wager associated with the particular wager area. Payout indicators 13 may be placed on the wagering surface to indicated payout odds for the various wagers, thereby permitting players to readily determine what payouts they will receive for placing winning wagers. For example, payout odds of 4 - 1 means that for every one dollar placed on a winning wager (i.e., for every one dollar player wager), a player will receive four dollars payout. The wagering surface may be divided into two or more wager groups 10 containing similar or related wagers, for example, grouping one-roll wagers, red-white-blue wagers, white-blue-red wagers, blue-striped-bonus wagers, striped-bonus wagers, aggregate wagers, and the like, as discussed in further detail below.
FIG. 3 illustrates a wager group of a preferred embodiment of the present invention. Wager areas 14 included in this wager group include wagers dependent on the total rolled values of dice 1 - 4 , as well as the value of bonus die 5 , and may be called “aggregate wagers”, “final roll wagers” or “final roll bets”. These final roll wagers are wagers on an aggregate event defined by combining the outcomes of the individual events; that is, the aggregate event may defined by combining the values of the outcome of the rolls of dice 1 - 4 , 1 - 4 plus bonus die 5 , or combinations thereof. Examples of aggregate events may therefore include “total of 17 for dice 1 - 4 ” and “total of 17 for dice 1 - 4 and red for dice 5 ”, among others.
Wager areas in this wager group include wagers on the total of the rolled values of dice 1 - 4 , 21, wagers that the total of the rolled values of dice 1 - 4 are over or under 14 (“over-under” wagers), 22, and block wagers, that is, wagers that the total of the rolled values of dice 1 - 4 will be one of a predefined block of several values, 23. For example, block wagers may be on: blocks of two aggregate values (e.g., that the total will be one of 18 or 22), blocks of three aggregate values (e.g., that the total will be one of 7, 14 or 21), blocks of four aggregate values (e.g., that the total will be one of 6, 11, 17 or 22), blocks of five aggregate values (e.g., that the total will be one of 4, 9, 13, 18 or 22), or blocks of six aggregate values (e.g., that the total will be one of 4, 9, 13, 18, 21 or 22).
Also included in this wager group are “specialty wagers”, 24, such as “four deuces” (i.e., that each die, excluding the bonus die, will show a two), any two pair (i.e., that the dice, excluding the bonus die, will show two numbers each repeated on two dice), all even (i.e., that the value of each die, excluding the bonus die, will be an even value), three of a kind (i.e., that the dice, excluding the bonus die, will show the same number repeated on three dice), four of a kind (i.e., that the dice, excluding the bonus die, will show the same number repeated on all four dice), and the like.
The over-under wagers just discussed are best implemented in embodiments having an even number of dice or other random event generators such as prize wheels so that the set of all possible outcomes includes a “pivot number”; that is, a single median value within the set of all possible outcomes. Other embodiments may include sets of all possible outcomes which have more than a single pivot number; that is, two or more median values within the set of all possible outcomes. In such embodiments, over or under wagers may be adjusted to be over the highest of pivot numbers and below the lowest of pivot numbers. The pivot number may also be referred to as the “house number”.
Tables 1 and 2 provide a complete list of wagers illustrated in FIG. 2 , including odds of winning and payout odds of the present preferred embodiment.
TABLE 1
Single Aggregate Value
Wager
Odds
Payout
4, 24
1296-1
1000-1
5, 23
324-1
250-1
6, 22
129.6-1
100-1
7, 21
64.8-1
50-1
8, 20
37-1
28-1
9, 19
23.1-1
18-1
10, 18
16.2-1
12-1
11, 17
12.5-1
10-1
12, 16
10.4-1
8-1
13, 15
9.3-1
7-1
14
8.9-1
6-1
TABLE 2
Wager
Odds
Payout
Any Five-Result Block Wager (e.g., total
3.5-1
3-1
equaling any of 4, 9, 13, 18 or 22, etc.)
Four-Result Block Wagers 4-10-12-21, 6-11-
4.7-1
4-1
17-22 and 7-16-18-24
Four-Result Block Wagers 5-9-13-20 and 8-
4.5-1
4-1
15-19-23
Any Three-Result Block Wager (e.g., total
6-1
5-1
equaling any of 4, 11 or 18, etc.)
Over/Under (i.e., over 14 or under 14)
1.3-1
1-1
Over/Under plus Bonus Die (e.g., over 14 plus
5.8-1
5-1
red)
Any Triple
10.1-1
8-1
Under 10
9.3-1
9-1
Any Two Pair
12.5-1
12-1
All Even/Odd (i.e., each die even or each die
15-1
14-1
odd)
Any Straight (e.g., 2-3-4-5, etc.)
26-1
18-1
Over 20 (i.e., the total of the dice being
36-1
35-1
greater than 20)
Big 6 (i.e., total equaling any of 4, 5, 6, 22, 23
42.2-1
40-1
or 24)
Triple 3's (i.e., three dice each showing 3)
60.7-1
50-1
Aces Over Any Pair (i.e., a pair of aces and
80-1
75-1
any other pair)
Any Four of a Kind
215-1
200-1
4 or 24 (i.e., the total equaling 4 or 24)
647-1
500-1
Four Deuces (i.e., each die showing 2)
1295-1
1000-1
Any Four of a Kind Plus White
647-1
600-1
4 or 24 Plus Blue
1943-1
1500-1
Four Deuces Plus Red
3887-1
3000-1
FIG. 4 illustrates another wager group of a preferred embodiment of the present invention. Wager areas 14 included in this wager group include wagers on the outcome of the roll of the red die (“single” or “single wager”), red and white dice (“double” or “double wager”), or red, white and blue dice (“trifecta” or “trifecta wager”). For example, a single wager made in wager area 31 wins when the number 3 is rolled on the red die. A double wager made in wager area 32 wins when the number 3 is rolled on the red die and the number 6 is rolled on the white die (that is, both conditions must be met for the wager to be successful). In a similar fashion, a trifecta wager made in wager area 33 wins when the number 3 is rolled on the red die and the number 6 is rolled on the white die and the number 2 is rolled on the blue die (that is, all three conditions must be met for the wager to be successful). The payout odds for winning single wagers are shown in box 34 , for winning double wagers in box 35 , and for winning trifecta wagers in box 36 . Table 3 provides a complete list of wagers illustrated in FIG. 4 , including odds of winning and payout odds of the present preferred embodiment.
TABLE 3
Wager
Odds
Payout
Any Single (e.g., 1, 2, etc.)
5-1
4.5-1
Any Double (e.g., 1-1, 1-2, etc.)
35-1
33-1
Any Trifecta (e.g., 1-1-1, 1-1-2, etc.)
215-1
200-1
FIG. 5 illustrates another wager group of a preferred embodiment of the present invention. Wager areas 14 included in this wager group include wagers on the outcome of the roll of the white die (single), white and blue dice (double), or white, blue and striped dice (trifecta). These wagers operate in the same manner as the wagers disclosed in connection with FIG. 4 , with the white die substituted for the red die of the previous wager group, the blue die substituted for white die of the previous wager group, and the striped die substituted for the blue die of the previous wager group. The odds of winning and payout odds are the same as those tabulated in Table 3.
FIG. 6 illustrates an additional wager group of a preferred embodiment of the present invention. Wager areas 14 included in this wager group include wagers on the outcome of the roll of the blue die (single), blue and striped dice (double), or blue, striped and bonus dice (trifecta). The odds of winning an payout odds for the wagers of this wager group are shown in Table 4.
TABLE 4
Wager
Odds
Payout
Any Single (e.g., 1, 2, etc.)
5-1
4.5-1
Any Double (e.g., 1-1, 1-2, etc.)
35-1
33-1
Any Trifecta (e.g., 1-1-red, 1-1-blue, etc.)
107-1
100-1
Finally, FIG. 7 illustrates another wager group of a preferred embodiment of the present invention. Wager areas 14 included in this wager group include wagers on the outcome of the roll of the striped die (single) or striped and bonus dice (double). The odds of winning and payout odds for the wagers of this wager group are shown in Table 5.
TABLE 5
Wager
Odds
Payout
Any Single (e.g., 1, 2, etc.)
5-1
4.5-1
Any Double (e.g., 1-red, 1-blue, etc.)
18-1
15-1
From the foregoing, it may be seen that wager groups having wagers on the bonus random event may include wagers which are determined in whole or in part by the outcome of the bonus event.
The steps of the present preferred embodiment may be summarized by the flow chart of FIG. 8 . The game begins with the one or more wagers being made in step 1 . Following step 1 , the random events are generated in step 2 . Next, in step 3 , the aggregate results are determined, for example, by summing the resulting values of dice 1 - 4 . Finally winning wagers are paid in step 4 according the payout odds defined for them. Of course, other sequences may be employed without departing from the present invention. For example, each random event may be generated individually, with all wagers capable of being determined upon the completion of such event being paid at that point (as opposed to being paid only upon the completion of all events).
While the preceding preferred embodiments utilize dice, other random or pseudo-random event generators may be utilized. These include, among others, carnival, “wheel of chance”, or prize-wheel type wheels, such as those manufactured by Kardwell International, Inc., P.O. Box 33, Mattituck, N.Y. 11952 and as illustrated in FIG. 9 , multiple roulette type wheels, air mix type random number generators such as is disclosed in U.S. Pat. No. 5,121,920 and those manufactured by Smartplay International Inc., One Linda Lane, Suite B, Southampton, N.J. 08088, gravity fed random number generators such as those manufactured by Smartplay International Inc., bingo cages, such as those manufactured by Kardwell International, Inc., and the like.
Similarly, the entirety of the present invention may be implemented as an electronic or computer based game. In such embodiments, a computer consisting of a display device, 91 , central processing unit, 92 , input device such as a keyboard, touchscreen or dedicated mechanical buttons, 93 , volatile and non-volatile memory, 94 , central processing unit, 95 , pseudo-random number generator, 96 (which may be in the form of a computer routine executed by central processing unit 95 ), may be utilized to implement the game of chance of the present invention. Alternatively, dedicated logic may be utilized in place of a programmed computer. Such devices, which may be in a form similar to video poker type machines currently well known to those of skill in the art, may be programmed to present applicable wagers to players, accept wagers from players, generate the necessary random or pseudo-random events, and pay winning wagers in accordance with payout odds associated with the winning wagers.
While particular embodiments of the present invention have been shown and described, it will be apparent to those skilled in the pertinent art that changes and modifications may be made without departing from the invention in its broader aspects.
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A method of playing a game of chance comprising the steps of defining a set of wagers on the outcome of a plurality of differentiable random events, said random events defining an aggregate event, defining a set of payout odds associated with said wagers, accepting at least one player wager for at least one wager in said set of wagers, generating said plurality of differentiable random events, and paying winning wagers according to said payout odds.
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FIELD OF THE INVENTION
[0001] The present invention relates generally to the field of bioinformatics and its applications to functional genomics and advanced genetic engineering. More particularly, the present invention contemplates a method for identifying effector molecules capable of modulating gene network integration and which facilitate genetic multi-tasking and the regulation of complex suites of programmed responses within, on and between eukaryotic cells. The present invention permits, therefore, the identification of a new generation of proteome and nucleome modulators useful in a range of therapeutic and trait-modifying protocols. The ability to manipulate genetic networks within a cell and within whole organisms also provides a sophisticated genetic engineering approach of introducing new traits and to influencing the genetic architecture and, hence, to enable cell and organismal programming or re-programming. The identification of effector molecules and their target or receiver sites, further enables the development of diagnostic protocols for a range of conditions or physiological or genetic states of an organism, for example, in modulating stem cell differentiation, quantitative traits, aging or the development of pathological conditions.
BACKGROUND OF THE INVENTION
[0002] Bibliographic details of references provided in the subject specification are listed at the end of the specification.
[0003] Reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in any country.
[0004] The current understanding of the relationship between genetic information and biological function is predicated in the one gene-one protein hypothesis and in the classical studies of the lac operon and the “genetic code”, i.e. the triplet code specifying amino acids in protein coding sequences. The concept of DNA as a relatively stable, heritable source of template information for proteins, transduced through a temporary and discrete RNA readout has influenced ideas on the structure of genetic systems. Accordingly, cells and organisms are thought of as being built from a myriad of structural and catalytic proteins, whose expression is generally controlled by other regulatory proteins which bind to DNA. This is a biochemical rather than an informatic perspective, which, apart from local analysis of promoter function, gives little thought to the problem of how complex programs of gene activity in the higher organisms might be integrated and regulated in four dimensions.
[0005] Genome sequencing projects have shown that the core proteome sizes of Caenorhabditis elegans and Drosophila melanogaster are of similar size and each only about twice the size of yeast and some bacteria, despite these animals' every appearance of possessing more than twice the complexity of microorganisms (Chervitz et al., Science 282: 2022-2028, 1998; Rubin et al., Science 287: 2204-2215, 2000), leading to the conclusion that “the evolution of additional complex attributes is essentially an organizational one; a matter of novel interactions that derive from the temporal and spatial segregation of fairly similar components” (Rubin et al., Science 287: 2204-2215, 2000). This conclusion is reinforced by the finding that the human genome has only about 30,000 protein coding genes (Roest Crollius et al., Nature Genet. 25: 235-238, 2000; Consortium, Nature 409: 860-921, 2001; Venter et al., Science 291: 1304-1351, 2001), the vast majority of which are shared in common with the mouse. The increased complexity of the higher eukaryotes is related, at least in part, to the production of different protein isoforms from the same gene by alternative splicing (Croft et al., Nature Genet. 24: 340-341, 2000). However, perhaps the most surprising and yet so far least considered feature of the genomes of the complex organisms, relative to simpler organisms, is the huge increase in the output of non-protein-coding RNA sequences, which have been estimated to account for around 97-98% of all transcriptional output from the human genome (Mattick, EMBO Reports 2: 986-991, 2001) (see below).
[0006] The view that phenotypic variation in complex organisms results from the differential use of a set of core components is becoming common (Duboule and Wilkins, Trends. Genet. 14: 54-59, 1998) and includes such concepts as “synexpression groups” (Niehrs and Pollet, Nature 402: 483-487, 1999), “syntagms” of interacting genes (Huang, Int. J. Dev. Biol. 42: 487-494, 1998) and gene cassettes (Jan and Jan, Proc. Natl. Acad. Sci. USA 90: 8305-8307, 1993), the re-use of modules in signaling pathways (Pawson, Nature 373: 573-580, 1995; Hunter, Cell 100: 113-127, 2000a) and enhanced rates of evolution by varying connections between modular network components (Hartwell et al., Nature 402: C47-52, 1999; Holland Nature 402: C-41-44, 1999). These concepts have been drawn primarily from electrical circuit design and have focussed principally on the modules rather than on the interconnecting control architecture of the system.
[0007] Particular network models, which range in size from single regulated circuits (Mestl et al., J. Theor. Biol. 176: 291-300, 1995; Mendoza and Alvarez-Buylla, J. Theor. Biol. 193: 307-319, 1998; Yuh et al., Science 279: 1896-1902, 1998) to complete genomes (Thieffry et al., Bioessays 20: 433-440, 1998) have demonstrated that feedback subnetworks can exhibit computational behaviors including “learned behavior” (Bhalla and Iyengar, Science 283: 381-387, 1999) that switching networks and transcriptional control networks can exhibit dynamical stability (Wolf and Eeckman, J. Theor. Biol. 195: 167-186, 1998; Smolen et al., Am. J. Physiol. 277: C777-790, 1999) and that feedback circuits can implement oscillators governing cell cycles and circadian clocks (Dano et al., Nature 402: 320-322, 1999; Haase and Reed, Nature 401: 394-397, 1999; Shearman et al., Science 288: 1013-1019, 2000). Stochastic noise and time delays allowing feedback, molecular memory and oscillations can be incorporated into such circuit models (Smolen et al., Am. J. Physiol. 277: C777-790, 1999) generating probabilistic phenotypic variation (McAdams and Arkin, Proc. Natl. Acad. Sci. USA 94: 814-819, 1997) and amplification of signals (Hasty t al., Proc. Natl. Acad. Sci. USA 97: 2075-2080, 2000). Some of these models have been verified by synthesizing circuits in cells to feature bistability, oscillations and stochastic destruction of temporal correlations (Becskei and Serrano, Nature 405: 590-593, 2000; Elowitz and Leibler, Nature 403: 335-338, 2000; Gardner et al., Nature 403: 339-342, 2000).
[0008] However, such models are unsuited to the analysis of global cellular connectivity and dynamics as they cannot be scaled up to large network sizes, since linear increases in the number of interconnected circuit nodes requires quadratic increases in the number of interconnecting molecules. This leads to an explosive increase in model size which severely constrains numerical simulations using current computing technologies (see e.g. Weng et al., Science 284: 92-96, 1999). A number of alternate approaches have sought to avoid this size explosion by treating sub-networks as active integrated logic components which are interconnected into larger networks (McAdams and Shapiro, Science 269: 650-656, 1995) or by exploiting hierarchically organized control systems to significantly decrease analytical complexity (van der Gugten and Westerhoff, Biosystems 44: 79-106, 1997).
[0009] In work leading up to the present invention, the inventors reasoned that biology has solved this problem differentily, and that the types of network control architecture which are used to integrate and multi-task computers and which are used in the brain to coordinate complex activities such as motor coordination and cognition, may also be employed by molecular biological networks to generate phenotypic complexity and variability.
[0010] Multi-tasking is employed in every computer where control codes (program instructions) of n bits set the central processing circuit to process one of 2 n different operations. Sequences of control codes (a program) can be internally stored in memory creating a self-contained programmed response network—a computer—as originally defined by von Neumann in 1945 (von Neumann, First Draft of a report on the EDVAC. In: B. Randall, ed. The origins of digital computers: selected papers. Spring, Berlin, 1982). Prior to the arrival of the von Neumann computing architecture, a computer could only be reprogrammed by laborious re-wiring of the central processing unit, while subsequently re-programming simply required loading new control codes into memory. In all computing networks, processing requires not only stored program instructions, but also communication between nodes to synchronize and integrate network activity. The present inventors propose, in accordance with the present invention, that gene networks could exploit similar technology using internal controls based on RNA to multi-task components and sub-networks to generate a wide range of programmed responses, such as in differentiation and development. This system has interesting and perhaps mutually informative analogies with small world networks and dataflow computing.
[0011] Existing genetic circuit models, although sophisticated, ignore endogenous controlled multi-tasking and consider each molecular sub-network (involving a few genes for instance) to be sparsely interconnected, and either off or on to express only one dynamical output (see e.g. McAdams and Shapiro, Science 269: 650-656 1995; Bhalla and Iyengar, Science 283: 381-387 1999; Weng et al., Science 284: 92-96 1999). Such models require more complex genetic programs to be built from many sub-networks encoded by exponentially large numbers of genes, a severe constraint, both in theory and in practice. In contrast, multi-tasking via n controls (single molecules suffice) can, in theory, achieve exponential (2 n ) multi-tasking of sub-network dynamical outputs, and allow a wide range of programmed responses to be obtained from limited numbers of sub-networks (and genetic coding information). The imbalance between the exponential benefit of controlled multi-tasking and the small linear cost of control molecules makes it likely that evolution will have explored this option. Indeed, this may have been the only feasible way to lift the constraints on the complexity and sophistication of genetic programming.
[0012] Complex organisms require two levels of genetic programming for their autopoeitic development from a fertilised embryo. The genomes of these organisms must specify the functional components of the system, mainly proteins, which have been the primary focus of genetic and genomic research to date. Damage to these components (by mutation) is also very obvious (as in monogenic diseases), just as damaging the components of any structure is obvious. The genomes of these organisms must also specify the control architecture which deploys these components in sophisticated suites of differentiation and development. Damage to this architecture is much more subtle, because of the nature and complexity of this information (which primarily affects quantitative trait variation). Traditionally it has been assumed that this architecture is embedded in the cis-acting control sequences which regulate gene expression in conjunction with trans-acting proteins acting at a variety of levels. However, as noted above, the vast majority of the transcriptional output of the genomes of the higher organisms, up to 97-98% in humans, is noncoding RNA. This noncoding RNA is derived from the introns of both protein-encoding and non-protein-encoding (noncoding RNA) genes, and the exons of noncoding RNA genes, which appear to comprise at least half of all transcripts from the human genome. Putting together the extent of introns in protein coding genes with the estimate of the number of non-coding RNA genes suggests that at least 50% of the human genome is actively transcribed into non-coding RNAs. Thus, either that the human genome is replete with useless transcription or these RNAs are fulfilling some unexpected function(s).
SUMMARY OF THE INVENTION
[0013] Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.
[0014] Nucleotide and amino acid sequences are referred to by a sequence identifier number (SEQ ID NO:). The SEQ ID NOs: correspond numerically to the sequence identifiers <400>1 (SEQ ID NO:1), <400>2 (SEQ ID NO:2), etc. A summary of the sequence identifiers is provided in Table 1. A sequence listing is provided after the claims.
[0015] The present invention is predicated in part on the proposal that non-coding RNAs have evolved to form a second tier of gene expression in the eukaryotes, and that these molecules (or their processed derivatives) act as endogenous controls for genetic multitasking and regulating complex suites of gene expression. Since intronic RNAs are produced in parallel with protein encoding sequences, their most logical (general) function would be networking, i.e. a molecular memory of recent transcription events which allows activity at one locus to be communicated directly to others. If this is the case, then it can be predicted that these RNAs are further processed into multiple species, each one capable of transmitting information independently to different targets. This is similar to the types of networks that exist in other complex information systems such as the brain, where secondary outputs (termed efference signals) underlie sensory awareness, motor coordination, and cognition, and wherein the patterns of neural activation depend on the flux of “hidden units”, collectively referred to as the “hidden layer” (Mattick and Gagen. Molec. Biol. Evol. 18: 1611-1630, 2001). At face value, such efference RNAs (eRNAs) would enable an enormous increase in network connectivity and functionality over the situation where system activity is solely regulated through protein-based feedback loops which relay metabolic and environmental state information. They would also allow a much more sophisticated and genomically compact regulatory system than would be possible using proteins alone, especially for integrating the complex subroutines that operate during embryonic differentiation and development. Moreover, if a system utilizing an RNA communication network has evolved, it is also predicted that many genes have evolved solely to express RNA, as higher order regulators in the network. These noncoding RNAs would be expected to interact with, and to transmit signals to, a variety of cellular targets, including other RNAs, genes (DNA/chromatin), and proteins. It would also be predicted that a significant proportion of these interactions, perhaps the majority, would occur via sequence-specific interactions between the eRNAs (transmitters) and homologous target sequences in other RNAs or the genome (receivers), i.e. that the specificity of signalling is embedded in the primary sequence of the RNA transmitter and the RNA or DNA receiver as a kind of “bit string” or “zip code”. In both cases these transmitter and receiver sequences are encoded in the genome and potential interacting pairs within this regulatory network will be recognisable by sequence homology using rules that apply to duplex or higher order DNA-RNA or RNA-RNA interactions. In the case of RNA-protein interactions, the interacting partners will be identified by direct experimental procedures and/or ab initio from sequence analysis when the algorithms for this become available.
[0016] In accordance with the present invention, it is proposed that efference RNA signals integrate and regulate gene activity in eukaryotes at a variety of levels. It is also proposed that this RNA network was a fundamental advance in the genetic operating system of the eukaryotes, which lies at the heart of the programmed responses which direct cellular and differentiation and organismal development. At face value such a system has enormous advantages over a regulatory circuitry that relies simply on protein feedback loops, especially when attempting to integrate large sets and different levels of gene activity. If this is so, it further suggests that the evolution of a more advanced genetic operating system based on a highly parallel RNA-based communication network may have been the fundamental prerequisite for the emergence of complex organisms. It also implies that the basis of species diversity and quantitative trait variation in complex organisms is primarily embedded in the control architecture of the system, rather than structural variation in the protein components themselves (although this will also contribute). This in turn has considerable implications for understanding and modifying the genetic programming of the higher organisms and the genetic factors underpinning complex traits.
[0017] In accordance with the present invention therefore, it is proposed that RNA sequences derived from introns of protein-encoding genes and from introns and exons of non-protein-encoding transcripts have evolved to function as network control molecules in higher organisms, freeing such organisms from the constraints of a simple single-output protein-based genetic operating system. The recognition that such RNA sequences, referred to herein as efference or eRNAs, are genetic signalling modifiers permits the rational design of a range of signal modifiers including the identification of corresponding receiver DNA, RNA and protein molecules and permits rational modification of physiological, biochemical and genetic output to alter inter alia organismal differentiation and development to modify quantiative traits and to alter physiological parameters underlying disease and disease susceptibility. The recognition of the importance of eRNAs in defining the genetic architecture of a cell further enables cell and organismal programming or re-programming. This includes the identification and modification of eRNA transmitter sequences or their target sequences to alter the epigenetic status and accessiblity of genomic loci, gene transcription, alternative splicing, RNA turnover, mRNA translation and signal transduction systems. This is useful in directing the differentiation and development, for example of stem cells. It also enables the development of novel diagnostic and therapeutic protocols.
[0018] In addition, the present invention further enables the identification of embedded structural motifs which are involved in protein/RNA complex interaction.
[0019] The recognition that eRNAs and their receiver targets are involved in genetic network signalling permits the rational design of eRNAs and their analogs and to identify target sequences to thereby modulate genetic signalling pathways. The present invention enables, therefore, genetic engineering of cells at a highly sophisticated level. The present invention further provides a computer system for identifying eRNAs or DNA sequences encoding same as well as receiver DNA, RNA and proteins. Such a computer system includes software, hardware, computer codes, user interfaces and databases acquiring storing and retrieving genetic data and/or physiological or other biological data associated with eRNAs or DNAs encoding same.
[0020] Furthermore, the recognition of the role of eRNAs in determining the genetic architecture of a cell or group or family of cells, enables the design of protocols and genetic and chemical agents which can influence this architecture. Accordingly, agents can now be identified which can program a cell to differentiate, proliferate and/or re-new or re-program an already differentiated or partially differentiated cell to exhibit characteristics of another cell type.
[0021] The present invention provides, therefore, a method for modulating the genetic make up of a cell or the phenotype of a cell as well as agents useful for same. The present invention further enables high throughput screening protocols for agents which act via eRNAs or their receiver targets. Such agents include enogenous molecules such as RNA's or products identified by natural products screening or the screening of chemical libraries.
[0022] An example of eRNA is the shared intronic sequence of GRIA2, GRIA3 and GRIA4 genes shown in FIG. 6. The present invention extends to homologous eRNAs having at least 70% identity to the nucleotide sequence shown in FIG. 6 and to nucleotide sequences capable of hybridzing to the sequence shown in FIG. 6 or its complementary form under low stringency conditions.
[0023] The present invention is further useful in manipulating stem cells to differentiate along a particular pathway and, hence, be involved in tissue repair, regeneration and/or augmentation.
TAABLE 1 SUMMARY OF SEQUENCE IDENTIFIERS (SEQ ID Nos.) Seq ID No. Description 1 Nucleotide sequence of intron from human Chr19 be- tween nucleotides 38234 and 167860 2-43 Olgonucleotide human sequence enquiries 44 Nucleotide sequence of intron from human Chr12 be- tween 156966 and 180225 45-52 Olgonucleotide human sequence enquiries 53 Nucleotide sequence of intron on human Chr12 between nucleotide 156966 and 180225 54-81 Oligonucleotide sequence enquiries 82-121 Putative eRNA sequences for S. cerevisiae
BRIEF DESCRIPTION OF THE FIGURES
[0024] [0024]FIG. 1 is a schematic representation of sub-network, an uncontrolled regulated network and a controlled multi-tasked network. Panel (a) shows an uncontrolled sub-network wherein nodes take limited numbers of regulatory inputs r k and generate limited numbers of protein outputs g k . Here, g 1 regulates n 2 while being subject to feedback interactions from g 2 (dotted line). Panel (b) shows the same sub-network with each node expressing a multiplex output of protein product g k and many control molecules c k each capable of targeted interactions to multi-task the sub-network. A sample interactions (shown as dot-dash lines) include control c 1 determining the alternative splicing of the node n 3 output giving g 3 or g 3 , the latter of which regulates node n 2 when expressed, while nodes n 1 and n 3 each feedback controls onto the other. It is evident that controls increase interconnectivity which increases network dynamical output complexity.
[0025] [0025]FIG. 2 is a diagrammatic representation showing (A) a simple network involved in particular cellular functions and (B) a complex network involved in cellular differentiation and development.
[0026] [0026]FIG. 3 is a diagrammatic representation of a system used to carry out the instructions encoded by the storage medium of FIGS. 4 and 5.
[0027] [0027]FIG. 4 is a diagrammatic representation of a cross-section of a magnetic storage medium.
[0028] [0028]FIG. 5 is a diagrammatic representation of a cross-section of an optically readable data storage system.
[0029] [0029]FIG. 6 is a diagrammatic representation of an eRNA network centred around the GRIA2, GRIA3 and GRIA4 genes. The eRNA comprises the nucleotide sequence which is a shared intronic sequence of the GRIA genes. The sequence is shown in the figure.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0030] The present invention is predicated in part on the recognition that eukaryotic cells have evolved a complex network of genetic signals which facilitates integration of gene activity and multi-tasking of the cellular proteome. It is proposed, in accordance with the present invention, that integration and multi-tasking of this sophisticated and complex genetic network is mediated at least in part by trans-acting, non-protein coding RNA molecules corresponding to introns or other non-coding RNA sequences of protein-encoding nucleotide sequences or introns and/or exons from RNA sequences of non-protein-encoding nucleotide sequences. The identification of these RNA molecules, referred to herein as efference RNAs or eRNAs, permits the development of a further level of functional genomics and advanced genetic engineering. In particular, eRNAs and/or their target or associated molecules or homologs, analogs, functional equivalents or synthetic forms are now obtainable and have utility as therapeutic agents and trait-modifying agents in eukaryotic cells such as vertebrate and invertebrate animal cells and plant cells. The eRNAs and their targets influence, therefore, the genetic architecture of the cell and, hence, these molecules were as well as analogs and homologs thereof have trait-modification potential. Reference to a “target” includes a “receiver” and includes nucleotide sequences in genomic DNA or RNA, including introns, exons 5′ or 3′ untranslated regions of genes or their transcripts (UTRs), as well as 5′ or 3′ flanking regions of genes and intergenic regions, which act as receivers of the eRNAs. Such targets are referred to herein as “receiver DNAs” or “receiver RNAs”. The targets may also be proteins with which eRNAs interact (i.e. “receiver proteins”). The eRNAs are regarded as “transmitters”.
[0031] Accordingly, one aspect of the present invention contemplates a method for identifying an eRNA or a DNA sequence comprising an eRNA-encoding sequence in the nucleome of a eukaryotic cell, said method comprising identifying non-protein-encoding nucleotide sequences within an RNA transcript or a DNA sequence encoding same in said nucleome, determining the nucleotide sequence of said non-protein-encoding nucleotide sequence and subjecting said sequence to phenotyping to determine its effect on one or more biological events within a cell or an organism and/or determining the degree to which said sequence is conserved or is variant in the organism's genome or in the genome of other species or genera of eukaryotic cells wherein a non-protein-encoding nucleotide sequence having a biological effect in a cell or a nucleotide sequence conserved within the genome or between different cells' nucleomes is deemed to be an eRNA or DNA sequence comprising a nucleotide sequence encoding same.
[0032] In a related embodiment, there is provided a method for identifying a receiver DNA or RNA, said method comprising identifying an eRNA by the method comprising identifying non-protein-encoding nucleotide sequences within an RNA transcript or a DNA sequence encoding same in said nucleome, determining the nucleotide sequence of said non-protein-encoding nucleotide sequence and subjecting said sequence to phenotyping to determine its effect on one or more biological events within a cell or an organism and/or determining the degree to which said sequence is conserved or is variant in the organism's genome or in the genome of other species or genera of eukaryotic cells wherein a non-protein-encoding nucleotide sequence having a biological effect in a cell or a nucleotide sequence conserved within the genome or between different cells' nucleomes is deemed to be an eRNA or DNA sequence comprising a nucleotide sequence encoding same and then contacting said eRNA with nucleome material and screening for interaction between the eRNA and a DNA or RNA wherein the detection of such interaction is indicative of a receiver molecule.
[0033] In a further related embodiment, the present invention provides a method for identifying a receiver protein, said method comprising identifying an eRNA by the method comprising identifying non-protein-encoding nucleotide sequences within an RNA transcript or a DNA sequence encoding same in said nucleome, determining the nucleotide sequence of said non-protein-encoding nucleotide sequence and subjecting said sequence to phenotyping to determine its effect on one or more biological events within a cell or an organism and/or determining the degree to which said sequence is conserved or is variant in the organism's genome or in the genome of other species or genera of eukaryotic cells wherein a non-protein-encoding nucleotide sequence having a biological effect in a cell or a nucleotide sequence conserved within the genome or between different cells' nucleomes is deemed to be an eRNA or DNA sequence comprising a nucleotide sequence encoding same and then contacting said eRNA with proteome material and screening for interaction between the eRNA and a protein wherein the detection of such interaction is indicative of a receiver protein.
[0034] In an alternative embodiment, bioinformatics is used to identify conserved nucleotide sequences of putative eRNAs or receiver sequences. An example of a non-bioinformatic method to detect eRNAs and/or receiver molecules is by gel retardation assays.
[0035] An “eRNA” means an “efference RNA” and corresponds to an RNA derived from intronic sequences of protein-encoding genes or derived from intronic and/or exonic sequences of non-protein-encoding transcripts which are involved in endogenous control of a genetic network within eukaryotic cells, including modulation of signalling and genetic, events within and between eukaryotic cells to alter differentiation and development and to alter gene expression patterns that may be useful in advanced genetic engineering of plants, animals and other eukaryotes and in the treatment of imbalances that underlie common diseases including cancer. An eRNA is regarded herein as a transmitter. A non-protein-encoding transcript means an RNA sequence transcribed from a gene but which is not translated into a protein sequence. Reference to a “genetic network” includes the genetic signals required to inter alia induce expression of a suite of genes, induce physiological changes within, on or between cells or facilitate multi-tasking of a cell's proteome. The genetic network may also be regarded as the genetic architecture of the cell. Such networking may involve the facilitation of RNA-DNA, RNA-RNA and RNA-protein interactions and may readily be observed by parameters such as alterations to gene expression, RNA splicing, DNA methylation, remodelling of chromatin, other signal transduction systems and cellular physiology, including responses to environmental variables. eRNAs act inter alia via receiver DNA, RNA or protein sequences.
[0036] Reference to an “intron” includes any RNA sequence which is capable of being excised from a primary RNA transcript (e.g. a pre-messenger RNA transcript). An “exon” includes any RNA sequence which is re-assembled to form a contiguous RNA after the removal of introns by splicing, which may form a messenger RNA (mRNA) containing protein-coding sequence, or a non-protein-coding RNA without protein-coding capacity. “Non-protein-encoding RNA sequences” also includes introns as well as RNA sequences 5′ of the authentic translation initiation site or 3′ of the translation termination codon. The latter two sites are generally referred to 5′ untranslated regions (UTR) or 3′ UTR of mRNA. The term “untranslated region” or “UTR” is a term of the art referring to the particular location of a genetic sequence relative to the translation initiation site. However, the use of these terms is not to exclude the possibility that some partial translation may occur in this region. For convenience, reference to a “protein” includes reference to a peptide or polypeptide. In a particularly preferred embodiment, the 3′ and 5′ UTRs or parts thereof act as receiver molecules for eRNAs.
[0037] An “RNA transcript” represents the sequence of ribonucleotides transcribed from a deoxyribonucleotide sequence of a gene. Thus, an RNA transcript includes and encompasses a primary gene transcript or pre-messenger RNA (pre-mRNA), which may contain one or more introns, as well as a messenger RNA (mRNA) in which any introns of the pre-mRNA have been excised and the exons spliced together. It is proposed, in accordance with the present invention, that some of the excised RNA introns in protein-coding transcripts or introns and exons in non-protein-coding transcripts act as eRNA molecules and modulate genetic signalling within a cell.
[0038] The “proteome” is regarded as the total protein within and on a cell. The “nucleome” is the total nucleic acid complement and includes the genome and all RNA molecules such as mRNA, heterogenous nuclear RNA (hnRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), small cytoplasmic RNA (scRNA), ribosomal RNA (rRNA), translational control RNA (tcRNA), transfer RNA (tRNA), eRNA, messenger-RNA-interfering complementary RNA (micRNA) or interference RNA (iRNA) and mitochondrial RNA (mtRNA).
[0039] It is particularly useful to identify eRNAs on the basis of conserved ribonucleotide sequences in intronic RNA sequences of protein-encoding nucleotide sequences or intronic and/or exonic sequences of non-protein-encoding nucleotide sequences or their corresponding deoxyribonucleotide sequences. Reference to “conserved” includes any polyribonucleotide or polydeoxyribonucleotide sequence sharing at least about 80% nucleotide complementarity to another sequence in the nucleome. Conserved sequences in the genome including 3′ and 5′ regions of genes is suggestive of a putative receiver molecule.
[0040] The term “similarity” as used herein includes partial or exact sequence identity or complementarity between compared sequences at the nucleotide level. In a preferred embodiment, nucleotide and sequence comparisons are made at the level of exact complimentarity or identity rather than partial identity or complementarity.
[0041] Terms used to describe sequence relationships between two or more polynucleotides include “reference sequence”, “comparison window”, “sequence similarity”, “sequence identity”, “sequence complementarity”, “percentage of sequence similarity”, “percentage of sequence identity”, “percentage of sequence complementarity”, “substantial similarity”, “substantial complementarity” and “substantial identity”. A “reference sequence” is at least 12 but frequently 15 to 18 and often at least 25 or above, such as 30 monomer units, inclusive of nucleotides, in length. Because two polynucleotides may each comprise (1) a sequence (i.e. only a portion of the complete polynucleotide sequence) that is similar between the two polynucleotides, and (2) a sequence that is divergent between the two polynucleotides, sequence comparisons between two (or more) polynucleotides are typically performed by comparing sequences of the two polynucleotides over a “comparison window” to identify and compare local regions of sequence similarity or complementarity. A “comparison window” refers to a conceptual segment of typically 12 contiguous residues that is compared to a reference sequence. The comparison window may comprise additions or deletions (i.e. gaps) of about 20% or less as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. Optimal alignment of sequences for aligning a comparison window may be conducted by computerised implementations of algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package Release 7.0, Genetics Computer Group, 575 Science Drive Madison, Wis., USA) or by inspection and the best alignment (i.e. resulting in the highest percentage homology over the comparison window) generated by any of the various methods selected. Reference also may be made to the BLAST family of programs as, for example, disclosed by Altschul et al. Nucl. Acids Res. 25: 3389 1997. A detailed discussion of sequence analysis can be found in Unit 19.3 of Ausubel et al. (1998).
[0042] The terms “sequence similarity”, “sequence identity” and “sequence complementarity” as used herein refers to the extent that sequences are identical or functionally or structurally similar or complementary on a nucleotide-by-nucleotide basis over a window of comparison using standard rules for DNA-DNA, RNA-RNA and RNA-DNA base pairing. Thus, a “percentage of sequence identity”, for example, is calculated by comparing two optimally aligned sequences over the window of comparison, determining the number of positions at which the identical nucleic acid base (e.g. A, T, C, G, I, U) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity or complementarity. For the purposes of the present invention, “sequence identity” between DNA sequences will be understood to mean the “match percentage” calculated by the DNASIS computer program (Version 2.5 for windows; available from Hitachi Software engineering Co., Ltd., South San Francisco, Calif., USA) using standard defaults as used in the reference manual accompanying the software. Similar comments apply in relation to DNA sequence similarity. Sequence complementarity in duplex and higher order RNA-RNA, RNA-DNA and RNA-protein interactions will be assessed by rules as described in Hermann. et al., Chem Biol, 6: R335-43. 1999; Masquida et al. Rna, 6: 9-15. 2000; Praseuth et al., Biochim Biophys Acta, 1489: 181-206 1999; Varani et al., EMBO Rep, 1: 18-23 2000.
[0043] Conveniently, an intronic or other protein-non-encoding sequence at the RNA or DNA level to a database of DNA or RNA sequences in the genome or nucleome and the identification of at least 80% similar sequences (e.g. determined by BLAST analysis) after optimal alignment is determined. The presence of one or more other homologous or complementary sequences in the database or between databases for different species, genera or families of invertebrate or non-invertebrate animals or plants is indicative of a candidate sequence involved in genetic network signal modulation.
[0044] Sequence similarity and complementarity provides one of a number of features or identifiers useful for analyzing the likelihood of a target RNA sequence being an eRNA. Other identifiers include the participation of the gene from which the potential eRNA is derived in a pathway or its involvement in multiple pathways such as part of the physiological or genetic networks contained within a cell. Furthermore, putative eRNA sequences may also share common secondary or tertiary structures. This may occur, for example, when the eRNA interacts with certain RNAses or ribosomes or nucleic acid binding proteins. Partly as a result of these features, apart from sequence determination, putative eRNA sequences may be detected by conventional genetic techniques such as deletional analysis, transgenesis, genetic silencing procedures (e.g. co-suppression, antisense techniques, RNAi induction) and the physiological effects of such procedures observed. Such physiological effects are referred to herein as a nucleotide sequence having a “biological effect”. Furthermore, the effect of eRNA may be demonstrated by ectopic expression studies. For example, intronic sequences from protein-coding sequences may be expressed on non-protein-coding sequences to determine the function of the eRNA in the absence of exon sequences or cis-acting elements in the transcript from which the eRNA is obtained. Transgenic animals and cells obtained therefrom in which genomic sequences have been replaced by cDNA sequences which do not contain the introns of the genetic sequences can also be employed.
[0045] The main advantage of RNA as a regulatory molecule is its compact size and sequence specificity. The likelihood is that most RNA signals will be transmitted through primary sequence-specific interactions with other RNAs and with DNA, forming complexes that are recognized by proteins containing particular types of domains. This provides an opportunity to identify both the potential transmitters and receivers (targets) in such networks, as well as the types of interacting proteins. Importantly, most of these interactions would be expected to involve RNA-RNA and RNA-DNA interactions (potentially including triplexes and other higher-order structures) that do not obey canonical Watson-Crick base-pairing rules. Thus, the present invention extends to algorithms which allow genomic sequence to be searched for these different types of interactions. Complete search algorithms, such as those based on suffix arrays and suffix trees are particularly useful to analyse this properly.
[0046] The ability of RNA to form strong interactions with other RNAs suggests that RNA-RNA and (to a lesser extent) RNA-DNA base pairing is stronger than DNA-DNA base pairing, and can allow for stable mismatches and the formation of particular secondary structures such as bulges, stems and loops, which, rather than being seen as mismatch errors (as in DNA repair), may also in fact contain embedded structural motifs that can be recognized by particular proteins. For example, perfect versus imperfect matching of microRNAs to their targets determines whether the mRNA target is actively degraded by the RNAi pathway or is translationally repressed.
[0047] Accordingly, it is proposed that the prediction can be made that different types of RNA signals and the different structures of the resulting complexes are recognized and acted on by particular classes of nucleic-acid-binding proteins. An understanding these secondary structural and mismatch rules enables the bioinformatic approaches to dissecting these networks at the genomic level. It also allows better prediction of the regulatory consequences of different types of RNA signals, by the development of specific algorithms to identify particular subsets that obey different sets of rules for the combination of sequence specificity and the type of secondary structure that is created by the interaction, bearing in mind that parts of the network will be silent in any given cell or lineage because an RNA transmitter or target is not expressed, or a DNA target has been made inaccessible by chromatin modification.
[0048] The present invention is predicated in part on the proposal that in order for a molecular genetic network to be capable of complex programming and multi-tasking, each of the gene sub-networks within a cell must produce numerous control molecules in parallel with their primary gene products, which dynamically communicate with other sub-networks (via transcriptional, splicing and translational controls, among others). Such a system would be expected to display an exponential increase in its ability to manage and integrate larger genetic datasets, and in its functionality and phenotypic range. In addition, because modulation of system dynamics can be readily achieved by mutation of control molecules, such a system should be able to explore new expression space at fast evolutionary rates over short evolutionary timescales.
[0049] An example of eRNA is the shared intronic sequence of GRIA2, GRIA3 and GRIA4 genes shown in FIG. 6. The present invention extends to homologous eRNAs having at least 70% identity to the nucleotide sequence shown in FIG. 6 and to nucleotide sequences capable of hybridzing to the sequence shown in FIG. 6 or its complementary form under low stringency conditions.
[0050] A controlled multi-tasked molecular network is schematically shown in FIG. 1, in contrast to an uncontrolled regulated network. This network architecture can be equally applied to computer networks, neural networks and cellular networks. An example of simple and complex genetic networks is shown in FIG. 2.
[0051] The nodes of a controlled multi-tasked network must be capable of generating and integrating multiple inputs and outputs. Such networks are generally stable and scale-free, with some nodes having high connectivity and others low connectivity, similar to most communication and social networks, including the Internet (Albert et al., Nature 406: 378-382, 2000). Multiply connected networks are widely employed in other complex information processing systems, including in neurobiology where secondary networking signals, termed “efference” signals, underlie sensory awareness and motor coordination (Bridgeman, Ann. Biomed. Eng. 23: 409-422 1995; Andersen et al., Annu. Rev. Neurosci 20: 303-330 1997). The concept of multiple inputs and outputs is also a well established feature of neural networks in cognition, language and memory (Plunkett et al., J. Child Psychol. Psychiatry 38: 53-80 1997; Elman, A Companion to Cognitive Science, Basil Blackwood Bechtel and Graham, Eds 1998). These networks involve densely connected webs of processing units that propagate and transform complex patterns of activity, and are capable of self-organization. They operate by a form of parallel distributed processing, whereby information is distributed across the system such that patterns of activation across sets of “hidden units” (i.e. controls), which define the state of the network, then determine the pattern of activation across output nodes (McClelland and Rumelhart, J. Exp. Psychol. Gen 114: 159-197 1985; McClelland and Plaut, Curr. Opin. Neurohol 3: 209-216 1993; Plunkett et al., J. Child Psychol. Psychiatry 38: 53-80 1997).
[0052] The assessment of the presence of similar nucleotide sequences in a genome or nucleome database is suitably facilitated with the assistance of a computer programmed with software, which inter alia adds or weighs index values (I V ) for each feature associated with the candidate sequences to provide a predictive value (P V ) corresponding to the likelihood of the candidate sequences being involved in modulating genetic network signalling. The features are selected from:—
[0053] (a) the transmitter sequence is derived from an intron in a protein-coding RNA transcript or an intron or an exon in a non-protein-coding RNA transcript or their DNA equivalents;
[0054] (b) the target receiver sequence lies in an intron or an exon in an RNA transcript or its DNA equivalent;
[0055] (c) the target receiver sequence lies in an intergenic genomic DNA sequence, such as a promoter or enhancer region;
[0056] (d) the target receiver is a DNA or RNA sequence capable of interaction with an eRNA;
[0057] (e) the target receiver sequence lies in a 5′ untranslated region of an RNA transcript or its DNA equivalent;
[0058] (f) the target receiver sequence lies in a 3′ untranslated region of an RNA transcript or its DNA equivalent;
[0059] (g) the target receiver is a protein capable of sequence-specific recognition of an eRNA and/or its target recognition sequences;
[0060] (h) the sequence is a DNA or RNA which recognizes and/or interacts with an eRNA;
[0061] (i) the sequence comprises at least 12 nucleotides;
[0062] (j) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence of the same genome or nucleome;
[0063] (k) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence in a genome or nucleome of a different species, genus or family of animal or plant cells;
[0064] (l) The sequence associates by its position to a feature from available databases, for example, Genbank, the Gene Ontology databse or SWISSPORT; and
[0065] (m) The sequence associates by its position to a protein (ie. falls within the transcript) and that protein's expression profile, as determined by microarray analysis, is modulated in a specific way during a phenomona of interest, for example, highly up or down regulated in the initial phase of meiosis.
[0066] In a preferred embodiment of the features (j) and (k), the sequence preferably has at least 90% and more preferably at least 95% nucleotide identity or complementarity to said at least one sequence (e.g. as determined by BLAST analysis) such as at least about 96%, 97%, 98%, 99% or 100%.
[0067] With respect to feature (i), the preferred number of nucleotides is from about 12 to about 100, more preferably from about 12 to about 50 and even more preferably from about 12 to about 30 such as about 22.
[0068] Preferably, the features are further selected from:—
[0069] (1) expression of the sequences mentioned in (e) is associated with the modulation of the same phenotype.
[0070] In accordance with the present invention, index values for such features are stored in a machine-readable storage medium which is capable of being processed by the processing means of the computer to provide a predictive value for a candidate sequence being involved in genetic regulation.
[0071] Thus, in another aspect, the invention contemplates a computer program product for assessing the likelihood of a candidate nucleotide sequence or group of nucleotide sequences being an eRNA or a receiver for an eRNA involved in network genetic signalling, said product comprising:—
[0072] (1) code that receives as input index values for one or more of features wherein said features are selected from:
[0073] (a) the transmitter sequence is derived from an intron in a protein-coding RNA transcript or an intron or an exon in a non-protein-coding RNA transcript or their DNA equivalent;
[0074] (b) the target receiver sequence lies in an intron or an exon in an RNA transcript or its DNA equivalent;
[0075] (c) the target receiver sequence lies in an intergenic genomic DNA sequence, such as a promoter or enhancer region;
[0076] (d) the target receiver is a DNA or RNA sequence capable of interaction with an eRNA;
[0077] (e) the target receiver sequence lies in a 5′ untranslated region of an RNA transcript or its DNA equivalent;
[0078] (f) the target receiver sequence lies in a 3′ untranslated region of an RNA transcript or its DNA equivalent;
[0079] (g) the target receiver is a protein capable of sequence-specific recognition of an eRNA and/or its target recognition sequences;
[0080] (h) the sequence is a DNA or RNA which recognizes and/or interacts with an eRNA;
[0081] (i) the sequence comprises at least 12 nucleotides;
[0082] (j) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence of the same genome or nucleome;
[0083] (k) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence in a genome or nucleome of a different species, genus or family of animal or plant cells;
[0084] (l) the sequence associates by its position to a feature from available databases, for example, Genbank, the Gene Ontology database, SWISSPORT
[0085] (m) The sequence associates by its position to a protein (ie. falls within the transcript) and that protein's expression profile, as determined by microarray analysis, is modulated in a specific way during a phenomona of interest, for example highly up or down regulated in the initial phase of meiosis.
[0086] (2) code that adds said index values to provide a sum corresponding to a predictive value for said candidate sequences; and
[0087] (3) a computer readable medium that stores the codes.
[0088] In a related embodiment, the present invention is directed to a computer program product for assessing the likelihood of a candidate nucleotide sequence or group of nucleotide sequences being a receiver molecule involved in network signalling via an eRNA, said product comprising:—
[0089] (1) code that receives as input index values for one or more of features wherein said features are selected from:—
[0090] (a) the target receiver sequence lies in an intergenic genomic DNA sequence, such as a promoter or enhancer region;
[0091] (b) the target receiver is a DNA or RNA sequence capable of interaction with an eRNA;
[0092] (c) the target receiver sequence lies in a 5′ untranslated region of an RNA transcript or its DNA equivalent;
[0093] (d) the target receiver sequence lies in a 3′ untranslated region of an RNA transcript or its DNA equivalent;
[0094] (e) the target receiver is a protein capable of sequence-specific recognition of an eRNA and/or its target recognition sequences;
[0095] (f) the sequence is a DNA or RNA which recognizes and/or interacts with an eRNA;
[0096] (g) the sequence comprises at least 12 nucleotides;
[0097] (h) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence of the same genome or nucleome;
[0098] (i) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence in a genome or nucleome of a different species, genus or family of animal or plant cells;
[0099] (j) The sequence associates by its position to a feature from available databases, for example, Genbank, the Gene Ontology database, SWISSPORT;
[0100] (k) The sequence associates by its position to a protein (ie. falls within the transcript) and that proteins expression profile, as determined by microarray analysis, is modulated in a specific way during a phenomona of interest, for example highly up or down regulated in the initial phase of meiosis.
[0101] (2) code that adds said index values to provide a sum corresponding to a predictive value for said candidate sequences; and
[0102] (3) a computer readable medium that stores the codes.
[0103] In a preferred embodiment, the computer program product comprises codes which assign an index value for each feature of a candidate sequence.
[0104] In a related aspect, the invention extends to a computer system for assessing the likelihood of a candidate sequence or group of candidate sequences being an eRNA involved in network genetic signalling wherein said computer system comprises:—
[0105] (1) a machine-readable data storage medium comprising a data storage material encoded with machine-readable data, wherein said machine-readable data comprise index values for one or more features, wherein said features are selected from:—
[0106] (a) the transmitter eRNA sequence is derived from an intron in a protein-coding RNA transcript or an intron or an exon in a non-protein-coding RNA transcript, or their DNA equivalent;
[0107] (b) the sequence comprises at least 12 nucleotides;
[0108] (c) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence of the same genome or nucleome;
[0109] (d) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence in a genome or nucleome of a different species, genus or family of animal or plant cells;
[0110] (e) the sequence comprises a secondary or tertiary structure having an activity; and
[0111] (f) the sequence exhibits catalytic activity;
[0112] (2) a working memory for storing instructions for processing said machine-readable data;
[0113] (3) a central-processing unit coupled to said working memory and to said machine-readable data storage medium, for processing said machine readable data to provide a sum of said index values corresponding to a predictive value for said candidate sequences; and
[0114] (4) an output hardware coupled to said central processing unit for receiving said predictive value.
[0115] Even yet another aspect of the invention extends to a computer system for assessing the likelihood of a candidate sequence or group of candidate sequences being a receiver RNA, DNA or protein involved in network genetic signalling wherein said computer system comprises:—
[0116] (1) a machine-readable data storage medium comprising a data storage material encoded with machine-readable data, wherein said machine-readable data comprise index values for one or more features, wherein said features are selected from:—
[0117] (a) the sequence is located in an intron or an exon in an RNA transcript or its DNA equivalent;
[0118] (b) the target receiver sequence lies in an intergenic genomic DNA sequence, such as a promoter or enhancer region;
[0119] (c) the sequence is located in a 5′ untranslated region of an RNA transcript or its DNA equivalent;
[0120] (d) the sequence is located in a 3′ untranslated region of an RNA transcript or its DNA equivalent;
[0121] (e) the sequence is a protein capable of sequence-specific recognition of an eRNA and/or its target recognition sequence;
[0122] (f) the sequence is an RNA or DNA which recognizes and/or interacts with an eRNA;
[0123] (g) the sequence comprises at least 12 nucleotides;
[0124] (h) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence of the same genome or nucleome;
[0125] (i) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence in a genome or nucleome of a different species, genus or family of animal or plant cells;
[0126] (j) the sequence comprises a secondary or tertiary structure having an activity; and
[0127] (k) the sequence exhibits catalytic activity;
[0128] (2) a working memory for storing instructions for processing said machine-readable data;
[0129] (3) a central-processing unit coupled to said working memory and to said machine-readable data storage medium, for processing said machine readable data to provide a sum of said index values corresponding to a predictive value for said candidate sequences; and
[0130] (4) an output hardware coupled to said central processing unit for receiving said predictive value.
[0131] A version of these embodiments is presented in FIG. 3, which shows a system 10 including a computer 11 comprising a central processing unit (“CPU”) 20 , a working memory 22 which may be, e.g. RAM (random-access memory) or “core” memory, mass storage memory 24 (such as one or more disk drives or CD-ROM drives), one or more cathode-ray tube (“CRT”) display terminals 26 , one or more keyboards 28 , one or more input lines 30 , and one or more output lines 40 , all of which are interconnected by a conventional bidirectional system bus 50 .
[0132] Input hardware 36 , coupled to computer 11 by input lines 30 , may be implemented in a variety of ways. For example, machine-readable data of this invention may be inputted via the use of a modem or modems 32 connected by a telephone line or dedicated data line 34 . Alternatively or additionally, the input hardware 36 may comprise CD. Alternatively, ROM drives or disk drives 24 in conjunction with display terminal 26 , keyboard 28 may also be used as an input device.
[0133] Output hardware 46 , coupled to computer 11 by output lines 40 , may similarly be implemented by conventional devices. By way of example, output hardware 46 may include CRT display terminal 26 for displaying a synthetic polynucleotide sequence or a synthetic polypeptide sequence as described herein. Output hardware might also include a printer 42 , so that hard copy output may be produced, or a disk drive 24 , to store system output for later use.
[0134] In operation, CPU 20 coordinates the use of the various input and output devices 36 , 46 coordinates data accesses from mass storage 24 and accesses to and from working memory 22 , and determines the sequence of data processing steps. A number of programs may be used to process the machine readable data of this invention. Exemplary programs may use for example the following steps:—
[0135] (1) inputting index values for at least one feature associated with a candidate sequence, wherein said features are selected from:—
[0136] (a) the sequence is an intron or exon in an RNA transcript or its DNA equivalent;
[0137] (b) the sequence is a 5′ untranslated region of an RNA transcript or its DNA equivalent;
[0138] (c) the sequence is a 3′ untranslated region of an RNA transcript or its DNA equivalent;
[0139] (d) the sequence is a DNA, RNA or protein which is capable of interaction with an eRNA;
[0140] (e) the sequence comprises at least 12 nucleotides;
[0141] (f) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence of the same genome or nucleome;
[0142] (g) the sequence has at least 80% nucleotide identity or complementarity to at least one sequence in a genome or nucleome of a different species, genus or family of animal or plant cells;
[0143] (h) the sequence comprises a secondary or tertiary structure having an activity; and
[0144] (i) the sequence exhibits catalytic activity;
[0145] (2) adding the index values for said features to provide a predictive value for said sequence; and (3) outputting said predictive value.
[0146] [0146]FIG. 4 shows a cross section of a magnetic data storage medium 100 which can be encoded with machine readable data, or set of instructions, for designing a synthetic molecule of the invention, which can be carried out by a system such as system 10 of FIG. 5. Medium 100 can be a conventional floppy diskette or hard disk, having a suitable substrate 101 , which may be conventional, and a suitable coating 102 , which may be conventional, on one or both sides, containing magnetic domains (not visible) whose polarity or orientation can be altered magnetically. Medium 100 may also have an opening (not shown) for receiving the spindle of a disk drive or other data storage device 24 . The magnetic domains of coating 102 of medium 100 are polarized or oriented so as to encode in manner which may be conventional, machine readable data such as that described herein, for execution by a system such as system 10 of FIG. 3.
[0147] [0147]FIG. 4 shows a cross section of an optically readable data storage medium 110 which also can be encoded with such a machine-readable data, or set of instructions, for screening a candidate molecule of the present invention, which can be carried out by a system such as system 10 of FIG. 3. Medium 110 can be a conventional compact disk read only memory (CD-ROM) or a rewritable medium such as a magneto-optical disk, which is optically readable and magneto-optically writable. Medium 100 preferably has a suitable substrate 111 , which may be conventional, and a suitable coating 112 , which may be conventional, usually of one side of substrate 111 .
[0148] In the case of CD-ROM, as is well known, coating 112 is reflective and is impressed with a plurality of pits 113 to encode the machine-readable data. The arrangement of pits is read by reflecting laser light off the surface of coating 112 . A protective coating 114 , which preferably is substantially transparent, is provided on top of coating 112 .
[0149] In the case of a magneto-optical disk, as is well known, coating 112 has no pits 113 , but has a plurality of magnetic domains whose polarity or orientation can be changed magnetically when heated above a certain temperature, as by a laser (not shown). The orientation of the domains can be read by measuring the polarisation of laser light reflected from coating 112 . The arrangement of the domains encodes the data as described above.
[0150] In essence, the subject computer software analyzes genomic or nucleomic databases for the presence of particular sequences which have one or more features as defined above. Each of these features carries a certain weight as to the importance in establishing that a target sequence is an eRNA or is a DNA sequence encoding an eRNA. Multiple features may be created by combining the features with certain biological effects as discussed above. For example, a conserved intron between species may combine with certain biological phenomena associated with a conserved deletion of this sequence. The resulting features, sub-features and multiple features and combinations thereof combine to produce a “fingerprint” or “descriptor” of not only an individual eRNA but also families of eRNAs and this may also provide a fingerprint of the gene expression status of a cell or animal or plant comprising cells at any given time.
[0151] The present system retrieves features and forms composite features from them. More than one feature can be combined in a variety of different ways to form these composite features. In particular, the composite feature can be any function or combination of a simple feature and other composite features. The function can be algebraic, logical, sinusoidal, logarithmic, linear, hyperbolic, statistical and the like. Alternatively, more than one feature can be obtained in a functional manner (e.g. arithmetic, algebraic). By way of example, a composite feature may equal the sum of two or more features or a composite feature may correspond to a sub-fraction of overlap of one or more features from another feature. Alternatively, a composite feature may equal a constant times one or more features. Of course, there are many other ways composite features can be defined.
[0152] The genome/nucleome databases may be from any eukaryotic cell such as from a vertebrate or invertebrate, including mammalian, avian, reptilian and amphibian animals, as well as from plants. The term “plants” includes monocotyledonous and dicotyledonous plants. It is particularly useful to employ the analysis function aspect of the present invention to human genome databases.
[0153] Computer programs may also be designed to screen nucleic acid molecule similarity at the secondary or tertiary levels. Furthermore, epidemiological studies together with polymorphism mapping may identify conserved polymorphisms in otherwise non-homologous nucleotide sequences. This would suggest an eRNA which is active at the secondary or tertiary levels.
[0154] Although not intending to limit the present invention to any one theory or mode of action, it is proposed that the eRNA molecules are “eRNA senders” or “eRNA transmitters” in the sense that they function as trans-acting networking molecules. eRNA senders have target molecules in the form of DNA, RNA and protein receivers. The receiver molecules may be located anywhere in the proteome, genome or nucleome. The identification of an eRNA permits the identification of these receiver molecules. Furthermore, again not intending to limit the present invention to any one theory or mode of action, it is proposed that there may be a connection between interference RNA (RNAi) and eRNA. RNAi is induced by, for example, double standard RNA generally corresponding to at least part of a coding strand of a gene. It is proposed, herein, that eRNAs may also induce RNAi and in fact be the true inducer of RNAi.
[0155] Consequently, another aspect of the present invention contemplates a method of inducing post transcription gene silencing (PTGS) of a gene carrying a nucleotide receiver sequence, said method comprising expressing an eRNA having said receiver nucleotide sequence which induces an RNAi capable of targeting said receiver sequence in an mRNA transcript of said gene. The ability to induce specific RNAi mediated PTGS or transcriptional gene silencing (TGS) using eRNAs or their homologs or analogs will greatly enhance the ability to modify traits in plant and animal cells.
[0156] RNAi, both in therapeutic and experimental usage, is complicated by an effect known as RNAi transitivity. When a gene is silenced by a RNAi signal, if the transcript of the gene has within it a sequence exactly homologous to the transcript of another gene it is possible for the second gene to be silenced as well, an effect which could lead to invalid experimental results or side-effects in therapy.
[0157] Thus, another aspect of the present invention is the utilization of eRNA networks to predict the scope and effect of transitive RNAi, by analysing the sequence of the targeted gene and comparing it to known effectors in the gene regulatory network.
[0158] Another aspect of the present invention provides an eRNA molecule identified by the method comprising identifying non-protein-encoding nucleotide sequences within an RNA transcript or a DNA sequence encoding same in said nucleome, determining the nucleotide sequence of said non-protein-encoding nucleotide sequence and subjecting said sequence to phenotyping to determine its effect on one or more biological events within a cell and/or determining the degree to which said sequence is conserved in the cell's genome or in the genome of other species or genera of eukaryotic cells wherein a non-protein-encoding nucleotide sequence having a biological effect in a cell or a nucleotide sequence conserved within the genome or between different cells' nucleomes is deemed to be an eRNA or DNA sequence comprising a nucleotide sequence encoding same.
[0159] Yet another aspect of the present invention is directed to a receiver DNA or RNA identified by the method comprising identifying non-protein-encoding nucleotide sequences within an RNA transcript or a DNA sequence encoding same in said nucleome, determining the nucleotide sequence of said non-protein-encoding nucleotide sequence and subjecting said sequence to phenotyping to determine its effect on one or more biological events within a cell and/or determining the degree to which said sequence is conserved in the cell's genome or in the genome of other species or genera of eukaryotic cells wherein a non-protein-encoding nucleotide sequence having a biological effect in a cell or a nucleotide sequence conserved within the genome or between different cells' nucleomes is deemed to be an eRNA or DNA sequence comprising a nucleotide sequence encoding same and then contacting said eRNA with nucleome material and screening for interaction between the eRNA and a DNA, RNA or protein wherein the detection of such interaction is indicative of a receiver molecule.
[0160] Still another aspect of the present invention provides a receiver protein identified by the method comprising identifying non-protein-encoding nucleotide sequences within an RNA transcript or a DNA sequence encoding same in said nucleome, determining the nucleotide sequence of said non-protein-encoding nucleotide sequence and subjecting said sequence to phenotyping to determine its effect on one or more biological events within a cell and/or determining the degree to which said sequence is conserved in the cell's genome or in the genome of other species or genera of eukaryotic cells wherein a non-protein-encoding nucleotide sequence having a biological effect in a cell or a nucleotide sequence conserved within the genome or between different cells' nucleomes is deemed to be an eRNA or DNA sequence comprising a nucleotide sequence encoding same and then contacting said eRNA with proteome material and screening for interaction between the eRNA and a protein wherein the detection of such interaction is indicative of a receiver protein.
[0161] Determination of methylation profiles within a cell and more particularly changing profiles in differentiating, aging or mutating cells is a convenient way of identifying epigenetic signatures in the genome and therefore identifying putative genetic targets for the presence of putative eRNAs or their corresponding receiver sequences.
[0162] One convenient method is described in an International Application filed 14 Sep. 2002 in the name of The University of Queensland and involves an amplification-based assay procedure to determine the methylation profile of nucleotides in the genome of a cell or group of cells. More particularly, the nucleotides are in the form of CpG or CpNpG sites. The ability to determine genomic and transgene methylomes in a cell or group of cells is an important tool in functional genomics and in developing the next generation of gene-expression modulating agents. Combining methylation profile with mapping enables a determination of the epigenetic consequences of internal and external stimuli. For example, methylation profiles may correlate with disease conditions or a propensity for a disease condition to develop or monitoring the aging process or the development process of cells. Furthermore, the methylation profile can be used to determine genes which either are expressed or are not expressed in certain disease states or with certain phenotypic traits. The identification of a condition or predisposition for development of a condition leads to the selection of targets for the identification of eRNAs or receiver sequences for eRNAs.
[0163] The amplification-based technology is referred to as amplified methylation polymorphisms (AMP). The AMP technology determines the methylation profile of many thousands of CpG or CpNpG sites around the genome and provides a genetic profile of the methylation status of these sites. This genetic signature is the methylome fingerprint of a cell's or group of cells' genome.
[0164] The AMP technology involves amplification of DNA markers in the form of small inverted repeats comprising the CpG or CpNpG sites but where amplification depends on the methylation status of the cytosines within the amplicon or nearby.
[0165] The protocol uses, in one form, a single arbitrary decamer oligonucleotide primer containing the recognition sequences of a methylation-sensitive restriction enzyme. These short oligonucleotide primers containing such recognition sequences are referred to herein as AMP primers. The recognition sequences for the methylation-sensitive restriction enzyme are located in the middle of the primer followed by up to four selective nucleotides, extending to the 3′ end. AMP profiles are generated from both undigested genomic DNA and genomic DNA digested with the methylation sensitive enzyme. Comparison of the profiles from digested and undigested genomic DNA reveals three classes of AMP markers: digestion resistant (Class I) indicative of methylation, digestion sensitive (Class II) indicative of non-methylation, and digestion dependent (Class III). The nature of the last class of AMP markers is proposed to represent physically-linked cis-acting inhibitory sequences which suppress amplification of Class III markers from undigested template. Digestion with the enzyme removes the inhibitor from the amplicon, thereby allowing amplification. The digestion-dependent (Class III) markers are proposed to encompass a methylated restriction site or sites in the amplicon sequence flanked by a non-methylated restriction site and then the putative inhibitory sequence. Digestion-dependent markers represent, therefore, junctions between methylated and non-methylated DNA in the genome. Cloning, sequencing and mapping AMP markers shows that they often correspond to CpG islands, features known to be landmarks for genes in genomes. These are then proposed to be sites of eRNA or eRNA receiver systems.
[0166] Methylation enzymes contemplated herein include AatII, AciI, AclI, AgeI, AscI, AvaI, BamHI, BsaA1, BsaH1, BsiE, BsiW, BsrF, BssHII, BstBI, BstUI, Cla1, EagI, HaeII, HgaI, HhaI, HinPI, HpaII, MloI, MspI, NaeI, NarI, NotI, NruI and PmlI. HpaII is particularly preferred in accordance with the present invention.
[0167] Accordingly, another aspect of the present invention provides a method for identifying a gene having encoding a putative eRNA or comprising a receiver sequence for an eRNA said method comprising determining the methylation profile of one or more CpG or CpNpG nucleotides at one or more sites within the genome of a eukaryotic cell or group of cells by obtaining a sample of genomic DNA from the cell or group of cells, digesting a sub-sample of the sample of genomic DNA with HpaII which has a recognition nucleotide sequence corresponding to or within the sites, subjecting the digested DNA to an amplification means such as polymerase chain reaction (PCR) using primers comprising a nucleotide sequence capable of annealing to a non-cleaved form of a HpaII cleavable nucleotide sequence and subjecting the products of the PCR to separation or other detection means relative to a control, said control comprising another sub-sample of the sample of genomic DNA not subjected to digestion by HpaII but subjected to an amplification reaction using the same primers as for the digested DNA sample and then subjecting the products to the amplification reaction to the separation or detection means wherein the presence of PCR products in enzyme digested and non-digested samples is indicative of a HpaII-digestion-resistant marker (Hr), the absence and presence of PCR products in enzyme digested and undigested samples, respectively, is indicative of a HpaII-digestion-sensitive marker (HS) and the presence and absence of PCR products in enzyme digested and undigested samples, respectively, is indicative of a HpaII-digestion-dependent marker (H d ) wherein these sites are proposed to comprise genes or intergenic regions which are then screened for the presence of eRNAs or receive sequences.
[0168] The present invention is further described by the following non-limiting Examples.
EXAMPLE 1
A Role for Introns and Other Non-Coding RNAs in Dynamical Gene-Gene Communication, Genetic Multi-Tasking and Systems Integration
[0169] Potential cellular control molecules enabling multi-tasking and system integration must be capable of specifically targeted interactions with other molecules, must be plentiful (as limited numbers impair connectivity and adaptation in real and evolutionary time), and must carry information about the dynamical state of cellular gene expression. These goals are most directly or economically achieved by spatially and temporally synchronizing control molecule production with gene expression. Most protein-coding genes of higher eukaryotes are mosaics containing one or more intervening sequences (introns) of generally high sequence complexity, which are spliced out during pre-mRNA processing to generate a nuclear population of intronic RNA with concentration profiles linked to that of the exons, which are reassembled during this process to form mRNA, and which are subsequently translated into protein. The numbers of protein coding genes do not increase exponentially in complex organisms and hence cannot provide large scale cellular connectivity (which does increase exponentially). The genomes of higher organisms are, nevertheless, much larger than those of single celled organisms, with the vast majority of this size increase (after accounting for variable amounts of repetitive DNA) occurring within intron sequences and other non-protein-coding RNAs. Introns, therefore, fulfil the essential conditions for system connectivity and multi-tasking—(i) multiple output in parallel with gene expression; (ii) large numbers, especially if, as is likely (see below), they are further processed to smaller molecules after excision from the primary transcript; and (iii) the potential for specifically targeted interactions as a function of their sequence complexity. Sequences of just 20-30 nucleotides should generally have sufficient specificity for homology-dependent or structure-specific interactions. Introns are, therefore, excellent candidates for, and perhaps the only source of, possible control molecules for multi-tasking eukaryotic molecular networks, which relieve the problems associated with protein-based systems as genetic output can be multiplexed and target specificity can be efficiently encoded, assuming a receptive infrastructure.
EXAMPLE 2
Introns have Populated the Eukaryotic Lineage Late in Evolution
[0170] Modern nuclear introns are not ancient remnants of the prebiotic assembly of genes but the evolutionary descendants of self catalytic group II introns, which have similar splicing mechanisms (Lambowitz et al., Annu. Rev. Biochem. 62: 587-6221993; Eickbush, Nature 404: 940-941 2000). These elements appear to have penetrated the eukaryotic lineage late in evolution (Cavalier-Smith, Trends Genet. 7: 145-148 1991; Palmer et al., Curr. Opin. Genet. Dev. 1: 470-477, 1991; Mattick, Curr. Opin. Genet. Dev. 4: 823-831 1994; Stoltzfus et al., Science 265: 202-207 1994; Cho and Doolittle, J. Mol. Evol. 44: 573-584 1997; Wolf et al., J. Theor. Biol. 195: 167-186 1998) and to have expanded initially by retrotransposition (Cousineau et al., 2000; Eickbush, 2000) and later (after their sequence constraints were reduced by the evolution of the spliceosome) by other mutational, recombinational and insertional processes (Tarrio et al., Proc. Natl. Acad. Sci. USA 95: 1658-1662 1998). Self-catalytic group II introns do occur in bacteria, usually in tRNA genes (Ferat et al., Nature 364: 358-361 1993; Martinez-Abarca et al., Mol. Microbiol. 38: 917-926 2000) and the likely reason that introns are generally absent from prokaryotic protein coding sequences is the intimate coupling of transcription and translation in these cells, which does not allow time for intron excision (Mattick, Curr. Opin. Genet. Dev. 4: 823-831 1994).
[0171] The evolution of the nucleus and the separation of transcription and translation in the eukaryotes provided the opportunity for these introns to invade protein coding genes, as long as their removal by self splicing was efficient enough not to interfere with mRNA and protein production. The subsequent evolution of the spliceosome (involving the devolution of internal cis-acting catalytic RNAs into trans-acting spliceosomal RNAs and recruitment of accessory proteins) (Lambowitz et al. Annu. Rev. Biochem. 62: 587-622, 1993; Mattick, Curr. Opin. Genet. Dev. 4: 823-831 1994; Newman, Curr. Opin. Genet. Dev. 4: 298-304 1994; Stoltzfus, J. Mol. Evol. 49: 169-181 1999; Yean et al., Nature 408: 881-884 2000) made intron processing easier, which reduced the negative selection against them and allowed them more latitude. It also relaxed their internal sequence requirements, leaving them free to evolve and to explore new evolutionary space, based on RNA molecules produced in parallel with protein coding sequences (Mattick, Curr. Opin. Genet. Dev. 4: 823-831 1994). This would have been accelerated by the co-evolution of receptor systems for these molecules, involving RNA-protein, RNA-RNA and RNA-DNA/chromatin interactions, in the same way as other complex systems such as the ribosome and the spliceosome have evolved (Stoltzfus, J. Mol. Evol. 49: 169-181 1999). It is proposed, therefore, that intron-derived RNAs may have evolved trans-acting functions.
EXAMPLE 3
Intron Density Correlates with Developmental Complexity
[0172] Intron size and sequence complexity correlates well with developmental complexity, and introns comprise the majority of pre-mRNA sequences in the higher organisms. In developmentally simple eukaryotes like Schizosaccharomyces pombe, Aspergillus and Dictyostelium , introns comprise only 10-20% of the primary transcript, and are generally small with an average length of less than 100 bases and density about 1-3 introns per kilobase of protein coding sequence. These data are consistent with hybridization kinetic analyses of the relative sequence complexity of hnRNA (“heterogeneous nuclear RNA”) versus mRNA in lower eukaryotes (Davidson, 1976). In the higher plants there are 2-4 introns per gene of average length about 250 bases comprising about 50% of the primary transcript. In animals the average intron size rises to about 500 bases in Drosophila and C. elegans , and to about 3400 in human (6-7 introns per gene, average over 95% of the primary transcript) (Palmer et al., Curr. Opin. Genet. Dev. 1: 470-477, 1991; Deutsch et al. Nucleic Acids Res. 27: 3219-3228, 1999; Consortium, Nature 409: 860-921 2001; Venter et al., Science 291: 1304-1351 2001).
EXAMPLE 4
Introns have the Signatures of Information
[0173] Introns (and other non-protein coding RNAs, see below) of higher organisms exhibit all the signatures of information. They generally have high sequence complexity (Tautz et al., Nature 322: 652-656 1986) although one must distinguish between introns that may have evolved function and those that have not (which will be more degenerate) and take account of the differing proportions of functional and non-functional introns in lineages of different developmental complexity. While introns generally show less conservation than adjacent protein coding sequences, which are subject to strong constraints, so also do adjacent promoters and 5′ and 3′ untranslated regions of mRNA. The plasticity and more rapid evolution of these regulatory sequences does not mean they are non-functional and the present inventors suggest the same holds, in general, for introns.
EXAMPLE 5
Non-Coding RNAs Comprise the Majority of Genomic Output
[0174] Many (if not most, see below) transcripts from the genomes of higher organisms do not encode proteins at all (Eddy, Curr. Opin. Genet. Dev. 9: 695-699 1999; Erdmann et al., Nucleic Acids Res. 27: 192-195 1999). Where they have been examined these non-protein-coding transcripts are conserved and clearly functional. Well documented examples include XIST (involved in female X chromosome inactivation) (Brockdorff, Curr. Opin. GEnet. Dev. 8: 328-333 1998; Lee et al., Cell 75: 843-854 1999; Hong et al., Mamm, Genome 11: 220-224 2000) and H19 (mutants of which promote tumor development) (Wrana, Bioessays 16: 89-90 1994; Hurst et al. Trends Genet. 15: 134-135, 1999), both of which are imprinted and differentially spliced without encoding any protein. Others include roX1 and roX2 RNAs involved in dosage response (male X-chromosome activation) in Drosophila , heat shock response RNA in Drosophila , oxidative stress response RNAs in mammals, His-1 RNA involved in viral response/carcinogenesis in human and mouse, SCA8 RNA involved in spinocerebellar ataxia type 8 which is antisense to an actin-binding protein, and ENOD40 RNA in legumes and other plants (Eddy, Curr. Opin. Genet. Dev. 9: 695-699 1999; Erdmann et al., Nucleic Acids Res. 27: 192-195 1999; Nemes et al., Hum. Mol. Genet. 9: 1543-1551 2000). The 200 kb bithorax-abdominal A/B locus of Drosophila produces seven major transcripts (there may be minor ones as well), only three of which encode proteins, but all of which have phenotypic signatures and are developmentally regulated (Akam et al., Quant. Biol. 50: 195-200 1985; Hogness et al., Quant. Biol. 50: 181-194 1985; Lipshitz et al., Genes Dev. 1: 307-322 1987; Sanchez-Herrero et al., Drosophila. Development 107: 321-329 1989). These are not isolated examples. Many loci, including imprinted loci, express non-coding antisense and intergenic transcripts, some of which are alternatively spliced and developmentally regulated (Ashe et al., Genes Dev. 11: 2494-2509 1997; Lipman, Nucleic Acids Res. 25: 3580-3583 1997; Potter et al., Mamm. Genome 9: 799-806 1998; Lee et al., Nature Genet. 21: 400-404 1999; Filipowicz, Acta. Biochim. Pol. 46: 377-389 2000; Hastings et al., J. Biol. Chem. 275: 11507-11513 2000; Nemes et al., Hum. Mol. Genet. 9: 1543-1551 2000), as well as being stably detectable in the nucleus (Ashe et al., Genes Dev. 11: 2494-2509 1997).
EXAMPLE 6
Examples of Gene Regulation and Communication by Introns and Non-Coding RNAs
[0175] The activity of the heterochronic genes lin-14 and lin-41, which regulate developmental timing in C. elegans , are controlled by lin-4 and let-7 gene products encoding small RNAs that are antisense to repeated elements in the 3′ untranslated region of target mRNAs, and which appear to inhibit translation by RNA-RNA interactions (Lee et al., Cell 75: 843-854 1993; Wightman et al., C. elegans. Cell 75: 855-862 1993; Feinbaum et al., Caenorhabditis elegans . Dev. Biol. 210: 87-95 1999; Reinhart et al., Caenorhabditis elegans. Nature 403: 901-906 2000) possibly by targeting the mRNA for endoribonuclease attack (Nashimoto, FEBS Lett. 472: 179-186 2000). Lin-4 and let-7 do not contain obvious protein coding sequences, and the surrounding genomic sequences suggests that both are derived from functional introns surrounded by vestigial exons (Lee et al., Cell 75: 843-854 1993; Reinhart et al., Caenorhabditis elegans. Nature 403: 901-906 2000). Moreover, let-7 is functionally conserved in other bilaterian animals, from mollusks to mammals (Pasquinelli et al., Nature 408: 86-89 2000). Interestingly, the size of these RNAs (21-22 nt) is similar to that produced by the RNA interference (RNAi) pathway (Bass, Cell 101: 235-238 2000; Parrish et al., Mol. Cell. 6: 1077-1087 2000; Yang et al., Curr. Biol. 10: 1191-1200 2000; Zamore et al., Cell 101: 25-33 2000; Sharp, Genes Dev 15: 485-490 2001) (see below).
[0176] It has also been discovered that most small nucleolar RNAs (a group of more than 100 stable RNA molecules concentrated in the nucleolus) derive from processed introns of other genes, which encode various ribosomal proteins (e.g. L1, L5, L7, L13, S1, S3, S7, S8, S13 and others), ribosome-associated proteins (e.g. eIF-4A), nucleolar proteins (e.g. nucleolin, laminin, fibrillarin), the heat shock protein hsc70 and the cell-cycle regulated protein RCC1, among others (Prislei et al., Gene 163: 221-226 1993; Sollner-Webb, Cell 75: 403-405 1993; Bachellerie et al., Biochem. Cell. Biol. 73: 835-843 1995; Maxwell et al., Annu. Rev. Biochem. 64: 897-934, 1995; Nicoloso et al., J. Mol. Biol. 260: 178-195 1996; Rebane et al., Gene 210: 255-263 1998; Filipowicz et al., Acta. Biochim, Pol. 46: 377-389 1999; Filipowicz, Proc. Natl. Acad. Sci. USA 97: 14035-14037 2000). These provide both clear examples of dual gene outputs, and potential instances of coordinate regulation (efference control) involving intronic sequences, in this case of ribosomal biogenesis and cell growth (Pelczar et al., Mol. Cell. Biol. 18: 4509-4518 1998; Smith et al., Mol. Cell. Biol. 18: 6897-6909 1998; Tanaka et al., Genes Cells 5: 277-287 2000). More tellingly, some genes have so evolved that their protein coding capacity no longer exists, and their primary product is intron-derived small nucleolar RNAs (Tycowski et al., Nature 379: 464-466 1996; Bortolin et al., RNA 4: 445-454 1998; Pelczar et al., Mol. Cell. Biol. 18: 4509-4518 1998; Smith Smith et al., Mol. Cell. Biol. 18: 6897-6909 1998; Tanaka et al., Genes Cells 5: 277-287 2000) leading to the statement that “genes generating functionally important RNAs exclusively from their intron regions are probably more frequent than has been anticipated” (Bortolin et al., RNA 4: 445-454 1998).
[0177] These nucleolar RNAs are processed from introns by specific mechanisms involving endonucleolytic cleavage by double stranded RNase III-related enzymes (Caffarelli et al., X laevis. Biochem. Biophys. Res. Commun. 233: 514-517 1997; Chanfreau et al., EMBO J. 17: 3726-3737 1998; Qu et al., Mol. Cell. Biol. 19: 1144-1158 1999) (also implicated in RNAi, transgene silencing and methylation (Mette et al., EMBO J. 19: 5194-5201 2000)—see below), exonucleolytic trimming (Cecconi et al., Nucleic Acids Res. 23: 4670-4676 1995; Mitchell et al., Nature Struct. Biol. 7: 843-8461997; Allmang et al., EMBO J. 18: 5399-5410 1999a; Allmang et al., Genes Dev. 13: 2148-2158 1999b; van Hoof et al., Cell 99: 347-350 1999; van Hoof et al., EMBO J. 19: 1357-1365 2000) and possibly even adjacent RNA sequences that have self cleaving activity (Prislei et al., Gene 163: 221-226 1995). This processing occurs in large RNA processing complexes called exosomes, which are also involved in processing rRNA and small nuclear RNAs, and which contain at least 10 3′-5′ exonucleases, helicases and RNA binding proteins and which are found in both the nucleus and the cytoplasm (Mitchell, et al., Cell 91: 457-466 1997; Allmang et al., EMBO J. 18: 5399-5410 1999a,b; van Hoof et al. Cell 99: 347-350, 1999; Mitchell et al., Nature Struct. Biol. 7: 843-846 2000).
EXAMPLE 7
Intron Processing, Stability, Decay and Memory
[0178] After splicing, introns (initially in lariat form) are debranched (Ruskin et al., Science 229: 135-140 1985), a process that is itself subject to regulation (Ruskin et al., Science 229: 135-140 1985; Qian et al., Nucleic Acids Res. 20: 5345-5350 1992), but subsequent events are unknown. The inventors suggest that it is likely that excised introns are processed by specific pathways similar to those used to produce small nucleolar RNAs, and which generate multiple smaller species which can function independently as transacting signals in the network, affecting the metabolism of other RNAs and the modulation of chromatin structure, among other things (see below).
[0179] There are other documented examples of small transacting functional RNAs processed from longer transcripts (Sit et al., Science 281: 829-832 1998; Cavaille et al., Proc. Natl. Acad. Sci. USA 97: 14311-14316 2000). There are also large numbers of ribonucleases and other RNA-related proteins in plants and animals (see below), most of whose functions and substrates are not well defined. Such processing may also involve other splicing pathways (Santoro et al., Mol. Cell. Biol. 14: 6975-6982 1994; Kreivi et al., Curr. Biol. 6: 802-805 1996) and guide RNAs, possibly derived from introns or other non-protein-coding RNAs. These have been described as “riboregulators” (in relation to antisense RNAs) (Delihas, Mol. Microbiol. 15: 411-414 1995) and the “ribotype” (in relation to alternatively spliced mRNAs) (Herbert et al., Nature Genet. 21: 265-269 1999a), and may be considered to be part of the “soft wiring” of the cell (Herbert et al., Acad. Sci. 870: 119-132 1999b; Mattick, Curr. Opin. Genet. Dev. 4: 823-831 1994).
[0180] The decay characteristics of eRNAs are likely to be important to their function. Both short- and long-lived eRNAs provide a molecular memory of prior gene activation status, a significant efficiency gain over using bistable regulated gene networks as memories (Gardner et al., Escherichia coli. Nature 403: 339-342 2000). Differential eRNA decay (Qian et al., Nucleic Cids Res. 20: 5345-5350 1992) and diffusion rates would create spatially and temporally complex signal pulses that enable specific communication speeds, half lives and maximal communication radii for eRNA information transfer, allowing fine control of cellular activities.
EXAMPLE 8
Transvection and Chromatic Structure
[0181] The inventors propose predict that if eRNAs do have an important function in regulating gene expression, there should be genetic clues from intensively studied systems. A good candidate is the Drosophila bithorax complex, which is the archetypal developmental control locus, and which has been subjected to a considerable amount of genetic and molecular scrutiny. The bithorax region of this complex locus covers over 100 kb and contains 3 transcription units, one of which (Ubx) contains large introns and is differentially spliced to produce several variants of the morphogenetic homeobox protein UBX (Hogness et al., Quant. Biol. 50: 181-194 1985; Duncan, Annu. Rev. Genet. 21: 285-319 1987). The others are located upstream and are referred to as the early and late bxd units, and do not appear to encode proteins. Mutants of this locus can be classified into Ubx alleles, which disrupt the protein coding sequence and the abx, bx, pbx, and bxd alleles, which are located either within the introns of the Ubx unit (abx, bx) or in the 40 kb upstream region (pbx, bxd) and which affect the spatial pattern of UBX expression. The latter alleles are thought to represent cis-acting regulatory sequences controlling Ubx expression and are usually interpreted in terms of conventional enhancer elements, despite the fact that they are themselves transcribed. The bxd transcription unit produces a 27 kb transcript early in embryogenesis, which has a number of large introns, and is subject to differential splicing to give various small (˜1.2 kb) polyA+RNAs which do not contain any significant open reading frame (Akam et al., Quant. Biol. 50: 195-200 1985; Hogness et al., Quant. Biol. 50: 181-194 1985; Lipshitz et al., Genes. Dev. 1: 307-322 1987). The expression of this transcript is highly regulated during embryogenesis, in a pattern that is partially reflexive of Ubx transcript (Akam et al., Quant. Biol. 50: 195-200 1985; Irish et al., EMBO J. 8: 1527-1537 1989). A number of bxd insertional mutations have no effect on the amount or the size of the bxd polyA+RNA, suggesting that this species is irrelevant to the observed phenotypes and that the real import of the transcription and processing of this gene is to produce intronic RNAs (Hogness et al., Quant. Biol. 50: 181-194 1985). The “cis-regulatory” elements in this region also appear to be able to regulate the expression of Ubx in trans, since defective elements can be complemented by wild-type sequences on the other chromosome.
[0182] This phenomenon (partial complementation, or “allelic cross-talk”, between a mutation in a “cis-regulator” on one chromosome and one in the coding region of the adjacent gene on the other chromosome) has been known for many years, and is termed “transvection” (Judd, Cell 53: 841-843 1988; Pirrotta, Bioessays 12: 409-414 1990). Transvection has been observed in a number of different loci, and appears to be synapsis-dependent, since translocation of the “regulatory” sequences to other chromosomal sites normally diminishes or eliminates this trans-complementation of gene expression patterns (Judd, Cell 53: 841-843 1988; Pirrotta, Bioessays 12: 409-414 1990; Wu et al., Curr. Opin. Genet. Dev. 9: 237-246 1999). Mechanistically this has been interpreted in terms of enhancer elements from one copy of the gene being able to interact directly with its homolog on the other chromosome (i.e. to influence both promoters) because of their close alignment (Geyer et al., Drosophila. EMBO J. 9: 2247-2256 1990), although there are other propositions, mostly based on the same theme of chromosome pairing (Wu et al., Curr. Opin. Genet. Dev. 9: 237-246 1999). However, translocation of these regulatory sequences can in fact lead to a spectrum of transvection effects, ranging from weak to strong, suggesting that remote action is possible (Micol et al., Genetics 126: 365-373 1990) and that a simple model of chromosome pairing and transcriptional crossover is incorrect (Goldsborough et al., Nature 381: 807-810 1996). Moreover, these effects may be simply interpreted by regarding the “cis-acting regulatory regions” as encoding separate (non-coding RNA) genes.
[0183] Transvection at distance is accentuated in the presence of mutant alleles of the Polycomb gene (which normally acts to maintain repression of transcription of Ubx and other genes in cells where it was not initially activated) and at many loci is dependent on the zeste gene product, which acts in opposition to polycomb-group proteins to enhance transcription (Wu et al., Trends Genet. 5: 189-194 1989; Laney et al, Genes Dev. 6: 1531-1541 1992; Pirrotta, Biochim. Biophys. Acta 1424: M1-8 1999), indicating that factors other than chromosome pairing are involved in this process (Castelli-Gair et al., EMBO J. 9: 4267-4275 1990; Castelli-Gair et al., Genetics 126: 177-184 1990). Zeste null mutants do not affect chromosome pairing, even though transvection at some loci is entirely dependent on zeste (Gemkow et al., Drosophila melanogaster. Development 125: 4541-4552 1998; Pirrotta, Biochim. Biophys. Acta 1424: M1-8 1999). Moreover it has been shown that a region in the vicinity of the late bxd transcript which can attenuate Ubx expression can exert its action independent of its position (Castelli-Gair et al., Development 114: 877-184 1992a; Castelli-Gair et al., Mol. Gen. Genet. 234: 117-184 1992b). To explain such observations one has either to invoke DNA looping over enormous (interchromosomal) distances to bring regulatory proteins into contact with the Ubx promoter, or a (diffusible) substance expressed from these sequences, i.e. RNA.
[0184] Similar observations have been made at the downstream abdA-AbdB region of the bithorax complex which also encode homeotic proteins controlling segment identity. As in the case of bithorax itself, the sequences upstream of abdA and AbdB, which are referred to as the infrabdominal (iab) region, are thought to function as cis-acting regulatory elements, despite the fact that this region, like bxd, is also itself transcribed. Transvection (involving iab and abdA/AbdB alleles) at this locus is synapsis (pairing) independent and relatively insensitive to location, again suggesting that a trans-acting RNA may be involved (Hendrickson et al., Drosophila melangaster, Genetics 139: 835-848 1995; Hopmann et al., Genetics 139: 815-833 1995; Sipos et al., Genetics 149: 1031-1050 1998). The efficiency of this transvection is also different in different tissues, indicating that the state of differentiation has an effect on this process (Sipos et al., Genetics 149: 1031-1050 1998). Another (small, 800 bp) “element” in this region (Mcp) has also been shown to be capable of “trans-silencing”, independent of homology or homology pairing in the immediate vicinity of Mcp transgene inserts. The inventors propose that Mcp encodes a trans-acting RNA, whose ability to communicate with its target loci is affected by spatial separation and by polycomb/zeste mediated effects on chromatin architecture.
[0185] These genetic phenomena are connected, with common features being non-protein-coding RNAs and dynamic interactions and remodeling of chromatin involving DNA methylation and trithorax- and polycomb-group proteins, occurring in large complexes with a variety of other proteins, including histone modifying factors and transcription factors. The influence on transvection and other phenomena of complexes containing trithorax- and polycomb-group proteins may, therefore, be interpreted more easily in terms of maintaining, enhancing or inhibiting accessibility of these sites to trans-acting RNAs and/or executing signals from such RNAs.
EXAMPLE 9
Genetic Programming and the Evolution of Complex Organisms
[0186] The evolution of complex phenotypes is usually understood to proceed by a sequence from cells that were entirely unregulated and whose dynamics were governed by rate processes and input constraints. The existence of these cells provided the preconditions for the appearance of regulatory mechanisms which fine tuned rate processes. The inventors propose that these regulated networks, following a change in gene structure and output in the eukaryotic lineage, provided the necessary precondition for the appearance of controlled multi-tasked networks, which in turn, led to the appearance of programmed response networks capable of implementing stored sequences of dynamical activities in response to internal and external stimuli. Further, the inventors suggest that there is only one plausible mechanism for the evolution and control of multi-tasking in cell and developmental biology and that far from being evolutionary junk, nuclear introns and other non-protein-coding RNAs have evolved this function.
[0187] The majority of information in a multi-tasked network is held in control sequences. Non-protein-coding RNAs comprise the majority of the genomic output and unique sequence information in the higher eukaryotes and the evidence is growing that these RNAs are functional, as is the realization that RNA metabolism in these organisms is much more complex than previously realized.
[0188] The three critical steps in the evolution of this system were (i) the entry of introns into protein coding genes in the eukaryotic lineage, (ii) the subsequent relaxation of internal sequence constraints by the evolution of the spliceosome and the exploration of new sequence space, and (iii) the co-evolution of processing and receiver mechanisms for transacting RNAs, which are not yet well characterized but which are likely to involve the dynamic modeling and re-modeling of chromatin and DNA, as well as RNA-RNA and RNA-protein interactions in other parts of the cell. Steps (ii) and (iii) probably occurred, at least initially, by constructive neutral evolution (Stoltzfus, 1999), involving biased variation, epistatic interactions and excess capacities underlying a complex series of steps giving rise to novel structures and operations, and later by molecular co-evolution (Dover et al., Biol. Sci. 312: 275-289 1986). Once this system of RNA communication began to be established, the rate of evolution of functional introns would have accelerated (by positive selection), and led also to the evolution of other non-protein-coding RNAs, which are also usually spliced and are probably derived from genes that had lost their protein coding capacity, as appears to have occurred in the case of transcripts producing small nucleolar RNAs.
[0189] In practical terms then, the inventors propose that functional introns provide a cellular memory of recent transcriptional events and underpin a multiple output parallel processing system where gene activity at one locus can connect to others in real time, allowing integration and multi-tasking of a sophisticated network of cellular activity. In this scheme, non-protein-coding RNAs are control molecules in the network that do not require concomitant production of protein. Thus, there are two levels of information produced by gene expression in the higher organisms—mRNA and eRNA—allowing the concomitant expression of both structural (i.e. protein-coding) and networking information, the latter involving multiplex contacts between different genes and gene products via RNA signals that are implicit in primary transcripts. As some genes have evolved to express only eRNA and some genes lack introns, there are three types of genes in the higher organisms—those that encode only protein (which are rare), those that encode only eRNA, and those that encode both.
[0190] One prediction of this model is that many core proteins in the higher eukaryotes will be multi-tasked, i.e. have different roles in different sub-networks to produce different phenotypic outcomes. This appears to occur. For example, it has been shown that glycogen synthase kinase-3β participates both in the specification of the vertebrate embryonic dorsoventral axis (via the Wnt/wingless signaling pathway) and in the NF-ηB-mediated cell survival response following TNF activation (Hoeflich et al., Nature 406: 86-90 2000). Both cytochrome c and a flavoprotein (apoptosis-inducing factor) have redox functions in mitochondria as well as specific apoptogenic functions (Chinnaiyan, Neoplasia 1: 5-15 1999; Daugas et al., FEBS Lett. 476: 118-123 2000; Loeffler et al., Exp. Cell Res. 256: 19-26 2000). The XPD gene product functions in both transcription and excision repair of DNA (Lehmann, Genes Dev. 15: 15-23 2001). There are many other documented examples of proteins that participate in more than one developmental and signalling pathway (sub-network) (see e.g. Boutros et al., Mech. Dev. 83: 27-37 1999; Szebenyi et al., Int. Rev. Cytol. 185: 45-106 1999; Coffey et al., J. Neurosci. 20: 7602-7613 2000; O'Brien et al., Proc. Natl. Acad. Sci. USA 97: 12074-12078 2000). There are also examples of proteins having different, even antagonistic, functions in different settings, often as a result of alternative splicing (Jiang et al., Proc. Soc. Exp. Biol. Med. 220: 64-72 1999; Lopez, Annu. Rev. Genet. 32: 279-305 1998; Hastings et al., J. Biol. Chem. 275: 11507-11513 2000), a process that we predict will turn out to be regulated and guided not simply by tissue-specific RNA binding proteins/splicing factors but also by trans-acting RNAs produced by the activity of other genes (see, e.g. Hastings et al., J. Biol. Chem. 275: 11507-11513 2000). Consequently, developmental and phylogenetic profiling efforts will need to assign a range of biological, in addition to biochemical, functions to individual proteins and their splice variants in the network.
[0191] A multi-tasked network allows the rapid exploration of exponentially many protein expression profiles without equivalent increase in the size of the controlled parent network. The model therefore also predicts that the core proteome will be relatively stable in the higher organisms, which appears to be the case (Duboule et al., Trends Genet. 14: 54-59 1998; Rubin et al., Science 287: 2204-2215 2000) and that phenotypic variation will result primarily and quite easily from variation in the control architecture, rather than duplication and mutation of gene sub-networks. Once in place, therefore, a controlled multitasked network enables not only the efficient programming of different cellular phenotypes in the differentiation and development of multicellular organisms, but also rapid evolutionary radiation during expansions into uncontested environments, such as initially observed in the Cambrian explosion and as seen after major extinction events.
[0192] The corollary is that prokaryotes and simpler eukaryotes operating on simple protein control circuitry are limited in their phenotypic range, genome size and complexity not by the available diversity of polypeptide structures and chemistry, but by a primitive genetic operating system incapable of supporting integrated multi-tasking of gene networks. This would also explain why the Earth was restricted to simpler unicellular and colonial life forms for over 3 billion years, and the rapid evolution of complex life forms after the conditions for feasible parallel outputs were satisfied by the entry of introns into the eukaryotic lineage around 1.2 billion years ago, and the subsequent evolution of the necessary infrastructure for sending and receiving intronic and other non-protein-coding RNA signals.
[0193] Genomes are datasets with controls. The present invention examines, therefore, biology and genomes from the viewpoint of information and network theory and unifies a wide range of evolutionary and molecular genetic observations, including the long lag then sudden appearance of developmentally sophisticated multicellular organisms, the plasticity of phenotypic diversity despite the relative conservation of the core proteome and a wide range of unexplained molecular genetic phenomena that all intersect with RNA, the enabling molecule.
EXAMPLE 10
eRNA Regulators of HOX, ets-Domain Transcription Factor and Immunoglobulin Gene Expression
[0194] A method to identify eRNA elements and potential eRNA elements and/or their targets has been developed. The method searches the database of choice for known and predicted introns. The sequences of the known and predicted introns may then be compared in a BlastN search to identify from the non-redundant genome databases genes that are homologous to eRNA elements. eRNA elements may be embedded within introns or other non-coding RNA such as a 3′ or 5′ untranslated region (UTR). The method may also be used to screen such non-coding RNA sequences for eRNA elements. Short regions of homology between 19 and 200 nucleotides are considered significant to detect eRNA as it is known that short homologous regions of approximately 21 nucleotides act to modulate gene expression. The subject method identifies homologous sequences or complementary sequences which may be eRNA or target sequences.
[0195] A predicted intron sequence derived from chr19:38234-167860 is used in a BlastN search of the non-redundant human genome database to identify potential eRNA elements. The search reveals that this intron sequence comprise a number of candidate eRNA elements which may be directed to the regulation of multiple genes. eRNA elements are identified within introns by searching other parts of the genome, including protein- and non-protein-encoding regions, for homology with a candidate eRNA sequence. eRNA elements from this intron are proposed to be involved in regulation of activity of the ets-domain transcription factor, the human chloride channel transporter gene and the developmentally regulated HOX gene. This intron potentially contains an eRNA element directed to the regulation of immunoglobulin gene expression and an eRNA element directed to the regulation of expression of the gene encoding the nuclear factor of κ light polypeptide enhancer (NFκB1).
[0196] Predicted intron derived from chr19 between nucleotide sequences 38234-167860:
gtaggtggggaaggggtgtcaggtgggtactgcagatgggctctaggacctcggccttcaag ttgtgtctgcccgcctcttgctactgtcttggatattttaaagtccttttgacgttgttctg atttctgggcaggggacagagtaagtgtgtatttgctctgagactgttaatttggtatttcc atcccaagttacagggaagacctcaggctgcaggttcctagctccgggctgaggtggcttgt ggaggcagacagctgttgtctggaagtgcagagggctgggggctggccaggctgttactgag ttcagaataggaggaaagagtgtgtagcaaagtcggcgctccttggccactgccagcattca gagttgtcttgtttgccttgccttaaacgttgccttcctggacgcctacaaagtcaggttgt aaccgctggccactgctgtgctcactggcagcccctgatttacgtgaggacctcaagtgtgt gttgggcagaattccccagcgcttcccgtacaccccnccacccccagtgcagcatcgctcgg tgcgtggctggtggactggaggagtgtgcgtgccggcagcactgccaggcacgtgcctaatg ctctggccctgtgtgtttgtgttttcttcccgatttctgag [SEQ ID NO: 1] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|10280826|gb|AC012531.11|AC012531 Homo sapiens, clone RP11-83K1, complete sequence Length = 171949 Score = 40.1 bits (20), Expect = 1.9 Identities = 20/20 (100%) Strand = Plus/Minus Query: 273 agtgcagagggctgggggct 292 [SEQ ID NO: 2] |||||||||||||||||||| Sbjct: 168539 agtgcagagggctgggggct 168520 [SEQ ID NO: 3] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|2992476|gb|AC003666.1|AC003666 Homo sapiens Xp22 BAC GS-551019 (Genome Systems Human BAC library) and cosmids U199A7 and U209F2 (Lawrence Livermore X chromosome cosmid library) containing part of human chloride channel 4 gene, complete sequence Length = 151750 Score = 40.1 bits (20), Expect = 1.9 Identities = 20/20 (100%) Strand = Plus/Plus Query: 264 ttgtctggaagtgcagaggg 283 [SEQ ID NO: 4] |||||||||||||||||||| Sbjct: 102216 ttgtctggaagtgcagaggg 102235 [SEQ ID NO: 5] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|4689496|gb|AC006948.4|AC006948 Homo sapiens chromosome 17, clone hRPK.334_M_10, complete sequence Length = 168558 Score = 40.1 bits (20), Expect = 1.9 Identities = 20/20 (100%) Strand = Plus/Minus Query: 563 tggctggtggactggaggag 582 [SEQ ID NO: 6] |||||||||||||||||||| Sbjct: 20775 tggctggtggactggaggag 20756 [SEQ ID NO: 7] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|8894241|emb|AL157952.8|AL157952 Human DNA sequence from clone RP5- 875K15 on chromosome 11p12-14.1 Contains the gene for the eta-domain transcription factor EHF, ESTs, STSs and GSSs, complete sequence [Homo sapiens] Length = 114022 Score = 40.1 bits (20), Expect = 1.9 Identities = 20/20 (100%) Strand = Plus/Plus Query: 243 gcttgtggaggcagacagct 262 [SEQ ID NO: 8] |||||||||||||||||||| Sbjct: 64983 gcttgtggaggcagacagct 65002 [SEQ ID NO: 9] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|32387|emb|X61755.1|HSHOX3D Human HOX3D gene for homeoprotein HOX3D Length = 4968 Score = 40.1 bits (20), Expect = 1.9 Identities = 20/20 (100%) Strand = Plus/Minus Query: 273 agtgcagagggctgggggct 292 [SEQ ID NO: 10] |||||||||||||||||||| Sbjct: 166 agtgcagagggctgggggct 147 [SEQ ID NO: 11] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to >gi|14718391|gb|AC021120.6|AC021120 Homo sapiens clone RP11-34708, complete sequence Length = 193980 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Minus Query: 156 tttgctctgagactgttaa 174 [SEQ ID NO: 12] ||||||||||||||||||| Sbjct: 131889 tttgctctgagactgttaa 131871 [SEQ ID NO: 13] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|2894631|gb|AC004152.1|AC004152 Homo sapiens chromosome 19, fosmid 37308, complete sequence Length = 37635 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Minus Query: 280 agggctgggggctggccag 298 [SEQ ID NO: 14] ||||||||||||||||||| Sbjct: 20673 agggctgggggctggccag 20655 [SEQ ID NO: 15] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|14091927|gb|AC025212.5|AC025212 Homo sapiens chromosome 18, clone RP11-289A1, complete sequence Length = 182258 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Minus Query: 116 gttgttctgatttctgggc 134 [SEQ ID NO: 16] ||||||||||||||||||| Sbjct: 51238 gttgttctgatttctgggc 51220 [SEQ ID NO: 17] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|13489123|gb|AC078776.12|AC078776 Homo sapiens 12 BAC RP11-15519 (Roswell Park Cancer Institute Human BAC Library) complete sequence Length = 95801 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 630 tgtgtgtttgtgttttctt 648 [SEQ ID NO: 18] ||||||||||||||||||| Sbjct: 58720 tgtgtgtttgtgttttctt 58738 [SEQ ID NO: 19] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|1302657|gb|U52112.1|HSU52112 Homo sapiens Xq28 genomic DNA in the region of the L1CAM locus containing the genes for neural cell adhesion molecule L1 (L1CAM), arginine-vasopressin receptor (AVPR2), C1 p115 (C1), ARD1 N-acetyltransferase related protein (TE2), renin-binding protein> Length = 174424 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Minus Query: 278 agagggctgggggctggcc 296 [SEQ ID NO: 20] ||||||||||||||||||| Sbjct: 73811 agagggctgggggctggcc 73793 [SEQ ID NO: 21] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|10567853|gb|AC035147.3|AC035147 Homo sapiens chromosome 5 clone CTD- 2309M13, complete sequence Length = 104939 Score = 38.2 bits (19), Expect = 7.6 Identities = 22/23 (95%) Strand = Plus/Plus Query: 626 gccctgtgtgtttgtgttttctt 648 [SEQ ID NO: 22] ||||||||||||||| ||||||| Sbjct: 100838 gccctgtgtgtttgtcttttctt 100860 [SEQ ID NO: 23] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|9755473|gb|AC006452.4|AC006452 Homo sapiens PAC clone RP4-592P3 from 7q31-q35, complete sequence Length = 121703 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 278 agagggctgggggctggcc 296 [SEQ ID NO: 24] ||||||||||||||||||| Sbjct: 117068 agagggctgggggctggcc 117086 [SEQ ID NO: 25] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|9954648|gb|AC018758.2|AC018758 Homo sapiens chromosome 19, BAC CTB- 6117 (BC52850), complete sequence Length = 185409 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Minus Query: 630 tgtgtgtttgtgttttctt 648 [SEQ ID NO: 26] ||||||||||||||||||| Sbjct: 150073 tgtgtgtttgtgttttctt 150055 [SEQ ID NO: 27] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|9937750|gb|AC008750.7|AC008750 Homo sapiens chromosome 19 clone CTD- 2616J11, complete sequence Length = 143044 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Minus Query: 464 agcccctgatttacgtgag 482 [SEQ ID NO: 28] ||||||||||||||||||| Sbjct: 118714 agcccctgatttacgtgag 118696 [SEQ ID NO: 29] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|9506357|gb|M16230.2|SUSSMP1 Strongylocentrotus purpuratus spicule matrix protein SM37, partial cds; and spicule matrix protein SM50 precursor, gene, exon 1 Length = 14091 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 631 gtgtgtttgtgttttcttc 649 [SEQ ID NO: 30] ||||||||||||||||||| Sbjct: 14057 gtgtgtttgtgttttcttc 14075 [SEQ ID NO: 31] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|14596303|emb|AL356l57.14|AL356157 Human DNA sequence from clone RP11- 733D4 on chromosome 10, complete sequence [Homo sapiens] Length = 198917 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 276 gcagagggctgggggctgg 294 [SEQ ID NO: 32] ||||||||||||||||||| Sbjct: 86783 gcagagggctgggggctgg 86801 [SEQ ID NO: 33] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|14594822|emb|AJ314754.1|APL314754 Anas platyrhynchos IgM gene (partial), mIgM gene (partial), IgA gene (partial), mIgA gene (partial) and IgY gene (partial), clones 5.1, 13.1, 2.1 and PCR 00-106 Length = 48796 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 404 gccttcctggacgcctaca 422 [SEQ ID NO: 34] ||||||||||||||||||| Sbjct: 19162 gccttcctggacgcctaca 19180 [SEQ ID NO: 35] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|7012904|gb|AF213884.1|AF213884S1 Homo sapiens nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1) gene, complete cds Length = 190000 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 156 tttgctctgagactgttaa 174 [SEQ ID NO: 36] ||||||||||||||||||| Sbjct: 92988 tttgctctgagactgttaa 93006 [SEQ ID NO: 37] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|2588626|gb|AC003081.1|AC003081 Human BAC clone CTB-9H2 from 7q31, complete sequence [Homo sapiens] Length = 149566 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 395 ttaaacgttgccttcctgg 413 [SEQ ID NO: 38] ||||||||||||||||||| Sbjct: 114135 ttaaacgttgccttcctgg 114153 [SEQ ID NO: 39] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|9187146|emb|AL133553.9|AL133553 Human DNA sequence from clone GS1- 174L6 on chromosome 1 Contains part of the gene for TPR (translocated promoter region (to activated MET oncogene)), a gene for a novel protein (MSF: megakaryocyte stimulating factor), ESTs, STSs and GSSs, complete sequ> Length = 190655 Score = 38.2 bits (19), Expect = 7.6 Identities = 25/27 (92%) Strand = Plus/Plus Query: 126 tttctgggcaggggacagagtaagtgt 152 [SEQ ID NO: 40] |||||||| ||||||||||||| |||| Sbjct: 182695 tttctgggtaggggacagagtatgtgt 182721 [SEQ ID NO: 41] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted gi|6735496|emb|AL121925.10|HSJ966J20 Human DNA sequence from clone RP5- 966J20 on chromosome 20 Contains STSs and GSSs, complete sequence [Homo sapiens] Length = 39260 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus Query: 505 gaattccccagcgcttccc 523 [SEQ ID NO: 42] ||||||||||||||||||| Sbjct: 1220 gaattccccagcgcttccc 1238 [SEQ ID NO: 43] Predicted intron sequence from chr19 between nucleotide 38234-167860 comprises potential eRNA elements targeted to gi|5123778|emb|AL035461.11|HS967N21 Human DNA sequence from clone RP5- 967N21 on chromosome 20p12.3-13. Contains the CHGB gene for chromogranin B (secretogranin 1, SCG1), a pseudogene similar to part of KIAA0172, the gene for a novel protein and KIAA1153, the gene for a novel MCM2/3/5 fam> Length = 139352 Score = 38.2 bits (19), Expect = 7.6 Identities = 19/19 (100%) Strand = Plus/Plus
EXAMPLE 11
eRNA Elements are Involved in the Regulation of Genes Expressed in Cancer
[0197] Jun Dimerization and TNFRSF6B Gene eRNA Element
[0198] A predicted intron sequence from chromosome 12 between nucleotide 156966-180225 is used in a BlastN search of the human genome database. The search identified eRNA elements residing in the intron with potential activities in the regulation of genes known to expressed in cancer.
[0199] A predicted intron residing on a fragment of DNA derived from chr12 between nucleotide sequences 156966-180225:—
gtaagtgcccttccgggagctcacacccgctctctgtctcccctgtccttcctctgcttcat tttttcctggactctgaccgatgtttgcgttagagtatgtttgaacgtggggtcgattggga aggattaagccttggtgctgaggctggatattgcaggaggatacagggtgaatggagccggc ggggcggggcgggccgggctgctgtgccgtggctgctgttgtgctgacaccctctttcctag agaaacagcctcttattcacaaccagctgatttgaaatttcctgcag [SEQ ID NO: 44] Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to gi|14749255|ref|XM_034220.1| Homo sapiens Jun dimerization protein p21SNFT (SNFT), mRNA Length = 980 Score = 44.1 bits (22), Expect = 0.053 Identities = 22/22 (100%) Strand = Plus/Plus Query: 184 ggcggggcggggcgggccgggc 205 [SEQ ID NO: 45] |||||||||||||||||||||| Sbjct: 186 ggcggggcggggcgggccgggc 207 [SEQ ID NO: 46] Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to gi|8246778|emb|AL121845.20|HSJ583P15 Human DNA sequence from clone RP4- 583P15 on chromosome 20 Contains ESTs, STSs, GSSs and ten CpG islands. Contains the TNFRSF6B gene for tumor necrosis factor receptor 6b (decoy), the 3′ part of the KIAA1088 gene, the ARFRP1 gene for ADP-ribosylation fa> Length = 120917 Score = 44.1 bits (22), Expect = 0.053 Identities = 22/22 (100%) Strand = Plus/Plus Query: 184 ggcggggcggggcgggccgggc 205 [SEQ ID NO: 47] |||||||||||||||||||||| Sbjct: 43351 ggcggggcggggcgggccgggc 43372 [SEQ ID NO: 48] Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to gi|14523048|ref|NG_000006.1| Homo sapiens genomic alpha globin region (HBA@) on chromosome 16 Length = 43058 Score = 42.1 bits (21), Expect = 0.21 Identities = 21/21 (100%) Strand = Plus/Plus Query: 185 gcggggcggggcgggccgggc 205 [SEQ ID NO: 49] ||||||||||||||||||||| Sbjct: 25749 gcggggcggggcgggccgggc 25769 [SEQ ID NO: 50] Score = 38.2 bits (19), Expect = 3.3 Identities = 22/23 (95%) Strand = Plus/Plus Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to gi|14336674|gb|AE006462.1|AE006462 Homo sapiens 16p13.3 sequence section 1 of 8 Length = 258002 Score = 42.1 bits (21), Expect = 0.21 Identities = 21/21 (100%) Strand = Plus/Plus Query: 185 gcggggcggggcgggccgggc 205 [SEQ ID NO: 51] ||||||||||||||||||||| Sbjct: 154885 gcggggcggggcgggccgggc 154905 [SEQ ID NO: 52] Score = 38.2 bits (19), Expect = 3.3 Identities = 22/23 (95%) Strand = Plus/Plus
EXAMPLE 12
eRNA Elements Which Overlap and Which are Directed to the Regulation of Multiple Genes
[0200] A predicted intron sequence derived from chr12 between nucleotides: 156966-18022 is used in a BlastN search of the non-redundant human genome database to identify potential eRNA elements. The search reveals that a plurality of putative eRNA elements are embedded within a single intron and that a single eRNA element may perform regulatory functions directed at multiple genes. eRNA elements are identified within introns by searching other parts of the genome, including protein- and non-protein-encoding regions, for homology with a candidate eRNA sequence. eRNA elements from this intron are potentially involved in regulation of X-chromosome activity as well as several unannotated genes derived from human DNA.
[0201] Predicted intron sequence from chr12 between nucleotide 156966-180225:—
gtatgtaccgtgctgggaccacttccccaggtgccttccccacccagccaggtctgtagttt tgaaagtcttgtatagctttttccttggtttaaaagcaataaatgcccactggagataaatt agaaaatatggaagaaagctataaaaaagaaactaaaaaaatctcttgtaattccaccactc aaatataactttttttcttaaaaaattttttttctcttacttagagacaggcagggtctggc tctgtcccccaggctggagtgcagtggtgccatcatagctcactgcagcctcaacctcttgg gctcaaggcattctctcgcctcagcctcctgagcagctgggactgcaggcatgagccatggt tcctgggcattttctcttgatattttgatgaagcagcctctttgtccccaggtcatagctgc ttaagacactatgtacagagatcttagttgaatgagacaagtgacttctggctgtgccctgc agataggccttgggtgcagccatggtttgtagattcccctggagaaatccaagcaacacaca tgtatttggtactcactaagtgcctacagaaccaaaccgaaactgggccgcactggggagga gatcaccgtggagaccggagggcgcactcacggagagt [SEQ ID NO: 53] Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to: gi|13162510|gb|AC011443.6|AC011443 Homo sapiens chromosome 19 clone CTC- 218B8, complete sequence Length = 156776 Score = 151 bits (76) , Expect = 7e-34 Identities = 112/124 (90%) Strand = Plus/Minus Query: 238 cagggtctggctctgtcccccaggctggagtgcagtggtgccatcatagctcactgcagc 297 [SEQ ID NO: 54] |||||||| ||||||| |||||||||| ||||||||| || ||||| |||||||||||| Sbjct: 49308 cagggtcttgctctgttgcccaggctggggtgcagtggcgcaatcatggctcactgcagc 49249 [SEQ ID NO: 55] Query: 298 ctcaacctcttgggctcaaggcattctctcgcctcagcctcctgagcagctgggactgca 357 [SEQ ID NO: 56] ||||||||| |||||||||| ||| ||| |||||||||||||||||||||||||||| || Sbjct: 49248 ctcaacctcctgggctcaagccatcctcccgcctcagcctcctgagcagctgggactaca 49189 [SEQ ID NO: 57] Query: 358 ggca 361 |||| Sbjct: 49188 ggca 49185 Score = 101 bits (51), Expect = 6e-19 Identities = 93/107 (86%) Strand = Plus/Minus Query: 247 gctctgtcccccaggctggagtgcagtggtgccatcatagctcactgcagcctcaacctc 306 [SEQ ID NO: 58] |||||||| |||||||||||||| |||||||| |||| |||||||||||||||| | ||| Sbjct: 81907 gctctgtcacccaggctggagtgtagtggtgcaatcagagctcactgcagcctccaactc 81848 [SEQ ID NO: 59] Query: 307 ttgggctcaaggcattctctcgcctcagcctcctgagcagctgggac 353 [SEQ ID NO: 60] |||||||||| || ||| | ||||||||||||||| |||| |||| Sbjct: 81847 ctgggctcaagcaatcctcccacctcagcctcctgagtagctaggac 81801 [SEQ ID NO: 61] Score = 101 bits (51), Expect = 6e-19 Identities = 105/123 (85%) Strand = Plus/Plus Query: 248 ctctgtcccccaggctggagtgcagtggtgccatcatagctcactgcagcctcaacctct 307 [SEQ ID NO: 62] ||||||| ||||||||||||||||||||||| ||| | |||||||||| |||| |||| Sbjct: 79220 ctctgtcacccaggctggagtgcagtggtgcgatcttggctcactgcaacctccgcctcc 79279 [SEQ ID NO: 63] Query: 308 tgggctcaaggcattctctcgcctcagcctcctgagcagctgggactgcaggcatgagcc 367 [SEQ ID NO: 64] |||| ||||| |||||| |||||||||||| ||| |||||||||| ||||| || ||| Sbjct: 79280 tgggttcaagtgattctcctgcctcagcctcccgagtagctgggactacaggcgtgtgcc 79339 [SEQ ID NO: 65] Query: 368 atg 370 ||| Sbjct: 79340 atg 79342 Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to: gi|6649930|gb|AF031075.1|AF031075 Homo sapiens chromosome X, cosmid Qc8D3, complete sequence Length = 44163 Score = 1453 bits (733), Expect = 0.0 Identities = 747/754 (99%) Strand = Plus/Plus Query: 1 gtggggacaaacagaaagacacaaggaacaattagaggctctccatagcaatgtcagaga 60 [SEQ ID NO: 66] |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Sbjct: 22925 gtggggacaaacagaaagacacaaggaacaattagaggctctccatagcaatgtcagaga 22984 [SEQ ID NO: 67] Query: 61 tagggcagagcggatggtggtgacaacgctctgacaaacgttactattgaacgagagtca 120 [SEQ ID NO: 68] |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Sbjct: 22985 tagggcagagcggatggtggtgacaacgctctgacaaacgttactattgaacgagagtca [SEQ ID NO: 69] Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to gi|4508111|gb|AC005072.2|AC005072 Homo sapiens BAC clone CTB-181H17 from 7q21.2-q31.1, complete sequence Length = 69367 Score = 147 bits (74), Expect = 1e-32 Identities = 110/122 (90%) Strand = Plus/Plus Query: 238 cagggtctggctctgtcccccaggctggagtgcagtggtgccatcatagctcactgcagc 297 [SEQ ID NO: 70] |||||||| |||||||| ||||||||||||| ||||||||| |||||||||||||||||| Sbjct: 46265 cagggtcttgctctgtcacccaggctggagttcagtggtgcaatcatagctcactgcagc 46324 [SEQ ID NO: 71] Query: 298 ctcaacctcttgggctcaaggcattctctcgcctcagcctcctgagcagctgggactgca 357 [SEQ ID NO: 72] ||||| ||| |||||||||| || ||| | ||||||||||||||| ||||||||||||| Sbjct: 46325 ctcaaactcctgggctcaagcaatcctcccacctcagcctcctgagtagctgggactgca 46384 [SEQ ID NO: 73] Query: 358 gg 359 || Sbjct: 46385 gg 46386 Score = 93.7 bits (47), Expect = 1e-16 Identities = 86/99 (86%) Strand = Plus/Minus Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to: gi|13624997|emb|AL356214.20|AL356214 Human DNA sequence from clone RP11- 30E16 on chromosome 10, complete sequence [Homo sapiens] Length = 163964 Score = 133 bits (67) , Expect = 2e-28 Identities = 106/119 (89%) Strand = Plus/Minus Query: 250 ctgtcccccaggctggagtgcagtggtgccatcatagctcactgcagcctcaacctcttg 309 [SEQ ID NO: 74] ||||| |||||||||||||||||||| |||||||| ||||||||||||||||||||| || Sbjct: 115382 ctgtcacccaggctggagtgcagtggcgccatcatggctcactgcagcctcaacctcctg 115323 [SEQ ID NO: 75] Query: 310 ggctcaaggcattctctcgcctcagcctcctgagcagctgggactgcaggcatgagcca 368 [SEQ ID NO: 76] +TL,1 |||||||| ||| || ||||||||||||||| |||||| ||| |||||||| |||| Sbjct: 115322 ggctcaagccatcctaccacctcagcctcctgagtagctggaactacaggcatgggcca 115264 [SEQ ID NO: 77] Score = 97.6 bits (49), Expect = 9e-18 Identities = 97/113 (85%) Strand = Plus/Minus Predicted intron sequence from chr12 between nucleotide 156966-180225 comprises potential eRNA elements targeted to: gi|3165399|gb|AC003684.1|AC003684 Homo sapiens Xp22 BAC GSHB-519E5 (Genome Systems Human BAC library) complete sequence Length = 210954 Score = 135 bits (68), Expect = 4e-29 Identities = 95/104 (91%) Strand = Plus/Plus Query: 241 ggtctggctctgtcccccaggctggagtgcagtggtgccatcatagctcactgcagcctc 300 [SEQ ID NO: 78] ||||| |||||||| | |||||||||||||||||||||||||| |||||||||||||||| Sbjct: 46790 ggtctcgctctgtcactcaggctggagtgcagtggtgccatcacagctcactgcagcctc 46849 [SEQ ID NO: 79] Query: 301 aacctcttgggctcaaggcattctctcgcctcagcctcctgagc 344 [SEQ ID NO: 80] || ||||||||||||| ||| ||||| |||||||||||||||| Sbjct: 46850 aaattcttgggctcaagccatcctctcacctcagcctcctgagc 46893 [SEQ ID NO: 81] Score = 113 bits (57), Expect = 2e-22 Identities = 99/113 (87%) Strand = Plus/Minus
EXAMPLE 13
Generic Methods for Determining the Effect of Putative eRNA
[0202] A protein-encoding gene (1), which comprises at least one intron suspected of encoding an eRNA, is modified to prevent translation of the encoded protein but to otherwise preserve transcription of the primary transcript.
[0203] A gene so modified (2) is conveniently prepared by oligonucleotide-directed (or site-directed) mutagenesis to convert the start codon (ATG) of the gene to a non-start codon (e.g., AAG or TAG) and to introduce a stop codon (e.g., TAG, TAA, TGA) closely downstream (e.g., within 30 bases) of the normal start codon. The site-directed mutagenesis involves hybridizing an oligonucleotide encoding the desired mutation to a template DNA, wherein the template is the single-stranded form of a plasmid or bacteriophage containing the unaltered or parent gene sequence. After hybridization, a DNA polymerase is used to synthesize an entire second complementary strand of the template that will thus incorporate the oligonucleotide primer and will code for the selected alteration in the parent gene sequence. The resultant heteroduplex molecule is then transformed into a suitable host cell, usually a prokaryote such as E. coli . After the cells are grown, they are plated onto agarose plates and screened using the oligonucleotide primer having a detectable label to identify the bacterial colonies having the mutated or modified gene.
[0204] The intron(s) of the parent and modified genes are removed by site-directed mutagenesis or by other standard techniques to provide (3) a modified gene encoding an intronless primary transcript from which a wild-type protein can be translated and (4) a modified gene encoding an intronless primary transcript from which a wild-type protein cannot translated.
[0205] Each of the above genes (1-4) is then inserted into a suitable expression vector and the construct so produced is transfected into cells. Expression of the inserted genes (1-4) in the transfected cells will result, respectively, in:—
[0206] (a) a normal primary transcript, including introns, from which a functional wild-type protein can be produced;
[0207] (b) a primary transcript, excluding introns, from which a functional wild-type protein can be produced;
[0208] (c) a primary transcript, including introns, from which a functional wild-type protein cannot be produced; and
[0209] (d) a primary transcript, excluding introns, from which a functional wild-type protein cannot be produced.
[0210] The phenotypic effects of (a)-(d) are then compared (e.g., by pairwise comparisons) to discriminate which effects may be ascribed to protein and which may be ascribed to eRNA.
[0211] Alternatively, genetic complementation to discriminate whether putative eRNA sequences are encoding genuine trans-acting RNAs or cis-acting transcription factor binding sites, can be assessed by allelic replacement with an intronless gene and determination of the phenotypic effect thereof, followed by complementation with the intron-containing gene which cannot produce a protein (e.g. because its translational start codon has ben rendered non-functional by site-directed mutation). If wild-type function is restored by the latter, the complementing genetic factor must be an eRNA derived from the intron. Appropriate secondary controls are employed to confirm whether a transcript is produced and spliced normally (e.g., using Northern blots) and whether a protein is or is not expressed (e.g., using Western blots) as appropriate to the particular construct.
EXAMPLE 14
Idenfication of eRNA Candidates in Meiotic Genes
[0212] A subset of nucleotide repeats in the S. cerevisiae genome is obtained and then filtered by taking intronic sequences of all known meiotic genes and removing all repeated sequences not in the sequences of the introns. This leaves a putative signal of an eRNA gene regulation network. In Table 2, the gene carrying an intron which is repeated is identified in the left hand column. The nucleotide sequence of the repeat intronic sequence is then shown in the penultimate left hand column.
[0213] These 16mer sequences are then screened for potential receiver sequences in 245,000 sequences in the genome. In Table 2, there are three types of putative receiver sequences which are located in two regions:
[0214] i) within a gene (third most right column); or
[0215] ii) in an intergenic region located:
[0216] a) upstream (second most right hand column); or
[0217] b) downstream (most right hand column).
[0218] Many of these genes are known to be involved in meiotic processes, including cell division. The chance that any given sequence of 16 nucleotides would occur accidently at more than one locus in the yeast genome is less than 1 in 100. The odds against an accidental finding that sequences from introns of genes involved in meoisis occur in or near a set of other genes involved in meiosis is astronomically small, and thus this network must be real. Consequently, this confirms that the identifier of potential eRNA and receiver sequences is a significant event, supporting the concept of eRNA networking. The role of any particular candidate eRNAs in the network may be determined and confirmed by analyses such as set out in Example 13.
TABLE 2 eRNA AND RECEIVE SEQUENCES IN SACCHAROMYCES CEREVISIAE MEIOTIC GENES Intron Bearing Gene SEQ ID No. Repeat Hit Upstream Downstream AMA1 82 CTTATTTTTTCATT RPL15A YLR030W (119) AT (581) 83 TTTTTCATTATGAA PHA2 AA 84 AAAATATTTGTTAG CWH43 TA DMC1 85 CTGCTGTAGAGGTT RIM15 YFL032W (332) CT (113) 86 CTAATAATTTGGAA YNL156C AGGA 87 ATAACATTTTTAAA ATP3 (167) FIG1 (291) AC SEC8 88 GGTTCTTTCCCCCT MNN4 (136) YKT9 (671) TT 89 CTAATAATTTGGAA YNL156C AGG ARP8 HFM1 90 AAGTGGTTTTTCTG YCR024C GA 91 TAGATAATAAAAG PPA1 (112) RPN1 (133) AAA 92 CTAGATAATAAAA YPL141C MKK2 (117) GAA (1336) HOP2 93 GTTAAGTATTTTTT HXT12 YIL169C (273) TA (2999) YOL155C (102) HXT11 (1625) MMS2 94 CCTTTCAAAACTTA FIT1 (586) YDR535C (1120) TA 95 ATTTGTTAGTATAT MAM33 (8) RPS24B (473) GT PCH2 96 TCTTTCTTTCCTTCT SGT1 (201) ASE1 (114) T 97 TATGTTTTTTTCTTT YLR379W T 98 TCTTCATAAAAAA YGL034C HOP2 (165) GCA (1881) 99 TTCTTTTTCTTTCTT NOG1 (144) SSU1 (728) TC 100 GTATGTTTTTTTCT YKL063C MSN4 (807) TT (903) 101 CTTTTTCTTTCTTTC SPP41 CTT 102 TTTTTTTCTTTTATT YGL131C CT 103 TTTTATTCTACTTTT TH(GUG)E1 CHO1 (64) A (152) RAD14 104 AATTTAACGATGA NVJ1 (101) UTP9 (118) GATG 105 CAAACACAGAATC YDL189W ATTT 106 CGATGAGATGAGC URA7 (144) MRPL16 (315) TGTG SRC1 107 TTTTTTTTGTTTTTG VPS25 (888) URA8 (101) A 108 TTAATTTTTTTTGA YMR192W AT 109 TAATTTTTTTTGAA SUL1 (333) PCA1 (701) TTT 110 TTTTTTTTGAATTTT BUR6 (38) TR(ACG)E (356) T YAP3 (220) TV(AAC)H (18) RPL34B MMF1 (372) (409) 111 TTTTTTTGAATTTTT VPS45 (429) PAN2 (82) T YAP3 (219) TV(AAC)H (19) YPR078C MRL1 (332) (273) 112 AGTTTTAATTTTTT MSC6 GDS1 (354) TT (1559) 113 TTTTTTTTTGTTTTT SAP4 G 114 TTTTTTTGTTTTTGA YHR032W YHR033W (60) TTT (399) 115 TTGAATTTTTTTTT YOR154W GT 116 TTTTAATTTTTTTTG RAD59 A 117 AATAAATTGTACTC STT4 AC 118 TTTTTGAATTTTTTT YAP3 (216) TV(AAC)H (22) TT YPR078C MRL1 (335) (270) MCM1 (201) ARG80 (534) 119 AAAATTCAAAAAA YAP3 (221) TV(AAC)H (17) AAT 120 AAAAAAATTCAAA YAP3 (218) TV(AAC)H (20) AAA YPR078C MRL1 (333) (272) YLR211C 121 TTTTTTTTTGTTCAT KGD1 (130) AYR1 (341) G
EXAMPLE 15
GRIA 3RNA Network
[0219] [0219]FIG. 6 provides and example of an eRNA network centred around the GRIA2, GRIA3 and GRIA4 genes which all share parts of an intronic sequence shown in the Figure. It is proposed that this intronic sequence is an eRNA.
[0220] Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features.
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1
121
1
661
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human
misc_feature
(533)..(533)
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1
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2
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DNA
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DNA
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4
20
DNA
human
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5
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DNA
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20
DNA
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DNA
human
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11
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12
19
DNA
human
12
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13
19
DNA
human
13
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14
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DNA
human
14
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15
19
DNA
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15
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16
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DNA
human
16
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17
19
DNA
human
17
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18
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DNA
human
18
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19
19
DNA
human
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20
19
DNA
human
20
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21
19
DNA
human
21
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22
23
DNA
human
22
gccctgtgtg tttgtgtttt ctt 23
23
23
DNA
human
23
gccctgtgtg tttgtctttt ctt 23
24
19
DNA
human
24
agagggctgg gggctggcc 19
25
19
DNA
human
25
agagggctgg gggctggcc 19
26
19
DNA
human
26
tgtgtgtttg tgttttctt 19
27
19
DNA
human
27
tgtgtgtttg tgttttctt 19
28
19
DNA
human
28
agcccctgat ttacgtgag 19
29
19
DNA
human
29
agcccctgat ttacgtgag 19
30
19
DNA
human
30
gtgtgtttgt gttttcttc 19
31
19
DNA
human
31
gtgtgtttgt gttttcttc 19
32
19
DNA
human
32
gcagagggct gggggctgg 19
33
19
DNA
human
33
gcagagggct gggggctgg 19
34
19
DNA
human
34
gccttcctgg acgcctaca 19
35
19
DNA
human
35
gccttcctgg acgcctaca 19
36
19
DNA
human
36
tttgctctga gactgttaa 19
37
19
DNA
human
37
tttgctctga gactgttaa 19
38
19
DNA
human
38
ttaaacgttg ccttcctgg 19
39
19
DNA
human
39
ttaaacgttg ccttcctgg 19
40
27
DNA
human
40
tttctgggca ggggacagag taagtgt 27
41
27
DNA
human
41
tttctgggta ggggacagag tatgtgt 27
42
19
DNA
human
42
gaattcccca gcgcttccc 19
43
19
DNA
human
43
gaattcccca gcgcttccc 19
44
295
DNA
human
44
gtaagtgccc ttccgggagc tcacacccgc tctctgtctc ccctgtcctt cctctgcttc 60
attttttcct ggactctgac cgatgtttgc gttagagtat gtttgaacgt ggggtcgatt 120
gggaaggatt aagccttggt gctgaggctg gatattgcag gaggatacag ggtgaatgga 180
gccggcgggg cggggcgggc cgggctgctg tgccgtggct gctgttgtgc tgacaccctc 240
tttcctagag aaacagcctc ttattcacaa ccagctgatt tgaaatttcc tgcag 295
45
22
DNA
human
45
ggcggggcgg ggcgggccgg gc 22
46
22
DNA
human
46
ggcggggcgg ggcgggccgg gc 22
47
22
DNA
human
47
ggcggggcgg ggcgggccgg gc 22
48
22
DNA
human
48
ggcggggcgg ggcgggccgg gc 22
49
21
DNA
human
49
gcggggcggg gcgggccggg c 21
50
21
DNA
human
50
gcggggcggg gcgggccggg c 21
51
21
DNA
human
51
gcggggcggg gcgggccggg c 21
52
21
DNA
human
52
gcggggcggg gcgggccggg c 21
53
658
DNA
human
53
gtatgtaccg tgctgggacc acttccccag gtgccttccc cacccagcca ggtctgtagt 60
tttgaaagtc ttgtatagct ttttccttgg tttaaaagca ataaatgccc actggagata 120
aattagaaaa tatggaagaa agctataaaa aagaaactaa aaaaatctct tgtaattcca 180
ccactcaaat ataacttttt ttcttaaaaa attttttttc tcttacttag agacaggcag 240
ggtctggctc tgtcccccag gctggagtgc agtggtgcca tcatagctca ctgcagcctc 300
aacctcttgg gctcaaggca ttctctcgcc tcagcctcct gagcagctgg gactgcaggc 360
atgagccatg gttcctgggc attttctctt gatattttga tgaagcagcc tctttgtccc 420
caggtcatag ctgcttaaga cactatgtac agagatctta gttgaatgag acaagtgact 480
tctggctgtg ccctgcagat aggccttggg tgcagccatg gtttgtagat tcccctggag 540
aaatccaagc aacacacatg tatttggtac tcactaagtg cctacagaac caaaccgaaa 600
ctgggccgca ctggggagga gatcaccgtg gagaccggag ggcgcactca cggagagt 658
54
60
DNA
human
54
cagggtctgg ctctgtcccc caggctggag tgcagtggtg ccatcatagc tcactgcagc 60
55
60
DNA
human
55
cagggtcttg ctctgttgcc caggctgggg tgcagtggcg caatcatggc tcactgcagc 60
56
60
DNA
human
56
ctcaacctct tgggctcaag gcattctctc gcctcagcct cctgagcagc tgggactgca 60
57
60
DNA
human
57
ctcaacctcc tgggctcaag ccatcctccc gcctcagcct cctgagcagc tgggactaca 60
58
60
DNA
human
58
gctctgtccc ccaggctgga gtgcagtggt gccatcatag ctcactgcag cctcaacctc 60
59
60
DNA
human
59
gctctgtcac ccaggctgga gtgtagtggt gcaatcagag ctcactgcag cctccaactc 60
60
47
DNA
human
60
ttgggctcaa ggcattctct cgcctcagcc tcctgagcag ctgggac 47
61
47
DNA
human
61
ctgggctcaa gcaatcctcc cacctcagcc tcctgagtag ctaggac 47
62
60
DNA
human
62
ctctgtcccc caggctggag tgcagtggtg ccatcatagc tcactgcagc ctcaacctct 60
63
60
DNA
human
63
ctctgtcacc caggctggag tgcagtggtg cgatcttggc tcactgcaac ctccgcctcc 60
64
60
DNA
human
64
tgggctcaag gcattctctc gcctcagcct cctgagcagc tgggactgca ggcatgagcc 60
65
60
DNA
human
65
tgggttcaag tgattctcct gcctcagcct cccgagtagc tgggactaca ggcgtgtgcc 60
66
60
DNA
human
66
gtggggacaa acagaaagac acaaggaaca attagaggct ctccatagca atgtcagaga 60
67
60
DNA
human
67
gtggggacaa acagaaagac acaaggaaca attagaggct ctccatagca atgtcagaga 60
68
60
DNA
human
68
tagggcagag cggatggtgg tgacaacgct ctgacaaacg ttactattga acgagagtca 60
69
60
DNA
human
69
tagggcagag cggatggtgg tgacaacgct ctgacaaacg ttactattga acgagagtca 60
70
60
DNA
human
70
cagggtctgg ctctgtcccc caggctggag tgcagtggtg ccatcatagc tcactgcagc 60
71
60
DNA
human
71
cagggtcttg ctctgtcacc caggctggag ttcagtggtg caatcatagc tcactgcagc 60
72
60
DNA
human
72
ctcaacctct tgggctcaag gcattctctc gcctcagcct cctgagcagc tgggactgca 60
73
60
DNA
human
73
ctcaaactcc tgggctcaag caatcctccc acctcagcct cctgagtagc tgggactgca 60
74
60
DNA
human
74
ctgtccccca ggctggagtg cagtggtgcc atcatagctc actgcagcct caacctcttg 60
75
60
DNA
human
75
ctgtcaccca ggctggagtg cagtggcgcc atcatggctc actgcagcct caacctcctg 60
76
59
DNA
human
76
ggctcaaggc attctctcgc ctcagcctcc tgagcagctg ggactgcagg catgagcca 59
77
59
DNA
human
77
ggctcaagcc atcctaccac ctcagcctcc tgagtagctg gaactacagg catgggcca 59
78
60
DNA
human
78
ggtctggctc tgtcccccag gctggagtgc agtggtgcca tcatagctca ctgcagcctc 60
79
60
DNA
human
79
ggtctcgctc tgtcactcag gctggagtgc agtggtgcca tcacagctca ctgcagcctc 60
80
44
DNA
human
80
aacctcttgg gctcaaggca ttctctcgcc tcagcctcct gagc 44
81
44
DNA
human
81
aaattcttgg gctcaagcca tcctctcacc tcagcctcct gagc 44
82
16
DNA
Saccharomyces cerevisiae
82
cttatttttt cattat 16
83
16
DNA
Saccharomyces cerevisiae
83
tttttcatta tgaaaa 16
84
16
DNA
Saccharomyces cerevisiae
84
aaaatatttg ttagta 16
85
16
DNA
Saccharomyces cerevisiae
85
ctgctgtaga ggttct 16
86
18
DNA
Saccharomyces cerevisiae
86
ctaataattt ggaaagga 18
87
16
DNA
Saccharomyces cerevisiae
87
ataacatttt taaaac 16
88
16
DNA
Saccharomyces cerevisiae
88
ggttctttcc cccttt 16
89
17
DNA
Saccharomyces cerevisiae
89
ctaataattt ggaaagg 17
90
16
DNA
Saccharomyces cerevisiae
90
aagtggtttt tctgga 16
91
16
DNA
Saccharomyces cerevisiae
91
tagataataa aagaaa 16
92
16
DNA
Saccharomyces cerevisiae
92
ctagataata aaagaa 16
93
16
DNA
Saccharomyces cerevisiae
93
gttaagtatt ttttta 16
94
16
DNA
Saccharomyces cerevisiae
94
cctttcaaaa cttata 16
95
16
DNA
Saccharomyces cerevisiae
95
atttgttagt atatgt 16
96
16
DNA
Saccharomyces cerevisiae
96
tctttctttc cttctt 16
97
16
DNA
Saccharomyces cerevisiae
97
tatgtttttt tctttt 16
98
16
DNA
Saccharomyces cerevisiae
98
tcttcataaa aaagca 16
99
17
DNA
Saccharomyces cerevisiae
99
ttctttttct ttctttc 17
100
16
DNA
Saccharomyces cerevisiae
100
gtatgttttt ttcttt 16
101
18
DNA
Saccharomyces cerevisiae
101
ctttttcttt ctttcctt 18
102
17
DNA
Saccharomyces cerevisiae
102
tttttttctt ttattct 17
103
16
DNA
Saccharomyces cerevisiae
103
ttttattcta ctttta 16
104
17
DNA
Saccharomyces cerevisiae
104
aatttaacga tgagatg 17
105
17
DNA
Saccharomyces cerevisiae
105
caaacacaga atcattt 17
106
17
DNA
Saccharomyces cerevisiae
106
cgatgagatg agctgtg 17
107
16
DNA
Saccharomyces cerevisiae
107
ttttttttgt ttttga 16
108
16
DNA
Saccharomyces cerevisiae
108
ttaatttttt ttgaat 16
109
17
DNA
Saccharomyces cerevisiae
109
taattttttt tgaattt 17
110
16
DNA
Saccharomyces cerevisiae
110
ttttttttga attttt 16
111
16
DNA
Saccharomyces cerevisiae
111
tttttttgaa tttttt 16
112
16
DNA
Saccharomyces cerevisiae
112
agttttaatt tttttt 16
113
16
DNA
Saccharomyces cerevisiae
113
tttttttttg tttttg 16
114
18
DNA
Saccharomyces cerevisiae
114
tttttttgtt tttgattt 18
115
16
DNA
Saccharomyces cerevisiae
115
ttgaattttt ttttgt 16
116
16
DNA
Saccharomyces cerevisiae
116
ttttaatttt ttttga 16
117
16
DNA
Saccharomyces cerevisiae
117
aataaattgt actcac 16
118
17
DNA
Saccharomyces cerevisiae
118
tttttgaatt ttttttt 17
119
16
DNA
Saccharomyces cerevisiae
119
aaaattcaaa aaaaat 16
120
16
DNA
Saccharomyces cerevisiae
120
aaaaaaattc aaaaaa 16
121
16
DNA
Saccharomyces cerevisiae
121
tttttttttg ttcatg 16
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The present invention relates generally to the field of bioinformatics and its applications to functional genomics and advanced genetic engineering. More particularly, the present invention contemplates a method for identifying effector molecules capable of modulating gene network integration and which facilitate genetic multi-tasking and the regulation of complex suites of programmed responses within, on and between eukaryotic cells. The present invention permits, therefore, the identification of a new generation of proteome and nucleome modulators useful in a range of therapeutic and trait-modifying protocols. The ability to manipulate genetic networks within a cell and within whole organisms also provides a sophisticated genetic engineering approach of introducing new traits and to influencing the genetic architecture and, hence, to enable cell and organismal programming or re-programming. The identification of effector molecules and their target or receiver sites, further enables the development of diagnostic protocols for a range of conditions or physiological or genetic states of an organism useful, for example, in modulating stem cell differentiation, quantitative traits, aging or the development of pathological conditions.
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BACKGROUND OF THE INVENTION
This invention relates to a pneumatic rotary tool, and more particularly to an air inlet valve construction for such a tool.
The invention has been developed as an improvement on the pneumatic rotary tool disclosed in U.S. Pat. No. 5,918,686 issued Jul. 6, 1999, entitled Pneumatic Rotary Tool, incorporated herein by reference, hereinafter referred to as the '686 patent.
In the tool disclosed in the '686 patent, the flow of air to the air motor thereof is under primary control of a trigger-operated air valve (indicated at 65 in the '686 patent), which is referred to in the patent as the primary air valve. Paraphrasing lines 37-45, column 7 of the patent, in using the tool the operator, using his index finger, squeezes the trigger to open the valve and the speed at which the tool operates depends on how far inward he pulls the trigger. While the tool has been generally satisfactory, inexperienced operators may encounter some difficulty in squeezing the trigger to attain and maintain a relatively low speed when that is needed for the work to be performed.
SUMMARY OF THE INVENTION
Accordingly, among the several objects of this invention may be noted the provision of a tool of the type shown in the '686 patent improved to the extent of making it easier for the user to attain and maintain a low speed of the air motor, whereby the user may readily attain and maintain a particular low-speed setting or a high speed setting, as needed for the job at hand; the provision in the tool of valve means including the primary air valve of the '686 patent invention for the dual stage speed purpose; the provision of a pistol-grip type of tool such as shown in the '686 patent wherein the pull on the trigger controls the speed setting; and the provision of valve means for the stated purpose of economical construction and capable of economic assembly.
In general, a pneumatic rotary hand tool of this invention comprises a housing having an air motor therein, the housing having an inlet passage for flow of air to the motor for driving it and valve means for controlling the flow of air through the inlet passage. The inlet passage has an upstream facing valve seat, the valve means comprising members in the passage upstream of the seat one of which has a stem extending downstream therefrom past the seat. A spring biases said members in downstream direction to a closed position with respect to the seat. The stem extends generally axially in said passage in said closed position of said members. A deflector for the stem is operable by one holding the tool for deflecting the stem angularly from said generally axial position to a first angularly deflected position wherein said valve members establish flow of air to the motor at a relatively low rate for low-speed operation thereof and further to a second farther angularly deflected position wherein said valve members establish flow of air to the motor at a relatively high rate for high-speed operation thereof.
Other objects and features will be in part apparent and in part pointed out hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a generally schematic vertical section of a pneumatic rotary hand tool similar to FIG. 2 of the '686 patent but showing valve means in accordance with this invention instead of the valve indicated at 65 in the '686 patent, the valve means being shown in off position wherein it completely blocks the flow of air;
FIG. 2 is an enlarged fragment of FIG. 1;
FIG. 3 is a view similar to FIG. 2 illustrating the valve means in a low-flow position;
FIG. 4 is a view similar to FIGS. 2 and 3 illustrating the valve means in a high-flow position;
FIG. 5 is an enlarged view with parts shown in section of an assembly per se of components of the valve means; and
FIG. 6 is a view generally in section on line 6 — 6 of FIG. 5 .
Corresponding reference characters indicate corresponding parts throughout several views of the drawings.
DETAILED DESCRIPTION
Referring to the drawings, first more particularly to FIG. 1, a pneumatic rotary hand tool having novel primary valve means of this invention is shown as comprising a pistol-like housing generally designated 1 having a pistol grip or handle 3 and a chamber 5 above the grip 3 in which reposes an air motor 7 for driving a shaft 9 for a tool (not shown) extending out of the chamber 5 . In the grip 3 is an air inlet passage designated 11 in its entirety for flow of air under pressure supplied thereto via a flexible hose (not shown) connected to a swivelling fitting 13 at the entrance end of the passage. At 15 is indicated a combination selector valve for selection of operation of the air motor 7 in forward or reverse direction and selection of the torque generated by the air motor. In the grip 3 alongside the inlet passage 11 is an air exhaust passage 17 . All this is essentially disclosed in the '686 patent, to which reference may be had for details (not critical so far as the present invention is concerned). It is to be understood that the selector valve 15 and swivelling fitting 13 may be eliminated without departing from the scope of the present invention. The present invention involves the provision in the inlet passage 11 of the valve means designated in its entirety by the reference numeral 19 , replacing the primary air valve designated by the reference numeral 65 in the '686 patent, said valve means 19 being trigger-operable as will be subsequently described.
The inlet passage 11 is formed by a lower counterbore 21 extending up from the lower end of the grip 3 more than half way up the grip to a second counterbore 23 of slightly smaller diameter than the lower counterbore, and a bore 25 extending up from the second counterbore having a relatively thin-walled tubular insert 27 secured in the bore 25 as by being press-fitted therein extending up from the upper end of the second counterbore. The upper end of the second counterbore and the lower end of the tubular insert define a upstream-facing (downward facing) shoulder 29 . A ring 31 is secured in the second counterbore 23 up against the shoulder 29 , as by being press-fitted in the second counterbore, said ring having an annular boss 33 projecting downwardly therefrom surrounding the central opening 35 in the ring (and the boss) constituting a relatively narrow annular valve seat. As shown, the opening 35 is very slightly less than the internal diameter of the tubular insert 27 .
The valve means 19 comprises in association with the valve seat 33 two valve members generally designated 37 and 39 , respectively in the inlet passage upstream of the seat 33 , one of which, namely the member 39 , has a stem generally designated 41 extending downstream therefrom through a central opening 43 in the other member, namely member 37 , through the central opening 35 in the bossed ring 31 , and up into the space 45 in the inlet passage 11 downstream of the ring 31 (the space in insert 27 ). A spring 47 biases the members 39 and 37 in downstream direction (in the direction toward the seat 33 ) to the closed position in which they are illustrated in FIGS. 1 and 2 wherein the stem 41 extends generally axially in downstream direction in the inlet passage 11 . At 49 is indicated a trigger-operated rod which constitutes a deflector for the stem 41 operable by one holding the tool for deflecting the stem angularly from its aforesaid generally axial position to a first angularly deflected (tilted) position such as that in which it is shown in FIG. 3 wherein the valve members 37 and 39 establish flow of air to the motor 7 at a relatively low rate for low-speed operation of the motor, and deflecting the stem farther to a second angularly deflected (tilted) position, such as that in which it is shown in FIG. 4, wherein the valve members establish flow of air to the motor at a relatively high rate for high-speed operation of the motor.
The valve member 39 , the one having the stem 41 extending downstream therefrom, comprises a disk 51 , preferably of sheet metal, having a downstream face designated 53 and an upstream face designated 55 (see FIG. 5 ). The stem 41 extends downstream from the downstream face 53 generally from the center thereof. Referring more particularly to FIG. 5, the stem 41 has a relatively short upstream portion 57 of circular cross-section immediately adjacent the disk 51 , a somewhat longer portion 59 of circular cross section and of larger diameter than portion 57 immediately downstream of (above) portion 57 forming an annular groove 61 around portion 57 between the lower end of portion 59 and the disk 51 . At the downstream (upper) end of portion 59 the stem 41 has an annular groove 63 . Downstream of the groove 63 , the stem has a tapered portion 65 widening in downstream direction from an upper relatively long portion 67 of circular cross-section of relatively small diameter. The diameter of the disk 51 is slightly less than the diameter of the counterbore 23 , the disk, in its closed position fitting somewhat loosely therein generally in a plane at right angles thereto. Referring more particularly to FIG. 6, the disk is shown as having a plurality (e.g. four) arcuate slots 69 extending on a circle adjacent its periphery constituting ports for flow of air as will be subsequently described.
The second of the two valve members, namely the member 37 , comprises a generally annular or ring-shaped member positioned between the downstream face 53 of the disk 51 and the valve seat 33 . This annular member 37 has the generally central opening 43 . The stem 41 extends downstream from disk 51 through this opening surrounding portion 59 of the stem, the opening 43 being of larger diameter than portion 59 to provide an annular passage 73 for flow of air upward around portion 59 as will be subsequently described. An O-ring 75 in groove 61 in the stem seals the upstream (lower) end of said passage 73 in the closed position of the valve members 37 and 39 in which they are shown in FIGS. 1 and 2 with the lower face 77 of member 37 in flatwise engagement with the upper face 53 of disk 51 and maintains the annular member 37 generally centered (i.e. coaxial) with respect to portion 59 of the stem. Annular member 37 is shown (FIG. 6) as having a main ring-shaped portion 79 of circular outline, the diameter of which is somewhat greater than that of valve seat 33 , with a plurality of radially outwardly extending projections 81 , e.g. four such projections at 90° intervals.
The spring 47 presses upwards on the disk 51 and thereby biases the disk downstream toward member 37 and, via the disk, biases member 37 toward the closed position of FIGS. 1 and 2 against the valve seat 33 . In detail, the upper face 53 of the disk engages the lower face 77 of member 37 and the upper face 82 of member 37 engages the seat. The stem 41 has a part 83 thereon spaced downstream of member 37 when the stem is in the generally axial position of FIGS. 1 and 2 (and FIG. 5 ), this part, which is constituted by a flat (e.g. sheet metal) ring or collar on the stem at the lower end of the taper having inwardly directed teeth 85 snapped into the groove 63 in the stem, having a function to be described.
The trigger-operated rod 49 extends from the trigger 87 of the tool across the exhaust passage 17 in openings indicated at 89 and 91 into the space 45 where its inner end is engageable with the stem 41 adjacent the upper end of the stem (the upper end of portion 67 of the stem). The trigger 87 is slidable in a cavity 93 in the forward side of the grip 3 adjacent the upper end of the grip. The forward end of the rod 49 is secured in the trigger as indicated at 95 . Forward (outward) movement of the trigger is limited by a stop 97 . Rod 49 is slidably guided in the openings 89 and 91 . Without pull on the trigger, as illustrated in FIGS. 1 and 2, the valve means 19 under the bias of spring 47 is held in the closed position wherein member 37 engages the seat 33 and the stem 41 is in a generally axial position extending generally centrally (axially) within the inlet passage 11 . The rod 49 is generally in position retracted from the stem 41 , having been pushed out to this position by the stem under the spring bias; thus the trigger 87 is in forward position determined by its engagement with the stop 97 . By pulling (squeezing) the trigger 87 to push the rod 47 inward a limited distance within a limited range, readily sensed by the user pulling the trigger, the rod (acting as a deflector for the stem 41 ) deflects the stem angularly (i.e. tilts the stem) from its generally axial position of FIGS. 1 and 2 to a first angularly deflected (tilted) position such as shown in FIG. 3 without moving member 37 away from the valve seat 33 . While part 83 (the flat collar) on the stem angles down toward the member 37 , it stops short of moving member 37 . However, on tilting of the stem 41 to said first angularly deflected position (which may be in the range from somewhat past the FIG. 2 position to the FIG. 3 position in which the collar 83 is contiguous to member 37 ), the disk 51 is angled down away from member 37 , opening up a relatively restricted path for flow of air at a relatively low rate through the ports 69 in the disk 51 to the space opened up between the downstream face 53 of disk 51 and the upstream face 77 of member 37 , thence through the annular space 73 and up around the flat collar 83 , the central opening 35 in ring 31 to the upper space 45 in the inlet passage 11 . The O-ring 75 moves down with disk 51 to open up space 73 .
By pulling (squeezing) the trigger 87 to push rod 49 farther inward than above described, the stem 41 is still farther angularly deflected (tilted) as shown in FIG. 4 resulting in part 83 (the flat collar) on the stem engaging and moving valve member 37 away from the valve seat 33 thereby establishing relatively high-rate flow of air through the inlet passage 11 to the motor 7 . The high-rate flow is generally via the ports 89 in disk 51 (and to some extent around the disk 51 ), thence through the spaces at the periphery of member 37 between projections 81 , around collar 83 and through the opening 35 in ring 31 .
In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.
As various changes could be made in the above constructions without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
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A pneumatic rotary tool including a housing and an output shaft projecting from the housing for transmitting torque to an object. An air motor drives rotation of the output shaft in the forward and reverse directions. Air passages extend from an air inlet to the motor for delivering pressurized air to the motor. A spring biases the lower portion of a valve within the air passage in a closed position, to restrict the flow of air through the air passage. The upper portion of the valve comprises a stem. When an operator squeezes a trigger on the pneumatic rotary tool, a deflector connected to the trigger deflects the stem to a first angularly deflected position, the valve thereby allows a relatively low rate of air flow to the motor for low-speed operation thereof. As the operator continues to squeeze the trigger, the stem is deflected to a second angularly deflected position, allowing a relatively high rate of air flow to the motor for high-speed operation thereof.
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This Non-provisional application claims priority under 35 U.S.C. §119(a) on Patent Application No(s). 10-2003-0020073 filed in Korea on Mar. 31, 2003, the entire contents of which are hereby incorporated by reference.
BACKGROUND OF THE INVENTION
1. Field of Invention
The present invention relates to a refrigerator, and more particularly, to a dispenser for a refrigerator, which can allow water to be dispensed outside without opening a door of the refrigerator.
2. Description of the Prior Art
Refrigerators recently sold on the market have dispensers that allow water to be dispensed from the interiors of the refrigerators to the outside without opening doors of the refrigerators. Since the dispensers can allow water to be dispensed without opening the doors of the refrigerators, they can prevent cold air within the refrigerators from leaking out and also provide users with convenience of use of the refrigerators. The dispensers are typically installed at the doors of the refrigerators. Generally, a portion of an outer surface of a door of each refrigerator is recessed inward, and a dispenser is then installed within the recessed portion.
FIG. 1 shows a front face of a refrigerator with a dispenser. In the refrigerator, a storage space is formed within a main body 10 of the refrigerator. The storage space roughly comprises a refrigerating chamber and a freezing chamber. The refrigerating and freezing chambers are opened and closed by a refrigerating chamber door 12 and a freezing chamber door 14 , respectively. Reference numerals 16 and 16 ′ designate handles for the doors of the refrigerator.
A dispenser 18 is provided on a front surface of the door 12 . The dispenser 18 is supplied with water from the main body 10 through a water supply tube 20 installed within the door 12 . The water supply tube 20 is installed through a hinge portion on which the door 12 pivots to be opened and closed.
The dispenser 18 is provided with a water-dispensing button 24 operated by a user, and a dispensing port 26 at a position adjacent to the water-dispensing button 24 . Water delivered from a water reservoir (not shown) installed within the main body 10 through the water supply tube 20 is discharged from the dispensing port 26 . That is, when the user pushes the water-dispensing button 24 upward, the water delivered from the water reservoir (not shown) installed within the main body 10 is discharged from the dispensing port 26 .
The dispensing port 26 is typically provided on a ceiling of a recessed portion in the door 12 where the dispenser 18 is installed. The water-dispensing button 24 is formed to protrude behind and downward beyond the dispensing port 26 . Reference numeral 28 designates a water-collecting portion for collecting remaining water.
Meanwhile, FIG. 2 shows the configuration of a major portion of the dispenser 18 . That is, the water-dispensing button 24 is mounted slidably upward and downward in the dispenser 18 , an actuating switch 30 is placed at a relatively upper position over the water-dispensing button 24 , and the dispensing port 26 is installed at an upper position above and in front of the water-dispensing button 24 and at a leading end of the water supply tube 20 so as to discharge water downward.
Therefore, when the water-dispensing button 24 is pushed upward, a resilient rib 32 of the actuating switch 30 interlocked with the water-dispensing button 24 is also pushed upward so that the actuating switch 30 can be turned on. The dispensing port 26 is opened upon reception of a signal from the actuating switch 30 and allows water to be dispensed outside.
However, such a conventional refrigerator described above has the following problems.
Since the water-dispensing button 24 is generally operated by a cup, the dispensing port 26 is inevitably installed in the vicinity of the water-dispensing button 24 to securely deliver water to the cup. Further, the resilient rib 32 of the actuating switch 30 is connected directly to the water-dispensing button 24 in the prior art. Thus, the actuating switch 30 , the water-dispensing button 24 and the dispensing port 26 are inevitably installed to be closer to one another.
In view of such a constitution, water may be easily transferred to the actuating switch 30 if the direction of the water discharged from the dispensing port 26 deviates slightly or water leaks out at a connection of the dispensing port 26 to the water supply tube 20 . Moreover, since the resilient rib 32 is connected directly to the water supply button 24 , water splashed on the water-dispensing button 24 may be transferred to the actuating switch 30 via the resilient rib 32 .
Consequently, since water may be easily transferred to the actuating switch 30 in the prior art, a short circuit may occur in the actuating switch, resulting in damage to the actuating switch 30 in critical circumstances.
SUMMARY OF THE INVENTION
Accordingly, the present invention is conceived to solve the problems in the prior art. An object of the present invention is to protect an actuating switch for providing signals for opening and closing a dispensing port of a dispenser for a refrigerator against water.
According to an aspect of the present invention for achieving the object, there is provided a dispenser for a refrigerator, comprising a housing that is mounted on a front surface of a door to define an external appearance and has a recessed portion formed to be depressed rearward; a dispensing port for discharging water delivered from a main body of the refrigerator to the recessed portion of the housing; a water-dispensing button unit having a water-dispensing button pressed by means of force exerted by a user to receive a signal necessary for the discharge of the water from the dispensing port; an actuating switch operated by the water-dispensing button unit to generate a signal for opening and closing the dispensing port; and a driving lever for connecting the actuating switch and the water-dispensing button to drive the actuating switch by means of the operation of the water-dispensing button.
A penetration portion may be formed at an upper end of the recessed portion of the housing so that the water discharged from the dispensing port can be delivered to the recessed portion.
The water-dispensing button unit may comprise a support frame for guiding the movement of the water-dispensing button; and a resilient member disposed between the support frame and the water-dispensing button to provide force to the water-dispensing button in one direction.
The water-dispensing button unit may be provided, at mutually corresponding positions of the water-dispensing button and the support frame, with catching ribs and guide ribs for guiding the movement of the water-dispensing button and regulating the moved position of the water-dispensing button, respectively.
An ON/OFF driving protrusion of the actuating switch may be operated by an elastically deformable resilient rib provided at a side of the actuating switch, and the resilient rib may be operated by one end of the driving lever.
The driving lever may pivots on a hinge portion such that both ends thereof move in the same manner as a seesaw, and one end of the driving lever may be connected to and interlocked with the water-dispensing button through a connection protrusion and the other end thereof may be in contact and interlocked with the actuating switch.
The other end of the driving lever that is in contact with the actuating switch may be placed at a position relatively higher than the end of the driving lever that is connected to the water-dispensing button with respect to the hinge portion.
The both ends of the driving lever may define a predetermined angle around the hinge portion, and the other end of the driving lever that is in contact with the actuating switch may be placed at a position relatively higher than the end of the driving lever that is connected to the water-dispensing button.
The dispenser may further comprise a partition between the actuating switch and the dispensing port.
The dispensing port, the actuating switch and the driving lever may be placed in a seating recess formed to be depressed on the front surface of the door, and the water-dispensing button unit may be provided at an upper end of the recessed portion of the housing.
According to another aspect of the present invention, there is provided a dispenser for a refrigerator, comprising a housing that is mounted on a front surface of a door to define an external appearance and has a recessed portion formed to be depressed rearward; a dispensing port for discharging water delivered from a main body of the refrigerator through a penetration portion formed at an upper end of the recessed portion of the housing; a water-dispensing button unit having a water-dispensing button pressed by means of force exerted by a user to receive a signal necessary for the discharge of the water from the dispensing port; an actuating switch operated by the water-dispensing button unit and turned on and off in such a manner that a resilient rib provided at a side of the actuating switch presses a driving protrusion thereof by means of elastic deformation of the resilient rib so as to generate a signal for opening and closing the dispensing port; a driving lever for connecting the actuating switch and the water-dispensing button to drive the actuating switch by means of the operation of the water-dispensing button; and a partition disposed between the actuating switch and the dispensing port to prevent the water discharged from the dispensing port from being transferred to the actuating switch.
The water-dispensing button unit may comprise a support frame for guiding the movement of the water-dispensing button; and a resilient member disposed between the support frame and the water-dispensing button to provide force to the water-dispensing button in one direction.
The driving lever may pivot on a hinge portion such that both ends thereof move in the same manner as a seesaw, and one end of the driving lever may be connected to and interlocked with the water-dispensing button through a connection protrusion and the other end thereof may be in contact and interlocked with the actuating switch.
The other end of the driving lever that is in contact with the actuating switch may be placed at a position relatively higher than the end of the driving lever that is connected to the water-dispensing button with respect to the hinge portion.
The both ends of the driving lever may define a predetermined angle around the hinge portion, and the other end of the driving lever that is in contact with the actuating switch may be placed at a position relatively higher than the end of the driving lever that is connected to the water-dispensing button.
According to the present invention, there is an advantage in that it is possible to prevent a short circuit occurring in the actuating switch due to water dispensed by the dispenser.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other objects and features of the present invention will become apparent from the following description of a preferred embodiment given in conjunction with the accompanying drawings, in which:
FIG. 1 is a front view showing a front face of a conventional refrigerator;
FIG. 2 is a schematic view showing the configuration of a major portion of a conventional dispenser for a refrigerator;
FIG. 3 is a sectional view showing the inner configuration of a refrigerator employing a preferred embodiment of a dispenser for a refrigerator according to the present invention;
FIG. 4 is a front view showing the configuration of a front face of the refrigerator employing the embodiment of the present invention;
FIG. 5 is a perspective view showing the configuration of a major portion of the embodiment of the present invention; and
FIG. 6 is a perspective view schematically showing the configuration of a major portion of the embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Hereinafter, a preferred embodiment of a dispenser for a refrigerator according to the present invention will be described in detail with reference to the accompanying drawings.
FIG. 3 is a sectional view showing the inner configuration of a refrigerator employing a dispenser for a refrigerator according to an embodiment of the present invention, and FIG. 4 is a front view showing the configuration of a front face of the refrigerator employing the dispenser according to the embodiment of the present invention.
As shown in the figures, the interior of a main body 50 of the refrigerator is partitioned into a refrigerating chamber 52 and a freezing chamber 54 in an up and down direction. The refrigerating chamber 52 is disposed at a relatively upper portion of the main body 50 , and the freezing chamber 54 is disposed at a relatively lower portion thereof.
The main body 50 is provided with a refrigerating chamber door 56 and a freezing chamber door 58 to selectively open and close the refrigerating and freezing chambers 52 and 54 , respectively. In the embodiment, the door 56 is pivotably supported by the main body 50 through hinges 57 provided at right upper and lower ends in FIG. 3 .
The refrigerating and freezing chamber doors 56 and 58 are provided with door handles 56 ′ and 58 ′, respectively. The door handles 56 ′ and 58 ′ are portions that a user grasps with his/her hand to exert force thereon, thereby opening and closing the doors 56 and 58 .
A filter 60 is installed within the refrigerating chamber 52 . The filter 60 serves to purify water. The filter 60 is supplied with the water through a supply tube 62 connected to an external water supply source 61 .
A valve 64 is provided at a side of the main body 50 . The valve 64 serves to distribute the water, which has passed through the filter 60 , among a water reservoir 66 , an ice maker 68 and the like. The water reservoir 66 and the ice maker 68 are provided in the refrigerating and freezing chambers 52 and 54 , respectively. The water reservoir 66 stores the water purified by the filter 60 , and the ice maker 68 makes ice from the water purified by the filter 60 .
The main body 50 is provided with main body-side tubing 70 for delivering the water stored in the water reservoir 66 to the refrigerating chamber door 56 . A leading end of the main body-side tubing 70 is exposed beyond an upper end of the main body 50 and extends through the upper hinge 57 to communicate with door-side tubing 72 installed within the door 56 .
The door-side tubing 72 is installed through an insulation layer 78 formed between an outer case 74 for defining an external appearance of at least a front surface of the refrigerating chamber door 56 and an inner case 76 for defining an external appearance of a back surface of the refrigerating chamber door.
Meanwhile, a dispenser 80 is provided in the front surface of the door 56 . The dispenser 80 is a portion for dispensing the water delivered from the water reservoir 66 to the outside of the door 56 . An external appearance of the dispenser 80 is defined by a housing 81 . The housing 81 is mounted on the outer case 74 for constituting the front surface of the door 56 .
The housing 81 has a recessed portion 81 ′ formed in such a manner that a front surface of the housing is depressed rearward. A corresponding recessed portion should also be formed in a front surface of the outer case 74 at a position corresponding to the recessed portion 81 ′. A penetration portion 82 is formed at an upper end of the recessed portion 81 ′. The penetration portion 82 is a portion through which water that will be discharged through a dispensing port 84 or the like to be described later is delivered to the recessed portion 81 ′. A drain water collector 83 is provided at a lower end of the recessed portion 81 ′.
The dispensing port 84 is provided at a leading end of the door-side tubing 72 . The dispensing port 84 allows the water delivered from the water reservoir 66 to be discharged through the penetration portion 82 to a cup placed in the recessed portion 81 ′. Both side ends of the dispensing port 84 are provided with fixing portions 84 ′.
A seating recess 85 is formed to be depressed on the outer case 74 at a position corresponding to the penetration portion 82 of the housing 81 and a back surface of a portion of the housing above the penetration portion. The seating recess 85 may be formed on the outer case 74 itself, or on a surface of the insulation layer 78 by partially cutting away a corresponding portion of the outer case 74 . The seating recess 85 cannot be easily viewed from the outside since it is concealed by the housing 81 .
Fastening bosses 86 for fixing the dispensing port 84 are formed at respective positions within and adjacent to the seating recess 85 . One of the fastening bosses 86 is formed to protrude by a predetermined height within the seating recess 85 , and the other of the fastening bosses is formed to be slightly depressed at a position adjacent to the seating recess 85 . Fastening holes are formed in the fastening bosses 86 , respectively.
A partition 90 is formed over a predetermined range within the seating recess 85 . The partition 90 divides the interior of the seating recess into a portion where the door-side tubing 72 and the dispensing port 84 are placed and a portion where an actuating switch 92 is installed. More specifically, the partition 92 serves to prevent the water discharged from the dispensing port 84 or the like from being transferred to the actuating switch 92 .
The actuating switch 92 is operated by a water-dispensing button 112 to be described later and serves to allow water to be discharged through the dispensing port 84 . For example, the actuating switch 92 operates a valve disposed between the dispensing port 84 and the water reservoir 66 so that water can be discharged from the water reservoir 66 through the dispensing port 84 .
The actuating switch 92 is formed with an elongated, protruding resilient rib 94 and a driving protrusion 96 that comes into contact with the resilient rib 94 . The driving protrusion 96 is pressed by the resilient rib 94 and then senses an operating signal. Reference numeral 98 designates a connection terminal. The operating switch 92 is installed in a region of the seating recess 85 isolated from the dispensing port 84 by means of the partition 90 .
A driving lever 100 is installed in the seating recess 85 . The driving lever 100 is constructed to pivot on a hinge portion 102 so that both ends of the driving lever can move in the same manner as a seesaw. Further, the driving lever 100 is constructed such that the both ends thereof define a predetermined angle around the hinge portion 102 rather than a straight line. The angle defined by the both ends of the driving lever 100 can be variously determined according to the positions of the actuating switch 92 and the water-dispensing button 112 to be described later. With such a constitution, one of the ends of the driving lever 100 on the side of the actuating switch 92 is placed at a position relatively higher than the other end of the driving lever on the side of the water-dispensing button 112 . This is to prevent water from moving toward the actuating switch 92 due to the weight of the water.
The hinge portion 102 can be constructed, for example, by forming a hinge pin (not shown) on the driving lever 100 and a hinge hole (not shown) into which the hinge pin is inserted at a corresponding portion of the seating recess 85 , or vice versa.
The other end of the driving lever 100 , i.e. the end thereof on the side of the water-dispensing button 112 to be described later, is formed with a connection protrusion 104 . The connection protrusion 104 is formed to extend toward the back surface of the housing 81 in a state where the driving lever 100 is installed within the seating recess 85 . The end of the driving lever 100 opposite to the other end thereof with the connection protrusion 104 is in contact with the resilient rib 94 .
The other end of the driving lever 100 with the connection protrusion 104 and the opposite end thereof extend in a direction generally perpendicular to the direction of gravity. This is to prevent water, which has been discharged from the dispensing port 84 and is falling due to gravity, from being transferred to the actuating switch 92 through the resilient rib 94 or the like.
Next, a water-dispensing button unit 110 is installed at the upper end of the recessed portion 81 ′ of the housing 81 , i.e. at a position adjacent to the penetration portion 82 . The water-dispensing button unit 110 operates the driving lever 100 to turn on the actuating switch 92 .
The water-dispensing button unit 110 is provided with the water-dispensing button 112 . The water-dispensing button 112 protrudes downward by a predetermined length from an upper portion of the recessed portion 81 ′ and is installed to move in an up and down direction. The water-dispensing button 112 is pushed upward by a cup grasped by a user to operate the driving lever 100 .
Catching ribs 113 are formed to protrude in opposite directions at both side ends of the water-dispensing button 112 . A back surface of the water-dispensing button 112 is provided with a structure that can be firmly connected to the connection protrusion 104 of the driving lever 100 . For example, the back surface of the water-dispensing button is provided with an insertion hole into which the connection protrusion 104 can be inserted.
The water-dispensing button 112 is placed on a support frame 114 formed at the upper end of the recessed portion 81 ′. The support frame 114 is constructed to partially surround the water-dispensing button 112 . The support frame 114 is formed with a support protrusion 116 protruding in the vertical moving direction of the water-dispensing button 112 . One end of a return spring 118 is supported by the support protrusion 116 . The other end of the return spring 118 is supported by an upper end of the water-dispensing button 112 so that the water-dispensing button 112 can be moved to the original position when force pressing the water-dispensing button 112 is eliminated.
The support frame 114 has guide ribs 120 at both ends thereof. The catching ribs 113 are movably placed between the guide ribs 120 and an upper end of the support frame 114 so that the up and down movement of the water-dispensing button 112 can be guided. Of course, the catching ribs 113 are caught by the guide ribs 120 such that the guide ribs serve to prevent the catching ribs from being further moved downward.
Next, the operation of the dispenser for the refrigerator according to the present invention constructed as above will be described in detail.
Water supplied from the external water supply source 61 is purified through the filter 60 and then delivered to the ice maker 68 and the water reservoir 66 . The water stored in the water reservoir 66 is discharged from the dispensing port 84 through the main body-side tubing 70 and the door-side tubing 72 as the dispenser 80 is operated.
The discharge from the dispensing port 84 due to the operation of the dispenser 80 will be described below. When a user pushes the water-dispensing button 112 with a cup, the water-dispensing button 112 moves upward while overcoming elastic force of the return spring 118 within the support frame 114 .
When the water-dispensing button 112 is moved, the driving lever 100 connected to the water-dispensing button 112 through the connection protrusion 104 is pivoted. The driving lever 100 is pivoted counterclockwise on the hinge portion 102 due to the upward movement of the water-dispensing button 112 . The end of the driving lever 100 presses the driving protrusion 96 of the actuating switch 92 by means of the pivoting of the driving lever 100 . When the driving protrusion 96 is pressed, the actuating switch 92 senses that the water-dispensing button 112 has been operated.
A sensing signal generated from the actuating switch 92 drives a valve for allowing water to be discharged from the dispensing port 84 . Therefore, the water stored in the water reservoir 66 is discharged from the dispensing port 84 and then dispensed into the cup of the user.
Meanwhile, when a desired amount of water is filled into the cup of the user, the user separates the cup from the water-dispensing button 112 . Thus, the water-dispensing button 112 is moved to the original position due to the restoring force of the return spring 118 . That is, the catching ribs 113 are moved downward along between the upper end of the support frame 114 and the guide ribs 120 and then caught by the guide ribs 120 . In such a state, the water-dispensing button 112 cannot be further moved downward.
As the water-dispensing button 112 is moved downward, the driving lever 100 connected to the water-dispensing button 112 through the connection protrusion 104 is pivoted clockwise on the hinge portion 102 . With the clockwise pivoting of the driving lever 100 , the driving lever 100 does not press the resilient rib 94 any longer. Therefore, the resilient rib 94 is restored to an original state and the driving protrusion 96 is also returned to the original state, thereby turning off the actuating switch 92 . In such a state, water is not discharged from the dispensing port 84 any longer.
Meanwhile, water is hardly transferred to the actuating switch 92 while the water is discharged from the dispensing port 84 in the dispenser 80 as described above. This is because the partition 90 is disposed between the dispensing port 84 and the actuating switch 92 .
Further, since the actuating switch 92 is connected to the water-dispensing button 112 through the driving lever 100 , the actuating switch 92 is spaced relatively further apart from the dispensing port 84 and the water-dispensing button 112 . Thus, a portion of the water discharged from the dispensing port 84 is not transferred to the actuating switch 92 .
The scope of the present invention is not limited to the embodiment described above and those skilled in the art can make various modifications and changes thereto within the scope of the invention.
For example, parts provided within the seating recess 85 may be provided on the back surface of the housing 81 and only the water-dispensing button 112 may be exposed to the front of the recessed portion 81 ′ of the housing 81 .
According to the dispenser for the refrigerator of the present invention specifically described above, it is expected to obtain the following advantages.
Since the actuating switch is operated through the driving lever by the water-dispensing button in the present invention, the distance between the dispensing port from which water is discharged and the actuating switch is relatively increased. Thus, it is possible to prevent water from being transferred to the actuating switch while water discharged from the dispensing port falls due to gravity.
Since the partition is disposed between the actuating switch and the dispensing port, a portion of water is not transferred toward the actuating switch even though the portion of water is splashed aside. Thus, malfunction of the actuating switch due to a short circuit can be avoided.
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The present invention relates to a dispenser for a refrigerator. The dispenser includes a housing that is mounted on a front surface of a door to define an external appearance and has a recessed portion formed to be depressed rearward; a dispensing port for discharging water delivered from a main body of the refrigerator to the recessed portion of the housing, a water-dispensing button unit having a water-dispensing button pressed by force exerted by a user to receive a signal necessary for the discharge of the water from the dispensing port; an actuating switch operated by the water-dispensing button unit to generate a signal for opening and closing the dispensing port; and a driving lever for connecting the actuating switch and the water-dispensing button to drive the actuating switch by the operation of the water-dispensing button According to the present invention, the water discharged from the dispensing port is effectively avoided from being transferred to the actuating switch, thereby preventing the occurrence of a short circuit in the actuating switch.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional application of U.S. NonProvisional patent application Ser. No. 11/541,161 filed on Sep. 29, 2006. This application claims the benefits of and priority to U.S. Provisional Patent Application Ser. No. 60/722,073 entitled “MODIFIED ACME SCREW/NUT SET” which was filed on Sep. 29, 2005, the entire contents of which are hereby incorporated by reference herein.
BACKGROUND
[0002] 1. Field of the Disclosure
[0003] The present disclosure relates to an Acme screw/nut set, and more particularly to an Acme screw/nut set having a modified thread design.
[0004] 2. Background of the Art
[0005] Drive mechanisms for different applications utilizing a lead screw as a driver usually use a standard Acme screw class G or C. A standard centralizing Acme screw/nut set class C has defined tolerances per ANSI B1.8 specification. Those tolerances provide very low clearances between the thread of the nut and the thread of the screw. For example: a 1½-5 ACME thread class 2C has the following clearances:
[0006] for a major diameter a radial clearance is R min =0.0012″ to 0.0098″ and
[0007] for a pitch diameter an axial clearance is A min =0.0025″ to 0.14″.
[0008] The clearances are extremely low for the lower tolerance range. Therefore, a problem arises when using dissimilar materials with significantly different thermal expansion coefficients (e.g. steel and nylon). That is, the clearances will close quickly when the temperature of the joint increases due to the heat generated by friction between the components in the drive mechanism. The problem is especially prevalent in a design where the nut is confined in a rigid housing, thereby restricting radial expansion and allowing expansion of the nut material mainly in the inward direction. The lack of clearance between the screw and the nut may initially result in a grinding noise and finally in seizing the motion of the joint.
[0009] The following example is illustrative:
[0010] Assume the following materials and dimensions:
Acme screw D=1½″ major diameter and P=0.200″ made of carbon steel Acme Nut (modified) of same basic thread with O.D.=1.125″ and 2.5″ long made of nylon 6 with a thread engagement L=2.312″ Nut housing made of aluminum with bore B=2.125″ dia. Carbon steel has a coefficient of thermal expansion
CTE s 8.1*10 E-6 in./in. ° F.
Nylon 6 has a coefficient of thermal expansion
CTE n 0.45*10 E-4 in./in. ° F.
Aluminum housing has a coefficient of thermal expansion
CTE h 13.1*10 E-6 in./in. ° F.
[0020] For the screw/nut pair in this example, it would take a temperature increase (ΔT) of 17° F. from the ambient temperature to close the gap of 0.0012″.
[0021] The relevant calculations for determining the effect of a temperature rise on the gap are as follows:
[0022] The nut material would expand radially inward (Rn) (assuming zero outward expansion allowed by the housing)
[0000] Rn=ΔT *CTE n *D= 17*0.45*10* E -4*1.5=0.0011475″
[0023] The screw material would expand radially outward (Rs)
[0000] Rs=ΔT *CTE s *D= 17*8.1*10 *E -6*1.5=0.00020655″
[0024] The housing material would expand radially outward (Rh) (allowing the nut to expand outward the same amount). However, the expansion of the housing material is to a lesser degree than the expansion of the screw and the nut, due at least in part to the fact that the temperature of the housing material rises only approximately 30% of the temperature rise of the two other components (based on taken measurements).
[0000] Rh= 0.3 *ΔT *CTE h (aluminum)* B= 0.3*17*13.1*10* E -6*2.125=0.00014187″
[0025] The total expansion (R) of the joint in a radial direction may be calculated as follows:
[0000] R=Rn+Rs−Rh= 0.0011475+0.00020655=0.00014197=0.001212″
[0000] The temperature of the Acme screw/nut surface may be subjected to temperatures up to 200° F. based on the material specification of nylon 6, for example, for a high load condition. Accordingly, undue friction and potential binding of machine parts may occur. The screw/nut design of the present disclosure may ameliorate such occurrences.
SUMMARY
[0026] The present disclosure relates to a nut and screw set which reduce the amount of hindered motion therebetween caused by thermal expansion of the screw and the nut. The nut and screw set includes a screw (e.g., made of steel) and a nut (e.g., made of plastic). The screw (e.g., a 1½-5 Acme screw) includes a plurality of screw threads and the nut includes a plurality of nut threads, such that the screw and the nut and threadably engagable with each other. The nut threads are sized to reduce hindered motion between the screw and the nut as a result of thermal expansion of the screw and the nut. The temperature change which causes the thermal expansion is disclosed to be between about 100° F. to about 160° F.
[0027] In a disclosed embodiment, the screw has a first coefficient of thermal expansion and the nut has a second coefficient of thermal expansion. The two coefficients of thermal expansion are not equal in an embodiment.
[0028] In an embodiment, the nut and screw set also includes a housing which is dimensioned to at least partially cover the nut. Additionally, a disclosed nut includes a nut groove which is defined between two adjacent nut threads. The width of the nut groove is disclosed to be in the range of about 0.079 inches to about 0.082 inches.
[0029] The present disclosure also relates to a method of modifying a nut in a nut and screw set to reduce hindered motion between the screw and the nut as a result of thermal expansion of the screw and the nut. A disclosed method includes providing a nut and a screw, calculating the amount of thermal expansion for the nut and the screw for a predetermined change in temperature, and increasing the width of the nut groove if the calculated amount of thermal expansion is greater than the existing width of the nut groove.
[0030] The present disclosure also relates to a method of determining the width of grooves of a nut in a nut and screw set to optimize operation therebetween and while considering thermal expansion of the nut and the screw.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the disclosure and, together with a general description of the disclosure given above, and the detailed description of the embodiments given below, serve to explain the principles of the disclosure.
[0032] FIG. 1 is a side view in partial cross-section of a screw/nut set in accordance with an embodiment of the present disclosure;
[0033] FIG. 2 is an enlarged side view in cross-section of a modified Acme thread configuration on major diameter in accordance with an embodiment the present disclosure;
[0034] FIG. 3 is a side view in cross-section of a modified Acme thread configuration on a major diameter in accordance with an embodiment of the present disclosure with the details showing the relation between radial and axial clearances in the thread; and
[0035] FIG. 4 is an enlarged side view in cross-section of a modified Acme thread configuration on a major diameter in accordance with an embodiment of the present disclosure.
DETAILED DESCRIPTION
[0036] Various embodiments of the presently disclosed Acme screw/nut set are described in detail with reference to the figures, in which like reference numerals identify corresponding elements throughout the several views. The abbreviation “e.g.” in the figures stands for “for example” indicating that the dimensions and angles shown in the figures are exemplary dimensions and angles.
[0037] In the context of drive mechanisms and other mechanical devices, a high load application commonly creates a high amount of friction and, consequently, a high temperature condition. The modification of an Acme nut in accordance with the present disclosure minimizes noise generation, excessive friction and motion seizure in a high load condition for Acme screws. A method of calculating the radial clearance required on the major thread diameter, in an effort to minimize loss of performance and motion is also disclosed.
[0038] Referring now to FIG. 1 , a screw/nut set 10 in accordance with the present disclosure is shown. Screw/nut set 10 includes an Acme screw 15 and a nut 20 . Nut 20 is illustrated mounted within nut housing 25 . Screw 15 may be an Acme Screw class C, and Acme nut 20 shown in FIG. 1 may include a modified internal thread in accordance with the present disclosure. Screw/nut set 10 illustrated in FIG. 1 is representative of a 1½-5 screw having a diameter (x) equal to 1.50 inches. The diameter (y) of nut 20 is equal to 2.125 inches. These dimensions are provided as examples only and not provided to, nor intended to, limit the scope of this disclosure. It is contemplated that this disclosure is not directed to any one particular size screw and/or nut. Rather, the present disclosure may be applied to a plurality of screws and nuts having a plurality of different dimensions.
[0039] The following formula is applied to determine the minimum required clearance as a function of a predetermined temperature rise (ΔT) above the ambient temperature. The minimum required clearance is defined as the clearance necessary to essentially prevent seizure of the motion of the mechanical components at the elevated temperatures encountered during normal working conditions.
[0040] Since nut 20 is restrained on its outer periphery by housing 25 , as the temperature of nut 20 increases, nut 20 will expand radially inward. An assumption is being made that there will be no outward expansion of nut 20 due to the restraining force exerted by nut housing 25 . The amount of thermal expansion of nut 20 is calculated by the following equation where Rn is representative of the amount of thermal expansion. CTEn represents the coefficient of thermal expansion of the nut material, ΔT represents the raise in temperature from the ambient temperature, and D represents the major diameter of nut 20 .
[0000] Rn=ΔT *CTE n*D
[0041] Similarly, screw 15 is a solid mass and, therefore, will expand radially outward as its temperature increases. The amount of thermal expansion of screw 15 is calculated by the following equation where Rs is representative of the amount of thermal expansion of screw 15 . CTEs represents the coefficient of thermal expansion of the screw material, ΔT represents the raise in temperature from the ambient temperature, and D represents the major diameter of Acme screw 15 .
[0000] Rs=ΔT *CTE s*D
[0042] The material of nut housing 25 will also expand radially outward as its temperature increases. The amount of thermal expansion of the housing 25 is calculated by the following equation where Rh is representative of the amount of thermal expansion of nut housing 25 . Nut 20 is able to expand radially outward in an amount which is proportional to the amount of expansion of nut housing 25 . CTEh represents the coefficient of thermal expansion of the housing material, ΔT represents the raise in temperature from the ambient temperature, and the variable B represents the diameter of the bore of nut housing 25 .
[0000] Rh= 0.3 *ΔT* CTE h*B
[0043] The required clearance on the major diameter due to the thermal expansion may be calculated by the following equation:
[0000] R=Rn+Rs−Rh=ΔT* CTE n*D+=ΔT *CTE s*D− 0.3 *ΔT* CTE h*B
[0000] R=ΔT{D (CTE n +CTE s )−0.3*CTE h*B}
[0044] Utilizing the values in the example described above, the following results are obtained:
[0000] R= 17{1.5(0.45*10 *E -4+8.1*10* E -6)−0.3*13.1*10* E -6*2.125}=0.001212″
[0045] Thus, the total radial clearance required on the major diameter of the thread including a factor of safety (g) is calculated as follows:
[0000] Rt=Rn+Rs−Rh+g=ΔT* CTE n*D+=ΔT *CTE s*D− 0.3 *ΔT* CTE h*B+g
[0000] Rt=ΔT{D (CTE n +CTE s )−0.3*CTE h*B}+g
[0000] The factor of safety contemplates, for example, extra radial clearance on the major diameter of the thread for grease retention and a misalignment accommodation.
[0046] Applying the values of the example given above with a temperature rising from 70° F. to 200° F. (ΔT=130° F.) and factor of safety of g=0.004″ the total clearance will be as follows:
[0000] Rt = 130{1.5(0.45*10 *E -4+8.1*10 *E -6)−0.3*13.1*10 *E -6*2.125+0.004=0.0133″
[0000] The clearance value may be rounded up to 0.014″+0.003″.
[0047] Since there will be an axial backlash increase due to the radial clearance increase, the width of the internal thread of nut 20 is adjusted to achieve a minimum axial clearance, in the design of the modified centralized AcmesScrew/nut set 10 in accordance with the present disclosure.
[0048] Referring now to FIG. 2 , a modified Acme thread configuration on major diameter in accordance with the present disclosure is illustrated. Width X 1 of screw thread 30 on major diameter and width X 2 of thread groove 35 of nut 20 also on the major diameter are shown as per ANSI B 1.8 standard without any modification. Thread 30 of screw 15 remains unchanged. Screw 15 is shown crowded to the one side of the thread 35 of nut 20 .
[0049] The axial clearance expanded from Amin.=0.0025″ to 0.0058″ based on the relationship between radial and axial clearances shown in FIG. 3 . Referring to FIG. 3 , an Acme thread modified on major diameter in accordance with the above-described example is illustrated. The detail views in FIG. 3 illustrate the relationship between radial and axial clearances in the thread.
[0050] The increase in axial clearance (backlash) is governed by the following equations:
[0000] Δ A/ΔR=tg 14.5° where Δ R=Rt−R min. (from previous calculations)
[0000] Δ A =( Rt=R min)* tg 14.5°
[0051] Therefore, the total backlash ΔAr due to an increase in radial clearance and an initial minimum axial backlash is a sum of ΔA and Amin.
[0000] Δ Ar −Δ A+A min.=( Rt−R min.)* tg 14.5 °+Ad min.
[0052] In the example described herein:
[0000] Δ Ar =(0.014−0.0012)* tg 14.5°+0025=0.0128*0.2586+0025=0.0058″
[0000] In accordance with an embodiment of the present disclosure, groove 35 of nut 20 is widened to accommodate an axial thermal expansion difference between the material of screw 15 and the material of nut 20 . The expansion of nut 20 in the axial direction is calculated in accordance with the following equation:
[0000] Δ An=ΔT* CTE n*L L—length of the nut
[0053] Next, the expansion of screw 15 in the axial direction for the length of nut 20 is calculated in accordance with the following equation:
[0000] Δ As=ΔT* CTE s*L
[0054] Thus, the total required axial backlash due to the thermal expansion may be calculated in accordance with the following equation:
[0000] At=ΔAn−ΔAs=ΔT* CTE n*L−ΔT* CTE s*L=ΔT*L *(CTE n− CTE s ) where ΔAn>ΔAs
[0055] The value derived from this calculation represents the minimum backlash at the pitch diameter. Groove 35 of nut 20 may be physically enlarged to provide this backlash. As determined above, the backlash is equal to ΔAr and is due to the increase of clearance in the radial direction. Consequently, groove 35 of nut 20 may be widened based on the difference between total thermal expansion requirement At and an existing backlash ΔAr as shown in the following equation to determine Afin:
[0000] Afin=At−ΔAr=ΔT*L* (CTE n −CTE s )−( Rt−R min)* tg 14.5 °−A min
[0000] Afin=ΔT*L* (CTE n −CTE s )−[(Δ T{D (CTE n +CTE s )−0.3*CTE h*B}+g−R min ]*tg 14.5 °−A min
[0056] After applying the values from the example described above, the following value Afin can be derived from the above formula:
[0000]
Afin
=
130
*
2.312
*
(
.45
*
10
*
E
-
4
-
8.1
*
10
*
E
6
)
-
[
130
{
1.5
(
.45
*
10
*
E
-
4
+
8.1
*
10
*
E
-
6
)
-
.3
*
13.1
*
10
*
E
-
6
*
2.125
}
+
.004
-
.0012
]
*
tg
14.5
°
-
.0025
.
Afin
=
.00546
”
[0057] This Afin value is the dimension value which has to be added to the existing width of groove 35 of nut 20 . In the example described herein, the minimum width for the top of groove 35 is 0.0738″ based on ANSI B1.8 (see FIG. 2 ). After adding 0.00546 (Afin) to that dimension the final groove width Wg is:
[0000] Wg=0.079″
[0058] The additional axial clearance may be added to the Wg dimension if necessary. In this case, due to the flexibility of the plastic nut material with an unobstructed expansion flow in the axial direction, no additional clearance was implemented other than the positive tolerance.
[0059] As illustrated in FIG. 4 , nut 20 of the drawing calls for 0.079″+0.003/−0.000. FIG. 4 shows the Acme nut drawing in cross-section detail with the circled dimension 0.079+0.003/−0.000.
[0060] While the above description contains many specifics, these specifics should not be construed as limitations on the scope of the present disclosure, but merely as illustrations of various embodiments thereof. For example, although the above embodiments are described with reference to one particular configuration of a screw/nut set, the present disclosure may find application in conjunction with screw/nut sets having many different configurations and dimensions. Accordingly, it is contemplated that the disclosure is not limited to such an application and may be applied to various screw/nut sets. Those skilled in the art will envision many other possible variations that are within the scope and spirit of the present disclosure.
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A nut and screw set for reducing the amount of hindered motion therebetween is disclosed. The nut and screw set includes a screw and a nut. The screw includes a plurality of screw threads. The nut includes a plurality of nut threads. The nut threads are threadably engagable with the screw threads. The nut threads are sized reduce hindered motion between the screw and the nut as a result of thermal expansion of the screw and the nut.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is the US National Stage of International Application No. PCT/EP2005/053877, filed Aug. 5, 2005 and claims the benefit thereof. The International Application claims the benefits of German application No. 10 2004 043 529.4 filed Sep. 8, 2004, both of the applications are incorporated by reference herein in their entirety.
FIELD OF INVENTION
[0002] The present invention relates to a method for regulating an air/fuel mixture of a multicylinder Otto engine having cylinder-specific individual catalytic converters and a joint main catalytic converter mounted downstream of the individual catalytic converters.
BACKGROUND OF THE INVENTION
[0003] To purify the exhaust gas of Otto engines, a lambda-regulated 3-way catalytic converter, upstream of which a pre-catalytic converter is optionally connected close to the engine, is customarily used nowadays. A customary lambda regulation for the main catalytic converter common to all the cylinders and an optionally provided pre-catalytic converter is described, for example, in “Handbuch Verbrennungsmotor” [Internal combustion engine manual], 2 nd edition, Richard van Basshuysen/Fred Schäfer, pp. 559 to 561. The lambda regulation regulates the air/fuel ratio lambda (λ) with the aid of signals from a lambda probe (pre-cat probe) connected upstream of the main catalytic converter and optionally a lambda probe (post-cat probe) connected downstream of the main catalytic converter. The lambda regulation usually comprises a so-called forced excitation, which superimposes on a stochiometric lambda setpoint a periodic fluctuation in the form of a λ pulse in order to optimise the efficiency of the catalytic converter. The lambda regulation also usually comprises a so-called control or trim regulation, by means of which the signal from the pre-cat probe is corrected depending on the signal from the post-cat probe in order to offset ageing-determined measurement errors by the pre-cat probe. For further details of a conventional lambda regulation of this type comprising forced excitation and control or trim regulation, the reader is referred to the literature cited.
[0004] The previously known lambda regulation is a regulation averaged over all the cylinders, which cannot take into account cylinder-specific special features. From DE 102 06 402 C1, a method for cylinder-selective lambda regulation has already been made known, in which the signal from the lambda probe (pre-cat probe) is cyclically resolved by a microcontroller such that the lambda signal can be assigned to the individual cylinders and individual exhaust-gas packets from these cylinders thus recorded.
SUMMARY OF INVENTION
[0005] The object of the present invention is to specify a method for regulating the mixture of a multicylinder Otto engine comprising cylinder-specific individual catalytic converters and a joint main catalytic converter mounted downstream of the individual catalytic converters, in which a cylinder-specific mixture regulation is enabled with the aid of a lambda probe common to the individual catalytic converters.
[0006] The invention and advantageous embodiments of the invention are defined in the claims.
[0007] The present invention assumes a system configuration in which an individual catalytic converter is assigned to each of the individual cylinders and a joint main catalytic converter, mounted downstream of the individual catalytic converters, is provided. The individual catalytic converters are arranged as closely as possible to the internal combustion engine and may be installed, e.g. directly mounted, in the respective elbows in order to achieve a startup of the individual catalytic converters in as short a time as possible. To record the air/fuel ratio λ, a joint lambda probe mounted downstream of the individual catalytic converters is provided.
[0008] The catalytic converters are configured respectively as 3-way catalytic converters, the individual catalytic converters having a predetermined yet relatively low oxygen storage capacity. The cylinder-specific lambda regulation comprises a cylinder-specific forced excitation by means of which a periodic fluctuation is modulated onto a mean lambda setpoint value in the form of lean-mixture and rich-mixture half-waves.
[0009] According to a first aspect of the invention, if the number of cylinders of the entire internal combustion engine or at least of a bank of cylinders is even, half of the cylinders are forcibly excited cylinder-specifically in the opposite direction to the other half of the cylinders in order to achieve a balance of the cylinder-specific torque contributions of the cylinders. Thus, for example, in a 4-cylinder engine, two cylinders are “enriched” and the other two cylinders simultaneously “enleaned”. In this way, a complete torque balance can be achieved. A further advantage of this solution is that this can be achieved in a simple manner using the method of forced excitation known in the art.
[0010] In order to maintain the converting effect of the cylinder-specific catalytic converters even where there are dynamic mixture disturbances (e.g. in stationary operating states), the oxygen loading of the individual catalytic converters produced by the forced excitation is adapted to ageing-determined changes in the oxygen storage capacity. This adaptation is possible while retaining the torque equalization.
[0011] A further advantage of this solution is that the individual catalytic converters can be operated within the range of their oxygen storage capacity; i.e. the forced excitation does not necessarily have to be driven to the extent that the individual catalytic converters reach the limit of their oxygen storage capacity in stationary operation.
[0012] According to a second aspect of the invention, a trim regulation of the mixture is provided for each of the individual catalytic converters, the air/fuel ratio downstream of the individual catalytic converters being recorded with only one joint lambda probe. Since in the given system configuration differences between the air and/or fuel masses introduced into the individual cylinders (fill differences and differences of injected fuel masses) affect the operation of the cylinder-specific individual catalytic converters, operation of the individual catalytic converters with an air/fuel ratio (λ) that is within the so-called catalytic converter window is not guaranteed. However, as is known, maximum utilization of the individual catalytic converters is possible only if all the individual catalytic converters are operated at optimum efficiency in the catalytic converter window. According to the invention, the mixture is therefore subjected to cylinder-specific trim regulation for each of the catalytic converters.
[0013] In the inventive method, cylinder-specific lambda signals are reconstructed in a cyclically resolved manner from the signal of the joint lambda probe, and a cylinder-specific trim regulation is then carried out with the aid of these reconstructed cylinder-specific lambda signals.
[0014] Here, the procedure adopted is preferably such that in advance the cylinder-specific forced excitation is adapted to the oxygen storage capacity of the individual catalytic converters such that the oxygen loading of the individual catalytic converters produced by the forced excitation reaches at the end of each lean-mixture half-wave of the forced excitation a target oxygen loading of the order of magnitude of its oxygen storage capacity, a mean reference value lying in the catalytic converter window is obtained from constant waveforms of reconstructed cylinder-specific lambda signals over all the cylinders and this mean reference value is used as a reference variable, and signal deviations of the reconstructed cylinder-specific lambda signals from the mean lambda reference value are used as a control deviation of the trim regulation.
[0015] The trim regulation provided according to the invention consequently makes use of the oxygen storage capacity of the individual catalytic converters. The constant waveforms of the cylinder-specific lambda signals are produced as a consequence of the oxygen storage of the individual catalytic converters, and to a certain extent they form the reference point for determining the cylinder-specific deviations of the air/fuel ratio.
[0016] The invention consequently enables stochiometric trimming of the mixture of each of the cylinder-specific individual catalytic converters with a single lambda probe, in order to operate all the individual catalytic converters in the catalytic converter window and thus to achieve the maximum degree of efficiency of the individual catalytic converters in a stable long-term manner.
[0017] Depending on the possible speed of reconstruction of the cylinder-specific lambda signals, the trim regulation is usefully carried out with a P-component and an I-component (high speed of signal reconstruction) or with only an I-component (low speed of signal reconstruction).
[0018] If necessary, the cylinder-specific trim regulation for the individual catalytic converters can be overlaid with the average-value trim regulation over all the cylinders, which is customarily used as standard today in order to correct age-determined measurement errors by the lambda probe.
[0019] A further advantage of the invention is that when determining the mean lambda setpoint value from constant waveforms of the cylinder-specific lambda signals over all the cylinders an offset error of the lambda probe does not affect the measurement result. An additional lambda probe for offset-error compensation is not therefore absolutely necessary, though it can of course be provided.
[0020] A third aspect of the invention relates to the lambda regulation for the main catalytic converter mounted downstream of the individual catalytic converters. In this connection, the invention provides that, when defining the parameters of the lambda regulation, configured in the usual manner, for the main catalytic converter and of an optionally provided average-value trim regulation, the oxygen storage capacity of the individual catalytic converters is taken into account. This taking into account is usefully effected by taking into account the period of time which lapses between a changeover of fuel injection caused by a rich-mixture or lean-mixture breakdown of an individual catalytic converter and the signal deviation of the relevant cylinder-specific lambda signal caused hereby.
[0021] It is also usefully provided that the lambda regulation for the main catalytic converter distinguishes between operating states with constant signal waveforms (oxygen storage not exceeded) and operating states with signal deviations of the cylinder-specific lambda signals (oxygen storage exceeded) and adapts its behaviour by correspondingly adapting the controller parameters and/or controller structure to these two operating states.
[0022] These measures enable improvement in the quality of control of the lambda regulation for the main catalytic converter by taking into account the different operating states of the lambda regulation in the form of adaptation of the controller parameters and/or structural changeovers of the regulation.
[0023] A general advantage of the aspects described of the present invention is that the joint lambda probe for the individual catalytic converters can be a binary or continuous probe and the signal of this lambda probe can be used as a reference variable for regulating the mixture of multiple cylinder-specific individual catalytic converters.
BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Further details of the invention will be explained with reference to the drawings, in which:
[0025] FIG. 1 shows a schematic diagram of a system configuration for the post-treatment of exhaust gas from a 4-cylinder internal combustion engine;
[0026] FIG. 2 shows a k pulse of a forced excitation and a reconstructed λ signal for a first cylinder of the internal combustion engine;
[0027] FIG. 3 shows a λ pulse and a reconstructed λ signal for a second cylinder;
[0028] FIG. 4 shows the signal of a joint lambda probe, taking into account the two cylinders according to FIGS. 2 and 3 .
DETAILED DESCRIPTION OF INVENTION
[0029] FIG. 1 shows an example of a system configuration according to the invention for a 4-cylinder Otto internal combustion engine BKM comprising four cylinders Z 1 -Z 4 , cylinder-specific individual catalytic converters K 1 -K 4 and a main catalytic converter HK, mounted downstream of the individual catalytic converters. A lambda probe LS 1 , whose signal is fed to an electronic control unit ECU, is arranged between the individual catalytic converters K 1 -K 4 and the main catalytic converter HK in the joint exhaust-gas tract. A further lambda probe LS 2 , whose signal is also fed to the electronic control unit ECU, is usefully connected downstream of the main catalytic converter HK. The electronic control unit performs mixture regulation in the form of a cylinder-specific lambda regulation in order to regulate the air/fuel ratio λ of cylinders Z 1 -Z 4 .
[0030] The lambda regulation comprises a cylinder-specific forced excitation in the form of a λ pulse which is modulated onto a mean lambda setpoint (0.998) and thus generates lean-mixture half-waves (λ=1.028) and rich-mixture half-waves (λ=0.968), see the above curves in FIGS. 2 and 3 .
[0031] According to the first aspect of the invention, the cylinder-specific forced excitation is, as already explained in the introduction, carried out for half of the cylinders respectively in the opposite direction to that for the other half of the cylinders. Thus, for example, the rich-mixture half-waves of cylinders Z 2 and Z 4 are assigned to the lean-mixture half-waves of cylinders Z 1 and Z 3 (and vice versa), as is clear from a comparison of FIGS. 2 and 3 . This enables a complete balance of the torque contributions of the cylinders, provided an even number of cylinders is provided in each bank or in each entire internal combustion engine.
[0032] Here, the same duration and amplitude of the λ pulses of the forced excitation are selected for both groups of cylinders, as can also be seen from FIGS. 2 and 3 .
[0033] In order to maintain the converting effect of the cylinder-specific individual catalytic converters K 1 to K 4 even where there are dynamic disturbances of the mixture, the oxygen loading of the individual catalytic converters produced by the forced excitation is adapted to ageing-determined changes in the oxygen storage capacity of the individual catalytic converters (ageing adaptation).
[0034] In the given system configuration as per FIG. 1 , differences in the air and/or fuel masses introduced into the individual cylinders Z 1 to Z 4 affect the operation of the individual catalytic converters K 1 to K 4 such that deviations can occur of the cylinder-specifically tuned lambda values from the optimum lambda setpoint value. These deviations may lie in the order of±3%. Without additional measures, the individual catalytic converters would then no longer be being operated at optimum efficiency in the catalytic converter window.
[0035] In order to compensate for these deviations of the cylinder-specific lambda values from the optimum lambda setpoint value, according to the second aspect of the invention a cylinder-specific trim regulation of the mixture is carried out for each of the individual catalytic converters K 1 to K 4 . The procedure adopted here is preferably as follows:
[0036] The cylinder-specific forced excitation is adapted in advance to the oxygen storage capacity of the individual catalytic converters such that the oxygen loading of the individual catalytic converters caused by the forced excitation reaches at the end of each lean-mixture half-wave a target oxygen loading of the order of magnitude of their oxygen storage capacity. If the oxygen storage capacity of the individual catalytic converters stands for example at 10 mg, the amplitude of the forced excitation at 0.3 (λ=1.03) and a cylinder filling MAF=200 mg/stroke, then it can be calculated from this that approx. 7 lean half-waves, and thus 7 operating cycles, are required in order to achieve the target oxygen loading of the individual catalytic converter concerned under the constraints assumed. The forced excitation is therefore configured in this example such that each lean-mixture half-wave and each rich-mixture half-wave of the λ pulse extends over 7 operating cycles.
[0037] These preconditions result in a signal λLS 1 from the lambda probe LS 1 , as shown, for example, in FIG. 4 . As can be seen, the probe signal λLS 1 , which is shown in the example, taking only the two cylinders Z 1 and Z 2 into account, has a constant waveform over the greatest part of the duration of a λ pulse. This constant waveform is produced as a result of the oxygen storage of the individual catalytic converters K 1 to K 4 . The signal from the lambda probe LS 1 shown in FIG. 4 also shows signal deviations Δλ, which stem from lean-mixture breakdowns and rich-mixture breakdowns of the catalytic converters K 1 and K 2 . The oxygen storage of K 1 and K 2 has to a certain extent been exceeded.
[0038] For the cylinder-specific trim regulation which is carried out by the electronic control unit ECU or else a separate controller, cylinder-specific lambda signals λZ 1 and λZ 2 are reconstructed in a cyclically resolved manner from the signal from the lambda probe LS 1 , as shown in the lower halves of FIGS. 2 and 3 . The reconstructed signals λZ 1 and λZ 2 have constant waveforms and signal deviations Δλ, as can be seen in the lower halves of FIGS. 2 and 3 .
[0039] For the trim regulation, it is necessary on the one hand to determine from constant waveforms of the reconstructed signals λZ 1 and λZ 2 over all the cylinders a mean reference value λref which forms the yardstick for the catalytic converter window. On the other hand, the signal deviations Δλ, shown in a bump-like manner, of the reconstructed lambda signals λZ 1 , λZ 2 , which stem from corresponding lean-mixture or rich-mixture breakdowns of the individual catalytic converters, must be interpreted as rich or lean disturbances. These signal deviations Δλ then give rise to a corresponding trim regulation response.
[0040] In the cylinder-specific trim regulation, the reference value λref determined from the constant waveforms of the reconstructed lambda signals serves as a reference variable and the signal deviations Δλ as a control deviation.
[0041] The type of controller used depends on the possible speed of reconstruction of the cylinder-specific lambda signals λZ 1 , λZ 2 . Where the speed of signal reconstruction is high, a trim controller with P- and I-components is used, whereas when the speed of signal reconstruction is low a trim controller with an I-component is used.
[0042] An advantage of the described cylinder-specific trim regulation of the mixture for the individual cylinders is that when the mean lambda reference value λref over all the cylinders is obtained any offset error of the lambda probe LS 1 does not affect the measurement result. A post-cat probe like the lambda probe LS 2 for offset error compensation is not therefore absolutely necessary.
[0043] As an additional measure, however, a conventional and customarily used average-value trim regulation over all the cylinders Z 1 to Z 4 can be superimposed on the cylinder-specific trim regulation, wherein the signal of the lambda probe LS 2 connected downstream serves as a monitoring signal. This superimposed average-value trim regulation serves to stabilize exhaust gas cleaning over the service life.
[0044] In other respects, measures are provided in order to deactivate the cylinder-specific trim regulation if it is ascertained when monitoring the oxygen storage capacity of the individual catalytic converters K 1 -K 4 that the oxygen storage capacity of one of the individual catalytic converters is less than its oxygen loading required by forced excitation. In this case, the cylinder-specific trim regulation would lead to false results since lean-mixture and rich-mixture breakdowns of the individual catalytic converters due to forced excitation cannot be separated from breakdowns due to cylinder-specific differences.
[0045] According to the third aspect of the invention, the lambda regulation provided for the main catalytic converter HK, which can for example be configured as in the bibliographical reference mentioned in the introduction “Handbuch Verbrennungsmotor” [Internal combustion engine manual], takes into account the oxygen storage capacity of the individual catalytic converters K 1 to K 4 . As mentioned in this bibliographical reference, the lambda regulation normally uses a PII 2 D controller with a P-component, an I-component, an I 2 -component and a D-component, as well as a limitation due to non-stationary conditions. When determining a filtered lambda setpoint value, the gas runtime and the delay behaviour of the lambda probe are also taken into account. Furthermore, a mean-value trim regulation can be provided for shifting the characteristics of the signal of the lambda probe LS 1 by means of the signal of the lambda probe LS 2 connected downstream.
[0046] The oxygen storage capacity of the individual catalytic converters K 1 to K 4 can for example be taken into account by recording the period of time between a fuel injection changeover and a deviation Δλ caused hereby in the cylinder-specific lambda signal λ 1 or λ 2 concerned ( FIGS. 2, 3 ). If a lean-mixture or rich-mixture breakdown of an individual catalytic converter takes place, this can be detected from the corresponding fuel injection changeover. This point in time is consequently known. In addition, the time of the change in the cylinder-specific lambda signal caused hereby can be detected. Consequently, the period which has lapsed between these two points in time can be recorded.
[0047] From this, appropriate conclusions can then be drawn for the lambda regulation. In particular, the controller parameters of the lambda controller can be adapted to the recorded period of time. The longer, for example, the corresponding time period (dead time) is, the slower, for example, the corresponding controller parameters (I-component) will be made.
[0048] It is also provided that the lambda regulation for the main catalytic converter HK distinguishes between operating states with constant signal waveforms and operating states with signal deviations of the cylinder-specific lambda signals λ 1 , λ 2 and adapts its behaviour by correspondingly adapting the controller parameters and/or controller structure to these two operating states.
[0049] The lambda regulation thus distinguishes between the particular operating state in which oxygen is stored in the individual catalytic converters and the signal of the lambda probe LS 1 is therefore extremely slow (ideally assumed as a constant waveform), and an operating state in which a lean-mixture or rich-mixture breakdown of the individual catalytic converters takes place and therefore a signal deviation of the lambda signal LS 1 can immediately be detected. The lambda regulation carries out, depending on these two operating states, a case distinction, whereby, for example, it changes over the controller parameters. A different or an additional measure may be the changeover of the controller structure, whereby for example a PI-controller is made into just a P-controller and the I-component is then connected subsequently.
[0050] By means of these measures, the quality of control of the lambda regulation for the main catalytic converter HK is increased by taking into account the different operating states of the lambda regulation in the form of parameter adaptations and/or structural changeovers.
[0051] In the exemplary embodiment described, the lambda probe LS 1 connected upstream is configured as a continuous probe. It can, however, also be a binary lambda probe, without modifying in any way the basic principle of the present invention.
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According to one embodiment of the inventive method, half the cylinders of an in-line cylinder arrangement or the entire internal combustion engine are forcibly excited cylinder-specifically in opposite direction to the other half of the cylinders in order to balance the cylinder-specific total torque. According to another embodiment of the invention, trim regulation which compensates differences between the air quantities and/or fuel quantities introduced into the individual cylinders with the aid of the signal of a joint lambda probe is done cylinder-specifically for the individual catalytic converters. The invention also relates to lambda regulation for the joint main catalytic converter mounted downstream of the cylinder-specific individual catalytic converters.
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FIELD OF THE INVENTION
The present invention relates to controlling temperatures in electronic components and especially to controlling the temperatures of electronic components in a tactical missile.
BACKGROUND OF THE INVENTION
During the flight of a missile, waste heat is generated by the guidance and control systems. This heat must be dissipated. If the heat is not removed from the systems, they can overheat and fail. During supersonic flight, the outside surface of the missile is too hot to act as a radiator. Accordingly, the excess heat must be absorbed internally.
Flight time for tactical missiles is typically fairly short, on the order of five or six minutes at the most. During this time the electronics packages involved in controlling the flight generate a substantial amount of heat. This heat has been absorbed by appropriately sized metal heat sinks inside the missile. Typically a computer chip may have a copper or aluminum plate, with or without fins, fastened to it to store and re-radiate excess heat. Such heat sinks are able to keep the temperature of the electronics packages below unacceptable levels for the short time required for flight, although they add weight that does not directly increase performance.
The use of heat sinks for each thermally sensitive component ignores the heat capacity of other internal components of the missile such as the structural frame that holds the missile together and the propellant. A heat management system that uses the heat capacity of these internal components could reduce the size of or entirely eliminate many individual heat sinks within the missile.
Tactical missiles are also extensively bench tested and reprogrammed. This testing and reprogramming may take substantially longer than the actual flight time, especially where there are repeated simulations of combat situations. The heat sinks suitable for a six minute flight cannot keep the electronics packages cool enough for a lengthy test or reprogramming.
In the past the electronic components have been kept cool during testing and reprogramming by testing and programming briefly and then allowing the components to cool down. This has the disadvantage of prolonging testing and reprogramming times.
In another approach the components have been kept from overheating by making temporary mechanical connections between the internal heat sinks and the missile housing (skin) during testing. These mechanical connections have been made with thermal diodes that allow heat to flow from the heat sink to the housing so long as the housing is cooler than the heat sink. Such thermal diodes degrade missile performance by adding weight and expense.
Active cooling loops have also been used. These cooling loops provide internal cooling during testing and reprogramming by circulating a fluid heat transfer medium through passages inside the missile. While this allows cooling of the electronics during testing and reprogramming, the space occupied by the cooling system is wasted during tactical flight, thereby decreasing missile performance.
Sometimes specific hardware is created to cool the entire missile during testing and reprogramming. This is effective in the laboratory or at the factory, but usually the cooling equipment is not easily taken into the field for reprogramming during combat.
SUMMARY OF THE INVENTION
The present invention creates a thermal ground plane within a missile. The thermal ground plane connects all thermally significant components within the missile and keeps them at a uniform temperature. During the missile flight the ground plane absorbs excess heat keeping components cool and distributes heat quickly to heat absorbing components within the missile. During testing and reprogramming, the ground plane is attached to an external heat dissipation device through an opening in the skin of the missile. High flow rates of heat through the ground plane and its external cooling device maintain the electronics at a steady-state temperature below the unsafe operating temperature limit during testing and reprogramming.
The thermal ground plane is established within the missile using a heat pipe. This device relies on the circulation and phase change of a fluid to move heat from hotter regions to cooler regions. The heat pipe is connected to all the internal devices that need cooling and to any internal structure that can absorb heat. During tactical flight, the phase change of the fluid from liquid to gaseous and its re-condensation in cooler regions of the heat pipe where energy is absorbed provide enough thermal capacity to keep the components from over heating. Excess heat is rapidly transferred to structural, heat absorbing components of the missile. During testing the external cooling device is connected to the cool region of the heat pipe to draw excess heat out of the missile.
The invention improves missile performance since there are no wasted components carried during tactical flight and little wasted space. In addition, waste heat can be managed comprehensively rather than on a component by component basis.
A preferred embodiment uses a heat pipe to establish a thermal ground plane. Heat pipes have very high thermal conductivity, allowing heat to move rapidly. Like an electrical ground plane which has minimal resistance to the flow of electricity, a thermal ground exhibits minimal resistance to heat flow. For example, a heat pipe may have 10 times the thermal conductivity of a copper bus similarly configured. High thermal conductivity is an important feature of the present invention, and other devices or materials exhibiting high thermal conductivity could be used instead of the heat pipe. For example, encapsulated graphite fiber bundles could be used. The heat pipe may include branches which extend from it to absorb heat from high heat components. The branches may be made of metal such copper or may themselves be heat pipes.
BRIEF DESCRIPTION OF DRAWING
The various features and advantages of the present invention may be more readily understood with reference to the following detailed description taken in conjunction with the accompanying drawing.
The Figure shows the front end portion of a tactical missile in vertical cross section to show internal heat generating and heat absorbing components connected to each other by a heat pipe and a removable external heat dissipation device, all in accordance with the present invention.
DESCRIPTION OF PREFERRED EMBODIMENTS
The missile 10 shown in the drawing figure is a tactical missile intended for flight of at most about five or six minutes at supersonic speeds. The missile 10 has a cylindrical shape with a rounded nose. The missile 10 is given its external shape by a skin or shell 12 . The missile 10 includes an internal structural frame shown schematically as bulkheads 14 a - 14 c . Inside, the missile 10 has propellant 16 , a power supply 18 , and various electronic components 20 a - 20 f used to control its flight.
The missile 10 also includes a heat pipe 22 which connects some but not all of the components inside the missile. The heat pipe 22 forms a thermal ground plane which keeps all the components 14 , 16 , and 20 connected to it at nearly the same temperature, much as an electric ground bus does for electric potentials.
The figure shows an external heat dissipation device 24 which is described below. This device is used during testing and reprogramming of the missile to maintain the thermal ground plane established by the heat pipe 22 at an acceptably cool temperature.
The heat pipe 22 is a conventional heat pipe, including a hollow metal cylinder 30 with a wick 32 lining its inside surface. A heat transfer fluid is place inside the lined cylinder 30 and the cylinder is sealed. As is well known in the art, heat pipes work by absorbing heat when the working fluid evaporates and giving up heat when the working fluid condenses. The working fluid moves in its liquid state from cooler regions to hotter regions through capillary action in the wick 32 , while the vapor travels freely down an open core in the center of the heat pipe from the hotter regions to the cooler regions. Suitable wicking materials and fluids are known to those skilled in the art, taking into account the application in a rapidly moving object and the temperature ranges to be encountered.
The heat pipe 22 is connected to all the heat generating devices 20 a - 20 f that need to be kept from overheating and to every available heat sink 14 , 16 within the missile. Various techniques are used to connect the heat sources to the heat pipe 22 . Any connection is suitable so long as it has a high thermal conductivity and so allows thermal energy to be transferred to the heat pipe as rapidly as it is generated. For example electronics packages 20 a and 20 b are shaped to fit around at least part of the outside of the heat pipe 22 . They can be attached to the heat pipe 22 using any suitable cement or bonding arrangement that has a high thermal conductivity. Circuit boards 20 c may include supporting flanges 34 to mount the circuit board to the heat pipe 22 . The supporting flanges 34 , in turn, are connected to or integral with metal heat sinks (not shown) connected to the circuit boards to conduct heat from sources of heat such as computer chips to the flange. For especially hot components radial branches 36 , 38 may be used. Branch 36 is itself a heat pipe, one end of which is connected to the component 20 d generating heat, and the other end of which is connected to the central heat pipe 22 . The connection is made by any suitable means known to those skilled in the art that allows for the rapid flow of heat from the branch heat pipe 36 to the central heat pipe 22 . Any branches from the central heat pipe 22 can be flat plate heat pipe 38 where added efficiency in heat transfer is required or where the heat sources are more widely spread.
The heat pipe 22 is also connected to all possible heat sinks within the missile. These include by way of example, the bulkheads 14 a - 14 c and the propellant 16 . It is preferable to arrange the heat generating elements 20 a - 20 f and heat absorbing elements 16 within the missile 10 so that heat generating ones are at one end and the heat absorbing elements are at the other end of the heat pipe. In the drawing the heat generating elements 20 a - 20 f are located toward the forward end of the missile while the heat absorbing propellant 16 is located aft. The bulkheads 14 a - 14 c are located between the two ends of the heat pipe 22 for structural reasons. Arranging the hottest elements at one end of the heat pipe 22 and the coolest elements at the other facilitates capillary flow of the liquid working fluid from the cooler region to the hotter region.
Some components, such as the thermal battery 18 , are insulated from the heat pipe. This is appropriate treatment for any component that generates heat but is not adversely affected by it. For similar reasons the bulkheads 14 are not directly connected to the skin 12 . At supersonic speeds the skin 12 is heated by friction with the air. This heat is kept from the components 14 , 16 , 18 , and 20 inside the missile in part by not coupling the skin directly to the bulkheads 14 , but instead using insulating fastening systems (not shown).
The heat pipe 22 has a high thermal conductivity, approximately 10 times what a comparably sized and shaped copper bus would achieve. The actual performance of the heat pipe 22 depends on numerous factors including the working fluid chosen, the material and diameter of the heat pipe, and the temperature range over which the heat pipe must operate.
The heat pipe 22 works in a manner analogous to an electrical circuit ground plane, maintaining everything connected to it at a common temperature. The heat pipe 22 has excellent thermal conductivity. Once heat is generated by components 20 attached to the heat pipe 22 , the heat is first absorbed by evaporating the fluid within the heat pipe. This fluid moves down the heat pipe 22 to cooler regions where it condenses, giving up its heat to, for example, bulkheads 14 and the propellant 16 , or to any other element in the missile 10 that can absorb heat and that is connected to the heat pipe. Because of the rapid heat transfer, using heat pipe 22 means that the management of excess heat generated by the electronic components can be based on the heat capacity virtually the entire missile 10 (structural components, e.g., 14 , propellant 16 and heat pipe 22 ) and not just specific heat sinks for individual heat generating components. With the ability to use the whole missile as a heat sink, it is easier to keep critical electronic components below a maximum allowable temperature, for example, 85 degrees centigrade (85° C.)
Static testing and reprogramming of missile 10 may take a substantial period of time. An external heat dissipation device 24 is provided to maintain the heat pipe 22 at a stable, acceptably cool temperature. The external, removable heat dissipation device 24 is analogous to an electrical ground wire connected to the missile and other electric equipment to prevent shocks, sparks, or the buildup of static electric charge.
The external heat dissipation device 24 extends through an opening 40 in the missile skin and makes a thermal connection with the heat pipe 22 . The external heat dissipation device 24 is able rapidly to draw heat out of the heat pipe 22 . The heat pipe 22 has a boss 42 to create an enlarged region for contact with and heat transfer to the external heat dissipation device 24 . A tapered bore 44 in the boss 42 works for this purpose, but other shapes are also possible. A mechanism such as screw threads or a clamp (not shown) hold the external heat dissipation device 24 in contact with the heat pipe 22 to assure a good thermal connection.
The external heat dissipation device 24 , may for example, be a conduit (not shown) with liquid coolant running through it. The coolant may be cooled by a conventional refrigeration apparatus. The external heat dissipation device and 24 may also be another heat pipe 46 . In that case, the external heat dissipation device heat pipe 46 has a large surface area such as the fins 48 on its external end portion for transferring heat. An external fan 50 may be used to force an air flow and increase heat transfer. Using a heat pipe 46 and external fan 50 as the external heat dissipation device has the advantage of simplicity and economy over a probe cooled with refrigerant, and is readily available for use in the field. With the external heat dissipation device 24 attached, the missile may be tested and or reprogrammed without overheating. The external heat dissipation device 24 draws heat from the heat pipe, keeping the electronic components 20 which generate heat below critical maximums. When the missile numeral 10 is ready for flight the external heat dissipation device 24 may be removed and the opening 40 in the skin 12 closed with a suitable plug.
Thus it is clear that the present invention provides a method an apparatus for keeping electronic components 20 from overheating both during short missile flights and during prolonged bench testing or reprogramming of the missile, with little sacrifice in missile performance. It is to be understood that the described embodiments are merely illustrative of some of the many specific embodiments which represent applications of principles of the present invention. Numerous other arrangements can be readily devised by those skilled in the art without departing from the scope of the invention.
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A tactical missile includes a heat pipe connecting heat sources with heat sinks within the missile. The system includes a removable external heat dissipation device that connects to the heat pipe while the missile is being tested or reprogrammed. The external heat dissipation device draws heat out of the heat pipe and so maintains the electronic components acceptably cool during extended testing or reprogramming. During the relatively short tactical flight, the heat pipe transfers heat from the electronic components to the heat sinks within the missile. The high heat transfer rate of the heat pipe enables elements such as structural members and propellant to be used as heat sinks, elements not heretofore incorporated into thermal management of the heat generating electronic components.
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FIELD OF THE INVENTION
This invention relates to a resin composition, furniture, electrical household appliances and molded objects which have excellent antibacterial activity and aesthetic appearance, and is safe, and in which these properties are retained for a prolonged period of time.
BACKGROUND ART
In recent years, an orientation towards cleanliness has increased among consumers, particularly women, and tables, containers and the like have been required to be provided with antibacterial activity. Additionally, in hospitals, work benches with antibacterial activity are required in order to prevent in-hospital infections.
In order to meet such a demand, conventional tables, of which the surface is covered with a resin composition where an antibacterial agent or the like is kneaded into a synthetic resin (see Patent Document 1), and containers that have been formed by molding such a resin composition (see Patent Document 2) have been used.
Patent Document 1: Japanese Unexamined Patent Publication H7 (1995)-289359 Patent Document 2: Japanese Unexamined Patent Publication 2002-322355
SUMMARY OF THE INVENTION
Even though conventional tables and containers are provided with antibacterial activity, a problem arises that the contained antibacterial agent is not completely harmless to the human body. In addition, there is a problem where the antibacterial agent is lost as time passes, and the antibacterial activity decreases. Furthermore, the appearance of tables and containers, into which an antibacterial agent has been kneaded, does not become better.
Therefore, an object of this invention is to provide a resin component where a laminated film, having at least a metal layer made of antibacterial metal and synthetic resin films which cover the two sides of the metal layer, is mixed into a synthetic resin, and to provide furniture, electrical household appliances and molded objects with such a resin composition where the surface of the furniture is coated with this resin composition or the molded objects are manufactured by molding this resin composition, and thereby, excellent antibacterial activity, aesthetic appearance and safety are gained, and these properties are retained for a prolonged period of time.
In order to solve the above described problems, a resin composition according an embodiment of the invention contains a laminated film, having at least a metal layer made of antibacterial metal and synthetic resin films that coat the two sides of the metal layer, and a synthetic resin.
In addition, a resin composition according to an advantageous embodiment, the above described antibacterial metal is silver.
In addition, a resin composition according to a further embodiment of the invention, the form of the above described laminated film is any of a powder particle form, a thread form and a strip form.
In addition, a resin composition according to a feature of the invention, the elution of silver ions cannot be prevented even when the metal layer of the laminated film is completely buried in the synthetic resin, and thus, the antibacterial activity is not lost.
In addition, a resin composition according to a further feature of the invention, a spark phenomenon due to radio waves does not occur to the resin composition in which the elusion of silver ions cannot be prevented.
In addition, a resin composition according to another advantageous embodiment, the melting point and the softening point of the synthetic film that forms the resin composition are lower than the melting point and the softening point of the synthetic resin films that form the laminated film which is contained in this resin composition, and thereby, the resin composition has an aesthetic appearance with excellent metal luster.
In addition, a piece of furniture or an electrical home appliance according to another embodiment has at least a portion of the external surface coated with the resin composition according to the invention.
In addition, a molded object according to a further embodiment is formed by molding the resin composition according to the invention.
A resin composition according to the present invention, as well as furniture, electrical home appliances and molded objects using the same, have excellent antibacterial activity and aesthetic appearance and are safe, and there is an advantage such that these properties are retained for a prolonged period of time.
Furthermore, in the case where silver is used in the antibacterial metal layer that forms a laminated film of the resin composition with this metal layer being completely buried in the synthetic resin layer which forms this laminated film, there is an advantage where the elusion of silver ions cannot be prevented, and the spark phenomenon due to radio waves does not occur.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an enlarged diagram showing the configuration of a surface portion of a top board that forms a table according to this invention.
FIG. 2 is an enlarged diagram showing the configuration of a surface portion of a top board that forms another table.
FIG. 3 is a diagram showing the configuration of a glitter.
FIG. 4 is a cross sectional diagram showing a molded object according to this invention, and an enlarged diagram showing a portion of the same.
A: top board
A 1 : coating layer
A 2 : base
B: molded object
1 : synthetic resin
2 : glitters
2 a: synthetic resin films
2 b: metal layers
2 c: adhesive
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 is an enlarged diagram showing the configuration of a surface portion of top board A that forms a table (furniture) according to this invention in a cross section in the lateral direction of top board A. As shown in this diagram, a coating layer A 1 is provided on the surface of top board A. Here, coating layer A 1 is formed by mixing a synthetic resin 1 and glitters 2 , and after that, applying the mixture to a base A 2 made of paper, wood or the like, which is then dried. In addition to this, as shown in FIG. 2 , coating layer A 1 can be formed by scattering glitters 2 on top of base A 2 , and after that, coating the surface with a synthetic resin. Here, the amount of glitters 2 is approximately 2 wt % to 10 wt % of the total weight of coating layer A 1 , taking the product price and antibacterial activity into consideration.
Synthetic resin 1 is not particularly limited as long as it is a synthetic resin with which base A 2 , which forms top board A, can be coated. Thus, polyolefin based resins such as polyethylene and polypropylene, melamine resins, acryl resins, vinyl acetate resins, urethane resins, ABS resins, polyamide resins and polyester resins can be cited as examples of the above described resin.
Here, from among these resins, resins having a melting point and a softening point that are lower than those of the synthetic resin films and the adhesive resin which form glitters 2 are preferable, taking the compatibility with glitters 2 into consideration, and in the case where the synthetic resin films are made of polyester (polyethylene terephthalate), resins such as melamine, polyethylene and polypropylene are more preferable, taking the product cost and the like into consideration. In the case where a resin of which the melting point and the softening point are equal to or higher than those of the synthetic resin films and the adhesive that form glitters 2 is used, the synthetic resin films and the adhesive are softened or melted during the process, and thus, the metal gloss is lost and the aesthetic appearance is lessened though the function is maintained, and therefore, care should be taken. In the case where the resin is polyester (polyethylene terephthalate), for example, a polyester naphthalate film can be used for glitters 2 , and a resin of which the resistance to heat is higher than that of polyethylene terephthalate can be used as the resin for bonding the below described vapor deposited metal films, and thereby, the antibacterial activity and the aesthetic appearance with a metal color can be secured.
FIG. 3 is an enlarged diagram of a glitter 2 , and glitter 2 is formed of synthetic resin films 2 a, metal layers 2 b and an adhesive 2 c, is a laminated film in approximately square form where the length of one side is approximately 0.1 mm to 1 mm, and has been cut linearly or in a zigzag so that metal layers 2 b are exposed to the outside. Here, other laminated films may be used instead of glitters 2 as long as they are provided with a metal layer and synthetic resin films which coat the two sides of this metal layer.
For example, a laminated film may be one synthetic resin film layer where the metal layer side is coated with a resin compared to glitter 2 , which has two metal layers 2 b. In addition, a layer for coating the metal color may be provided on the surface on the side opposite to the side on which the metal layer has been vapor deposited on the synthetic resin film so that the aesthetic appearance having two or three color tones may be provided. In addition, the form of a laminated film may be a thread form or a strip form instead of an approximately square powder particle form like that of glitters 2 , and the size is not particularly limited.
Such glitters 2 are manufactured, for example, by forming a metal layer 2 b on a synthetic resin film 2 a through the vapor deposition of an ion exchangeable metal, subsequently bonding synthetic resin films on which a metal layer has been formed to each other with an adhesive 2 c so that metal layers 2 b are located on the inside, and cutting this sandwich structure linearly or in a zigzag, lengthwise and crosswise.
Films made of polyester, nylon, polyethylene, polypropylene and the like can be cited as synthetic resin films 2 a, of which the thickness is approximately 5 μm to 50 μm, preferably approximately 6 μm to 25 μm, taking function and product cost into consideration.
Metal layers 2 b are formed of an antibacterial ion exchangeable metal, such as silver, copper or zinc, and from among these, silver, which is safe, does not change in color or rust, and has high antibacterial activity is optimal. In addition, the thickness of the metal layers is approximately 20 nm to 150 nm, and preferably, approximately 50 nm to 100 nm, taking function and product cost into consideration.
Polyurethane based adhesives, polyester based adhesives and acryl based adhesives can be cited as adhesive 2 c, and polyurethane based, polyester based, acryl based or polycarbonate based adhesives are preferable.
Here, this invention is not limited to the above described embodiments, and may be modified in a variety of manners within the technical scope of the invention.
Though a table which is a piece of furniture is described as an example in the above described embodiments, in addition to this, such pieces of furniture as desks, chairs and sofas, electrical household appliances such as electrical rice cookers, electrical dishwashers, washing machines and vacuum cleaners, as well as containers and the like may be provided.
In addition, instead of coating the surface of a base with a resin composition as that described above, a molded object may be manufactured through injection molding, injection compression molding, blow molding or extrusion molding of this resin composition. In addition, FIG. 4 is an enlarged cross sectional diagram showing a portion of a molded object B (basin), and as shown in this diagram, molded object B contains glitters 2 in a synthetic resin 1 . Here, the components of synthetic resin 1 , the configuration of glitters 2 and the ratio of synthetic resin 1 to glitters 2 are the same as those in the above described coating layer A 1 , and therefore, the description thereof is omitted.
Furthermore, stationery goods, such as ballpoint pens and mechanical pencils, bath products, such as baths, basins and lids for baths, bathroom products, such as toilet seats and brushes, kitchen products, such as cutting boards, rice chests and food containers, cleaning goods, such as garbage cans and brooms, goods which are touched by an unspecified large number of people, such as hand straps in trains and public phone receivers, cartridges for water purifiers and water purifiers in bowl form which are put into cartridges and the like can be cited as examples of the above described molded objects.
EXAMPLE 1
Next, as a first example according to this invention, a surface material for the top board of a table (test piece 1) and a polypropylene plate (test piece 2) were manufactured, and a variety of tests were conducted, and using this example, this invention is described in further detail.
First, the manufacture of glitters is described. Pure silver was deposited on a polyester film having a thickness of 9 μm in accordance with an ion vapor deposition method, and thus, a metal layer having a thickness of 50 nm was formed. Next, polyester films having a metal layer as that described above were bonded to each other with a polyester based adhesive so that the metal layers were located on the inside, and thereby, a sandwich structure was manufactured. Finally, the laminated film was cut lengthwise and crosswise in a zigzag using a shredder or a cutter, so that glitters were manufactured.
Next, the manufacture of the test pieces is described. A sheet of paper to be used as a surface material for the top board of a table was colored, and glitters as those described above were scattered on top, and this was coated from the top with a melanin resin, and then, the resin was hardened, so that test piece 1 was manufactured. Here, the weight ratio of the glitters to the melanin resin was 1%, and the glitters were scattered uniformly and in a dispersed state.
In addition, glitters as those described above were dispersed and mixed into polypropylene that was melted at 170° C., so that the weight ratio of the glitters to the polypropylene became 10%, and after that, the polypropylene was left to cool, so that test piece 2 was manufactured. Here, both test pieces 1 and 2 had a beautiful silver gloss.
The test for antibacterial activity is described below.
When a test for antibacterial activity was conducted on test piece 1 in accordance with JIS Z2801 (film contact method), excellent antibacterial activity with an antibacterial activity value of 4.8 was exhibited. Here, Staphylococcus aureus NBRC 12732 was used as a test bacterial strain.
The silver ion elution test is described below.
When the amount of eluted silver ions was measured for test piece 2 in accordance with an ICP method used for water quality testing and the like, silver ion elution of 86 ppb was found. It is said that, biologically, microorganisms such as bacteria die at 5 ppb to 10 ppb, and thus, it was found that test piece 2 had sufficient antibacterial activity.
As a result of this, it was found that the above described glitters have antibacterial functions due to the elution of ions of an antibacterial metal within the glitters, even when buried in the synthetic resin, as long as they are dispersed or scattered uniformly and with an appropriate weight ratio in the resin. No spark was found between radio waves and the metal that is included in the glitters, even when test piece 2 was put into a microwave oven and the switch thereof turned on.
EXAMPLE 2
Next, a second example according to this invention is shown.
The present example relates to a food preserving container that is formed by molding a resin composition according to the present invention.
First, the glitters used in the present example were prepared by cutting the above described laminated film, that is to say, the sandwich structure consisted of depositing pure silver on a polyester film having a thickness of 9 μm in accordance with an ion vapor deposition method, and thereby forming a metal layer having a thickness of 50 nm and bonding polyester films having a metal layer as that described above to each other with a polyester based adhesive so that the metal layers are located on the inside, lengthwise and crosswise in a zigzag.
In addition, this container is a food preserving container (the ratio of the glitters to the total weight is approximately 1%) formed by extrusion molding a material prepared by mixing 100% of polypropylene with 5% of a master batch of polypropylene made in such a manner as to include glitters prepared from the above described laminated film at a weight ratio of 20%. In addition, when 500 ml of water was put into this container, which was then put into a microwave oven and irradiated with microwaves for three minutes, the temperature of the water rose to approximately the same level as the water in the case of a container formed 100% of polypropylene, and no sparks were found during the irradiation with microwaves.
The results prove that the glitters were completely buried in the polypropylene resin, and silver which was exposed from the cross section during the manufacture of these glitters became of a state of complete isolation from the outside.
Here, as a comparison, when a towel into which threads formed by cutting a laminated film in long and narrow form as that described above from which the glitters were made were partially weaved, was wetted and irradiated with microwaves in the same microwave oven, a lot of bluish white sparks were clearly observed in the cross section of these threads.
It is well known that sparks between a metal and microwaves cause a great loss in the heating performance of the microwave oven, and as described above, the temperature of the water rose to the same level as in the case of a container made 100% of polypropylene, and therefore, it can be said that there was no loss in the heating performance of the microwave oven, and in addition, the fact that no sparks were found during irradiation with microwaves proves that not even a portion of these glitters was exposed from the above described food preserving container.
Next, a test for measuring elution of silver ions was carried out in accordance with frameless atomic absorption spectrophotometry using this container as a sample. First, the below described four types of solutions were prepared as solvents for elution, and the pH was adjusted to 5.0 in advance using dilute hydrochloric acid.
500 ml of each of these solutions for elution was poured into a container as that described above as a sample, which was then shaken in the lateral direction for one hour at 150 rpm using a shaker, and after that, was left still for 24 hours at a room temperature of 25° C. After that, this solvent for elution was filtered using highly pure filter paper (product number “No. 5C,” made by Toyo Filter Paper Co., Ltd., mass: 118 g/m 2 , thickness: 0.22 mm, time for filtering water: 570 s, bursting strength: 78 kPa, diameter of particles filtered out: 1 μm), and thus, a sample liquid was prepared.
Here, at the time of measurement of the sample liquid: “solution of 0.1 w/v % sodium chloride,” sodium chloride deposited on the frame of the atomic absorption photometer and hindered the measurement, and therefore, in pre-processing, this sample liquid was diluted five times before measurement, in order to reduce these effects.
The wavelength: 321.8 nm, which is absorbed by silver ions in the above described sample liquids, was measured in accordance with frameless atomic absorption spectrophotometry, and the following results were obtained. Here, the limit of determination was 1 ppb.
TABLE 1
Concentration of
No.
Elution liquid
eluted silver ions
1
Solution of 0.1 w/v % sodium chloride
Approximately 3 ppb
2
Solution of 0.1 w/v % ammonium
Less than 1 ppb
chloride
3
Solution of 0.5 w/v % ammonium
2 ppb
chloride
4
Solution of 1.0 w/v % ammonium
2 ppb
chloride
In the table, though the actually measured value of the “solution of 0.1 w/v % sodium chloride” of No. 1 was approximately 0.5 ppb, the numerical value multiplied by a dilution factor of 5 is shown.
It can be seen from the results of the above described “No. 1” that elution of silver ions of approximately 3 ppb was found in the solution of sodium chloride having a concentration of 0.1% with 99.9% of water. Furthermore, elution of silver ions was recognized in other elution liquids. Thus, the fact that silver ions were eluted from the above described glitters which were “completely” buried in polypropylene, which is a type of plastic, was proven in this test, following the silver ion elution test in the above described example. Here, the above described values can be increased by increasing the weight ratio of the glitters, and thus, it is easy to gain a container or the like having desired antibacterial activity. Accordingly, it is optimal to apply this example to containers or the like for containing food materials such as perishable foods of which the freshness must be preserved.
INDUSTRIAL APPLICABILITY
A resin composition, a piece of furniture, an electrical household appliance and a molded object according to this invention have excellent antibacterial activity due to an antibacterial metal which forms a laminated film, and an aesthetic appearance due to the gloss of this metal, and thus, can be used in various places where antibacterial activity is required. In addition, this antibacterial activity and aesthetic appearance are different from those using an antibacterial agent and are retained safely for a prolonged period of time, and therefore, applicability in various fields and for various products can be expected.
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A resin composition that excels in antibacterial action and realizes high aestheticity and safety, these properties retained for a prolonged period of time; and a relevant furniture, electrical household appliance and molding. Coating layer is superimposed on the surface of top board of table (furniture). This coating layer is formed by mixing synthetic resin with glitter and thereafter applying the mixture onto substrate of paper or wood, followed by drying. The glitter is produced by, for example, a process comprising forming a metal layer on a synthetic resin film through vapor deposition of an ion-exchangeable metal, subsequently bonding, with an adhesive, metal-clad synthetic resin films so that the metal layers come inside so as to obtain a sandwich structure and thereafter cutting the sandwich structure linearly or zigzag lengthwise and crosswise.
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REFERENCE TO RELATED APPLICATION
[0001] The present application is a continuation of U.S. patent application Ser. No. 11/267,830 filed Nov. 4, 2005, and hereby incorporates the same application herein by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention pertains generally to needle protection devices. More particularly, the present invention pertains to needle protection devices that use a cylindrical guard to extend beyond the needle's tip to prevent contact with the tip. The present invention is particularly, but not exclusively useful as a needle protection device that uses cooperation between a “V” shaped slot and a radially-extending boss to limit relative movement between the guard and the needle.
BACKGROUND OF THE INVENTION
[0003] Needles are very common in medical practices, and are frequently used to deliver medications or to draw blood for diagnosis. As a result of their intensive use, it is estimated that some 600,000 to 800,000 accidental needle stick injuries occur every year. Further, there are roughly 8,000,000 healthcare workers in the United States who are at risk of being stuck with a contaminated needle. As the risks involved in providing medical treatment have risen and individual safety and sanitation are taken into consideration, disposable or single-use type of injection devices have become prevalent. While safer than reusable injection devices, these needles must still be handled carefully and the needle tips must be covered before and after use.
[0004] Although currently there exist various needle protection devices, most require the user to take an affirmative step to cover the needle tip after its use, thereby causing potential risk of contact with the needle. Other devices require specially designed needles, plungers, or medicament chambers.
[0005] In light of the above, it is an object of the present invention to provide a protective device that can be installed on a needle to ensure there is only a single use of the needle. It is another object of the present invention to provide a protective device having a guard that passively covers and protects the needle after an injection. It is another object of the present invention to provide a protective device that controls movement of the guard relative to the needle. Still another object of the present invention is to provide a protective device that requires an affirmative step to uncover the needle, but automatically covers the needle after an injection. Yet another object of the present invention is to provide a protective device for a needle that is relatively easy to manufacture, reliable and easy to use, and is comparatively cost effective.
SUMMARY OF THE INVENTION
[0006] In accordance with the present invention, a needle protection device includes an adapter for holding a needle. The device also includes a guard having a cylindrical wall that is dimensioned to engage the adapter for relative axial movement therebetween. Such movement is biased by a spring that urges the guard away from the adapter. Further, the guard includes an orifice for selectively passing the needle therethrough. In order to guide relative movement between the adapter and the guard, the guard is provided with a “V” shaped slot having a first leg and a second leg with an apex therebetween. Correspondingly, the adapter is provided with a radially-extending boss. The boss is received within the slot to limit relative movement between the guard and the adapter.
[0007] As a result of cooperation between the slot and the boss mentioned above, the device is only moveable from a first position to a second position, and from the second position to a third position. In the first position, the boss is in the first leg of the slot and the needle partially extends through the orifice of the guard. In the second position, the needle fully extends through the orifice of the guard and the boss is held at the apex of the slot in response to a force opposing the biasing means. In the third position, the boss is in the second leg of the slot and the needle is retracted into the guard to protect the needle.
[0008] For the purposes of the present invention, the boss is provided with an engagement face that is designed to interact with the slot to ensure that the boss moves to the end of the second leg from the apex during movement of the guard from the second position to the third position. Specifically, the face is inclined toward the second leg, so that contact between the face on the boss and the edge of the slot causes the boss to move toward the end of the second leg.
[0009] In order to protect the needle before use, the device may further include a removable shield. Structurally, the shield includes a hollow portion for receiving the needle. Further, the shield includes a radially extending rib that can be selectively positioned in the orifice of the guard to prevent axial movement of the guard from the first position to the second position.
[0010] For the present invention, the device may further include a locking mechanism that locks the device in the third position, to thereby prevent further relative movement between the guard and the adapter. Specifically, the adapter is provided with a shoulder that extends radially outward, and the guard is provided with an abutment that extends radially inward. When the device moves into the third position, the shoulder and the abutment engage one another to prevent further relative movement between the guard and the adapter.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The novel features of this invention, as well as the invention itself, both as to its structure and its operation, will be best understood from the accompanying drawings, taken in conjunction with the accompanying description, in which similar reference characters refer to similar parts, and in which:
[0012] FIG. 1A is a perspective view of a needle protection device of the present invention;
[0013] FIG. 1B is a perspective view of the guard shown in FIG. 1A , illustrating the movement of the boss in the “V” shaped slot;
[0014] FIG. 2A is a cross section view of the needle protection device of FIG. 1A , as seen along line 2 - 2 in FIG. 1B ;
[0015] FIG. 2B is a cross section view of the needle protection device of FIG. 2A with the removable shield rotated for removal in accordance with the present invention;
[0016] FIG. 3 is a cross section view of the needle protection device of FIG. 2B , as seen along line 3 - 3 in FIG. 1B , with the shield removed and the needle inserted into a subject in accordance with the present invention;
[0017] FIG. 4A is a cross section view of the needle protection device of FIG. 3 , as seen along line 4 - 4 in FIG. 1B , with the needle withdrawn from the subject and the guard advanced to cover the needle tip in accordance with the present invention;
[0018] FIG. 4B is a cross section view of the needle protection device of FIG. 4A , as seen from a view taken ninety degrees from the view in FIG. 4A ; and
[0019] FIG. 5 is a side view of the slot and boss arrangement showing the configuration of the slot and the boss in the first, second and third positions.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0020] Referring initially to FIG. 1A , a needle protection device in accordance with the present invention is shown and generally designated 10 . As shown, the device 10 covers a needle 12 (shown in phantom) to prevent inadvertent contact with the needle tip 14 . For discussion of the present invention, the needle 12 defines an axis 16 , a proximal direction 15 and a distal direction 17 . Structurally, the device 10 includes a guard 18 having a cylindrical wall 20 that slidingly engages an adapter 22 . Further, the wall 20 includes a radially extending “V” shaped slot 24 that corresponds with and receives a boss 26 that extends radially outward from the adapter 22 . The slot 24 includes a first leg 28 which meets a longer second leg 30 at an apex 32 . As shown, the boss 26 is positioned in the first leg 28 of the slot 24 . For the purposes of the present invention, the slot 24 and boss 26 cooperate to guide axial movement of the guard 18 relative to the adapter 22 .
[0021] Still referring to FIG. 1A , the guard 18 is shown as including an axially extending orifice 34 that is formed with a long axis 36 and a short axis 38 . In addition to the guard 18 and the adapter 22 , the device 10 includes a removable shield 40 . In FIG. 1A , the shield 40 is shown passing through the orifice 34 and including radially extending grips 42 to facilitate rotation of the shield 40 about the axis 16 as discussed below. As shown, the device 10 further includes a spring 44 that biases the guard 18 away from the adapter 22 .
[0022] Referring to FIG. 1B , the boss 26 ′ is positioned in the first leg 28 of the slot 24 (i.e., the first position of the device 10 ), the boss 26 ″ is positioned at the apex 32 of the slot 24 (i.e., the second position of the device 10 ), and the boss 26 ″ is positioned in the second leg 30 of the slot 24 (i.e., the third position of the device 10 ). As can be understood from cross-referencing FIG. 1A with FIG. 1B , movement of the boss 26 between these positions results in rotational movement of the guard 18 about the axis 16 relative to the adapter 22 , particularly during movement from boss 26 ′ to boss 26 ″.
[0023] Referring now to FIGS. 2A and 2B , internal components and features of the device 10 can be seen. As shown, the adapter 22 includes an axially-extending and substantially cylindrical base member 46 centered about the axis 16 . Further, the adapter 22 includes a radially-extending cap member 48 . As shown, the adapter 22 has an external surface 50 and an internal surface 52 , with the internal surface 52 defining an internal cavity 54 . As further shown, the needle 12 passes through an aperture 56 formed in the cap member 48 .
[0024] Turning to the guard 18 , it can be seen from FIGS. 2A and 2B , that the cylindrical wall 20 includes an outer side 58 and an inner side 60 . As shown, the inner side 60 defines a chamber 62 in which the adapter 22 is partially received. The chamber 62 is further bounded by an end member 64 mounted to the cylindrical wall 20 and forming the orifice 34 . For the purposes of the invention, the spring 44 is positioned in the chamber 62 between the cap member 48 of the adapter 22 and the end member 64 of the guard 18 to bias the guard 18 axially away from the adapter 22 .
[0025] As further shown in FIGS. 2A and 2B , the device 10 includes a removable shield 40 having a hollow portion 66 for receiving the needle 12 . As shown in FIG. 2A , the shield 40 includes radially extending ribs 68 that are engaged with the guard 18 and the adapter 22 . In the orientation of FIG. 2A , the ribs 68 prevent axial movement of the guard 18 toward the adapter 22 . Cross-referencing FIG. 2A with FIG. 2B , it can be seen that the ribs 68 may be removed from contact with the guard 18 . Specifically, FIG. 2B depicts the shield 40 of FIG. 2A after the shield 40 has been rotated ninety degrees about the axis 16 . As a result, the ribs 68 are aligned with the long axis 36 of the orifice 34 (see FIG. 1A ) and the shield 40 may be removed from the device 10 .
[0026] Typically, the device 10 is stored and transported in the orientation shown in FIG. 2A . Before the needle 12 is used for an injection, the shield 40 is rotated as in FIG. 2B and is removed. Regardless of the position of the shield 40 , each of FIGS. 1A , 2 A and 2 B depict the device in a first position 70 in which the boss 26 is received within the first leg 28 of the slot 24 . After the shield 40 is removed, the guard 18 may be moved in the proximal direction 15 toward the adapter 22 if a sufficient force is applied thereto. Specifically, if a force greater than the biasing force of the spring 44 is applied.
[0027] In FIG. 3 , the result of an application of such a force is shown. As shown, the needle 12 has been injected into a subject 72 . As a result, the force of the subject 72 on the guard 18 has caused the guard 18 to move toward the adapter 22 . Specifically, the device 10 has moved to the second position 74 in which the boss 26 is positioned at the apex 32 of the slot 24 . When the boss 26 reaches the apex 32 , further movement of the guard 18 toward the adapter 22 is prevented by the interaction between the slot 24 and the boss 26 .
[0028] After the needle 12 has injected a fluid 76 into the subject 72 , the needle 12 is withdrawn from the subject 72 . During withdrawal, the spring 44 pushes the guard 18 away from the adapter 22 . At the same time, the boss 26 moves from the apex 32 to the second leg 30 (as shown in FIG. 4A ).
[0029] To ensure that the boss 26 moves to the end of the second leg 30 rather than back to the first leg 28 , the boss 26 is provided with an engagement face 78 . The face 78 is inclined toward the second leg 30 so that when the boss 26 moves out of the apex 32 it slides to the end of the second leg 30 .
[0030] Referring now to FIG. 4A , the device 10 is shown in its third position 80 with the boss 26 in the second leg 30 . As shown, the guard 18 is extended and fully covers the needle tip 14 . In order to prevent any further use of the needle 12 , the device 10 is provided with the locking mechanism 82 seen in FIG. 4B . FIG. 4B is a cross section view of the device 10 taken from a view ninety degrees from the view in FIG. 4A . Approximately ninety degrees from the bosses 26 shown in FIG. 4A are two shoulders 84 shown in FIG. 4B that extend radially outward from the adapter 22 . As further seen in FIG. 4B , the device 10 includes two corresponding abutments 86 that extend radially inward from the guard 18 . As shown, the shoulders 84 and abutments 86 are tapered. This construction allows the shoulders 84 to slide in the proximal direction 15 along the inner side 60 of the guard 18 until they pass the abutments 86 . Once the shoulders 84 pass the abutments 86 , the guard 18 can no longer be moved toward the adapter 22 . As a result, the device 10 is locked with the needle 12 protected by the guard 18 .
[0031] Referring now to FIG. 5 , the interaction between the slot 24 and the boss 26 can be clearly shown. In FIG. 5 , the boss 26 is shown in the various stations (indicated by 26 ′, 26 ″, and 26 ′″) it passes through during operation of the device 10 . Specifically, the boss 26 ′ is shown in the first leg 28 adjacent the first stop 88 when the device 10 is in the first position 70 . The first stop 88 may serve to prevent axial movement of the guard 18 away from the adapter 22 . As noted above, the shield 40 prevents axial movement of the guard 18 toward the adapter 22 when the ribs 68 are positioned between the guard 18 and adapter 22 . When the ribs 68 are disengaged from the guard 18 and the shield 40 has been removed, the spring 44 retains the boss 26 ′ in the first leg 28 .
[0032] When a force is applied to the guard 18 in the proximal direction 15 to move the guard 18 toward the adapter 22 , i.e., during an injection, the boss 26 ′ moves from the first stop 88 to its position as boss 26 ″ at the apex 32 . Movement of the guard 18 toward the adapter 22 may be stopped by contact between the boss 26 ″ and the apex 32 , or by contact between other components in the device 10 .
[0033] When the force in the proximal direction 15 is removed, i.e., during withdrawal of the needle 12 from the subject 72 , the spring 44 forces the guard 18 away from the adapter 22 in the distal direction 17 . As a result, the boss 26 ″ moves axially away from the apex 32 to its position at boss 26 ′″ in the second leg 30 of the slot 24 . As indicated by FIG. 5 , during movement from boss 26 ″ to boss 26 ′″, the engagement face 78 may contact the edge 90 of the slot 24 . Due to the inclination of the engagement face 78 toward the second leg 30 and the slope of the edge 90 of the slot 24 , contact between the boss 26 and the edge 90 of the slot 24 causes the boss 26 to move to the second stop 92 of the second leg 30 . Alternatively, the boss 26 ″ may move substantially in the proximal direction 15 directly to the second stop 92 of the second leg 30 . In either case, the spring 44 forces the guard 18 away from the adapter 22 until the boss 26 ′″ contacts the second stop 92 or until further axial movement of the guard 18 away from the adapter 22 is otherwise prevented. As shown in FIG. 4B , the locking mechanism 82 then prevents any further relative movement between the guard 18 and the adapter 22 .
[0034] While the particular Automatic Needle Guard for Medication Pen as herein shown and disclosed in detail is fully capable of obtaining the objects and providing the advantages herein before stated, it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims. Further, it is contemplated that the boss and slot cooperating structures may be reversed such that the boss be formed on the guard and the slot be formed in the adapter. Such an embodiment is considered to be an equivalent combination of structure to the specific embodiment disclosed and claimed herein.
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A device for selectively protecting a needle includes an adapter holding the needle and a guard engaging the adapter for relative movement therebetween. Further, the device includes a means for guiding movement between the adapter and the guard. Structurally, the guiding means includes a “V” shaped slot in the guard and a radially-extending boss on the adapter. The boss is received in the slot to limit relative movement between the guard and the adapter. Specifically, in a first position of the device, the boss is in a first leg of the slot and the needle partially extends beyond the guard. In a second position, the boss is held at the apex of the slot and the needle fully extends beyond the guard. In a third position, the boss is in the second leg of the slot and the needle is retracted into the guard to protect the needle.
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TECHNICAL FIELD
[0001] The present invention relates to rotating radiator screens of the type used, for example, on agricultural machines such as combine harvesters. More particularly, it relates to a way of obtaining an improved dynamic seal at the interface between the rotating screen and a wall surface of the machine so that debris-laden ambient air is forced to pass through and be filtered by the screen as it is drawn into the machine rather than slip in through the interface.
BACKGROUND AND SUMMARY
[0002] Rotating radiator screens are well known in the art. They are used to filter debris from an ambient air stream as it is drawn into the engine compartment of a work machine such as a combine harvester for cooling and other purposes. Typically, materials filtered from the airstream cling to the outside of the rotating screen until passing a “dead spot” that blocks incoming flow and causes the materials to lose their adhesion to the screen and drop off.
[0003] In spite of the long history of rotating radiator screens and a variety of improvements over the years, there still remains a problem in reliably sealing the interface between the rotating screen and the sidewall or other wall surface of the machine to prevent materials from being sucked into the machine without first passing through the screen itself. Various of kinds of mechanical seals have been tried over the years, including resilient skirts and the like, but none has been totally satisfactory for a number of reasons.
[0004] Accordingly, an important object of the present invention is to provide an improved dynamic sealing arrangement at the interface between the rotating screen and the adjacent wall surface so that debris-laden ambient air is discouraged from entering the machine through the interface and is instead forced to enter through the screen itself and be subjected to the filtering action that the screen provides. To this end, instead of attempting to block the entry of ambient air by mechanical or physical means at the interface, the present invention relies upon the creation of positive pressure in the region of the interface instead of suction pressure so as to repel the ambient air and the foreign materials carried thereby. In effect, a type of outflowing “air curtain” is created at the interface that moves in a generally axial direction at that location to prevent the ingress of ambient air to the interior of the machine without first passing through the filter surfaces of the screen.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] FIG. 1 is a side elevational view of a rotating radiator screen in accordance with the present invention in use on an exemplary form of work machine, in this instance a combine harvester;
[0006] FIG. 2 is an enlarged isometric view of the screen and adjacent wall surfaces of the harvester, as well as the internal combustion engine of the harvester whose cooling equipment is cooled by ambient air entering the machine via the rotating screen;
[0007] FIG. 3 is an isometric view similar to FIG. 2 but illustrating the door upon which the screen is mounted in an open condition to reveal the cooling equipment of the machine and details of construction of the rotating screen and associated structures;
[0008] FIG. 4 is an exploded isometric view of the screen and door upon which it is mounted;
[0009] FIG. 5 is an enlarged, fragmentary isometric view of the peripheral edge of the rotating screen illustrating details of the air-impinging fins at that location;
[0010] FIG. 6 is an enlarged cross-sectional view through the interface between the rotating screen and the adjacent wall surface taken substantially along sight line 6 - 6 of FIG. 2 and illustrating the way in which the fins create a positive pressure air curtain on the outside of the screen;
[0011] FIG. 7 is a bottom isometric view of a portion of a fin ring segment at the periphery of the screen as viewed in a direction similar to that of FIG. 5 ;
[0012] FIG. 8 is an outer edge view of the fin ring segment rotated 90° from the FIG. 7 orientation;
[0013] FIG. 9 is a top plan view of the fin ring segment rotated 180° from the FIG. 7 orientation and generally viewed from the same direction as FIGS. 2 and 4 ;
[0014] FIG. 10 is a slightly enlarged isometric view of the fin ring segment taken from a viewing direction somewhat similar to FIG. 9 ; and
[0015] FIG. 11 is a front isometric view of the fin ring segment taken from a radially outboard vantage point.
DETAILED DESCRIPTION
[0016] The present invention is susceptible of embodiment in many different forms. While the drawings illustrate and the specification describes certain preferred embodiments of the invention, it is to be understood that such disclosure is by way of example only. There is no intent to limit the principles of the present invention to the particular disclosed embodiments.
[0017] The combine harvester 10 illustrated in FIG. 1 is shown as one example of the type of machine with which a rotating radiator screen in accordance with the present invention may be utilized. In the illustrated embodiment, a rotating screen assembly 12 is mounted on the side of harvester 10 in a position for filtering ambient air as it is drawn into the engine compartment of the harvester.
[0018] As shown in FIGS. 2 , 3 , and 4 , screen assembly 12 is mounted on a suitable wall surface of harvester 10 having an inlet through which ambient air passes as it travels to the engine compartment. In the illustrated embodiment, such wall surface comprises the outer surface 14 of a door 16 hinged for swinging movement about a vertical axis between a closed position as illustrated in FIG. 2 and an open position as illustrated in FIG. 3 . An open box frame 18 supports door 16 and houses heat exchange equipment in the form of a cooling core 20 of the harvester and radiator sections 19 and 21 behind core 20 . A rotating fan (not shown) associated with an internal combustion engine behind core 20 and radiator sections 19 , 21 draws ambient air into heat exchange relationship with core 20 and radiator sections 19 , 21 .
[0019] Door 16 has a centrally disposed, circular air inlet 24 that is circumscribed by a circular flange ring 26 secured to and projecting axially outwardly from exterior surface 14 of door 16 . A framework 28 on door 16 spans inlet 24 and has portions that project axially outwardly from inlet 24 to rotatably support a driven shaft 30 that defines the axis of rotation of screen assembly 12 . At its axially inner end, shaft 30 has a large pulley 32 that is wrapped by an endless, flexible drive belt 34 . Belt 34 is looped around and driven by a small sheave 36 fixed to the output shaft 38 of a drive motor 40 also carried by framework 28 . Motor 40 may take a variety of different forms such as, for example, a hydraulic or electrical motor. A spring-loaded idler pulley 42 maintains tension in belt 34 .
[0020] Screen assembly 12 includes a generally drum-shaped, cylindrical screen 44 and a series or ring of air-flow-inducing fins 46 secured to screen 44 at an axially inner, peripheral edge 48 thereof. Screen 44 has an annular sidewall 50 and a circular endwall 52 at the axially outer end thereof. Both sidewall 50 and endwall 52 are formed from suitable foraminous material having openings or interstices that are of sufficient size to screen out undesirable trash and residue as it attempts to pass through screen 44 into inlet 24 . Screen assembly 12 is secured to shaft 30 via a mounting plate 54 at the outer end of shaft 30 , which plate 54 is attached to endwall 52 , thus rendering screen assembly 12 rotatable by motor 40 .
[0021] Framework 28 within the interior of screen assembly 12 supports a blocking member 56 ( FIG. 4 ) that creates a dead zone in the rotary path of travel of screen assembly 12 so that particles clinging to the sidewall 50 and endwall 52 of screen 44 drop off when they pass blocking member 56 . As shown in FIG. 4 , blocking member 56 includes a generally triangular upright plate 58 forming a dead zone for the endwall 52 of screen 44 and an arcuate base 60 extending axially inwardly from the radially outer extremity of plate 58 for cooperating with sidewall 50 .
[0022] FIGS. 5-11 illustrate details of construction of the ring of fins 46 and their relationship to the wall surface 14 of door 16 . As seen in those figures, a band 62 of annular configuration is fixed to screen sidewall 50 at the axially inner end thereof and serves to define peripheral edge 48 of screen 44 . A flat, annular mounting lip 64 circumscribes band 62 at a distance spaced axially outwardly from peripheral edge 48 and is fixed to band 62 so as to provide a means of mounting the ring of fins 46 to screen 44 . The ring of fins 46 is fixedly secured to lip 64 by rivets 66 or other suitable means.
[0023] In a preferred embodiment, the ring of fins 46 is presented by multiple arcuate fin segments 68 such as shown in FIGS. 7-11 that are arranged end-to-end around the periphery 48 of screen 44 to form a complete ring. In a most preferred embodiment, each segment 68 can be manufactured from sheet metal which is cut and stamped to produce a number of individual fins 70 at spaced apart locations along a flat base 72 from which fins 70 project. Base 72 is butted up against lip 64 and secured thereto by the rivets 66 . Holes 74 in base 72 provide clearance for rivets 66 .
[0024] Each fin 70 is integrally attached to the base 72 by a generally triangular leg 76 lying in the plane of base 72 . Each fin 70 is generally rectangular, although it will be seen from the drawings that the body of each fin widens progressively as the leading extremity is approached. Each fin 70 also presents an inclined, flat front face 78 that is sloped back with respect to the direction of rotation of screen assembly 12 as indicated by the arrow R in the figures. This is a counterclockwise direction as FIGS. 1 , 2 and 4 are viewed.
[0025] Due to the sloped back nature of each fin 70 , the axially innermost edge 80 of each fin 70 leads in the direction of rotation R, while the axially outermost edge 82 of fin 70 , where it is joined to leg 76 , trails. In addition, each fin 70 is outturned slightly such that face 78 is similarly outturned in a radial direction so that the radially inboard edge 84 of each fin 70 leads in the direction of rotation R while the radially outboard edge 86 trails. Thus, each fin 70 is inclined and canted in a manner to push air forwardly with respect to the direction of rotation R and radially outwardly with respect to the axis of rotation defined by drive shaft 30 .
[0026] The inside diameter of screen assembly 12 is greater than the outside diameter of flange ring 26 . Thus, as shown particularly in FIG. 6 , sidewall 50 of screen assembly 12 circumscribes flange ring 26 and is spaced radially outwardly therefrom a short distance so as to define an annular void region 88 . Additionally, the dimension of sidewall 60 in the axial direction is such that peripheral edge 48 at the axially inner end of band 62 is spaced a short distance axially outwardly from wall surface 14 of door 16 , presenting an annular gap 90 in open communication with region 88 , which is in turn in open communication with the interior of screen 44 . As shown also in FIG. 6 , fins 70 are of such size that the axially innermost edge 80 thereof is spaced axially outwardly from wall surface 14 to provide ample running clearance between fins 70 and wall surface 14 . Thus, at the interface between screen assembly 12 and wall surface 14 there is no physical contact between those components.
[0027] An annular baffle 92 surrounds fins 70 in radially outwardly spaced relation thereto and is fixed to wall surface 14 . Baffle 92 projects axially outwardly from wall surface 14 for a distance less than flange ring 26 such that baffle 92 is shorter than flange ring 26 . In one preferred embodiment, baffle 92 is approximately one-half the length of flange ring 26 . Baffle 92 has an inside diameter that is somewhat larger than the diameter of the circle defined by outboard edges 86 of fins 70 so as to provide ample running clearance for fins 70 . The height of baffle 92 in the axial direction is such that fins 70 project a short distance axially outwardly beyond baffle 92 as shown in FIG. 6 . It will be appreciated that baffle 92 and flange ring 26 effectively define an annular channel 84 within which fins 70 and the peripheral edge 48 of screen 44 travel during rotation of screen assembly 12 .
Operation
[0028] As motor 40 rotates screen assembly 12 in a counterclockwise direction viewing FIGS. 1 , 2 and 4 , ambient air is drawn into inlet 24 by the fan (not shown) associated with engine 22 . In order to reach inlet 24 , however, the air must first pass through screen 44 , including sidewall 50 and endwall 52 thereof. Consequently, debris is filtered out of the air stream by screen 44 and becomes adhered to sidewall 50 and endwall 52 . However, as screen 44 rotates past blocking member 56 , the adhered materials are dropped from screen 44 due to a lack of suction pressure in that area. Thus, screen 44 continuously sheds itself of adhered materials and does not become clogged.
[0029] As screen assembly 12 rotates, fins 70 travel within channel 94 . Front faces 78 of fins 70 impinge upon the air in channel 94 and force it in an axial direction along the exterior of sidewall 50 and away from wall surface 14 . Baffle 92 is instrumental in confining and directing the airflow axially outwardly away from wall surface 14 at this time, helping to create a region of positive pressure within channel 94 and an axially outwardly moving curtain of air that surrounds sidewall 50 for a short distance beyond the outer end of baffle 92 . Due to the presence of annular region 88 and gap 90 , some of the ambient air that has been drawn into the interior of screen 44 through sidewall 50 and end wall 52 moves along the outside of flange ring 26 through region 88 into channel 94 to continuously supply air for the curtain produced by fins 70 and baffle 92 .
[0030] As a result of the present invention, air-borne debris is not drawn into the interior of screen assembly 12 at the interface between wall surface 14 and peripheral edge 48 . Instead, it is repelled by the positive pressure within channel 94 and the moving air curtain. Instead of attempting to solve the sealing problem by obtaining a more effective mechanical seal between physically contacting, relatively moving surfaces at that location, a relatively friction-free air curtain seal with positive pressure outflow is created, providing many significant benefits.
[0031] The inventor(s) hereby state(s) his/their intent to rely on the Doctrine of Equivalents to determine and assess the reasonably fair scope of his/their invention as pertains to any apparatus not materially departing from but outside the literal scope of the invention as set out in the following claims.
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A rotating radiator screen has a series of fins surrounding the peripheral edge of the screen at its interface with a wall surface of the machine on which the screen is mounted. An annular baffle on the wall surface circumscribes the fins and cooperates with them in producing positive pressure and an axially outwardly moving curtain of air in the vicinity of the interface so as to oppose the ingress of ambient air and foreign materials at that location.
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FIELD OF THE INVENTION
[0001] The present invention is generally related to processes for making or manufacturing image transfer kits which enable the production of a desired image or design on a substrate which then may be used in a number of decorative applications.
BACKGROUND OF THE INVENTION
[0002] People wish to use decorative images in a number of applications. For instance, some people use decorative images to decorate their finger nails and their toe nails. In doing so, they normally encounter the problem of decorating their nails (either fingernails or toenails) with graphics and/or images that cannot withstand a protective coat of lacquer. The graphics and/or images are also apt to be dissolved by the same coat of lacquer when applied. As such, there is a need for an image transfer kit that will enable the desired image to withstand the coat of lacquer and remain durable for a number of days.
SUMMARY OF THE INVENTION
[0003] In light of the foregoing problems it is an object of the present invention to provide an image transfer kit that would enable an image to withstand a coat of lacquer applied on a user's nail. It is also an object of the present invention to provide a method for manufacturing an image transfer kit.
[0004] In an aspect of an embodiment of the present invention, the manufacturing method or process may include the steps of creating actual and silhouette film negatives of a desired image, applying a layer of transfer lacquer onto a substrate, applying a layer of high resolution lacquer over the layer of transfer lacquer, applying a layer of photoclear over the layer of high resolution lacquer, exposing the substrate to ultraviolet light following application of the photoclear layer, applying colored ink over the layer of photoclear and exposing the substrate to ultraviolet light following the application of colored ink.
[0005] In another aspect of an embodiment of the present invention, the process may include the steps of washing the substrate after the application of the transfer lacquer layer and drying the substrate after the washing.
[0006] In another aspect of an embodiment of the present invention, the process may include the steps of washing the substrate after the application of the high resolution lacquer layer and drying the substrate after the washing.
[0007] In another aspect of an embodiment of the present invention, the process may include the steps of washing the substrate after the application of the photoclear layer and drying the substrate after the washing.
[0008] In another aspect of an embodiment of the present invention, the process may include the steps of washing the substrate after application of the layer of colored ink and drying the substrate after the washing.
[0009] In an aspect of an embodiment of the present invention, the silhouette film negative may be placed between the ultraviolet light and the substrate when exposing the substrate to ultraviolet light following application of the photoclear layer.
[0010] In an aspect of an embodiment of the present invention, the actual film negative may be placed between the ultraviolet light and the substrate when the substrate is exposed to ultraviolet light following the application of colored ink.
[0011] In an aspect of an embodiment of the present invention, the process may further include the steps of applying a layer of white or clear ink over the layer of colored ink and applying a layer of adhesive to the layer of white or clear ink.
[0012] In an aspect of an embodiment of the present invention, the process may further include the steps of washing the substrate after the substrate's exposure to ultraviolet light following application of the photoclear layer, and drying the substrate after the washing process.
[0013] In an aspect of an embodiment of the present invention, the step of applying colored ink may be repeated each time for the number and quantity of inks required to generate the image. In another aspect of an embodiment of the present invention, this step of applying colored ink may include the step of determining which ink color components are required for the image.
[0014] In an aspect of an embodiment of the present invention, the process may include the step of exposing, after application of the clear or white ink, the substrate to ultraviolet light. In an aspect, during this process, the substrate may be exposed with the silhouette film negative placed between the ultraviolet light and the substrate. In another aspect of an embodiment of the present invention, the process may include the steps of washing the substrate after the substrate's exposure to ultraviolet light and drying the substrate after the washing.
[0015] In yet another aspect of an embodiment of the present invention, the image transfer kit may include a substrate, a layer of transfer lacquer atop the substrate, a layer of high resolution lacquer atop the layer of transfer lacquer, a layer of photoclear atop the layer of high resolution lacquer, an image, atop the layer of photoclear, a layer of clear or white ink laid upon the image, and a layer of adhesive on top of the layer of clear or white ink.
[0016] In yet another aspect of an embodiment of the present invention, the image may be formed by the integration of colored inks onto the substrate after exposure of both the silhouette and actual film negatives of the image to ultraviolet light in conjunction with the substrate at different stages of the process. In an aspect, each ink represents the colors needed to generate the colors of the image.
[0017] In yet another aspect of an embodiment of the present invention, the image transfer kit may include a backing layer atop the layer of adhesive. In one aspect, the backing layer may be made of silicone based paper.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The features and advantages of aspects of embodiments of the present invention will become more apparent from the detailed description set forth below when taken in conjunction with the claims and drawings, in which like reference numbers indicate identical or functionally similar elements. Additionally, the left-most digit of a reference number identifies the drawing in which the reference number first appears.
[0019] FIG. 1 illustrates a flow chart showing the manufacturing process according to an exemplary aspect of the present invention.
[0020] FIG. 2 illustrates an image transfer kit according to an exemplary aspect of the present invention showing the different layers or components of the kit.
DETAILED DESCRIPTION OF THE INVENTION
[0021] Referring now to FIGS. 1 and 2 , a flow chart showing the manufacturing process 100 and an image transfer kit 200 according to exemplary aspects of embodiments of the present invention are shown. As seen in FIG. 1 , the manufacturing process 100 may begin at step 102 with the creation of both actual and silhouette negatives of the image or design sought to be used. A silhouette negative may be used in order to capture or trap all the information contained in the image. In one aspect of an embodiment of the present invention, the silhouette negative may be slightly larger than the actual negative.
[0022] Following the creation of the negatives, a layer of transfer lacquer 204 , in step 104 is applied to a substrate 202 . In one aspect, substrate 202 may be made of vinyl, plastic or the like. In applying transfer lacquer layer 204 , a lacquer transfer rod may be used to create an even coating of the lacquer layer. Substrate 202 is then, in step 106 dried.
[0023] After the substrate has been dried in step 106 , a layer of high resolution lacquer 206 , is then applied over the initial transfer lacquer later 204 . The substrate, after application of the high resolution lacquer layer 206 , is then dried in step 110 . In another aspect of an embodiment of the present invention, a substance or layer of material, which is capable of enabling water based inks to adhere to it, may be used in lieu of the high resolution lacquer layer.
[0024] A layer of photoclear 208 , in step 112 , is applied on top of high resolution lacquer layer 206 . With the photoclear layer 208 as a barrier coat, the desired image may be protected from the layers or lacquer and a durable decorative image is provided, for instance, on finger or toe nail, if that is the desired decorative application. Following the application of photoclear layer 208 , a water based transfer rod may be used, in one aspect of an embodiment of the present invention, to even out the photoclear layer across substrate 202 . Substrate 202 , with photoclear layer 208 having been applied to it, is then dried in step 114 .
[0025] Substrate 202 , in step 116 , is exposed to ultraviolet light. In one embodiment, the silhouette negative of the image may be placed between the ultraviolet light and substrate 202 during this exposure step. Substrate 202 is then exposed for a predetermined amount of time after which it is washed (to remove any excess photoclear and/or lacquer) and dried in step 118 . In one aspect, the photoclear and lacquer layers would be hardened during this exposure step.
[0026] Next, a layer of ink 210 is applied on top of photoclear layer 208 in step 120 Ink layer 210 , in one aspect, may be evenly applied using either a solvent or water based transfer rod. In another aspect of an embodiment of the present invention, digital printing technology may be employed to replace manual application of the ink(s) onto the substrate. This would reduce production costs and increase the speed of production. Use of digital printing technology would also increase production flexibility and allow for more customized orders and/or designs/images to be used.
[0027] Ink layer 210 of substrate 202 is then dried in step 122 . After the ink layer has been dried in step 122 , the substrate, in step 124 , is exposed for a predetermined amount of time to ultraviolet light. In one aspect of an embodiment of the present invention, the actual negative of the image may be placed between the ultraviolet light and substrate 202 . At step 126 , after the exposure of the substrate to ultraviolet light, a determination is made as to whether to repeat the ink application process depending on the different inks—cyan, magenta, yellow and black—which are needed for the image. If an additional ink (or additional amount of a particular ink) is needed, the process reverts back to step 120 through step 126 until all inks (or requisite quantities) have been applied.
[0028] After application of the ink(s), the process proceeds to step 128 where a layer of either clear ink or white ink 212 is applied on top of ink layer 210 . This layer of clear ink or white ink 212 is then dried (step 130 ) and a layer of adhesive 214 , in step 132 , is applied on top of the layer of clear or white ink 210 .
[0029] Next, in step 134 , substrate 202 (now with the multiple layers) is once again exposed, for a predetermined amount of time, to ultraviolet light. In one aspect of an embodiment of the present invention, the silhouette negative may be placed between the ultraviolet light and substrate 202 during this step. Substrate 202 is then spray washed (to remove any excess clear or white ink) and dried in step 136 . At this point, an image transfer kit 200 is produced having a printed image on substrate 202 with adhesive layer 214 on the back of the image.
[0030] Referring now to FIG. 2 , an image transfer kit 200 according to an exemplary aspect of an embodiment of the present invention is shown. Image transfer kit 200 , as briefly described above and in one aspect of an embodiment of the present invention may have a substrate 202 upon which a layer of transfer lacquer 204 is applied and dried.
[0031] After the substrate has been dried, a layer of high resolution lacquer 206 , is then applied over the initial transfer lacquer later 204 . The substrate, after application of the high resolution lacquer layer 206 , is then dried. In an aspect of an embodiment of the present invention, a substance or layer of material, which is capable of enabling water based inks to adhere to it, may be used in lieu of the high resolution lacquer layer.
[0032] Once the layer of high resolution lacquer is dried, a layer of photoclear 208 is laid over the layer of high resolution lacquer 206 . Next, after drying, washing & drying and ultraviolet light treatment of substrate 202 with the transfer lacquer layer 204 , high resolution lacquer layer 206 and photoclear layer 208 , an ink layer 210 is laid over photoclear layer 208 Ink layer 210 provides the necessary colors or color combinations for the desired image. Next a layer of clear or white ink 212 is laid on top of ink layer 210 (i.e. the image generated by the application of inks) Finally, adhesive layer 214 is laid over the layer of clear or white ink 212 . In one aspect of an embodiment of the present invention, a backing sheet or layer (not shown) may be applied on top of the adhesive layer. In one aspect, the backing sheet may be made of silicone based paper.
[0033] Although this present invention has been disclosed with reference to specific forms and embodiments, it will be evident that a great number of variations may be made without departing from the spirit and scope of the present invention. For example, steps may be reversed, equivalent elements may be substituted for those specifically disclosed and certain features of the present invention may be used independently of other features—all without departing from the present invention as defined in the appended claims.
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A process of manufacturing an image transfer kit which enables the production of a desired image on a substrate which subsequently may be used in different decorative applications. The process may include the application of different layers of lacquer, photoclear and inks to a substrate in addition to the ultra-violet light treatment, washing and drying of the substrate at certain stages during the process. The produced image transfer kit may include the substrate, layers of transfer lacquer, high resolution lacquer, photoclear, clear or white ink, adhesive and the desired image.
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BACKGROUND OF THE INVENTION
This invention relates to optical reading or writing apparatus such as an optical disc memory for reading or writing information by light, more particularly to the apparatus for maintaining perpendicularity between the information-carrying medium and the optic axis of the incident beam of light.
FIG. 5 is a cross-sectional view of an optical reading or writing apparatus of the prior art, as presented in Japanese Utility Model Application Laid-open No. 135817/1985 and Patent Application Laid-open No. 186237/1982. The apparatus comprises: a disc-shaped information-carrying medium 1 that rotates around a central axis and on which information can be written and read by means of light; a spindle motor 2 to turn the information-carrying medium 1; a turntable 3 that supports the information-carrying medium 1 and transmits the revolution of the spindle motor 2; a clamper 4 that rotates together with the information-carrying medium 1 and holds it against the turntable 3; a clamper mount 5 that supports the clamper 4 while permitting it to turn freely; a sliding base 6 free to slide in the radial direction of the information-carrying medium 1; an optical head 7, mounted on the sliding base 6, that illuminates the information-carrying medium 1 with a light beam; a shaft 8 that supports the optical head 7 on the sliding base 6 and enables it to be tilted; an objective lens 9 mounted on the optical head 7, for directing the light beam onto the information-carrying medium 1, the lens being free to move both parallel to the optic axis 10 (in the focusing direction) and perpendicular to the optic axis 10 (in the tracking direction); and a tilt servo mechanism 11 for tilting the optical head 7 with the shaft 8 as a pivot. The optical head 7 and related components are shown in two positions in this drawing, one position near the center of the information-carrying medium 1 and one position near the circumference.
FIG. 6 is an enlarged view showing a detection means 12 for detecting any deviation from perpendicularity between the optic axis 10 and the surface of the informationcarrying medium 1. The detection means 12 comprises a lightemitting element 13, photosensors 14 and 15, and an operational amplifier 16 for the signals output by the photosensors 14 and 15. The detection means 12 can be mounted on the optical head 7 with the photosensors 14 and 15 located at equal distances from the light-emitting element 13. Any inclination of the detection means 12 with respect to the surface of the information-carrying medium 1 causes a difference in the intensity of light received by the two photosensors 14 and 15. The signal output from the operational amplifier 16 therefore indicates the inclination between this surface and the optic axis.
In an optical reading or writing apparatus with the structure of the prior art as described above, the information-carrying medium 1 is held between the turntable 3 and the clamper 4 as shown in FIG. 5 and rotated by the spindle motor 2. Due to shrinkage immediately after manufacture, aging changes, temperature variations, and other factors, the information-carrying medium 1 is generally warped into a concave shape as shown in the drawing.
When the sliding base 6, which slides in the radial direction of the information-carrying medium 1, reaches a position under the non-horizontal part of the surface near the circumference of the information-carrying medium 1, the optic axis 10 of the light beam from the optical head 7 mounted on the sliding base 6 is no longer perpendicular to the recording surface of the information-carrying medium 1. This state is detected by the detection means 12 shown in FIG. 6. In response to the signal output from the operational amplifier 16, the tilt servo mechanism 11 then operates to tilt the optical head 7 around the shaft 8 until perpendicularity between the optic axis 10 and the surface of the information-carrying medium 1 is restored.
If the optic axis 10 were permitted to remain nonperpendicular to the surface of the information-carrying medium 1, the spot of light would be focused onto the surface in a distorted shape. This causes such problems as follows. Namely, in information recording, the pits (holes) representing the information would be formed inaccurately on the surface, and in information reading, a carrier-to-noise ratio is reduced and a number of errors is increased. It would also become difficult to maintain tracking control; that is, to keep the spot right on the track on or from which the information should be recorded or reproduced. In digital optical disc systems using a diffraction method of tracking control to keep the spot right on the track, there would be considerable error in writing the information signal.
Since these problems are the result of nonperpendicularity between the optic axis 10 and the surface of the information-carrying medium 1, the tilt servo mechanism 11 tilts the optical head 7 to maintain a perpendicular relationship. The objective lens 9 also moves at the time of tilting, so the distance between the objective lens 9 and the surface of the information-carrying medium 1 undergoes considerable variation. In FIG. 5, the distance varies by as much as A to B between locations at which the surface of the information-carrying medium 1 is horizontal and locations at which it is not. In compensation for this variation, the objective lens 9 is moved parallel to the optic axis 10 to keep the light beam in focus on the recording surface of the information-carrying medium 1.
A problem in the optical reading or writing apparatus of the prior art as described above is that since the objective lens 9 must be sufficiently movable parallel to the optic axis 10 to adjust the focus, and the objective lens 9 is mounted on the optical head 7, the optical head 7 has to be fairly large. A large tilt servo mechanism 11 is also required to tilt the optical head 7. The large mass that must therefore be driven on the sliding base 6 in the radial direction of the information-carrying medium 1 raises an obstacle to high-speed driving (high-speed access to the information).
SUMMARY OF THE INVENTION
An object of the present invention is to solve the problems stated above.
Another object of the invention is to provide an optical reading or writing apparatus wherein an optical head is small in size and no tilt servo mechanism is required, hence a high driving (access) speed is possible.
According to the invention, there is provided an optical reading or writing apparatus comprising
an information-carrying medium on which information can be read or written optically, the information-carrying medium having the form of a disc rotating around a central axis and receiving a light beam from an optical head that is driven in the radial direction of the disc,
a detection means located near the information-carrying medium, for detecting the angle between the optic axis of the light beam and the surface of the information-carrying medium.
a temperature-adjusting element located near and facing the surface of the information-carrying medium, for creating a temperature difference between the two surfaces of the information-carrying medium and thereby causing a thermal deformation that bends the information-carrying medium in a desired direction, and
a control circuit for receiving a signal from the detection means and controlling the temperature-adjusting element by supplying energy to it in such a way as to maintain a perpendicular relationship between the surface of the information-carrying medium and the optic axis.
In this invention, perpendicularity between the surface of the information-carrying medium and the optic axis of the light beam incident on this surface is easily maintained. Besides preventing degradation of the reading and writing characteristics of the information, this invention enables the mechanism for focusing the light beam to be simplified, the size of the optical head to be reduced; and the tilting mechanism to be eliminated, thus allowing the optical reading or writing apparatus to operate with a high driving (access) speed.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-sectional drawing of an embodiment of the present invention in an optical reading or writing apparatus.
FIG. 1A shows a view of the embodiment shown in FIG. 1 from the direction of the arrow C.
FIG. 2 is a cross-sectional drawing of a second embodiment of the invention.
FIG. 2A shows a view of the second embodiment shown in FIG. 2 from the direction of the arrow C.
FIG. 3 is a cross-sectional drawing of a third embodiment of the invention.
FIG. 3A shows a view of the third embodiment shown in FIG. 3 from the direction of the arrow C.
FIG. 4 is a cross-sectional drawing of a fourth embodiment of the invention.
FIG. 4A shows a view of the fourth embodiment shown in FIG. 4 from the direction of the arrow C.
FIG. 5 is a cross-sectional drawing of the apparatus of the prior art.
FIG. 6 is an enlarged view of part of the apparatus of the prior art.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows a cross-sectional view of an embodiment of this invention. FIG. 1A is a view of the embodiment from direction C in FIG. 1. Components numbered from 1 to 10 and 12 to 16 in these drawings are the same as in the apparatus of the prior art.
In this embodiment, however, the optical head 7 is mounted in a fixed position on the sliding base 6, and the detection means 12 is located at the circumference of the information-carrying medium 1.
There is also provided a temperature-adjusting element 17 for creating a temperature difference between the two surfaces of the information-carrying medium 1, comprising in this embodiment a pair of heating elements 17A and 17B facing the two surfaces of the information-carrying medium 1 near its circumference. A control circuit 18 controls the temperature-adjusting element 17 by furnishing power to the heating elements 17A and 17B according to a signal output from the operational amplifier 16 in the detection means 12.
In the optical reading or writing apparatus constructed as described above, the disc-shaped information-carrying medium 1 is held on the turntable 3 by the clamper 4 and rotated by the action of the spindle motor 2. The detection means 12 detects the downward warp of the outer part of the information-carrying medium 1, indicated by the dashed lines in the drawing, and the detection signal of this warp is output from the operational amplifier 16. In response to this signal the control circuit 18 commands only the heating element 17B situated below the information-carrying medium 1 to generate heat, thus raising the lower surface of the information-carrying medium 1 to a higher temperature than the upper surface. Thermal expansion of the lower side of the information-carrying medium 1 then causes its outer part to bend upward until it reaches a flat, horizontal state. When the information-carrying medium 1 is horizontal and flat, the signal received from the detection means 12 causes the control circuit 18 to command the heating element 17B to stop generating heat. The surface of the information-carrying medium 1 can be maintained in the same plane by feedback of the output signal from the detection means 12 to the control circuit 18, thereby adjusting the temperature difference between the two surfaces of the information-carrying medium 1 so as to cause thermal deformation to cancel the original warp of the information-carrying medium 1. If the surface of the information-carrying medium 1 is held in this fixed plane, a perpendicular angle will be maintained between the surface of the information-carrying medium 1 and the optic axis 10 of the light beam incident on it despite motion of the optical head 7 in the radial direction. Degradation of the information reading and writing characteristics is thus prevented without causing any problems of mechanical control, and without the need for the tilt servo mechanism 11 to move the optical head 7 as in the prior art. Furthermore, since the distance A between the surface of the information-carrying medium 1 and the objective lens 9 on the optical head 7 does not vary, the objective lens 9 does not have to be moved parallel to the optic axis 10 as much as in the prior art; all that is required is a small motion to compensate for variations in positional relationships and to follow the surface deviation of the information-carrying medium 1. The size of the focus adjusting mechanism of the objective lens 9 can therefore be reduced, and with it the size of the optical head 7. As a result, the sliding base 6 can carry a much smaller mass than before, so the sliding base 6 and the optical head 7 can be driven at high speeds (enabling fast access time).
As an added effect, the temperature-adjusting element 17 can be used to remove condensed moisture. In this case heat is generated from both the upper and lower heating elements 17A and 17B, without deforming the information-carrying medium 1.
A second embodiment of this invention is shown in cross-sectional drawing in FIG. 2. FIG. 2A shows a view of the second embodiment from direction C. In this embodiment a greater number of heating elements 17A to 17D are provided.
The heating elements 17A and 17B are disposed in a radially outer region. The heating elements 17C and 17D are disposed in a radially inner region. The heating elements 17A and 17D can create a temperature difference in the radial direction on one surface of the information-carrying medium 1, enabling to afford finer control for correcting warp in the information-carrying medium 1. For instance, it may be so arranged that the outer portion is heated to the temperature higher than the inner portion. This arrangement is advantageous where the portion of information-carrying medium 1 facing the outer heating elements 17A and 17B has greater warp than the portion facing the inner heating elements 17C and 17D.
The detection means 12 can be driven in the radial direction in association with the movement of the optical head 7, for example by mounting the detection means 12 on the optical head 7 or the sliding base 6. In this case energizing of outer heating elements 17A and 17B are controlled in accordance with the outputs of the detection means 12 produced when the detection means 12 is in the radially outer region, while energizing of inner heating elements 17C and 17D are controlled in accordance with the outputs of the detection means 12 produced when detection means 12 is in the radially inner region.
Furthermore, there can be provided two detection means located at different radial positions. In this case, the outer heating elements 17A and 17B and the inner heating elements 17C and 17D can be controlled according to the respective outputs from the two detection means.
A third embodiment of this invention is shown in cross-sectional drawing in FIG. 3. FIG. 3A shows a view thereof from direction C. In this embodiment the temperature-adjusting element 17 comprises heating elements 17A and 17B and cooling elements 17E and 17F.
The heating element 17A and the cooling element 17E are disposed to face one surface of the information-carrying medium 1. The heating element 17B and the cooling element 17F are disposed to face the other surface of the information-carrying medium 1. The heating element 17A (or 17B) on one side of the information-carrying medium 1 and the cooling element 17F (or 17E) on the other side of the information-carrying medium 1 are activated simultaneously. If the heat generation by the heating element 17A (or 17B) and the heat absorption by the cooling element 17F (or 17E) are designed to be equal to each other, simultaneous use of them will not change the ambient temperature. In other words, correction of the warp can be achieved without affecting the environment.
A fourth embodiment of this invention is shown in cross-sectional drawing in FIG. 4. FIG. 4A shows a view thereof from direction C. In this embodiment the temperature-adjusting element 17 comprises semiconductor elements 17G and 17H employing the Peltier effect. The Peltier effect makes the upper surface of the elements 17G and 17H into a heat source and the lower surface into a heat sink, or vice versa, depending on the direction of current flow. The ambient temperature can therefore be held constant with only one type of element 17G and 17H.
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An information-carrying medium having the form of a disc is rotated around a central axis. The temperature of the disc is controlled by a temperature-adjusting element facing the surface of the disc.
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PRIORITY
This application claims the benefit of U.S. Provisional Application Ser. No. 61/574,821 filed Aug. 10, 2011, the entire contents of which are incorporated by reference herein.
FIELD OF THE INVENTION
The present invention relates generally to the field of medical instruments, and more particularly relates to surgical devices and methods that use radio frequency (RF) electrical energy for cutting and/or bulk removal by vaporization and coagulation with externally supplied liquid irrigants.
BACKGROUND OF THE INVENTION
Various types of electrosurgical devices are known and used in the medical field. Typically, such devices include a conductive tip that serves as an electrode in an electrical circuit which is completed either via a return electrode coupled to the patient or a return electrode mounted on the same device. Cutting and coagulation are essential operations of many electrosurgical devices. While the waveform of the supplied power to the electrode may affect the result, to a large extent the effect produced by a given device is determined by the density of the Radio Frequency (RF) current passing from the active electrode of the device to the tissue at the surgical site. High current density causes arcing to the tissue so as to produce cutting or bulk vaporization. Low current density causes tissue desiccation and hemostasis.
Bleeding is a common, yet undesired occurrence in medical surgical procedures because they may pose a threat to the patient, obscure the field of vision of the surgeon and interfere with the medical procedure. Stopping bleeding is time consuming and may be irritating to the physician. Various approaches to treat bleeding during surgery including medications, dressing and specialty devices are known
Another approach used in electrosurgical devices to switch from a cutting/evaporation mode to a coagulation mode is to change the power to the electrosurgical device, change the waveform, or both. For example, the medical staff may use a special interrupted waveform, like COAG, and a lower power level in order to treat bleeding. The problem with prior art electrosurgical devices has been that it is difficult to achieve both cutting/evaporation and coagulation in the same instrument even if a COAG waveform and a reduced power level are used either independently or jointly.
Muller et al. in U.S. Pat. No. 7,364,579 teaches an electrocautery device for achieving hemostasis, the device having an electrically conductive element, the element being either a freely rotating spherical element, or a “plug made of an electrically conductive porous material”. Also that “the conductive fluid emanating from the electrode/tip conducts the RF electrocautery energy away from the distal tip so that it is primarily the fluid, rather than the distal tip that actually accomplishes the cauterizing of tissue.” The devices taught by Mulier have geometry configured for cautery of surfaces and are used in conjunction with other cutting devices. The devices themselves are incapable of cutting tissue. In U.S. Pat. No. 7,794,460 Mulier et al. teaches a “fluid delivered out of a hollow electrocautery electrode/tip creates a virtual electrode which incises and cauterizes the tissue.” Although it is claimed that the fluid may “incise” the tissue, because the applied fluid spreads out freely over the tissue, it is incapable of “incising” or cutting the tissue. The device taught by Mulier is a cauterizing device only, both because of its electrode configuration (no cutting edges) and its continuous irrigant flow
In view of the foregoing problems it has been recognized as desirable to find an improved surgical device effective both for cutting/evaporation and also coagulation without the need to change either the power or the waveform.
SUMMARY OF THE INVENTION
In view of the foregoing considerations, the present invention is directed to an improved, dual-mode instrument. The present invention discloses devices having the ability to quickly change the current density at the electrode during use and thereby switch from the cutting/evaporation mode to the coagulation mode (dual-mode). In a first embodiment the current density is reduced by supplying an irrigant on command to the site only when desiccation is desired, the conductivity of the irrigant stream causing current to be dispersed where irrigant is in contact with the tissue. In a second embodiment the electrode device has a cutting edge with two adjacent regions, a first configured for high current density cutting and bulk vaporization, and a second configured for low current density for desiccation, again with irrigation supplied to the site selectively so as to control the current density. In a third embodiment the active electrode is an assembly having a first movable element and a second fixed element, the movable element in a first position contacting the tissue as a cutting element, and with the movable element in a second position the second fixed element contacting tissue so as to produce desiccation. In yet a fourth embodiment a “brush” of non-conductive fibers (bristles) spreads conductive irrigant over the site so as to reduce the current density and produce desiccation. In a fifth embodiment the nonconductive fibers are randomly oriented so as to form a wool or mat which is saturated with conductive irrigant which forms a conductive path for RF energy to tissue which contacts the nonconductive wool.
Irrigant may be supplied to the device by gravity from a hung bag, by a manual pump activated by the surgeon, or by a mechanical pump. Irrigant may be supplied to the surgical site upon manual action, or electrical activation by the surgeon.
Devices formed in accordance with the principles of this invention may be used for any surgical procedure in which highly vascular tissue is cut electrosurgically in a dry or semi-dry field. Examples include but are not limited to tonsillectomy, liver resection, and cosmetic procedures such as breast augmentation, breast reduction or tummy tucks.
The above-noted objects and features of the invention will become more fully apparent when the following detailed description is read in conjunction with the accompanying figures and/or examples. However, it is to be understood that both the foregoing summary of the invention and the following detailed description are of a preferred embodiment and not restrictive of the invention or other alternate embodiments of the invention. In particular, while the invention is described herein with reference to a number of specific embodiments, it will be appreciated that the description is illustrative of the invention and is not constructed as limiting of the invention. Various modifications and applications may occur to those who are skilled in the art, without departing from the spirit and the scope of the invention, as described by the appended claims. Likewise, it will be understood by those skilled in the art that one or more aspects of this invention can meet certain of the above objectives, while one or more other aspects can meet certain other objectives. Each objective may not apply equally, in all its respects, to every aspect of this invention. As such, the objectives disclosed herein should be viewed in the alternative with respect to any one aspect of this invention.
BRIEF DESCRIPTION OF THE FIGURES
Various aspects and applications of the present invention will become apparent to the skilled artisan upon consideration of the brief description of the figures and the detailed description of the present invention and its preferred embodiments that follows:
FIG. 1 depicts and electrosurgical system constructed in accordance with the principles of this invention.
FIG. 2 is a plan view of an active electrode for an electrosurgical device and system constructed in accordance with the principles of this invention.
FIG. 3 is a side elevational view of the objects of FIG. 2 .
FIG. 4 is a perspective view of the objects of FIG. 2 .
FIG. 5 is a distal axial view of the objects of FIG. 2 .
FIG. 6 is a plan view of an electrosurgical device for use with the active electrode of FIG. 2 .
FIG. 7 is a side elevational view of the objects of FIG. 6 .
FIG. 8 perspective views of the objects of FIG. 6 .
FIG. 9 is a distal axial view of the objects of FIG. 6 .
FIG. 10 is an expanded view of the distal portion of FIG. 6 .
FIG. 11 is a side elevational view of the objects of FIG. 10 .
FIG. 12 is a perspective view of the objects of FIG. 10 .
FIG. 13 is a distal axial view of the objects of FIG. 10 .
FIG. 14 is a plan view of an electrode for use in another alternate embodiment.
FIG. 15 is a side elevational view of the objects of FIG. 14 .
FIG. 16 is a perspective view of the objects of FIG. 14 .
FIG. 17 is a distal axial view of the objects of FIG. 14 .
FIG. 18 is a plan view of an irrigation collar for use with the electrode of FIG. 14 .
FIG. 19 is a side elevational view of the objects of FIG. 18 .
FIG. 20 is a side elevational sectional view of the objects of FIG. 14 at location A-A of FIG. 18 .
FIG. 21 is a perspective view of the objects of FIG. 18 .
FIG. 22 is a distal axial view of the objects of FIG. 18 .
FIG. 23 is a plan view of the electrode of FIG. 14 assembled to the irrigation collar of FIG. 18 .
FIG. 24 is a side elevational view of the objects of FIG. 23 .
FIG. 25 is a side elevational sectional view of the objects of FIG. 23 at location A-A of FIG. 23 .
FIG. 26 is a perspective view of the objects of FIG. 23 .
FIG. 27 is a distal axial view of the objects of FIG. 23 .
FIG. 28 is a plan view of another alternate embodiment having an extendable active electrode element and constructed in accordance with the principles of this invention, the active electrode being in a first extended position.
FIG. 29 is a side elevational view of the objects of FIG. 28 .
FIG. 30 is a plan view of the distal portion of the objects of FIG. 28 .
FIG. 31 is a side elevational sectional view of the objects of FIG. 30 at location A-A of FIG. 30 .
FIG. 32 is a perspective view of the objects of FIG. 28 .
FIG. 33 is a distal axial view of the objects of FIG. 28 .
FIG. 34 is an expanded perspective view of the distal portion of the objects of FIG. 32 .
FIG. 35 is a plan view of the alternate embodiment of FIG. 28 with the extendable active electrode element in the second retracted position.
FIG. 36 is a side elevational view of the objects of FIG. 35 .
FIG. 37 is a perspective view of the objects of FIG. 35 .
FIG. 38 is an expanded perspective view of the distal portion of the objects of FIG. 37 .
FIG. 39 is an expanded plan view of the objects of FIG. 37 .
FIG. 40 is a side elevational sectional view of the objects of FIG. 39 at location A-A of FIG. 39 .
FIG. 41 is an expanded plan view of the distal portion of another alternate embodiment constructed in accordance with the principles of this invention, the embodiment being like the embodiment of FIGS. 28 through 40 but with nonconductive fibers affixed to the distal end of the fixed electrode element to form an electrode brush.
FIG. 42 is a side elevational sectional view of the objects of FIG. 41 .
FIG. 43 is a plan view of the objects of FIG. 41 but with the movable electrode element being in the retracted position rather than the extended position of FIGS. 41 and 42 .
FIG. 44 is a side elevational sectional view of the objects of FIG. 43 at location A-A of FIG. 43 .
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A unifying concept of the embodiments of this invention is the ability of the devices herein disclosed to function in a first mode in which high-density RF energy is used to cut or vaporize tissue, and a second mode in which lower-density RF energy desiccates tissue to produce hemostasis. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present invention, the preferred methods, devices, and materials are now described. However, before the present materials and methods are described, it is to be understood that this invention is not limited to the particular compositions, methodologies or protocols herein described, as these may vary in accordance with routine experimentation and optimization. It is also to be understood that the terminology used in the description is for the purpose of describing the particular versions or embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.
DEFINITIONS
In the context of the present invention, the following definitions apply:
The words “a”, “an”, and “the” as used herein mean “at least one” unless otherwise specifically indicated.
In common terminology and as used herein, the term “electrode” may refer to one or more components of an electrosurgical device (such as an active electrode or a return electrode) or to the entire device, as in an “ablator electrode” or “cutting electrode”. Such electrosurgical devices are often interchangeably referred to herein as electrosurgical “probes” or “instruments”.
The present invention makes reference to an “active electrode” or “active element”. As used herein, the term “active electrode” refers to one or more conductive elements formed from any suitable metallic material, such as stainless steel, nickel, titanium, tungsten, and the like, connected, for example via cabling disposed within the elongated proximal portion of the instrument, to a power supply, for example, an externally disposed electrosurgical generator, and capable of generating an electric field.
In certain embodiments, the present invention makes reference to a “return electrode”. As used herein, the term “return electrode” refers to one or more powered conductive elements to which current flows after passing from the active electrode(s) back to the electrical RF generator. This return electrode may be located on the ablator device or in close proximity thereto and may be formed from any suitable electrically conductive material, for example a metallic material such as stainless steel, nickel, titanium, tungsten, aluminum and the like. Alternatively, one or more return electrodes, referred to in the art as “dispersive pads” or “return pads”, may be positioned at a remote site on the patient's body.
In certain embodiments, the present invention makes reference to “fluid(s)”. As used herein, the term “fluid(s)” refers to liquid(s), either electrically conductive or non-conductive, and to gaseous material, or a combination of liquid(s) and gas(as).
The term “proximal” refers to that end or portion which is situated closest to the user; in other words, the proximal end of an electrosurgical instrument of the instant invention will typically include the handle portion.
The term “distal” refers to that end or portion situated farthest away from the user; in other words, the distal end of an electrosurgical instrument of the instant invention will typically include the active electrode portion.
In certain embodiments, present invention makes reference to the vaporization of tissue. As used herein, the term “tissue” refers to biological tissues, generally defined as a collection of interconnected cells that perform a similar function within an organism. Four basic types of tissue are found in the bodies of all animals, including the human body and lower multicellular organisms such as insects, including epithelium, connective tissue, muscle tissue, and nervous tissue. These tissues make up all the organs, structures and other body contents. The present invention is not limited in terms of the tissue to be treated but rather has broad application to the vaporization any target tissue with particular applicability to the ablation, destruction and removal of problematic joint tissues.
The instant invention has both human medical and veterinary applications. Accordingly, the terms “subject” and “patient” are used interchangeably herein to refer to the person or animal being treated or examined. Exemplary animals include house pets, farm animals, and zoo animals. In a preferred embodiment, the subject is a mammal.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.
EXAMPLES
Hereinafter, the present invention is described in more detail by reference to the exemplary embodiments. However, the following examples only illustrate aspects of the invention and in no way are intended to limit the scope of the present invention. As such, embodiments similar or equivalent to those described herein can be used in the practice or testing of the present invention.
FIG. 1 depicts an electrosurgical system constructed in accordance with the principles of this invention. Electrosurgical device 100 constructed in accordance with the principles of this invention is connected by cord 20 to electrosurgical generator 22 , and by tubular element 24 to flow control element 26 , and therethrough by tubular member 28 to irrigant source 30 . In the preferred embodiment depicted, control element 26 is a foot control; in others control element 26 is a valve controlled by electrosurgical device 100 . The foot control 26 depicted has a fluid control means 32 which may be a valve which allows irrigant from source 30 to flow to device 100 when the foot control 26 is depressed. In another embodiment, foot control 26 fluid control means 32 is a deformable vessel having valves such that depressing the foot pedal causes a volume of irrigant to be expelled from the vessel and supplied to device 100 via tube 20 . When the volume is expelled, the foot pedal is allowed to return to its first position and the vessel refills with irrigant from source 30 via tube 28 .
It will be understood that foot control 26 may be replaced with another control means without departing from the principles of this invention. For instance, the control means may be part of the handle with an activation means such as a button or deformable vessel, or may be combined with the button for activating the electrosurgical generator such that activating the generator in a coagulate mode causes saline to flow to the surgical site.
In one embodiment tubular element 28 , fluid control means 32 and tubular member 24 are a tubing set having at the proximal end of element 28 a conventional spike for connection to an irrigant bag, and having at the distal end of element 24 a connector for attachment to device 100 . In another embodiment the tubing set is attached to and packaged with device 100 . In other embodiments elements are 24 , 28 and 32 are discrete elements.
FIGS. 2 through 5 depict an active electrode 120 constructed in accordance with the principles of this invention. Electrode 120 is formed from a suitable metal tubing of diameter 128 , the distal portion 124 of length 134 being coined to a thickness 130 and width 132 and the proximal portion 122 retaining its original shape. Distal-most end 138 may be trimmed to a predetermined desired shape such as, for instance, flat, arcuate, or having serrations or other irregularities to enhance cutting performance. Irrigation ports 136 at distal end 140 of proximal portion 122 are in communication with the lumen of proximal portion 122 . In a preferred embodiment, there are ports on the top and bottom side of electrode 120 . In other embodiments there is a port on the top only or on the bottom only.
As seen in FIGS. 6 through 13 , handle 101 of electrosurgical device 100 has a proximal end 102 from which pass cable 20 and tubular member 24 , and a distal end 104 to which is mounted proximal end 126 of electrode 120 . Means within handle 101 allow communication between the lumen of proximal portion 122 of electrode 120 and tubular member 24 such that irrigant from source 30 flows to irrigation ports 136 and therethrough to the surgical site when flow control 26 is activated. Handle 101 has a top surface 106 positioned on which are first button 108 and second button 110 , buttons 108 and 110 providing means for controlling electrosurgical generator 22 such that when button 108 is depressed RF current of a first waveform and first power level are supplied via means within device 100 to electrode 120 . When second button 110 is depressed, RF current of a second waveform and second power level are supplied to electrode 120 .
In use distal portion of 124 of electrode 120 is used to cut tissue. Irrigant is not supplied to the site, any fluid present being blood or other body fluids. Because the site is relatively dry, RF energy flows only from portions of portion 124 which contact or are in close proximity to tissue. If bleeding is encountered, footpedal 26 is depressed causing irrigant from supply 30 to flow to the surgical site. With conductive irrigant present, current flows from all portions of the electrode which are in contact with the irrigant to all portions of the tissue which are in contact with the irrigant. Because the area of tissue to which current flows is much greater than when operating in a dry environment without conductive irrigant, the energy density is much lower. The low density RF energy desiccates tissue in contact with the saline puddle so as to stop bleeding. When hemostasis has been achieved, the saline flow is terminated. When irrigant has been drained or removed from the region, cutting resumes.
FIGS. 14 through 17 depict an electrode 200 for an alternate embodiment formed in accordance with the principles of this invention. Electrode 200 has a proximal portion 202 of diameter 210 and length 212 suitable for mounting in a standard electrosurgical pencil. Middle portion 204 of diameter 220 larger than diameter 210 and length 230 has formed therein axial channel 222 having a bottom surface 224 coplanar with first surface 226 of distal portion 206 and terminating at its proximal end in proximal surface 242 . Distal to planar surface 226 first distal end surface 228 has formed therein grooves 232 . Second distal surface 234 terminates in distal radius 236 . Distal radius 236 of second surface 234 and first distal end surface 228 together form distal edge 240 .
FIGS. 18 through 22 depict an irrigation collar 250 for use with electrode 200 and constructed in accordance with the principles of this invention. Collar 250 has a tubular axial portion 252 having a lumen 254 of diameter 256 , diameter 256 of lumen 254 being slightly small than diameter 220 of middle portion 204 of electrode 200 , and a tapered tubular lateral portion 260 having a lumen 262 , lumens 262 and 254 being in communication. Lumen 254 has formed therein alignment key 266 .
FIGS. 23 through 27 depict an alternate embodiment device constructed in accordance with the principles of this invention. Device 300 is constructed by inserting electrode 200 into irrigation collar 250 , the angular alignment and relative axial position being established by channel 222 and key 266 . Because lumen 254 is slightly smaller than diameter 220 of middle portion 204 of electrode 200 , friction between the mating surfaces prevents unintended disassembly. Lumen 262 is in communication channel 222 such that when tubular member 24 ( FIG. 1 ) is attached to tapered lateral portion 260 of irrigation collar 250 a path is established for irrigant such that when flow control 26 is activated, irrigant from source 30 is supplied to the surgical site via channel 222 . In use, proximal end 202 of electrode 200 is inserted into a standard electrosurgical pencil. Tapered lateral portion 260 of collar 200 is connected to tubular element 24 ( FIG. 1 ), and therethrough to irrigant supply 30 with which it communicates. In a first mode of operation, irrigant is not supplied to the surgical site and any fluids present are blood or other body fluids. Current flows only from portions of the electrode in contact with, or in close proximity to tissue. Accordingly, the surgeon uses edge 240 to cut tissue and distal end surface 228 to vaporize regions of tissue, both regions being configured so as to produce high current densities. When bleeding occurs, irrigant from irrigant source 30 may be supplied to the site by activating footswitch 26 such that saline from tubular element 260 flows via lumen 262 to channel 222 and thereby to the distal end of distal region 206 . The supplied saline diffuses the RF energy in the same manner as the previous embodiment. Alternatively, the energy may be diffused over a large by “painting” the bleeding tissue with distal radius 236 of second surface 234 , the surface having no features to increase current density. If desired, irrigant may be supplied to the site as the surface is painted thereby increasing the area over which power is dissipated so as to achieve lower current density and improved tissue desiccation.
In yet another alternate embodiment constructed in accordance with the principles of this invention the device has two modes of operation based on the position of an active electrode having two elements, one fixed and one axially movable between a first position and a second position. In the first position the movable electrode element contacts tissue and functions as a cutting device. In the second position the movable electrode element is retracted within the fixed element of the electrode so as to create an irrigation port. Irrigant is supplied to the surgical site and the fixed portion of the electrode contacts tissue so as to desiccate tissue in contact with the fixed element or the supplied irrigant or both.
Referring now to FIGS. 28 through 34 depicting the device 400 with the movable element of the active electrode in its first extended position. Handle 401 is identical to handle 101 in all aspects except as noted. Handle 401 has a distal end 404 to which are mounted an active electrode assembly having a closed-distal-end tubular fixed element 406 with a distal end 420 , inner lumen 412 , and distal end wall 416 in which is formed opening 414 , and a movable blade element 408 having a distal end 418 . Handle 401 also has a lever 410 for controlling the position of movable active blade element 408 , lever 410 having a first position (shown) in which blade element 408 is extended and a second position in which blade element 408 is refracted. Through means within handle 401 , lumen 412 is in communication with tube 24 and therethrough with irrigant supply 30 such that lumen 412 if filled with irrigant. Because movable element 408 is positioned within opening 414 , irrigant cannot flow distally from lumen 412 therethrough.
FIGS. 35 through 40 depict device 400 with handle 410 in its second position and with the movable blade element 408 in the retracted position, distal end 418 being withdrawn into lumen 412 of fixed element 406 so as to allowing opening 414 in distal end wall 416 of fixed element 406 to function as an irrigation port. As best seen in FIG. 40 , irrigant 430 flows through lumen 412 to opening 414 and therethrough to tissue in contact with or close proximity to distal end 420 of fixed element 406 so as to disperse RF energy of an area sufficient to cause desiccation of tissue.
In yet another alternate embodiment of this invention, the dispersal of irrigant and therefore RF energy over an area is aided by nonconductive fibers (bristles) affixed to the distal end of the device so as to form a type of brush that provides pathways for the irrigant. In the illustrative depiction of such a device 500 shown in FIGS. 41 through 44 , the handle is identical to handle 401 of the embodiment of FIGS. 28 through 40 . Referring to FIGS. 41 through 44 , movable active electrode element 508 is identical to element 408 of embodiment 400 . Fixed electrode element 506 is like element 406 in that it has a distal end 520 , inner lumen 512 , and distal end wall 516 in which is formed opening 514 . Additionally, nonconductive fibers 540 are affixed to distal end 520 of fixed element 506 surrounding opening 514 in distal end wall 516 . As depicted in FIG. 44 , in which movable blade element 508 in the retracted position, distal end 518 being withdrawn into lumen 512 of fixed element 506 so as to allowing opening 514 in distal end wall 516 of fixed element 506 to function as an irrigation port. Irrigant 530 flows through lumen 512 to opening 514 and therethrough to nonconductive fibers 540 , fibers 540 directing and dispersing irrigant 530 to a region approximating the region of contact between the fibers and adjacent tissue. RF energy flowing through the irrigant is dispersed over the area defined by this region so as to decrease the current density to a level, which causes desiccation of tissue with resulting hemostasis.
In embodiment 500 the fibers are aligned like the bristles of a brush. In other embodiments the nonconductive fibers are randomly oriented to for a non-conductive wool, a mass of which is affixed to the fixed element of the active electrode. In these embodiments the conductive irrigant saturates the fibers such that any portion of the mass that contacts tissue will conduct low-density RF energy to the tissue so as to achieve hemostasis.
While embodiments with nonconductive fibers for enhancing and controlling the irrigant dispersal are depicted as modifications to device with movable active electrode elements, it will be recognized that other configurations using such fibers are possible and limited only by the desired medical application and the operational and engineering objectives of the designer.
All patents and publications mentioned herein are incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.
While the invention has been described in detail and with reference to specific embodiments thereof, it is to be understood that the foregoing description is exemplary and explanatory in nature and is intended to illustrate the invention and its preferred embodiments. Through routine experimentation, one skilled in the art will readily recognize that various changes and modifications can be made therein without departing from the spirit and scope of the invention.
Other advantages and features will become apparent from the claims filed hereafter, with the scope of such claims to be determined by their reasonable equivalents, as would be understood by those skilled in the art. Thus, the invention is intended to be defined not by the above description, but by the following claims and their equivalents.
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Herein disclosed are dual-mode electrosurgical devices designed to function in a first mode in which high-density RF energy is used to cut or vaporize tissue, and then a second mode in which lower-density RF energy desiccates tissue to produce hemostasis, as well as methods of performing electrosurgery using same. Devices formed in accordance with the principles of this invention may be used for any surgical procedure in which highly vascular tissue is cut electrosurgically in a dry or semi-dry field, examples of which include tonsillectomy, liver resection, and cosmetic procedures such as breast augmentation, breast reduction, breast mastopexy, and abdominoplasty.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a storage rack for an all terrain vehicle and more particularly to a container support rack which will accommodate containers of varying heights and diameters.
2. Description of the Prior Art and Objects
All terrain vehicles (ATV) are typically three or four wheeled vehicles having a seat for one or more passengers and a rear storage rack which typically includes a plurality of spaced apart horizontal steel tubes and a plurality of vertically spaced apart rearwardly horizontally disposed retaining tubes. These racks typically provide limited storage space for fishermen, farmers, bird watchers, and others who use all terrain vehicles to travel into the wilderness. Fishermen, for example, typically want to carry a minnow bucket and also a second bucket in which they place the fish which they catch. Bird watchers frequently want to separately store different bird seed. Also, a farmer may want a container for seed and a second container for tools or fertilizer. Accordingly, it is an object of the present invention to provide a new and novel storage rack for storing a plurality of containers on an ATV storage rack.
U.S. Pat. No. 6,179,180B1 issued to John F. Walker, on Jan. 30, 2001, discloses a carrier accessory for attaching containers having enlarged diameter rims thereon in a plurality of rings which are mounted on the rear of the all terrain vehicle. Frequently, fishermen, farmers, bird watchers, etc., have rimless containers or containers which have a smaller or larger diameter than the rings illustrated in the Walker patent and thus, the Walker device is of limited use. Accordingly, it is another object of the present invention to provide an all terrain vehicle storage rack which will accommodate rimless containers.
It is yet another object of the present inventions to provide an all terrain vehicle storage rack which will accommodate containers of varying diameters or breadths.
Yet another object of the present invention is to provide an all terrain storage rack of the type described which will accommodate rimless containers having varying heights.
Still another object of the present invention is to provide an all terrain storage vehicle of type described which includes a platform for underlying a container supported thereon and a container ring which envelopes a container supported thereon.
A further object of the present invention is to provide an all terrain vehicle storage rack of the type described which includes an L-shaped mounting bracket having a horizontal base which supports a container thereon and an upstanding leg on which a container retaining ring is mounted.
A still further object of the present invention is to provide an all terrain vehicle storage rack of the type described including rigidifying rods which span the terminal end of the base leg and are tangentially fixed to a portion of the retainer ring remote from the upstanding leg.
Still yet another object of the present invention is to provide an all terrain vehicle storage rack of the type described which includes a one-piece rigidifying rod which couples the base to a portion of the retainer ring remote from the upstanding leg.
A further object of the present invention is to provide an all terrain vehicle storage rack of the type described wherein the upstanding leg includes a plate having a pair of rows of vertically spaced apertures through which fasteners, such as U-bolts, are disposed to couple the plate to the support rack of an all terrain vehicle.
Another object of the present invention is to provide an all terrain vehicle of the type described in which the vertical leg includes an upstanding plate of a predetermined breadth and a transverse bar having terminal ends which are fixed are tangentially fixed to a pair of laterally spaced container receiving rings.
Another object of the present invention is to provide an all terrain vehicle storage rack of the type described wherein the horizontal leg include a pair of container support wings projecting laterally outwardly from opposite sides of the horizontal platform to provide a pair of laterally spaced container supports aligned with a pair of laterally spaced overlying container rings.
Yet another object of the present invention is to provide an all terrain vehicle storage rack of the type described including a rigidifying rod which spans the platform and the container support wings, and thence spans the container support wings and tangentially couples to a portion of each ring remote from the upstanding leg, and finally spans the terminal end of the horizontal platform and each ring.
The aforementioned Walker U.S. Pat. No. 6,179,180B1, discloses mounting brackets which are laterally or horizontally spaced apart a substantial distance that would prevent the use of the Walker bracket on many current ATV racks. Typically, the top rail on many ATV racks is relatively short and thus, the mounting brackets must be laterally closely spaced. Accordingly, it is another object of the present invention to provide a new and novel all terrain vehicle support rack which is adapted to be mounted on a wider variety of all terrain vehicle racks than the prior art permits.
The lack of an underlying support platform disclosed in the Walker patent seriously limits the load capacity thereof. Accordingly, it is another object of the present invention to provide a new and novel all terrain vehicle support rack which has a higher load capacity than the prior art.
In the prior art patented Walker construction, the buckets project downwardly below the brackets a substantial distance which, under certain conditions, can cause the bottom of the containers to come in contact with ground brush and debris and perhaps even the ATV rear tires. Accordingly, it is another object of the present invention to provide a new and novel all terrain vehicle storage rack which overcomes the problems with the existing prior art all terrain vehicle carrier accessories.
Other objects and advantages of the present invention will become apparent to those of ordinary skill in the art as the description thereof proceeds.
SUMMARY OF THE INVENTION
A storage rack for an all terrain vehicle including an L-shaped bracket having a horizontal leg for supporting a container thereon and an upstanding leg, mechanism for detachably coupling the upstanding leg to an all terrain vehicle; at least one endless bucket receiving retainer for freely receiving a container supported on the horizontal leg and coupled to the vertical leg; and upstanding hoop mounting rods spanning the horizontal leg and the ring.
DESCRIPTION OF THE DRAWINGS
The invention may be more readily understood by referring to the accompanying drawings, in which:
FIG. 1 is a top plan view of a storage rack constructed according to the present invention mounted on the rear end of an ATV storage rack;
FIG. 2 is a slightly reduced side elevational view thereof, part of the horizontal leg being broken away to better illustrate the loop support ring spanning the rear of the loop and the rear of the leg;
FIG. 3 is a rear elevational view thereof, taken along the line 3 — 3 of FIG. 1;
FIG. 4 is a bottom view thereof;
FIG. 5 is a front elevational view thereof;
FIG. 6 is a top plan view of a slightly modified embodiment for mounting a single bucket;
FIG. 7 is a front elevational view, taken along the line 7 — 7 of FIG. 6;
FIG. 8 is a sectional side elevational view, taken along the section line 8 — 8 of FIG. 6;
FIG. 9 is an enlarged view thereof without a bucket; and
FIG. 10 is a similar perspective view thereof mounting the bucket.
DESCRIPTION OF THE PREFERRED EMBODIMENT
A storage rack, generally designated 10 , constructed according to the present invention, is particularly adapted for use in mounting an article, such as a bucket or container, illustrated in platform lines at 11 , on a rear storage rack, generally designated 12 , mounted at the rear of an all terrain vehicle (ATV). The ATV storage rack 12 include a plurality of horizontally spaced apart parallel steel support tubes (not shown) and a pair of parallel, vertically spaced apart transversely extending, horizontal tubular members 16 and 18 located at the rear most portion of the rack 12 .
The storage rack 10 , constructed according to the present invention, includes an L-shaped frame, generally designated 20 , having a horizontal base leg 22 and a vertical leg 23 integrally coupled to the front end 24 of horizontal leg 22 . The base leg 22 includes an elongate horizontal plate 26 having laterally spaced downwardly diverging legs 28 and 30 which terminate in horizontal flanges 32 and 34 , respectively. The upstanding leg 23 includes a vertical plate 36 having laterally spaced forwardly diverging legs 38 and 40 terminating in terminal flanges 42 and 44 which lie in the same vertical plane and include laterally spaced apart rows 46 and 48 of vertically spaced apertures 50 and 52 , respectively, for receiving pairs of vertically spaced U-bolts 54 and 56 which are detachably held to tubular members 16 and 18 via nuts 62 and 64 are threaded onto the U-bolts 54 and 56 .
Welded, or otherwise suitably secured to the laterally outer faces of the depending legs 28 and 30 , are the laterally inner, downwardly extending, angled flanges 67 and 69 of laterally outwardly extending, container supporting wings or plates 66 and 68 , respectively, having terminal ends 70 and 72 , respectively, on which a pair of the containers or buckets 11 are vertically supported.
A pair of container retainer rings, loops or circular hoops 74 and 76 are mounted on the upstanding leg 23 via a transverse crossbar 78 welded to plate 36 and having terminal ends 80 and 82 which are tangentially welded to forward circumferential portions 84 and 86 of rings 74 and 76 , respectively. The rings 74 and 76 include bucket receiving apertures 75 and 77 therethrough for receiving articles such as bucket 11 having a predetermined diameter 83 . The loops or hoops 74 and 76 having an inner diameter 85 typically larger than the bucket diameter 83 .
A second rigidifying mount, generally designated 88 , is provided for supporting the forward diametrically opposite distal portions 90 and 92 of the rings 74 and 76 , respectively. The rigidifying mount 88 includes a transverse base rod 98 welded or otherwise suitably fixed to the undersides of the flanges 32 and 34 and including terminal ends 100 and 101 , respectively, welded or otherwise suitably fixed to the undersides 102 and 103 of the container support wings 66 and 68 , respectively. The mount 88 includes a pair of rearwardly and upwardly extending legs 94 and 96 which include forward ends 93 and 95 are welded to the terminal ends 100 and 101 , respectively, and to the undersides 102 and 103 , respectively, The rods 94 and 96 include upwardly extending integral rod portions 108 and 110 , respectively, which include upper ends 109 and 111 , respectively, tangentially welded to the forward distal ring portions 90 and 92 , respectively. The rigidifying mount 88 also includes a pair of downwardly converging rod sections 112 and 114 integral with the rods 108 and 110 , respectively, and having forwardly extending horizontal terminal rod sections 116 and 118 welded to the junctions 120 and 122 of the plate 26 and the legs 28 and 30 , respectively.
THE OPERATION
The storage rack 10 is coupled to the rear horizontal bars 16 and 18 of the ATV storage rack 12 via U-bolts 54 , 56 and nuts 62 , 64 in the position illustrated in FIGS. 1-5. A pair of buckets or containers 11 are disposed within the apertures 75 , 77 provided in the rings or hoops 74 , 76 , respectively, to be supported on the laterally outwardly extending container support wings 66 and 68 and the rods 98 , 94 and 96 , respectively. The breadth or internal diameters 85 of the rings 74 and 76 is greater than the maximum external diameters 83 of the containers 11 so that the containers can be easily removed from the rings. Also, the broader rings will allow containers 11 of different diameters to be freely set forth and supported therein.
ALTERNATE EMBODIMENT
The embodiment illustrated in FIGS. 6-8, generally designated 10 A, is generally similar to the embodiment illustrated in FIGS. 1-5 and generally similar parts are identified with generally similar reference characters followed by the letter A subscript.
The embodiment illustrated in FIGS. 6-8 differs from that illustrated in FIGS. 1-5 in that rather than supporting the bucket 11 A on the laterally extending wings and mounting rods, the bucket 11 A is supported on the base leg 22 A. Only one retainer ring 74 A is illustrated and the forward distal portion 84 A is tangentially welded directly to the vertical plate 36 A on the vertical leg 23 A. The rigidifying apparatus 88 A merely includes an inverted V-shaped rigid rod 128 having an upper apex 127 to the rear ring portion 90 A and downwardly diverging legs 129 and 130 terminating in forwardly extending rod sections 116 A and 118 A, respectively, welded to the junctions 120 A and 122 A of the base plate 26 A and the legs 28 A and 30 A, respectively.
It is to be understood that the drawings and descriptive matter are in all cases to be interpreted as merely illustrative of the principles of the invention, rather than as limiting the same in any way, since it is contemplated that various changes may be made in various elements to achieve like results without departing from the spirit of the invention or the scope of the appended claims.
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An all terrain vehicle storage rack including an L-shaped bracket having a base for supporting a container thereon and an upstanding leg for detachably mounting on the back of an all terrain vehicle storage rack. A forward portion of at least one container retaining ring is secured to the upstanding leg. A rear portion of the ring is secured and to a rigidifying bar which spans the terminal end of the base and a rear portion of the container ring.
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The present disclosure relates generally to spiral wound membrane elements.
BACKGROUND
The following discussion is not an admission that anything discussed below is citable as prior art or common general knowledge.
Typically, a spiral wound membrane element is made by wrapping one or more membrane leaves around a perforated central tube. One edge of a feed carrier sheet is placed in a fold of a generally rectangular membrane sheet. The fold of the membrane sheet is positioned along a perforated central tube. A permeate carrier sheet is provided between each pair of membrane sheets. Glue lines seal the permeate carrier sheet between adjacent membrane sheets along three edges, forming a membrane leaf. The fourth edge of the leaf is open to the perforated central tube. All of the sheets are wrapped around the perforated central tube.
In use, the spiral wound membrane element is housed in a pressure housing, also referred to as a pressure tube or a pressure vessel. A pressurized feedstock is delivered at an upstream end of the pressure housing and flows into the spiral wound membrane element. Within the spiral wound membrane element, the pressurized feedstock flows through the feed spacer sheets and across the surface of the membrane sheets. The membrane sheets may have a discriminating layer that is suitably sized for microfiltration, ultrafiltration, reverse osmosis or nanofiltration. A portion of the pressurized feedstock is driven through the discriminating layer by transmembrane pressure to produce a permeate stream. The permeate stream flows along the permeate carrier sheets into the central tube for collection outside the pressure housing. The components of the pressurized feedstock that do not pass through the membrane, also referred to as retentate, continue to move through the feed spacer sheets to be collected at a downstream end of the pressure housing.
Some specific industries (for example the dairy industry) require sanitary spiral wound membrane elements that meet the requirements of the Sanitary 3A Standards for Crossflow Membrane Modules. Sanitary problems can arise in areas of low flow, also referred to as areas of tight tolerance. In areas of tight tolerance, there is limited fluid access and therefore limited flushing to remove solids or provide sanitization solutions. One region that typically has tight tolerance is between an inner surface of the pressure housing and the outer surface of the spiral wound membrane element, referred to as the annular space.
A common solution to low flow in the annular space is to direct a portion of the feedstock flow into the annular space. This is referred to as bypass flow. Bypass flow improves flushing of the annular space; however, the bypass flow also reduces the volume of feedstock that passes through the spiral wound membrane element to contribute to the production of permeate.
Various factors affect permeate production including temperature, osmotic pressure gradients, polarization layer, the charge of materials, fouling and the balance of fluid pressures across the membrane sheets, referred to as transmembrane pressure. The pressure of the feedstock within the feed spacer sheets influences the transmembrane pressure. As the permeate volume increases, the pressure and velocity of the feedstock within the feed spacer sheets decreases. Furthermore, the flow of feedstock through the feed spacer sheets is exposed to resistance, which is a source of head loss. Due to the volume loss of the feedstock and the head loss, the pressure and velocity of the feedstock within the feed spacer sheet decreases along the length of the spiral wound membrane element. This decreased feed spacer sheet pressure decreases the transmembrane pressure and decreases overall permeate production. The decreased velocity reduces disruption of the polarization layer at the membrane surface, which further reduces permeate production.
Typically, more than one spiral wound membrane element is housed in one pressure housing. For example, in the dairy industry between one and ten spiral wound membrane elements can be housed in one pressure housing. The multiple spiral wound membrane elements are connected in series and they typically share a common central tube. A standard dairy feedstock is introduced into the upstream end of the pressure housing at a pressure of about 100 psi. Along the length of a given spiral wound membrane element, the feed spacer sheet pressure may decrease about 5 to 10 psi. This pressure decrease can accumulate when multiple spiral wound membrane elements are used in one pressure housing and decrease the production of permeate within a given pressure housing.
SUMMARY
An axial bypass sleeve for use with spiral wound membrane elements are disclosed in the detailed description below. Part of the axial bypass sleeve protrudes away from the axial bypass sleeve. Another part of the axial bypass sleeve allows fluid communication through the axial bypass sleeve.
The axial bypass sleeve has a top surface and a bottom surface. The axial bypass sleeve can be wrapped around a spiral wound membrane element with the bottom surface in proximity to the spiral wound membrane element. The axial bypass sleeve comprises a protrusion and one or more holes that define a flow path. The protrusion can be integral with the axial bypass controls sleeve or the protrusion can be a second component. The holes allow fluid communication between the top surface and the bottom surface of the axial bypass sleeve.
In operation, the axial bypass sleeve is wrapped around a spiral wound membrane element. The spiral wound membrane element and axial bypass sleeve are placed inside a pressure housing, either alone or in series with other spiral wound membrane elements. Pressurized feedstock is introduced into a feed end of the pressure housing. A portion of the pressurized feedstock will contribute to a pressurized stream of bypass flow through an annular space between the inner surface of the pressure housing and the outer surface of the spiral wound membrane element. The protrusion restricts the bypass flow at a downstream location within the annular space, which modifies the pressure of the bypass flow.
Due to the pressure decrease along the length of the feed spacer sheets, a pressure gradient can develop between the annular space and within the feed spacer sheets. Without being bound by theory, this pressure gradient may cause pressurized feedstock within the bypass flow to flow through the flow path and into the feed spacer sheets of the spiral wound membrane element. This increases the flow rate of the feedstock within the feed spacer sheet. The increased flow rate of feedstock within the feed spacer sheet may contribute to increasing the transmembrane pressure and permeate production may increase along the length of the spiral wound membrane element.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A is a top-plan view of an axial bypass sleeve.
FIG. 1B is a partial cut-away, side view schematic drawing of an axial bypass sleeve wrapped around a spiral wound membrane element.
FIG. 2A a top-plan view of a second axial bypass sleeve.
FIG. 2B is a partial cut-away, side view schematic drawing of the second axial bypass sleeve wrapped around a spiral wound membrane element.
FIG. 3 is a top-plan view of a third axial bypass sleeve.
FIG. 4 is a schematic cut away drawing of three spiral wound membrane elements located within a pressure housing, each spiral wound membrane wrapped by the second axial bypass sleeve.
FIG. 5 cross-sectional view taken along line 5 - 5 1 of FIG. 4 .
DETAILED DESCRIPTION
An axial bypass sleeve for use with a spiral wound membrane element is described below. The axial bypass sleeve has a top or outside surface and a bottom or inside surface. A part of the sleeve protrudes away from the top surface of the axial bypass sleeve and another part of the sleeve is open between the top and bottom surfaces. A protrusion can be integral with the axial bypass sleeve. Alternatively, the protrusion can be a separate component that is positioned proximal, upon or below the rest of the axial bypass sleeve.
The FIGS. 1 to 5 depict an axial bypass sleeve for use with spiral wound membrane elements, as further described below. The axial bypass sleeve comprises a protrusion and at least one opening to allow fluid communication through the axial bypass sleeve.
FIG. 1A depicts an axial bypass sleeve 10 . The axial bypass sleeve 10 is generally planar and comprises a protrusion 14 and at least one access port 16 . As will be described below, the planar axial bypass sleeve 10 can be wrapped around a spiral wound membrane element 100 and can form a cylinder-like body. The axial bypass sleeve 10 has a first edge 18 , a second edge 20 , a first side 22 and a second side 24 . The protrusion 14 is shown as a region that begins at the dotted line in FIG. 1 , and ends at, or near, the second edge 20 . The access ports 16 are shown as a series of perforations through the axial bypass sleeve 10 and positioned between the first edge 18 and the protrusion 14 . The access ports 16 can be any shape or design that permits fluid communication through the axial bypass sleeve 10 . Optionally, there can be a greater density of access ports 16 proximal to the protrusion 14 .
FIG. 1B shows the axial bypass sleeve 10 wrapped around a spiral wound membrane element 100 . The protrusion 14 is shown as a region of gradually increased thickness. A variety of different approaches can be used to increase the thickness of the protrusion 14 . For example, during the manufacture of the axial bypass sleeve 10 , more materials can be incorporated to form a protrusion 14 that is integral with the axial bypass sleeve 10 with a predetermined thickness. The final thickness of the protrusion 14 can be decreased, if desired, by cutting away material from the protrusion 14 so the protrusion 14 has a desired thickness. Optionally, the protrusion 14 can be added to the axial bypass sleeve 10 after manufacture by one or more additional parts, for example, a ring inserted upon, or below the axial bypass sleeve 10 to form the protrusion 14 .
The cut away section of FIG. 1B depicts the spiral wound membrane element 100 underneath the axial bypass sleeve 10 . The axial bypass sleeve 10 is wrapped by fixing the first side 22 and the second side 24 together. The first side 22 and the second side 24 can be fixed together by suitable fixation methods that may include, thermal bonding, ultrasonic welding, adhesives and the like. The axial bypass sleeve 10 may be tension wrapped around the spiral membrane element 100 and the fixing of the first side 22 and the second side 24 maintains that tension. The tension wrapping of the axial bypass sleeve 10 may prevent or decrease telescopic unraveling or compression of the spiral wound membrane element 100 , as is known to occur under standard operational conditions.
The spiral wound membrane element 100 has an upstream end 104 and a downstream end 106 . As will be discussed further below, the upstream end 104 receives the pressurized feedstock. The downstream end 106 is the end of the spiral wound membrane element 100 where a permeate flow (not shown) and a retentate flow (not shown) are collected. The axial bypass sleeve 10 is oriented upon the spiral wound membrane element 100 with the first edge 18 closest to the upstream end 104 and the second edge 20 closest to the downstream end 106 .
The spiral wound membrane element 100 wraps around the central tube 108 . The spiral wound membrane element 100 comprises a mixed layer 110 of multiple layers of membrane leaves. The mixed layer 110 is formed by wrapping the membrane leaves around the central tube 108 so that each of the membrane sheet, the permeate carrier sheet and the feed spacer sheet have one edge that is close to the central tube 108 and one edge that is distal from the central tube 108 . At the periphery of the mixed layer 110 , distal to the central tube 108 , is an outer layer 116 . The outer layer 116 comprises the distal edges of the membrane leaves. In the outer layer 116 , the distal edges of the feed spacer sheets extend to and optionally past the distal edges of the membrane sheet and permeate carrier sheet of a membrane leaf. The distal edge of one feed spacer sheet can terminate on the feed spacer sheet of another membrane leaf. In that case, the outer layer 116 comprises feed spacer sheets that cover the distal edges of the membrane sheets and permeate carrier sheets and the feed spacer sheets provide fluid communication with the mixed layer 110 below. The feed spacer sheets prevent the distal edges of one membrane leaf from coming in direct contact with another leaf. Direct contact between the distal edges of different membrane leaves can create unsanitary areas of tight tolerance.
Optionally, the feed spacer sheets do not terminate on other feed spacer sheets, rather each feed spacer sheet terminates before covering the distal edge of a membrane leaf. However, in this case the feed spacer sheets still prevent the distal edges of different membrane leaves from coming in direct contact, while providing fluid communication with the mixed layer 110 .
Adjacent the outer layer 116 is the axial bypass sleeve 10 . Optionally, a cage (not shown) can be positioned between the outer layer 116 and the axial bypass sleeve 10 . The cage can be made of similar materials as the feed spacer sheets, optionally of larger dimensions. The cage can assist in structurally reinforcing the mixed layer 110 and the outer layer 116 .
FIG. 2A depicts a second axial bypass sleeve 210 . The second axial bypass sleeve 210 is generally planar and comprises a protrusion in the form of tabs 214 , and access ports 216 that are associated with each tab 214 (as shown in FIG. 2B ). As described further below, the access ports 216 are formed by the cutting of the tabs 214 from the second axial bypass sleeve 210 . Optionally, the access ports 216 are holes that are cut through the axial bypass sleeve 210 and the tabs 214 are fixed to the axial bypass sleeve 210 .
The second axial bypass sleeve 210 comprises a first edge 218 , a second edge 220 , a first side 222 and a second side 224 . In FIG. 2 , the tabs 214 are shown as generally rectangular in shape but other shapes may also be used.
The tabs 214 can be formed by two cut lines 226 of equal length through the axial bypass sleeve 210 . The two cut lines 226 each have a first end 228 and a second end 230 . The two cut lines 226 are cut parallel to the first and second sides 222 , 224 . An upstream cut line 232 is cut perpendicular to the two cut lines 226 and forms provides an edgewise connection, also referred to as the upstream edge, between the two first ends 228 . The upstream cut line 232 is parallel to the first and second edges 218 , 220 and the upstream cut line 232 is closest to the first edge 218 of the axial bypass sleeve 210 . The tabs 214 also have a joined side 234 that is integral with the axial bypass sleeve 210 and opposite and parallel to the third cut line 220 . The joined side 234 is closest to the second edge 220 . The joined side 234 provides a pivot point that allows the tabs 214 to move to an extended position. Optionally, the joined side 234 may be indented or creased to facilitate pivoting.
For the purposes of this disclosure, in the extended position, the tab 214 is not aligned with the planar surface of the axial bypass sleeve 210 and an upstream edge of the tab 214 , formed by the upstream cut line 232 , extends away from the planar surface. In the extended position, the tabs 214 open the access ports 216 and allow fluid communication through the access ports 216 . The pivotal connection affords the tab 214 a wide range of positions, as indicated by an angle ranging from about 1° to about 180° relative to the planar body of the axial bypass sleeve 210 . Optionally, while in the extended position the tab 214 is at an angle ranging from about 1° to about 90°, or from about 1° to about 45°, or from about 1° to about 30°. All of these degree ranges are relative to the planar body of the axial bypass sleeve 210 . When the tabs 214 are in the extended position, the associated access ports 216 are open to provide fluid communication across the planar body.
FIG. 2B depicts the second axial bypass sleeve 210 wrapped around a spiral wound membrane element 100 . The tabs 214 are shown in the extended position.
FIG. 3 depicts a third axial bypass sleeve 310 . The third axial bypass sleeve 310 is very similar to the axial bypass sleeve 210 , described above. The third axial bypass sleeve 310 is generally planar and comprises tabs 314 and access ports 316 . The third axial bypass sleeve 310 has a first edge 318 , a second edge 320 , a first side 322 and a second side 324 . The tabs 314 are made by a combination of cut lines and holes made through the third axial bypass sleeve 310 . Optionally, the access ports 316 are holes that are cut through the axial bypass sleeve 310 and the tabs 314 are fixed to the axial bypass sleeve 310 .
The tab 314 has two primary holes 328 cut through the third axial bypass sleeve 310 . An upstream cut line 332 connects the two primary holes 328 . The primary holes 328 have an upstream side 338 that is closest to the first edge 318 and a downstream side 340 that is closest to the second edge 320 . Each primary hole 328 has a first lateral side 342 closest to the first side 322 and a second lateral side 344 closest to the second side 324 . The upstream cut line 332 connects the upstream sides 338 of the two primary holes 328 . Between the two primary holes 328 and closer to the second edge 320 , two secondary holes 330 are cut through the third axial bypass sleeve 310 . A secondary cut line 336 joins the downstream side 340 of each primary hole 328 with the secondary holes 330 .
Between the two secondary holes 330 is a joined side 334 that provides a pivot point that allows the tabs 314 to move through a range of the extended position. In the extended position, the primary holes 328 and the secondary holes 330 contribute to the access port 316 , which provides fluid communication through the planar body of the third axial bypass control sleeve 310 .
In comparison to the tabs 214 , the tabs 314 generally have a more curvilinear shape with fewer corners, creases and edges, which are a source of tight tolerance. Optionally, a variety of other methods may be used to create a similar curvilinear shape, or other shapes of the tabs 314 that do not act as a source of tight tolerance.
Optionally, the axial bypass sleeves 10 , 210 , 310 can be cylindrical, such as a heat shrink tube or other forms of deformable sleeves that can be positioned around the spiral wound membrane element 100 , as described below.
The axial bypass sleeves 10 , 210 , 310 can be constructed of a number of suitable materials that preferably meet food contact standards. Examples of suitable materials include polypropylene, low-density polyethylene, high-density polyethylene and porous plastics. Optionally, the axial bypass sleeves 10 , 210 , 310 can be constructed of metal or alloys, such as 300 series stainless steel. Further, the axial bypass sleeves 10 , 210 , 310 can also be constructed of metal or alloys that are encapsulated within another suitable material, for example, aluminum encapsulated in polypropylene.
The number of tabs 214 , 314 can vary depending upon the size of the axial bypass sleeve 210 , 310 , which may depend upon the size of the spiral wound membrane element 100 used in a given application. Further, there may be a longitudinal distribution of tabs 214 , 314 such that a smaller number, or a greater number, of tabs 214 , 314 are positioned towards the first edge 218 , 318 in comparison to the second edge 220 , 320 . Preferably, a greater number of tabs 214 , 314 are positioned towards the second edge 220 , 320 .
FIG. 4 depicts three spiral wound membrane elements 100 , 100 1 , 100 11 positioned within a pressure housing 150 . The pressure housing 150 has an upstream end 152 with an inlet pipe 153 and a down stream end 154 with an outlet pipe 155 . The upstream end 152 and the downstream end 154 define a longitudinal axis of the pressure housing 150 , shown as line X in FIG. 4 . The pressure housing 150 is tubular in shape with an inner surface 156 and an outer surface 158 .
Each spiral wound membrane element 100 , 100 1 , 100 11 is shown wrapped by a second axial bypass sleeve 210 , 210 1 , 210 11 . Any of the axial bypass sleeves 10 , 210 and 310 are suitable to be positioned around a spiral wound membrane element 100 . The three spiral wound membrane elements 100 , 100 1 , 100 11 may be connected in series and share a common central tube 108 . Although only three spiral wound membrane elements 100 are shown in FIG. 4 , there can be four to eight, or more, spiral wound membrane elements 100 within a given pressure housing 150 .
FIG. 4 shows the tabs 214 in an extended position and extending through the annular space 160 in contact with the inner surface 156 of the pressure housing 150 . FIG. 5 depicts the cross-sectional area of the annular space 160 through which bypass flow is restricted by the tabs 214 . For clarity, FIG. 5 only shows the next set of tabs 214 seen through the section of line 5 - 5 1 .
In operation, the inlet pipe 153 introduces a pressurized feedstock (not shown) at the upstream end 152 of the pressure housing 150 . This creates a pressure gradient within the pressure housing 150 that drives the feedstock from the upstream end 152 towards the down stream end 154 , along the longitudinal axis of the pressure housing 150 . At least a portion of the pressurized feedstock enters the first spiral wound membrane element 100 at the upstream end 104 . The portion of pressurized feedstock enters and travels through the feed spacer sheets of the spiral wound membrane element 100 . A portion of the pressurized feedstock crosses the membrane sheet to form a permeate stream. The permeate stream flows through the permeate carrier sheets to be collected in the central tube 108 . The remaining pressurized feedstock within the feed spacer sheets forms the retentate stream, which continues to flow through the feed spacer sheets and exits the first spiral wound membrane element 100 at the downstream end 106 .
A portion of the retentate will enter the second spiral wound membrane element 100 1 at the upstream end 104 1 . This portion of the retentate stream proceeds through the second spiral wound membrane element 100 1 forming a second permeate stream and a second retentate stream. The second permeate stream is collected in the central tube 108 . The second retentate stream exits the second spiral wound membrane element 100 1 at the down stream end 106 1 and at least a portion of the second retentate stream enters the third spiral wound membrane element 100 11 at the upstream end 104 11 . The third spiral wound membrane element 100 11 forms a third permeate stream and a third retentate stream. The first, second and third permeate streams are collected from the central tube 108 and the third retentate stream exits the down stream end 106 11 and collected by the outlet pipe 155 at the downstream end 154 of the pressure housing 150 .
A portion of the pressurized feedstock enters the annular space 160 at the upstream end 152 of the pressure housing 150 to provide bypass flow. Due to the orientation of the axial bypass sleeve 10 , 210 , 310 the bypass flow is restricted by the protrusion 14 or the tabs 214 , 314 . The restriction helps to maintain the pressure of the bypass flow through the annular space 160 . With specific reference to the second and third axial bypass sleeves 210 , 310 the bypass flow pushes, and holds, the tabs 214 , 314 in the extended position. While in the extended position, a fluid path is created between the annular space 160 , through the access ports 216 , 316 and into the outer layer 116 of the spiral wound membrane element 100 . Based upon the pressure gradient between the annular space 160 and the outer layer 116 , a portion of the bypass flow will pass through the access ports 16 , 216 , 316 and enter the outer layer 116 . When inside the outer layer 116 , the bypass flow will enter the feed spacer sheets and flow into the mixed layer 110 . This increases the flow rate and pressure within the feed spacer sheets through out the spiral wound membrane element 100 , which increases the transmembrane pressure and contributes to increase the permeate production.
Along the longitudinal axis of the pressure housing 150 , at or past the downstream end 106 of the spiral wound membrane element 100 , the bypass flow that does not pass through the access ports 16 , 216 , 316 will mix with the retentate produced in the spiral wound membrane 100 . A portion of this mixture will enter the spiral wound membrane element 100 1 and a portion will enter the annular space 160 to create a bypass flow around the spiral wound membrane element 100 1 . This mixing of bypass flow and retentate flow will occur downstream of each spiral wound membrane element 100 , 100 1 , 100 11 within the pressure housing 150 .
Optionally, the tabs 214 , 316 can be in the extended position prior to loading the spiral wound membrane element 100 into the pressure housing 150 . For example, the tabs 214 , 314 may be opened to an approximate 45° angle relative to the planar body of the axial bypass sleeve 210 , 310 . Of particular interest to a horizontally oriented pressure housing 150 , the tabs 214 , 314 that are positioned on the bottom of the spiral wound membrane element 100 may elevate the spiral wound membrane element 100 off the lower inner surface 156 of the pressure housing 150 . The elevation of the spiral wound membrane element 100 may ease the loading of the spiral wound membrane element 100 .
The pressurized bypass flow may push the tabs 214 , 314 into contact with the inner surface 158 of the pressure housing 150 . This contact may assist in the centering of the spiral wound membrane element and cause a more even distribution of bypass flow around the entire circumference of the spiral wound membrane element 100 , independent of the orientation of the pressure housing 150 .
The range of movement through the extended position allows the tabs 214 , 314 to accommodate dimensional differences between the outer diameter of various spiral wound membrane elements 100 and diameters of the inner surface 156 of various pressure housings 150 .
This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art.
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The present disclosure describes an axial bypass sleeve for use with a spiral wound membrane element. The axial bypass sleeve has a protrusion and an opening that defines a flow path to provide fluid flow communication through the axial bypass sleeve. In use, the axial bypass sleeve is wrapped around a spiral wound membrane element and both are placed in a pressure housing. A pressurized feedstock is introduced into the pressure housing. A portion of the pressurized feedstock flows through the spiral wound membrane element to produce a permeate stream and a retentate stream. A portion of the pressurized feed stock flows around the spiral wound membrane element, called bypass flow. The protrusion extends into the annular space to restrict the bypass flow. A portion of the bypass flow passes through the opening and enters into the spiral wound membrane element to increase permeate production.
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BACKGROUND OF THE INVENTION
The present invention concerns a method for colour printing and magnetic encoding of plastic cards, in particular pre-paid cards, smart cards and the like.
The invention comprises also a compact, reliable, efficient, low-cost machine embodying said method.
There is a huge and fast development and commercial use in every field of the so called smart-cards.
Consequently there has been a parallel development of processes, systems and machines for the plastic cards identification, implementing the different technologies that have been brought about in the last 20 years.
The field of said methods, systems, machines and the like is now-a-day a so-called patent crowded field.
Among the most important aspects of this recent and continuously improving technology we have to emphasize the following:
1) Magnetic Encoding, 2) Thermal Printing, 3) Printing Ribbon Colour Detection, 4) Control of the Heat Energy feed to the Thermal Printing.
About aspect 1), there is a large number of patents, such as WO/0016235 and U.S. Pat. No. 5,941,522 that mostly concern the mechanical complexity of the design of a Plastic Card Printer including a Magnetic Encoder. Generally, however, the encoding is carried out after (downstream along the card path) the Printing, whereby there is the drawback that cards that are printed well may nevertheless be poorly downloaded because they have undergone a bad encoding with a non-negligible card waste.
As to item 2) we limit ourselves to cite U.S. Pat. No. 5,486,057.
European Patent Application Publication n. 0 299 653 A2 concerns a Method and Apparatus for the Thermal Printing and the relevant Thermal Heat feeding.
Several systems and methods for the Ribbon Colour Detection have been proposed and implemented, such as those described in WO 00/34050, EP Publications N. 0189574 A2 and N. 0 624 480 A2 and French Pat. Pub. N. 2 783 460 A1.
UK Patent Application N. 2 258 550 A, International Patent Publication WO 96/06739 and EP Publication 0 573 336 A1, concern the Thermal Printing Control through the control of the Heat feed to the Printing Head.
Moreover, up to now, the overall printing, encoding, colour detecting, and printing thermal control have been managed by an electronic system based on a CPU (Central Processing Unit), that implements for each control aspect a SW (Software) driver which has to execute its function at the same time, all together and in real time.
The computational complexity of all these drivers, executed in multitasking, has required the use of CPUs with increasing performances and resources, which generally are expensive and difficult to manage.
Accordingly, the methods and apparatus described in the Published Patent Literature show, together with several merits, also many decisive and conditioning inconveniences. Just to mention a major drawback, the conventional apparatus must have a longitudinal length of at least four times the major dimension of a card.
First object of the present invention is to provide a general method which eliminates the drawbacks and insufficiencies of the Prior Art, in particular of the Art according to the above mentioned Patents.
Another object of the present invention is to provide a compact, reliable, efficient and low cost machine implementing said method.
SUMMARY OF THE INVENTION
The present invention concerns a method for ribbon colour thermal printing and/or encoding cards particularly pre-paid-, smart-, chip-cards and the like, by detecting the printing ribbon colour, controlling the thermal printing energy feed and driving said printing encoding and detecting.
According to a first feature of the invention, a) said encoding is carried out spacially upstream to said thermal printing and b) detection takes place spacially between said encoding and printing and contemporaneously to said printing.
Typically step a) is carried out by critically coordinating encoding and printing, in particular by encoding at a distance from the printing lower then card major dimension. Characteristically for step b) the detection is positioned in a plane vertically superposed to the plane containing aligned encoding and printing, so to minimize both the length between encoding and printing and the height of the detection over printing.
Advantageously encoding, printing and detection are controlled by hardware (HW) reprogrammable i.e. with FPGA) while the thermal printing is controlled by controlling the thermal energy feed with the aid of a space-time convolution algorithm.
The invention comprises a compact, reliable, efficient and low-cost machine characterized in that along the card path from the card feeder to the card unloader, the encoder is spatially upstream from the thermal printer at a distance not greater than the major dimension of the card; the colour sensor is positioned between said encoder and printer but in a plane superposed to the plane of said encoder and printer containing also the card path line; and the spatial distance between sensor and printer, minimizing both the length and the height of the machine, is equal to the major dimension of the ribbon colour panel.
Further features of the invention are recited in the claims at the end of the specification, which are however considered herein incorporated.
BRIEF DESCRIPTION OF THE DRAWINGS
The various features and advantages of the invention will better appear from the following description of the embodiments represented in the accompanying drawings, in which:
FIG. 1 : is a block diagram of the overall system; according to the invention, in which while the Card to be processed (C) undergoes the Magnetic Encoding ( 1 ) and the Thermal Printing ( 3 ) under critical coordination between said steps of Encoding and Printing, the colour ribbon (R) undergoes the Colour Detection ( 2 ) and the Thermal Printing( 3 ) under critical coordination of Detection and Printing. The general system of the invention comprises an overall lower operative block (OS) and an upper overall processing block (OP). In the subsystem OS the card (C) is characteristically submitted firstly to the Magnetic Encoding ( 1 ) and secondly to the Thermal Printing ( 3 ) while the Ribbon (R) is submitted to Colour Detection ( 2 ) and to the Thermal Printing ( 3 ).
FIG. 2 : is a flow chart of operative block OS;
FIG. 3 : is a schematic partial front view of an apparatus according to the invention;
FIG. 3A : is a top view of a card C having A as maximal dimension;
FIG. 3B : is a prospective view of a colour ribbon R with three panels P having B as maximum dimension;
FIG. 3C shows the distance B between the center X 2 of the sensor 2 , in which the ribbon colour detection takes place, and the point X 3 , corresponding to the Dot line of the Printing Head, B being the maximum dimension of the panels P;
FIG. 4 : shows a traditional architecture of an electronic board controlling a system like a card Printer and Encoder;
FIG. 5 : shows the innovative architecture implemented in this invention, where the I/O (Input/Output) peripherals are mostly controlled by reprogrammable HW;
FIG. 6 : is a schematic representation of the Colour Sensor according to a preferred embodiment o the invention;
FIG. 7 : is a block diagram of the control HW of the Colour Detector of FIG. 6
FIG. 8 : is a block diagram of the HW implemented into the Receiver Interface for elaborating the output signal of the Receiver Unit, being such unit presented in FIG. 7
FIG. 9 : is the flow-chart describing the Colour Detector behaviour described in FIG. 6
FIG. 9 a : is the explosion of the Transmission Sequence represented in the Flow Chart of FIG. 9
FIG. 9 b : is the decisional table used by the colour detector driver for interpreting the information obtained during the transmission sequence.
FIG. 10 : is a block diagram of the Thermal Printing Head (TPH)
FIG. 11 : is a representation of the control signals to the Printing Head.
FIG. 12 : is the block diagram of the HW Driver that pilot the Printing Head for the Energy feeding control
FIG. 13 : is the Arithmetic Logic Unit computing the data-stream that must be transmitted to the Printing Head for performing the four Printing phases.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The first feature of the invention is that the encoding ( 1 ) is upstream the printing ( 3 ) with which is spacially aligned while the colour detection ( 2 ) is in the space between said encoding and printing but in a plane vertically different from the plane containing printer and encoder.
This is possible by critically coordinating the magnetic encoding ( 1 ) and the thermal printing ( 3 ), in the sense that the magnetic encoding and the thermal printing share a common portion of the machine longitudinal dimension, both referring to the same alignment photocell (not represented).
In contrast, in the conventional positioning, the total machine longitudinal dimension is at least four times the length of a card. In fact one card length is reserved to the card feeder (CF), two card lengths are reserved to the thermal printing and one card length is reserved to the magnetic encoding.
Accordingly with the new general spacial disposition of the three elements of the invention, the total length of the machine is not over 3 times the card length, which represents a space saving of 25%
At the same time, and as shown in FIG. 3 the colour detector ( 2 ) is located in the space between the encoder ( 1 ) and thermal printer ( 3 ). The distance between the colour detector ( 2 ) and the thermal printer ( 3 ) must be critically equal to the maximum dimension (length) B ( FIG. 3C ) of the ribbon Panel, allowing (surprisingly) a precise ribbon synchronization under the printing head (TPH), without a further movement of the ribbon from the sensor alignment position to the printing position, controlled through a position sensor, like for instance an incremental encoder.
The positioning of the colour detector ( 2 ) with respect to the thermal printer ( 3 ) is shown in FIGS. 3 and 3C . By indicating with X 2 the center of sensor ( 2 ) and with X 3 the center of printer ( 3 ), the distance from X 2 to X 3 is characteristically just B i.e. the major dimension of the panel P of the colour ribbon R ( FIG. 3B ). In FIGS. 3 and 3B , RO 1 and RO 2 indicate the rollers of the ribbon bobbins.
As shown in the top portion of FIG. 1 , the system of the invention comprises an Overall Processing block OP including a Central Processing Unit CPU controlling Driver D 1 associated to the Magnetic Encoder ( 1 ), Driver D 2 associated to the Color Sensor ( 2 ) and Driver D 3 associated to the Thermal Printing Head ( 3 ). Said processing block OP controls the lower operating block OS.
It can be immediately anticipated that, according to an advantageous feature of the invention, all Drivers are implemented in Reprogrammable HW (Hardware) and fitted into Devices, well known with the name of Field Programmable Gate Array (FPGA), and particularly the ones based onto the SRAM (Static Random Access Memory) technology.
Returning to the Overall System OS of the invention ( FIG. 1 ) it can be appreciated that the card C entering the machine operative block OS can follow three paths, namely:
a) Path 1: the card coming from the FEEDER (CF), enters through the line CF — 1 the Magnetic Encoding ( 1 ) and through line C 1 — 3 the Thermal Printing ( 3 ) arriving to the terminal CARD UNLOADER (CU) b) Path 2: the card coming from the FEEDER (CF), enters through line CF — 3 the Thermal Printing ( 3 ) bypassing the Magnetic Encoding ( 1 ) and through line C 3 — U arrives to said CARD UNLOADER (CU) c) Path 3: the card coming from the FEEDER (CF), enters through line CF — 1 the Magnetic Encoding ( 1 ) and through line C 1 — U arrives to said CARD UNLOADER (CU) without entering the Thermal Printing ( 3 )
The Ribbon (R) from the Ribbon Feeder (RF) arrives through line RF — 2 to Colour Detector ( 2 ) and through line R 2 — 3 arrives to Printer ( 3 ) from which goes to the Ribbon Recovery (RR).
FIG. 2 shows the Flow Chart of the two above treatments (flows of the card and of ribbon).
At the START point of the Process the Card C coming from the Card Feeder CF can follow two different paths, depending on the fact that it has to undergo the Magnetic Encoding ( 1 ) or not.
Path CF — 1
Via path CF — 1 the Card undergoes the phase corresponding to the Magnetic Data Encoding ( 1 A) (Data are written on the tracks selected by the User), and immediately thereafter undergoes the Magnetic Data Decoding ( 1 B) (The written data are Read and Verified); thereafter if the read data are correct in IC, the card is ready for the possible Thermal Printing ( 3 ). In case the verifying phase ( 1 B) of the written data doesn't succeed, further attempts of Encoding ( 1 A) and Decoding ( 1 B) are attempted up to a predefined maximum number, after which it is decided that the card is defective and has to be ejected.
Path CF — 3
When Magnetic Encoding is not required the card can directly and rapidly proceed to the Thermal Printing phase, bypassing thus the unnecessary encoding and enhancing the efficiency.
After the Magnetic Encoding two more paths are possible for the Card.
Path C 1 — 3
Through path C 1 — 3 the Card enters the Thermal Printing ( 3 ) process all together with the Colour Ribbon (R). The card processing and the Ribbon processing are synchronized at the beginning of each Colour Panel Printing, when the Card has to reach the Start of Printing Position and the Ribbon, under the control of the Colour Detector ( 2 ), has to reach the beginning of the next Colour Panel to be Printed.
When all the colour panels of the Ribbon have been Printed, the Card can reach the Unloader position (CU), through the C 3 — U path.
Path C 1 — U
Through the path C 1 — U, the card, after Magnetically Encoding ( 1 ), (a Thermal Printing phase being unnecessary), is directly discharged into the Unloader (CU).
As it can be appreciated also from the flow chart of FIG. 2 , the system is advantageously flexible: indeed it allows to avoid printing not only of cards not to be printed but also of cards badly encoded, with not-negligible savings of ribbon, time and thermal energy. Similarly for the cards not to be encoded.
Reprogrammable HW Implementing the Process Drivers
The prior art in the electronic system implemented for the control of Plastic Cards Thermal Printers and/or Encoders, has as unique flexibility's element, the one related to the SW (Software) code executed by the Central Processing Unit. In those electronic systems, once the HW (Hardware) resources are defined, the only functional improvement can be obtained by working on the Execution Code.
FIG. 4 represents the general structure of a traditional non reprogrammable HW in which the I/O (Input/Output) peripherals (interfacing to Actuators and Sensors) are defined by an appropriate configuration of standard non reconfigurable components (substantially known persè). Generally it comprises the classic Central Processing Unit CPU, a System Bus ( 37 ), Data Memory ( 35 ), Code Memory ( 34 ), I/O peripherals ( 30 ), acting on the Actuator Drivers ( 39 ) and receiving signals from Sensor ( 32 ) on the Sensor Interface ( 40 ).
This conventional architecture is knowingly unsuitable to give a reprogrammable HW: indeed it is absolutely lacking flexibility to allow functional upgrading or debugging.
Such a kind of architecture does not allow the possibility of adding, improving, or correcting the HW functionalities over time.
This aspect represents a great limitation in particular for the following reasons:
1) Higher development time of the electronic system; 2) The HW defects related to problems not considered during engineering phase can not be solved on the already produced boards; 3) Once in production it is no longer possible to implement further features or to improve the actual HW solutions.
An aspect of the present invention is that the structures of the overall system (OS) and of the Overall Processing (OP) allow the implementation of the HW technology based on the use of components called Field Programmable Gate Arrays (FPGA), whose HW configuration can be defined in the so called “In System Programming” (ISP).
Such ISP configuration of the HW allows to configure the FPGA components under control of the Central Processing Unit, downloading via SW a bit-stream that can be previously stored into the system non volatile memory ( 41 ′ in FIG. 5 ).
FIG. 5 represents the general structure of a reconfigurable HW, according to the invention, in which the I/O peripherals ( 30 ′) (interfacing Actuators ( 31 ′) through the appropriate Driver ( 39 ′) and Sensors ( 32 ′) trough the Sensor Interface ( 40 ′)) consist now of components whose configuration can be downloaded by the Central Processing Unit (CPU) through an HW Configuration Interface ( 42 ′), reading the configuration file from a dedicated memory (Hardware Configuration Memory, 41 ′).
Summarizing, the reprogrammable HW of the invention is obtained simply by replacing the standard I/O peripherals with In System Programmable and reconfigurable devices (Static RAM based FPGA), and introducing in the prior block diagram a configuration memory ( 41 ′) and an appropriate interface between the FPGAs and the CPU.
The procedure to update the HW is composed of the following steps:
1) an appropriate function supplied by a BIOS (Bootstrap Initialization Operating System) of the Printer provides the possibility to update the HW configuration memory ( 41 ′), with the file corresponding to the new release of the HW functionalities. 2) At the initialization cycle, the CPU configures the reprogrammable HW ( 30 ′) with the updated release present into the HW Configuration Memory ( 41 ′), through an appropriate interface ( 42 ′).
The major advantages of the HW reconfigurability are:
a) shorter Time to Market of the new product; b) capability of updating, improving and debugging the HW functionality also for the electronic boards already present into the market; c) capability of implementing at a HW level, instead of a SW level, new functionalities with the purpose of freeing the CPU work of a certain number of tasks, so that it's possible to obtain an overall improvement of the system performances and Real-Time Process control of complex devices.
Accordingly a further advantage of the present invention, is the fact that the Overall Processing block (OP) has been based on the previously described technology, so that each critical operation is controlled by an HW Driver, implemented into SW reconfigurable FPGA.
What is really important to underline is that it is now possible to update the HW configuration of the drivers, also at the customer side, through a download operation that can happen using the standard connection port of the machine itself.
In the following paragraphs are described the single Driver Implementation, with more emphasis to the Color Sensor Control and the Thermal Energy Feeding for the monochromatic printing.
Colour Detection
Preferably the colour detector ( 2 ) structure is advantageously implemented as shown in FIG. 6 .
The Ribbon (R), before undergoing the Thermal Printing ( 3 ), enters the Colour Detector ( 2 ), passing in the space between a transmitting unit (Tx) and a receiving unit (Rx). The recognition of the ribbon colour, happens by interpreting the information given by receiver (Rx), relative to the components of the emitted light that is able to pass the filtering action given by the presence of the ribbon R.
A preferred and advantageous embodiment of the Colour Detector( 2 ) is described in FIG. 7 .
As previously announced, the Colour Detector ( 2 ) is composed of a transmitter unit (Tx), a receiver unit (Rx), an HW interface towards the transmitter unit (Tx 1 ), an HW interface towards the receiver unit (Rx 1 ) and a driver (D 2 ) that is internally divided into at least two sub-units, one controlling the Transmitter function (TxD) and the other controlling the Receiving function (RxD).
The Transmitter Unit (Tx) is composed of three LEDs (Light Emitting Diodes), respectively of colour Red (Tx# 1 ), Green (Tx# 2 ) and Blue (Tx# 3 ).
Those LEDs are driven by power switches present into the Transmitter Interface, according to the control signals supplied by the transmitter driver (TxD).
The light intensity emitted by each LED is controlled through series trimmers, not represented, that are regulated through a calibration procedure using a particular calibration equipment, that are not described in the present document, as they can be considered persè known and requires no further details.
The Transmitter Driver (TxD) is composed by a Finite State Machine that is triggered by a periodic event to drive in sequence LEDs Tx# 1 , Tx# 2 , Tx# 3 , with an activation pulse, Tled, with a duration of 20 microseconds. Such activation time, Tied, has been determined as the characteristic response time of the photo-detectors.
The receiver unit (Rx) is composed by three equivalent large-band photo-detectors Rx# 1 , Rx# 2 , Rx# 3 , one for each transmitter, and mechanically faced to each relevant transmitter.
The receiver interface (RxI) acts as signal conditioning HW shown in the Block Diagram represented in FIG. 8 .
The signal outgoing the Receiver Unit (RX), named S — IN, at first enters block RX — F 1 , a Gain Amplifier (G), to generate a signal SI which is more significant with respect to the power supply range.
S 1 then enters the block RX — F 2 , an AC Decoupler, that filters the signal over the frequency of 10 KHz, obtaining a signal S 2 . S 2 enters block RX — F 3 , which is a Peak detector, to obtain a signal S 3 that store the maximum value reached by S 2 .
Then S 3 enters block RX — F 4 (a Sample-and-Hold Stage,) that samples S 3 in the period corresponding to the transmitter activation, obtaining signal S 4 . Thereafter S 4 is compared with a threshold voltage (in RX — F 5 ) positioned in the middle of the power supply voltage range and the result is stored into a detection result register (in RX — F 6 ) at the end of the transmitter activation pulse.
Both RX — F 4 (Sample and Hold) and RXJF 6 (Detection result Register) are fed with the LED enabling signal.
A further aspect of the present invention is the critical control and coordination of the activities implemented by the Transmitter and the Receiver Units, to constantly keep the Central Processing Unit informed about the colour status during ribbon movement.
This activity of control and coordination of the overall Colour Detector ( 2 ) is assigned to the HW reprogrammable Driver (D 2 ), that is preferably implemented as a Finite State Machine (FSM)(persè known).
The behaviour of such Colour Detector-FSM can be described through an Hardware Description Language, like VHDL (Very high speed integrated circuit Hardware Description Language), simply translating the behavioural flow chart shown in FIG. 9 .
FIG. 9 represents the behaviour of the Colour Detector Driver (D 2 ) implemented to control the Colour Detector shown in FIG. 7 .
In particular, the colour detection is periodically activated by a Trigger Generator (TG) that starts the Transmitter Activation Sequence (TC — SEQ), described in detail by the flow chart represented in FIG. 9A .
Following the Transmitter Activation Sequence (Tx — SEQ) comes a decoding phase (COL — DEC) in which the information stored during the previous sequence are interpreted to determine the ribbon colour present under the sensor.
In FIG. 9A the Transmission Sequence is represented with more details.
In FIG. 9B describes the Colour Decoding Table used by the driver D 2 to decode the information obtained during the Transmission Sequence TxSEQ.
Summarizing the ribbon colour information is obtained by a reprogrammable HW, that has a repetitive behaviour. This Driver, periodically activated, excites in sequence the three transmitting LEDs Tx# 1 , Tx# 2 and Tx# 3 , and composing the three correspondent responses, obtains an information that is decoded using the Colour Detecting Table of FIG. 9B .
In conclusion, this section has presented an implementation of the preferred embodiment of the Colour Detector ( 2 ) Driver (D 2 ) onto an HW reprogrammable device.
The behaviour of the control function of this driver, is well suited for an HW implementation, since it is a repetitive control cycle that can be easily described through a Finite State Machine.
Such FSM behaviour can be easily translated into such HW implementation using an Hardware Description Language.
The result of the implementation into an HW level of the Colour Detector Driver (D 2 ) allows one to free the CPU of a hard duty, and at the same time allows one to have real time information of the ribbon colour.
Energy Feeding Control for a Thermal Printing Head
The core problem of a Thermal Card Printer is the heat control of the printing elements.
The thermal printing of plastic cards, uses the transfer of coloured pigments from a Ribbon (R) to the plastic card (C).
This ink transfer requires a flow of heating energy to the printing elements (DOTs), usually implemented as ceramic resistors, to carry the ink molecules to the separation temperature.
Once the transfer temperature is reached, it is needed to transfer to the DOT a further quantity of energy for modulating the quantity of pigment that it's needed to move from the ribbon to the card.
The device that allows the thermal transfer control, is a printing head (TPH in FIG. 3 ) in which the printing elements (DOTs) are realized through ceramic micro-resistors, ideally positioned on the straight line of contact, mediated by the ribbon, between the head and the card.
In FIG. 10 is shown the block diagram of the TPH functioning.
The TPH is composed of a shift-register (SR) on which is the data that defines the DOTs activation enable to the heating for the next printing. This insertion can happen while a previously inserted DOT line is running the heating cycle.
When the previous heating cycle is completed, the data present on the shift-register (SR) are loaded on a latch register (LR) whose outputs enable the power switches that feed the DOT.
When the control signal STROBE is activated, the DOTs that are enabled by the signals coming from the latch register (LR), are powered for the time of activation (Tstrobe) of the STROBE (STR), developing an energy of
Ed ={[(24V)^2/ R head]* T strobe}.
In an ideal case in which the printing elements were without thermal memory and without thermal interference (each thermally isolated), the calculation of the energy necessary to get the desired thermal state would be extremely simplified.
However, this simplification is not admissible when it's desired to get printings of excellent quality also in conditions of high speed, that is of a minimum delay between the printing of one line and of the following one.
A complete mathematical model of the thermal behaviour of the Dots, should consider the effects deriving from their printing history and the Energy contributions coming from all the neighboring heating elements.
A simplified, but effective, model considers the contributions of the first adjoining heating element, and the DOT history departing from the medium head temperature and taking into account the activity of each element just on the row before the present.
The heating control system, implemented in the present invention considers the non-ideality of the Printing Head, that are the DOT thermal memory and the thermal contribution that influences one dot printing area coming from the neighboring heating elements.
For simplification, the system will be here described as limited to the monochromatic printing and be named “Spacial and Temporal Convolution for the Dot energy feeding computation”.
The Energy feeding for each printing line, corresponding to one image vertical row, is decomposed in four fundamental components, that are:
1. Local Preheating: it is an heating phase that is applied to all such Dots that in the present printing line must be lighted (in correspondence of a Black Pixel) and in the preceding line were out (White Pixel). This preheating is necessary for carrying the coolest Dots to the medium head temperature. 2. Global Preheating: it is an heating phase that is applied to all the Dots for carrying them to the thermal transfer 3. Printing Heating: it is an heating phase that is applied to all the Dots that must sustain the thermal transfer temperature, for the time necessary to transfer in all the printing area (whose dimension is, for a 300 DPI resolution, of 84 μm*84 μm) the ribbon ink, 4. Convolution Heating: it is an heating phase that is applied to those lighted Dot, for which at least one of the neighbours is off. This heating applies a further energy contribution equivalent to the energy that a lighted Dot transfers onto the area of interest of the adjoining Dot.
FIG. 11 shows the control signals to the Printing Head (TPH), under such a control system.
In this figure are evident the DATA 0 input signal, the serializing CLOCK, the LACTH signal and the STROBE signal.
DATA 0 is serially inserted into the Shift-Register (SR), then the SR outputs are stored into the Latch Register (LR), and finally the STROBE signal activate when low, the Dot energizing phase.
The four heating phases are shown:
Phase 2 (P 2 ) corresponds to the Global Preheating, phase 1 (P 1 ) corresponds to the Local Preheating, Phase 4 (P 4 ) is the Convolution Heating and Phase 3 (P 3 ) is the Printing Heating.
This complex system has been developed into the HW Driver (D 3 ) of the Thermal Printing ( 3 ).
FIG. 12 shows the block diagram of the HW Driver (D 3 ) that pilots the Printing Head for the Energy feeding control.
At each printing Row, corresponding to a image line or Bitmap row of a Graphic RAM, the previous line data, stored into the Current Row Register set ( 60 ), are shifted into the Previous Row Register set ( 61 ), during the phase PA, and the CPU ( FIG. 1 ecc.) feeds the Current Row Register set ( 61 ) with the data corresponding to the current Image Line to Print during the phase PB.
The Arithmetic Logic Unit (ALU), computes the four data sequences to feed into the Thermal Printing Head, corresponding to the four Heating contributions previously described.
Each data sequence is fed into the TPH through a Serialize Unit (SU) that controls the TPH control signals, i.e. the Data, Clock and Latch.
The ALU unit feeds the Output Shift Register of the Driver (D 3 ) performing the computations described in FIG. 13 .
In FIG. 13 the mathematical procedure for obtaining the four data stream to feed into the Thermal Print Head is shown.
In particular:
STEP 1 corresponds to the Global PreHeating phase, in which all Dots have to be energized. In this case the Thermal Print Head is fed with a constant row RC, composed by all ones.
STEP 2 corresponds to the Local PreHeating phase, in which it is necessary to activate the Dots that are lighted in the current row RB=Row (Row i), and were not lighted in the previous row RA=(Row i−1). In this case the Thermal Print Head is fed with a row RD, achieved with the following formula: RD=RB and (not RA).
STEP 3 corresponds to the Printing Heating phase, in which the current Row (RB=Row i) is transferred into the Thermal Printing Head (TPH) to be Printed.
STEP 4 corresponds to the Convolution Heating phase, in which it is necessary to activate the Dots that are lighted in the current Row (RB=Row i), that have at least one neighbour that is off.
In this case the Thermal Print Head is fed with a row RD, obtained with the following formula:
RD =( RB[k] xor RB[k]<< 1) or ( RB[k] xor RB[k]>> 1)
After each step the Driver informs the CPU that the Head is ready for printing through an interrupt service routine, than the CPU pilots the STROBE signal to energize the selected Dots for the time required to each function to be performed.
In conclusion, in this paragraph an efficient system for the energy feeding of a thermal print head has been presented. This system considers the non idealities of the printing elements that are the thermal memory of each dot and the thermal interference that happens between neighboring dots.
This system for being efficiently implemented requires to demand a relevant part of the head control to an HW Driver.
An embodiment of such HW, that has been realized by means of a Field Programmable Gate Array, has been presented by describing its structure and basic working.
Once again the opportune system co-design, HW and SW, has allowed one to obtain an optimum trade-off between performance and printing quality, keeping a sufficient level of flexibility, so that this system is open to future improvements.
For illustrative clarity the invention has been described with particular reference to the embodiments represented in the accompanying drawings. It is obvious that all changes, alternatives, substitutions and the like to said embodiments which are in the reach of one skilled in the art are to be considered as falling within the scope and the spirit of the following claims.
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A method for ribbon color thermal printing and encoding cards, particularly pre-paid, smart cards, chip cards, and the like is disclosed. The method includes the steps of detecting the printing ribbon color, controlling the thermal printing energy feed and driving the printing, encoding and detection, in which the encoding is carried out at a location upstream of the thermal printing. The color detection is carried out at a location between the encoding and/or thermal printing, and at the same time as the printing.
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FIELD OF THE INVENTION
[0001] This invention concerns certain novel compounds or pharmaceutically acceptable salts or solvates thereof, processes for preparing these compounds, pharmaceutical compositions comprising them and their use in the treatment, prevention or delay of progression of proliferative disease, such as cancer.
BACKGROUND OF THE INVENTION
[0002] Histone deacetylases (HDACs) are zinc-containing enzymes which catalyse the removal of acetyl groups from the s-amino termini of lysine residues clustered near the amino terminus of nucleosomal histones. There are 18 known HDACs which may be divided into four classes based on their homology to yeast histone deacetylases: Class I (HDACs 1, 2, 3 and 8) which are related to the yeast RPD3 gene; Class II (HDACs 4, 5, 6, 7, 9 and 10) which are related to the yeast Hda1 gene; Class III, also known as the sirtuins, which are related to the Sir2 gene, and Class IV (HDAC11) which contains features of both Class I and II.
[0003] Deregulation of certain HDAC inhibitors has been associated with several cancers and HDAC inhibitors such as Trichostatin A have been shown to exhibit significant anti-tumour effects and inhibit cell-growth (Meinke, Current Medicinal Chemistry, 8, 211-235, 2001). According to Yoshida et al (Exper. Cell Res., 177,122-131, 1988), Trichostatin A causes arrest of rat fibroblasts at the G1 and G2 phases of the cell cycle, thereby implicating HDAC in cell cycle regulation. Furthermore, Trichostatin A has been shown to induce terminal differentiation, inhibit cell growth, and prevent the formation of tumours in mice (Finnin et al, Nature, 401, 188-193 (1999)).
[0004] Benzamide derivatives having HDAC inhibitory activity are disclosed in WO 2005/121073 and discussed in Zhou et al. J. Med Chem, 2008, 51, 4072-5.
[0005] The objective of the present invention is to provide alternative novel compounds that are selective for particular Class I HDAC enzymes, particularly HDAC 2 and/or 3.
SUMMARY OF THE INVENTION
[0006] In accordance with the present invention, the applicants have hereby discovered novel compounds, or pharmaceutically acceptable salts or solvates thereof, which possess HDAC inhibitory activity. In particular, the compounds of the invention demonstrate selectivity towards Class I HDAC enzymes, and are accordingly expected to be useful for their anti-proliferation activity and in methods of treatment of the human or animal body, for example in preventing or inhibiting tumour growth and metastasis in cancers. The compounds of the invention are also expected to be useful agents for the treatment of inflammatory conditions, such as rheumatoid arthritis. The present invention also relates to processes for the manufacture of the compounds defined herein, or pharmaceutically acceptable salts or solvates thereof, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of anti-proliferative/anti-inflammatory activity in warm-blooded animals such as man.
[0007] Also, in accordance with the present invention the applicants provide methods of using such compounds, or pharmaceutically acceptable salts thereof, in the treatment of cancer and/or inflammatory conditions such as rheumatoid arthritis.
DETAILED DESCRIPTION OF THE INVENTION
Definitions
[0008] Unless otherwise stated, the following terms used in the specification and claims have the following meanings:
[0009] The term “alkyl” is used herein to refer to a straight or branched chain alkyl moiety. The term “C 1-6 alkyl” refers to alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms. This term includes groups such as methyl, ethyl, propyl (n-propyl or isopropyl), butyl (n-butyl, sec-butyl or tert-butyl), pentyl, hexyl and the like. Suitably an alkyl group has 1, 2, 3 or 4 carbon atoms. The term alkyl also includes cycloalkyl or cycloalkyl-alkyl groups. For example, the term “C 1-6 alkyl” includes C 3-6 cycloalkyl groups, such as cyclopropyl, cyclobutyl and cyclohexyl and cycloalkyl-alkyl groups such as cyclopropylmethyl. An analogous convention applies to other generic terms, for example “alkenyl” and “alkynyl”.
[0010] The term “cycloalkyl” as used herein includes reference to an alicyclic moiety having 3 to 7 carbon atoms. This term includes groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
[0011] The term “alkoxy” as used herein include reference to —O-alkyl groups, wherein the alkyl moiety is a straight or branched chain. The term “C 1-6 alkoxy” and comprises 1, 2, 3, 4, 5 or 6 carbon atoms. Suitably, an alkoxy group has 1, 2, 3 or 4 carbon atoms. This term includes reference to groups such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentoxy, hexoxy and the like.
[0012] “Heterocyclyl” is a saturated, unsaturated or partially saturated monocyclic or bicyclic ring containing 4 to 12 atoms of which 1, 2, 3 or 4 ring atoms are chosen from nitrogen, sulphur or oxygen, which ring may be carbon or nitrogen linked, wherein a —CH 2 — group can optionally be replaced by a —C(O)—; wherein a ring nitrogen or sulphur atom is optionally oxidised to form the N-oxide or S-oxide(s); wherein a ring —NH is optionally substituted by acetyl, formyl, methyl or mesyl; and wherein a ring is optionally substituted by one or more halo. Suitable examples of the term heterocyclyl include morpholinyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and the like.
[0013] The term “aryl” means a cyclic or polycyclic aromatic ring system having from 5 to 12 carbon atoms. The term aryl includes both monovalent species and divalent species. Examples of aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl and the like.
[0014] The term “heteroaryl” as used herein includes reference to an aromatic heterocyclic ring system having 5 to 12 ring atoms, at least one of which (suitably 1, 2 or 3) is selected from nitrogen, oxygen and sulphur. The group may be a polycyclic ring system, having two or more rings, at least one of which is aromatic, but is more often monocyclic. Illustrative examples of heteroaryls include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazenyl, benzofuranyl, indolyl, isoindolyl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, isoquinolyl, quinazolinyl, and quinoxalinyl.
[0015] The term “halogen” as used herein refers to F, Cl, Br or I.
[0016] The term “oxo” is used herein to denote a double bonded oxygen atom. An oxo group is normally attached to a carbon atom so that oxygen atom and carbon together form a carbonyl (—C(O)—) group.
Compounds
[0017] According to a first aspect of the present invention, there is provided a compound of the formula (I):
[0000]
R a is independently selected from hydrogen, —C(O)O—R b or —C(O)NHR b , where R b is hydrogen or a C 1-6 alkyl group which is optionally substituted by one or more substituents independently selected from halogen, cyano, amino, hydroxy and C 1-2 alkoxy;
X is —C(O)—, —S—, —S(O)—, —S(O) 2 — or a C 1-2 alkylene linker;
R 1 is selected from hydrogen, oxo, or a C 1-2 alkyl group which is optionally substituted by halo, nitro or cyano;
or R 1 is a group:
[0000] -Q 1 -X 1 —R 2
wherein: Q 1 is a C 1-2 alkylene; X 1 is selected from —O—, —N(R x )—, —C(O)—, —C(O)—O—, —O—C(O)—, —C(O)N(R x )—, —N(R x )C(O)—; R x is selected from hydrogen or C 1-2 alkyl; R 2 is selected from hydrogen, C 1-4 alkyl, phenyl, wherein any C 1-4 alkyl or phenyl group is optionally substituted with one or more substituents selected from halogen, cyano, amino, hydroxyl, C 1-2 alkyl, C 1-2 alkoxy or a group:
[0000] X 2 —R 3
where X 2 is selected from —O—, —NH—, —C(O)—, —C(O)—O—, —O—C(O)—, —C(O)NH—, —NHC(O)—; R 3 is C 1-4 alkyl or C 2-4 alkenyl which is optionally substituted by halo, hydroxy, amino, cyano, C 1-2 alkyl, C 1-2 alkoxy, or a phenyl group which is optionally further substituted by one or more substituent groups selected from hydroxy, halo, cyano, nitro or methoxy; or R x and R 2 are linked such that, together with the nitrogen atom to which they are attached, they form a piperidine, piperazine, N-methyl piperazin-4-yl or morpholino ring; or a pharmaceutically acceptable salt or solvate thereof.
[0030] Particular novel compounds of the invention include, for example, compounds of the formula I, or pharmaceutically acceptable salts thereof, wherein, unless otherwise stated, each of R a , X and R 1 has any of the meanings defined hereinbefore or in any of paragraphs (1) to (11) hereinafter:—
(1) R a is independently selected from hydrogen, —C(O)O—R b or —C(O)NHR b , where R b is hydrogen or a C 1-4 alkyl group which is optionally substituted by one or more substituents independently selected from amino, hydroxy and C 1-2 alkoxy; (2) R a is independently selected from hydrogen, —C(O)O—R b or —C(O)NHR b , where R b is hydrogen or a C 1-2 alkyl group which is optionally substituted by one or more substituents independently selected from amino, hydroxy and C 1-2 alkoxy; (3) R a is hydrogen, —C(O)O—CH 3 , or —C(O)NH—CH 2 —CH 2 —NH 2 ; (4) X is selected from —S(O) 2 — and methylene; (5) X is methylene; (6) X is —S(O) 2 —; (7) R 1 is selected from hydrogen, oxo, C 1-2 alkyl optionally substituted by cyano;
or R 1 is a group:
[0000] -Q 1 -X 1 —R 2
wherein:
Q 1 is methylene;
X 1 is selected from —O—, —N(R x )—, —C(O)—, —C(O)—O—, —O—C(O)—, —C(O)N(R x )—, —N(R x )C(O)—;
R x is selected from hydrogen or C 1-2 alkyl; R 2 is selected from hydrogen, C 1-2 alkyl, phenyl, wherein any C 1-2 alkyl or phenyl group is optionally substituted with one or more substituents selected from halogen, cyano, amino, hydroxyl, C 1-2 alkyl, C 1-2 alkoxy or a group:
[0000] X 2 —R 3
where: X 2 is selected from —O—, —NH—, —C(O)—, —C(O)—O—, —O—C(O)—, —C(O)NH—, —NHC(O)—; R 3 is C 1-4 alkyl or C 2-4 alkenyl which is optionally substituted by halo, hydroxy, amino, C 1-2 alkyl, C 1-2 alkoxy, or a phenyl group which is optionally further substituted by one or more substituent groups selected from hydroxy or methoxy; or R x and R 2 are linked such that, together with the nitrogen atom to which they are attached, they form a piperidine, piperazine, N-methyl piperazine or morpholino ring; (8) R 1 is selected from hydrogen, oxo, C 1-2 alkyl optionally substituted by cyano;
or R 1 is a group:
[0000] -Q 1 -X 1 —R 2
wherein:
Q 1 is methylene; X 1 is selected from —C(O)—O—, or —C(O)N(R x )—; R x is hydrogen; R 2 is selected from hydrogen, C 1-2 alkyl, phenyl, wherein any C 1-2 alkyl or phenyl group is optionally substituted with one or more substituents selected from halogen, cyano, amino, hydroxyl, or a group:
[0000] X 2 —R 3
where: X 2 is selected from —C(O)—O— or —C(O)NH—; R 3 is C 1-4 alkyl or C 2-4 alkenyl which is optionally substituted by halo, hydroxy, amino, C 1-2 alkyl, C 1-2 alkoxy, or a phenyl group which is optionally further substituted by one or more substituent groups selected from hydroxy or methoxy; or R x and R 2 are linked such that, together with the nitrogen atom to which they are attached, they form a piperidine, piperazine, N-methyl piperazine or morpholino ring; (9) R 1 is selected from hydrogen, oxo or methyl optionally substituted by cyano;
or R 1 is a group:
[0000] -Q 1 -X 1 —R 2
wherein:
Q 1 is methylene; X 1 is selected from —C(O)—O—, or —C(O)N(R x )—; R x is hydrogen; R 2 is selected from hydrogen, C 1-2 alkyl, phenyl, wherein a C 1-2 alkyl or phenyl group is optionally substituted with one or more substituents selected from halogen, cyano, amino, hydroxyl, or a group:
[0000] X 2 —R 3
where: X 2 is selected from —C(O)NH—; R 3 is C 2-4 alkenyl which is optionally substituted by a phenyl group which is optionally further substituted by one or more substituent groups selected from hydroxy or methoxy; or R x and R 2 are linked such that, together with the nitrogen atom to which they are attached, they form a piperidine, piperazine, N-methylpiperazine or morpholino ring; (10) R 1 is oxo or methyl optionally substituted with cyano; (11) R 1 is oxo;
[0072] In a particular group of compounds of the invention, X is SO 2 or a methylene linker and R a and R 1 have any one of the definitions set out hereinbefore.
[0073] In a particular group of compounds of the invention, X is SO 2 or a methylene linker, R a is hydrogen and R 1 has any one of the definitions set out hereinbefore.
[0074] Particular examples of compounds of the invention include those shown below. It will of course be appreciated that, where appropriate, each compound may be in the form of the free compound, an acid or base addition salt, or a prodrug.
[0000]
[0075] The various functional groups and substituents making up the compounds of the formula I are typically chosen such that the molecular weight of the compound of the formula I does not exceed 1000. More usually, the molecular weight of the compound will be less than 750, for example less than 700, or less than 650, or less than 600, or less than 550. More preferably, the molecular weight is less than 525 and, for example, is 500 or less.
[0076] A suitable pharmaceutically acceptable salt of a compound of the invention is, for example, an acid-addition salt of a compound of the invention which is sufficiently basic, for example, an acid-addition salt with, for example, an inorganic or organic acid, for example hydrochloric, hydrobromic, sulfuric, phosphoric, trifluoroacetic, formic, citric or maleic acid. In addition a suitable pharmaceutically acceptable salt of a compound of the invention which is sufficiently acidic is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium or magnesium salt, an ammonium salt or a salt with an organic base which affords a physiologically-acceptable cation, for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine.
[0077] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (−)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”.
[0078] The compounds of this invention may possess one or more asymmetric centers; such compounds can therefore be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof. Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see discussion in Chapter 4 of “Advanced Organic Chemistry”, 4th edition J. March, John Wiley and Sons, New York, 2001), for example by synthesis from optically active starting materials or by resolution of a racemic form. Some of the compounds of the invention may have geometric isomeric centres (E- and Z-isomers). It is to be understood that the present invention encompasses all optical, diastereoisomers and geometric isomers and mixtures thereof that possess HDAC inhibitory activity.
[0079] It is also to be understood that certain compounds of the formula I may exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated forms that possess HDAC inhibitory activity.
[0080] It is also to be understood that certain compounds of the formula I may exhibit polymorphism, and that the invention encompasses all such forms that possess HDAC inhibitory activity.
[0081] Compounds of the formula I may exist in a number of different tautomeric forms and references to compounds of the formula I include all such forms. For the avoidance of doubt, where a compound can exist in one of several tautomeric forms and only one is specifically described or shown, all others are nevertheless embraced by formula I. Examples of tautomeric forms include keto-, enol-, and enolate-forms, as in, for example, the following tautomeric pairs: keto/enol (illustrated below), imine/enamine, amide/imino alcohol, amidine/amidine, nitroso/oxime, thioketone/enethiol, and nitro/aci-nitro.
[0000]
[0082] Compounds of the formula I containing an amine function may also form N-oxides. A reference herein to a compound of the formula I that contains an amine function also includes the N-oxide. Where a compound contains several amine functions, one or more than one nitrogen atom may be oxidised to form an N-oxide. Particular examples of N-oxides are the N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle. N-Oxides can be formed by treatment of the corresponding amine with an oxidizing agent such as hydrogen peroxide or a per-acid (e.g. a peroxycarboxylic acid), see for example Advanced Organic Chemistry , by Jerry March, 4 th Edition, Wiley Interscience, pages. More particularly, N-oxides can be made by the procedure of L. W. Deady ( Syn. Comm. 1977, 7, 509-514) in which the amine compound is reacted with m-chloroperoxybenzoic acid (MCPBA), for example, in an inert solvent such as dichloromethane.
[0083] The compounds of formula I may be administered in the form of a pro-drug which is broken down in the human or animal body to release a compound of the invention. A pro-drug may be used to alter the physical properties and/or the pharmacokinetic properties of a compound of the invention. A pro-drug can be formed when the compound of the invention contains a suitable group or substituent to which a property-modifying group can be attached. Examples of pro-drugs include in vivo cleavable ester derivatives that may be formed at a carboxy group or a hydroxy group in a compound of the formula I and in-vivo cleavable amide derivatives that may be formed at a carboxy group or an amino group in a compound of the formula I.
[0084] Accordingly, the present invention includes those compounds of the formula I as defined hereinbefore when made available by organic synthesis and when made available within the human or animal body by way of cleavage of a pro-drug thereof. Accordingly, the present invention includes those compounds of the formula I that are produced by organic synthetic means and also such compounds that are produced in the human or animal body by way of metabolism of a precursor compound, that is a compound of the formula I may be a synthetically-produced compound or a metabolically-produced compound.
[0085] A suitable pharmaceutically acceptable pro-drug of a compound of the formula I is one that is based on reasonable medical judgement as being suitable for administration to the human or animal body without undesirable pharmacological activities and without undue toxicity.
[0086] Various forms of pro-drug have been described, for example in the following documents:—
a) Methods in Enzymology , Vol. 42, p. 309-396, edited by K. Widder, et al. (Academic Press, 1985); b) Design of Pro-drugs, edited by H. Bundgaard, (Elsevier, 1985); c) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 “Design and Application of Pro-drugs”, by H. Bundgaard p. 113-191 (1991); d) H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1-38 (1992); e) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988); f) N. Kakeya, et al., Chem. Pharm. Bull., 32, 692 (1984); g) T. Higuchi and V. Stella, “Pro-Drugs as Novel Delivery Systems”, A.C.S. Symposium Series, Volume 14; h) E. Roche (editor), “Bioreversible Carriers in Drug Design”, Pergamon Press, 1987; and i) Ferguson et al. Drug Resistance Updates, 4, 225-232 (2001).
[0096] A suitable pharmaceutically acceptable pro-drug of a compound of the formula I that possesses a carboxy group is, for example, an in vivo cleavable ester thereof. An in vivo cleavable ester of a compound of the formula I containing a carboxy group is, for example, a pharmaceutically acceptable ester which is cleaved in the human or animal body to produce the parent acid. Suitable pharmaceutically acceptable esters for carboxy include
[0000] C 1-6 alkyl esters such as methyl, ethyl and tert-butyl, C 1-6 alkoxymethyl esters such as methoxymethyl esters, C 1-6 alkanoyloxymethyl esters such as pivaloyloxymethyl esters,
3-phthalidyl esters, C 3-8 cycloalkylcarbonyloxy-C 1-6 alkyl esters such as cyclopentylcarbonyloxymethyl and 1-cyclohexylcarbonyloxyethyl esters, 2-oxo-1,3-dioxolenylmethyl esters such as 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl esters and C 1-6 alkoxycarbonyloxy-C 1-6 alkyl esters such as methoxycarbonyloxymethyl and 1-methoxycarbonyloxyethyl esters.
[0097] A suitable pharmaceutically acceptable pro-drug of a compound of the formula I that possesses a hydroxy group is, for example, an in vivo cleavable ester or ether thereof. An in vivo cleavable ester or ether of a compound of the formula I containing a hydroxy group is, for example, a pharmaceutically acceptable ester or ether which is cleaved in the human or animal body to produce the parent hydroxy compound. Suitable pharmaceutically acceptable ester forming groups for a hydroxy group include inorganic esters such as phosphate esters (including phosphoramidic cyclic esters). Further suitable pharmaceutically acceptable ester forming groups for a hydroxy group include C 1-10 alkanoyl groups such as acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups, C 1-10 alkoxycarbonyl groups such as ethoxycarbonyl, N,N—(C 1-6 ) 2 carbamoyl, 2-dialkylaminoacetyl and 2-carboxyacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(C 1-4 alkyl)piperazin-1-ylmethyl. Suitable pharmaceutically acceptable ether forming groups for a hydroxy group include α-acyloxyalkyl groups such as acetoxymethyl and pivaloyloxymethyl groups.
[0098] A suitable pharmaceutically acceptable pro-drug of a compound of the formula I that possesses a carboxy group is, for example, an in vivo cleavable amide thereof, for example an amide formed with an amine such as ammonia, a C 1-4 alkylamine such as methylamine, a (C 1-4 alkyl) 2 amine such as dimethylamine, N-ethyl-N-methylamine or diethylamine, a C 1-4 alkoxy-C 2-4 alkylamine such as 2-methoxyethylamine, a phenyl-C 1-4 alkylamine such as benzylamine and amino acids such as glycine or an ester thereof.
[0099] A suitable pharmaceutically acceptable pro-drug of a compound of the formula I that possesses an amino group is, for example, an in vivo cleavable amide derivative thereof. Suitable pharmaceutically acceptable amides from an amino group include, for example an amide formed with C 1-10 alkanoyl groups such as an acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, N-alkylaminomethyl, N,N-dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(C 1-4 alkyl)piperazin-1-ylmethyl.
[0100] The in vivo effects of a compound of the formula I may be exerted in part by one or more metabolites that are formed within the human or animal body after administration of a compound of the formula I. As stated hereinbefore, the in vivo effects of a compound of the formula I may also be exerted by way of metabolism of a precursor compound (a pro-drug).
Synthesis
[0101] In a further aspect, the present invention relates to a process for preparing a compound of the invention as defined herein.
[0102] By way of illustration, compounds of the invention may be synthesised according to the procedures given herein. It will be understood that these processes are solely for the purpose of illustrating the invention and should not be construed as limiting. A process utilising similar or analogous reagents and/or conditions known to one skilled in the art may also be used to obtain a compound of the invention.
[0103] Any mixtures of final products or intermediates obtained can be separated on the basis of the physico-chemical differences of the constituents, in a known manner, into the pure final products or intermediates, for example by chromatography, distillation, fractional crystallisation, or by the formation of a salt if appropriate or possible under the circumstances.
Pharmaceutical Compositions
[0104] The compounds of the invention will normally be administered orally, intravenously, subcutaneously, buccally, rectally, dermally, nasally, tracheally, bronchially, by any other parenteral route, as an oral or nasal spray or via inhalation, The compounds may be administered in the form of pharmaceutical preparations comprising prodrug or active compound either as a free compound or, for example, a pharmaceutically acceptable non-toxic organic or inorganic acid or base addition salt, in a pharmaceutically acceptable dosage form. Depending upon the disorder and patient to be treated and the route of administration, the compositions may be administered at varying doses.
[0105] Typically, therefore, the pharmaceutical compounds of the invention may be administered orally or parenterally (“parenterally” as used herein, refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion) to a host. In the case of larger animals, such as humans, the compounds may be administered alone or as compositions in combination with pharmaceutically acceptable diluents, excipients or carriers.
[0106] Actual dosage levels of active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular patient, compositions, and mode of administration. The selected dosage level will depend upon the activity of the particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the compound at levels lower than required for to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved.
[0107] In certain embodiments, an appropriate dosage level will generally be about 0.01 to 500 mg per kg patient body weight per day which can be administered in single or multiple doses. In a particular embodiment, the dosage level is about 0.1 to about 250 mg/kg per day; more preferably about 0.5 to about 100 mg/kg per day. A suitable dosage level may be about 0.01 to 250 mg/kg per day, about 0.05 to 100 mg/kg per day, or about 0.1 to 50 mg/kg per day. Within this range the dosage may be 0.05 to 0.5, 0.5 to 5 or 5 to 50 mg/kg per day. For oral administration, the compositions may be provided in the form of tablets containing 1.0 to 1000 milligrams of the active ingredient, particularly 1.0, 5.0, 10.0, 15.0, 20.0, 25.0, 50.0, 75.0, 100.0, 150.0, 200.0, 250.0, 300.0, 400.0, 500.0, 600.0, 750.0, 800.0, 900.0 and 1000.0 milligrams of the active ingredient for the symptomatic adjustment of the dosage to the patient to be treated. The compounds may be administered on a regimen of 1 to 4 times per day, e.g. once or twice per day. The dosage regimen may be adjusted to provide the optimal therapeutic response.
[0108] According to a further aspect of the invention there is thus provided a pharmaceutical composition including a compound of the invention as defined herein, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
[0109] Pharmaceutical compositions of this invention for parenteral injection suitably comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
[0110] These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol or phenol sorbic acid. It may also be desirable to include isotonic agents such as sugars or sodium chloride, for example. Prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents (for example aluminum monostearate and gelatin) which delay absorption.
[0111] Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is typically mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or one or more: a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarding agents such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycol, for example.
[0112] Suitably, oral formulations contain a dissolution aid. The dissolution aid is not limited as to its identity so long as it is pharmaceutically acceptable. Examples include nonionic surface active agents, such as sucrose fatty acid esters, glycerol fatty acid esters, sorbitan fatty acid esters (e.g. sorbitan trioleate), polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, methoxypolyoxyethylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyethylene glycol fatty acid esters, polyoxyethylene alkylamines, polyoxyethylene alkyl thioethers, polyoxyethylene polyoxypropylene copolymers, polyoxyethylene glycerol fatty acid esters, pentaerythritol fatty acid esters, propylene glycol monofatty acid esters, polyoxyethylene propylene glycol monofatty acid esters, polyoxyethylene sorbitol fatty acid esters, fatty acid alkylolamides, and alkylamine oxides; bile acid and salts thereof (e.g. chenodeoxycholic acid, cholic acid, deoxycholic acid, dehydrocholic acid and salts thereof, and glycine or taurine conjugate thereof); ionic surface active agents, such as sodium laurylsulfate, fatty acid soaps, alkylsulfonates, alkylphosphates, ether phosphates, fatty acid salts of basic amino acids; triethanolamine soap, and alkyl quaternary ammonium salts; and amphoteric surface active agents, such as betaines and aminocarboxylic acid salts.
[0113] The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition such that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, and/or in delayed fashion. Examples of embedding compositions include polymeric substances and waxes.
[0114] The active compounds may also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients.
[0115] The active compounds may be in finely divided form, for example they may be micronised.
[0116] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and mixtures thereof. Besides inert diluents, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents. Suspensions, in addition to the active compounds, may contain suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth and mixtures thereof.
[0117] Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.
[0118] Compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolisable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilisers, preservatives, excipients and the like. The preferred lipids are the phospholipids and the phosphatidyl cholines (lecithins), both natural and synthetic. Methods to form liposomes are known in the art, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p 33 et seq.
[0119] Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers or propellants which may be required. Ophthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of this invention.
Therapeutic Uses
[0120] Compounds of the invention may be useful in the therapy of a variety of diseases and conditions. The subject of said therapy may be a human or an animal. Compounds of the invention may exhibit desirable potency, selectivity and microsomal stability. The compounds may be useful in the therapy of diseases or conditions in which HDACs are implicated.
[0121] In particular, compounds of the invention may be useful in the treatment or prevention of cancer and/or inflammatory conditions such as rheumatoid arthritis.
Cancer Treatment
[0122] In a particular embodiment of the invention, the compounds of the invention are for use in the treatment of cancer.
[0123] The term “cancer” as used herein includes reference to cellular proliferative or differentiative disorders, including all types of cancerous growths or oncogenic processes, metastatic tissues or malignantly transformed cells, tissues, or organs, irrespective of histopathologic type or stage of invasiveness. Included are malignancies of the various organ systems, such as those affecting lung, breast, thyroid, lymphoid, gastrointestinal, and genito-urinary tract, as well as adenocarcinomas which include malignancies such as most colon cancers, renal-cell carcinoma, prostate cancer and/or testicular tumors, non-small cell carcinoma of the lung, cancer of the small intestine and cancer of the esophagus. The term “carcinoma” refers to malignancies of epithelial or endocrine tissues including respiratory system carcinomas, gastrointestinal system carcinomas, genitourinary system carcinomas, testicular carcinomas, breast carcinomas, prostatic carcinomas, endocrine system carcinomas, and melanomas. Exemplary carcinomas include those forming from tissue of the cervix, lung, prostate, breast, head and neck, colon and ovary. This term also includes carcinosarcomas, e.g., which include malignant tumors composed of carcinomatous and sarcomatous tissues. An “adenocarcinoma” refers to a carcinoma derived from glandular tissue or in which the tumor cells form recognizable glandular structures. The term “sarcoma” is art recognized and refers to malignant tumors of mesenchymal derivation.
[0124] The compounds of the invention may also be useful in the treatment of a variety of proliferative disorders. Such disorders include hematopoietic neoplastic disorders. As used herein, the term “hematopoietic neoplastic disorders” includes diseases involving hyperplastic/neoplastic cells of hematopoietic origin, e.g., arising from myeloid, lymphoid or erythroid lineages, or precursor cells thereof. The diseases may arise from poorly differentiated acute leukemias, e.g. erythroblastic leukemia and acute megakaryoblastic leukemia. Additional exemplary myeloid disorders include acute promyeloid leukemia, acute myelogenous leukemia and chronic myelogenous leukemia; lymphoid malignancies such as acute lymphoblastic leukemias, including B-lineage and T-lineage types, chronic lymphocytic leukemia, prolymphocytic leukemia, hairy cell leukemia and Waldenstrom's macroglobulineniia. Additional forms of malignant lymphomas include non-Hodgkin lymphoma and variants thereof, peripheral T cell lymphomas, adult T cell leukemia/lymphoma, cutaneous T-cell lymphoma, large granular lymphocytic leukemia, Hodgkin's disease and Reed-Sternberg disease. In particular, the compounds may be used in the therapy of haematologic cancers such as leukaemia, non-small cell lung cancers, colonic cancers, breast cancers, ovarian cancers, renal cancers, melanoma, carcinoma, sarcoma and metastatic disorders.
[0125] Examples of cancerous disorders of the colon include, but are not limited to, non-neoplastic polyps, adenomas, familial syndromes, colorectal carcinogenesis, colorectal carcinoma, and carcinoid tumors.
[0126] Examples of cancerous disorders of the liver include, but are not limited to, nodular hyperplasias, adenomas, and malignant tumors, including primary carcinoma of the liver and metastatic tumors.
[0127] Examples of cancerous disorders of the ovary include, but are not limited to, ovarian tumors such as, tumors of coelomic epithelium, serous tumors, mucinous tumors, endometeriod tumors, clear cell adenocarcinoma, cystadenofibroma, brenner tumor, surface epithelial tumors; germ cell tumors such as mature (benign) teratomas, monodermal teratomas, immature malignant teratomas, dysgerminoma, endodermal sinus tumor, choriocarcinoma; sex cord-stomal tumors such as, granulosa-theca cell tumors, thecoma-fibromas, androblastomas, hill cell tumors, and gonadoblastoma; and metastatic tumors such as Krukenberg tumors.
[0128] Examples of cancerous disorders of the breast include, but are not limited to, proliferative breast disease including, e.g. epithelial hyperplasia, sclerosing adenosis, and small duct papillomas; tumors, e.g. stromal tumors such as fibroadenoma, phyllodes tumor, and sarcomas, and epithelial tumors such as large duct papilloma; carcinoma of the breast including in situ (noninvasive) carcinoma that includes ductal carcinoma in situ (including Paget's disease) and lobular carcinoma in situ, and invasive (infiltrating) carcinoma including, but not limited to, invasive ductal carcinoma, invasive lobular ‘carcinoma, medullary carcinoma, colloid (mucinous) carcinoma, tubular carcinoma, and invasive papillary carcinoma, and miscellaneous malignant neoplasms. Disorders in the male breast include, but are not limited to, gynecomastia and carcinoma.
[0129] In particular, the compounds may be useful in the therapy of a disorder selected from leukaemia, colonic cancer, melanoma and non-small cell lung cancer.
[0000] The Particular Role of HDAC-3 Inhibition There are 3 distinct classes of Zn-dependent HDACs targeted by HDAC inhibitors currently in clinical development; class I (HDACs 1, 2, 3 and 8), class II (HDACs 4, 5, 6, 7, 9 and 10) and class IV (HDAC11) 1 . In contrast to class II/IV enzymes, class I enzymes (and HDACs1-3 in particular) are widely expressed and are predominantly localized to the nucleus where they play key roles in suppressing gene expression in both normal and malignant cells. Whereas HDAC 1 and HDAC2 participate in various co-repressor complexes, HDAC3 is the only HDAC which is a “core” component of the closely related N-CoR and SMRT repressor complexes 2 . Additional HDACs have been shown to be associated with these corepressor complexes, but only HDAC3 is an essential component of stable (i.e. salt and detergent resistant) N-CoR/SMRT complexes. N-CoR/SMRT are also essential for HDAC3 activity 3,4 . Therefore, HDAC3 activity is tightly linked to N-CoR/SMRT and HDAC3 selective inhibitors are therefore expected to have therapeutic activity in cancers in which N-CoR/SMRT-mediated transcriptional dysregulation contributes to malignant development and progression.
[0130] In acute myeloid leukaemia (AML), N-CoR/SMRT complexes have been unequivocally linked to leukaemogenesis. AML is the most common acute leukaemia in adults, with approximately 2,200 new cases diagnosed and 2,100 deaths in the UK each year. The incidence of AML is expected to rise with an aging population and increased occurrence of therapy-related AML in previously treated cancer survivors.
[0131] The hallmark of AML is a block of normal cellular differentiation 5 . N-CoR/SMRT corepressor complexes play a central role in this differentiation block via transcriptional repression of differentiation promoting genes. For example, about 40% of AML contain recurrent chromosomal translocations giving rise to fusion proteins that drive transcriptional repression of genes. N-CoR/SMRT complexes have been shown play a central role in the suppression of gene expression mediated by the PML-RARα, AML1-ETO and CBFβ-MYH11 fusion proteins which, together, account for approximately one-third of AML cases 6-11 . Importantly, siRNA-mediated knock-down of HDAC3 is sufficient to block the transcriptional repressing activity of PML-RARα 12 directly validating HDAC3 inhibition as a strategy to overcome N-CoR/SMRT complex mediated transcriptional repression ( FIG. 1 ). All-trans retinoic acid (ATRA) is used a therapeutic agent in a specific subset of AML (acute promyelocytic leukaemia, APL) where it reverses retinoic acid receptor a (RARα)-mediated transcriptional repression, leading to growth inhibition, differentiation and apoptosis 13 . However, the majority of AML do not respond to ATRA and, in APL, de novo and acquired resistance are significant clinical problems. By targeting HDAC3, a central component of the transcriptional repression machinery, selective HDAC inhibitors offer a novel approach to “differentiation” therapy for AML.
[0132] The potential to target N-CoR/SMRT corepressor complexes via HDAC inhibitors in AML is clearly demonstrated using non-selective inhibitors. Non-selective HDAC inhibitors activate RARα-dependent gene expression and promote differentiation in AML cells, even in leukaemic cells which are resistant to ATRA 7,14 . HDAC inhibitors appear to have clinical activity in APL 15 , however, current HDAC inhibitors have not been optimised for selective activity against HDAC3.
[0133] In addition to AML, N-CoR/SMRT complexes have also been implicated in a number of other malignancies (including diffuse large B-cell lymphoma and some types of breast cancer) and siRNA-mediated knock-down of HDAC3 is sufficient to decrease proliferation, survival and/or migration in ovarian, colon, cervical and synovial carcinoma cell lines 16-22 . Thus, selective inhibition of HDAC3 is likely to be an effective strategy for the treatment of various cancer types, including more common epithelial malignancies
[0134] The compounds of the present invention show selectivity towards HDAC-3. Accordingly, these compounds are considered to be potentially useful therapeutic agents for the treatment of malignant disease in which N-CoR/SMT complexes are implicated, such as AML, diffuse large B-cell lymphoma, some types of breast cancer, as well as ovarian, colon, cervical and synovial cancers.
[0135] In a particular embodiment, the compounds of the invention are for use in the treatment of AML.
Inflammation
[0136] In a further embodiment, the compounds of the invention are for use in treatment inflammatory conditions, such as rheumatoid arthritis. There is increasing evidence becoming available in the literature to suggest that HDAC inhibitors are potentially useful agents for the treatment of inflammatory conditions such as rheumatoid arthritis (see, for example, Choo et al. Histone deacetylase inhibitors: new hope for rheumatoid arthritis? Curr. Pharm. Des 2008; 14(8):803-820; Halili et al. Histone deacetylase inhibitors in inflammatory disease. Curr Top Med Chem 2009; 9(3):309-319; Lin et al. Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br. J. Pharmacol 2007; 150(7):862-872; and Grabiec et al. Histone deacetylase inhibitors suppress inflammatory activation of rheumatoid arthritis patient synovial macrophages and tissue. J. Immunol 2010; 184(5):2718-2728).
FIGURES
[0137] FIG. 1 shows a diagram showing the HDAC3-mediated transcriptional repression in APL. The AML-associated PML-RARα fusion protein silences expression of genes normally required for myeloid cell differentiation by binding to retinoic acid response elements (RARE) in the promoter of RARα target genes and recruitment of SMRT/N-CoR corepressor complexes. In addition to HDAC3, the other “core” components of SMRT/N-CoR corepressor complexes are GPS2, TBL1 and TBL1R. Recruitment of HDAC3 leads to repression of target gene transcription Inhibition of HDAC3 activity (by small chemical compounds or siRNA) prevents PML-RARα-mediated repression leading to induction of RARα target gene expression and results in differentiation, cell cycle arrest and/or apoptosis in leukaemic cells. The model is based on PML-RARα positive APL but N-CoR/SMRT complexes are also involved in transcriptional repression mediated by other leukaemic fusion proteins and BCL-6 (in this case the complex is termed B-CoR).
[0138] FIG. 2( i ) shows the growth inhibition in HL60 and NB4 cells (4 day, MTS assay) as described in Example 18.
[0139] FIG. 2( ii ) shows the differentiation in HL60 cells (3 days, CD11b flow cytometry) as described in Example 18.
[0140] FIG. 2( iii ) shows the CYP26RNA expression in HL60 (left) and NB4 (right) cells (1 day assay, Q-RT-PCR) as described in Example 18.
EXAMPLES
[0141] The following Examples illustrate the invention. The numbering given in the structures refers to the location of atoms as identified by NMR.
General Procedure for 4-methylene-1,2,3,4-tetrahydroisoquinoline formation
[0142] Aryl iodide (1.0 mol equiv), nucleophile (1.1 mol equiv), Pd 2 dba 3 (0.025 mol equiv), tri-2-furylphosphine (0.05 mol equiv), K 2 CO 3 (2.0 mol equiv) and DMF (10-20 ml/mmol) were combined in a Schlenk tube with a stirrer bar, subjected to two freeze-pump-thaw cycles and charged with allene (0.5 bar). The Schlenk tube was thawed and stirred vigorously at 80° C. for 24 h, cooled to room temperature, diluted with H 2 O (60 ml) and extracted with EtOAc (2×20 ml). The combined organic extracts were washed with H 2 O (20 ml), dried (MgSO 4 ), filtered and concentrated in vacuo. Column chromatography of the residue afforded the product.
Intermediate 1: 1-[(2E)-3-(2-Iudophenyl)prop-2-enoyl]-4-methylpiperazine
[0143]
[0144] 2-Iodocinnamic acid (1.37 g, 5 mmol) and SOCl 2 (6 mL) were stirred at reflux for 2 h, and the excess SOCl 2 removed in vacuo. DCM (2×10 mL) was used to azeotrope residual traces of SOCl 2 . The solid residue was dissolved in DCM (10 mL), and N-methylpiperazine (1.00 g, 10 mmol) and NEt 3 (2.02 g, 20 mmol) added successively, dropwise over 1 min each at 0° C. with stirring. The resulting mixture was stirred for 18 h, washed successively with HCl (1M aq., 10 mL), NaHCO 3 (sat. aq., 10 mL) and brine (10 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. The residue was triturated with hexane to give the product as pale yellow needles (1.20 g, 67%), m.p. 120-122° C.
[0145] δH (CDCl 3 , 500 MHz): 7.89 (d, J 7.8, 1H, H-9), 7.78 (d, J 15.3, 1H, H-5), 7.52 (dd, J 7.5, 1.4, 1H, H-6), 7.34 (t, J 7.5, 1H, H-7), 7.02 (ddd, J 7.8, 7.5, 1.4, 1H, H-8), 6.70 (d, J 15.3, 1H, H-4), 3.77 (s, b, 2H, H-2), 3.67 (s, b, 2H, H-2), 2.45 (t, J 5.1, 4H, H-3), 2.33 (s, 3H, H-1).
[0146] δC (CDCl 3 , 75 MHz): 164.9, 145.6, 139.9, 138.9, 130.6, 128.4, 127.2, 120.7, 100.7, 54.7, 46.0, 42.1.
[0147] v/max (film) 2939, 2797, 1643, 1603, 1463.
Intermediate 2: 4-[(2E)-3-(2-Iodophenyl)prop-2-enoyl]morpoline
[0148]
[0149] Prepared in a similar manner to Intermediate 1 using 2-iodocinnamic acid (1.37 g) and morpholine (0.87 g). The product was obtained as pale yellow needles (1.18 g, 71%), m.p. 100-102° C.
[0150] δH (CDCl 3 , 500 MHz): 7.89 (d, J 7.8, 1H, H-8), 7.81 (d, J 15.3, 1H, H-4), 7.52 (dd, J 7.7, 1.4, 1H, H-5), 7.35 (dd, J 7.7, 7.6, 1H, H-6), 7.03 (ddd, J 7.8, 7.6, 1.4, 1H, H-7), 6.68 (d, J 15.3, 1H, H-3), 3.74-3.67 (m, 8H, H-1 & H-2).
[0151] δC (CDCl 3 , 75 MHz): 165.5, 146.5, 140.4, 139.2, 131.1, 128.9, 127.6, 120.5, 101.2, 67.3, 46.8, 42.9.
[0152] v/max (film) 3057, 2856, 1645, 1604, 1463.
Intermediate 3: Tert-Butyl (4-{[(2-aminophenyl)amino]carbonyl}benzyl)carbamate
[0153]
[0154] To a stirred solution of 4-{[(tert-butoxycarbonyl)amino]methyl}benzoic acid (2.37 g, 9.44 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (2.60 g, 9.44 mmol) in DMF (30 mL) was added o-phenylenediamine (1.43 g, 13.22 mmol). After stirring for 20 h at room temperature, the mixture was diluted with water (150 mL) and extracted with EtOAc (2×40 mL). The combined extracts were washed with water (40 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. The oily residue was triturated with Et 2 O to give the product as pale yellow needles (2.25 g, 70%), m.p. 160-162° C.
[0155] δH (DMSO-d 6 , 500 MHz): 9.63 (s, 1H, H-6), 7.95 (d, J 7.7, 2H, H-7), 7.50 (s, b, 1H, H-10), 7.37 (d, J 7.7, 2H, H-8), 7.18 (d, J 7.4, 1H, H-5), 6.98 (dd, J 7.8, 7.3, 1H, H-3), 6.80 (d, J 7.8, 1H, H-2), 6.61 (dd, J 7.4, 7.3, 1H, H-4), 4.90 (s, b, 2H, H-1), 4.21 (d, J 5.7, 2H, H-9), 1.42 (s, 9H, H-11).
[0156] δC (DMSO-d 6 , 75 MHz): 165.5, 156.2, 144.1, 143.5, 133.4, 128.1, 127.0, 126.8, 123.7, 116.6, 116.5, 78.3, 43.5, 28.6.
[0157] v/max (film) 3419, 3365, 3325, 2989, 1686, 1651, 1655, 1526.
[0158] m/z (EZ) (%) 342 (MH + , 100).
Intermediate 4: Ethyl 3-(2-iodophenyl)acrylate
[0159]
[0160] 2-Iodobenzaldehyde (2.11 g, 9.1 mmol) and ethyl (triphosphoranylidene)acetate (3.56 g, 10.2 mmol) were combined in DCM (50 mL) and stirred at room temperature for 1 h. The mixture was concentrated in vacuo and the residue filtered through a silica pad eluting with 9:1 v/v Et 2 O:pet. ether to afford the product as a yellow oil (2.53 g, 92%, 5.8:1 E:Z).
[0161] δH (CDCl 3 , 500 MHz): E isomer: 7.91 (d, J 15.8, 1H, H-4), 7.91 (d, J 7.9, 1H, H-8), 7.56 (d, J 7.7, 1H, H-5), 7.36 (dd, J 7.7, 7.5, 1H, H-6), 7.04 (dd, J 7.9, 7.5, 1H, H-7), 6.31 (d, J 15.8, 1H, H-3), 4.28 (q, J 7.1, 2H, H-2), 1.35 (t, J 7.1, 3H, H-1).
[0162] Z isomer: 7.85 (d, J 7.9, 1H, H-8), 7.41 (d, J 7.8, 1H, H-5), 7.31 (dd, J 7.8, 7.5, 1H, H-6), 7.01 (dd, 7.9, 7.5, 1H, H-7), 6.97 (d, J 12.1, 1H, H-4), 6.02 (d, J 12.1, 1H, H-3), 4.09 (q, J 7.1, 2H, H-2), 1.15 (t, J 7.1, 3H, H-1).
[0163] δC (CDCl 3 , 75 MHz): 166.7, 166.1, 148.1, 146.9, 140.4, 140.0, 138.9, 138.3, 131.6, 130.5, 130.2, 129.0, 127.9, 127.8, 121.8, 121.7, 101.6, 61.1, 60.7, 14.7, 14.4.
[0164] v/max (film) 2979, 1712, 1635, 1461.
Intermediate 5: 3-(2-Iodophenyl)-1-phenylprop-2-en-1-one
[0165]
[0166] 2-Iodobenzaldehyde (1.16 g, 5 mmol) and (triphenylphosphoranylidene)acetophenone (2.28 g, 6 mmol) were combined in DCM and stirred at reflux for 24 h, and the solvent removed in vacuo. Column chromatography (30 g SiO 2 , 8:1 v/v hexane:Et 2 O) afforded the product as a yellow oil (1.51 g, 90%, 3:1 E:Z).
[0167] δH (CDCl 3 , 500 MHz): E isomer: 8.03 (d, J 7.3, 2H, H-3), 7.98 (d, J 15.8, 1H, H-5), 7.93 (d, J 7.7, 1H, H-9), 7.69 (d, J 7.7, 1H, H-6), 7.60 (t, J 7.5, 1H, H-1), 7.51 (dd, J 7.5, 7.3, 2H, H-2), 7.40 (t, J 7.7, 1H, H-7), 7.34 (d, J 15.8, 1H, H-4), 7.08 (t, J 7.7, 1H, H-8). Z isomer: 7.86 (d, J 7.3, 2H, H-3), 7.77 (d, J 8.1, 1H, H-9), 7.46 (t, J 7.3, 1H, Ar—H), 7.35 (m, 2H, 2×Ar—H), 7.23 (d, J 7.7, 1H, H-6), 7.09 (m, 2H, Ar—H, H-5), 6.86 (dd, J 8.5, 7.3, 1H, Ar—H), 6.67 (d, J 12.4, 1H, H-4).
[0168] δC (CDCl 3 , 75 MHz): 194.1, 190.4, 147.9, 143.1, 140.1, 139.5, 138.7, 138.4, 137.8, 137.1, 133.1, 132.9, 131.3, 130.4, 129.7, 128.9, 128.7, 128.6, 128.4, 128.3, 127.8, 127.7, 127.5, 125.3, 101.7, 98.7.
[0169] v/max (film) 3058, 1663, 1604, 1578, 1459.
Intermediate 6: 1-[(2E)-3-(2-Iodophenyl)prop-2-enoyl]piperidine
[0170]
[0171] 2-Iodocinnamic acid (1.37 g, 5 mmol) and SOCl 2 (6 mL) were stirred together at reflux for 2 h, and the excess SOCl 2 removed in vacuo. DCM (2×10 mL) was used to azeotrope residual traces of SOCl 2 . The solid residue was dissolved in DCM (10 mL), and piperidine (0.85 g, 10 mmol) and NEt 3 (2.02 g, 20 mmol) added successively, dropwise over 1 min each at 0° C. with stirring. The resulting mixture was stirred for 18 h, washed successively with HCl (1M aq., 10 mL), NaHCO 3 (sat. aq., 10 mL) and brine (10 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. The residue was triturated with hexane to give the product as an off-white solid (1.17 g, 66%).
[0172] δH (CDCl 3 , 500 MHz): 7.88 (d, J 7.7, 1H, H-9), 7.74 (d, J 15.2, 1H, H-5), 7.52 (dd, J 7.7, 1.3, 1H, H-6), 7.34 (dd, J 7.7, 7.3, 1H, H-7), 7.01 (ddd, J 7.7, 7.3, 1.3, 1H, H-8), 6.72 (d, J 15.2, 1H, H-4), 3.66 (s, b, 2H, H-3), 3.58 (s, b, 2H, H-3), 1.72-1.60 (m, 6H, H-1, H-2).
[0173] δC (CDCl 3 , 75 MHz): 164.9, 144.9, 139.9, 139.2, 130.4, 128.4, 127.2, 121.5, 100.6, 47.2, 26.8, 24.6.
[0174] v/max (film) 2940, 2857, 1643, 1601, 1464, 1442.
Intermediate 7: 4-(Aminomethyl)-N-(2-aminophenyl)benzamide
[0175]
[0176] Tert-Butyl (4-{[(2-aminophenyl)amino]carbanyl}benzyl)carbamate (2.0 g, 5.87 mmol) was dissolved in HCl (37% aq., 20 mL) with stirring at room temperature. After stirring at room temperature for 1.5 h, the mixture was cooled to 0° C. and basified with KOH pellets, added singly over 20 min, to pH 14. The resulting yellow precipitate was collected by filtration, dissolved in hot THF (50 mL), and filtered. The solid was re-dissolved in hot THF (50 mL) and filtered. The combined filtrates were concentrated in vacuo to give the product as a pale yellow amorphous solid (1.23 g, 87%).
[0177] Found: 242.1286; C 14 H 16 N 3 O requires 242.1288.
[0178] δH (CD 3 OD, 500 MHz): 7.97 (d, J 8.1, 2H, H-7), 7.51 (d, J 8.1, 2H, H-8), 7.10 (d, J 7.7, 1H, H-5), 7.00 (dd, J 7.3, 7.2, 1H, H-3), 6.83 (d, J 7.2, 1H, H-2), 6.69 (dd, J 7.7, 7.3, 1H, H-4), 4.11 (s, 2H, H-9).
[0179] δC (CD 3 OD, 75 MHz): 168.3, 143.8, 138.4, 136.6, 130.4, 130.0, 129.0, 128.0, 125.6, 120.2, 119.2, 44.2.
[0180] v/max (film) 3260, 1636, 1526.
[0181] m/z (EZ) (%) 242 (100, MH + ), 505 (2MNa + )
Intermediate 8: (2E)-N-(2-Aminophenyl)-3-(2-iodophenyl)acrylamide
[0182]
[0183] 2-Iodocinnamic acid (0.685 g, 2.5 mmol) and SOCl 2 (3 mL) were stirred at reflux for 2 h, and the excess SOCl 2 removed in vacuo. DCM (2×10 mL) was used to azeotrope residual traces of SOCl 2 , and the solid residue was dissolved in DCM (10 mL). o-Phenylenediamine (0.810 g, 7.5 mmol) was added portionwise over 1 min at 0° C. with stirring, and NEt 3 (1.01 g, 10 mmol) was immediately added dropwise over 1 min at 0° C. After stirring at room temperature for 24 h, the mixture was washed with water (10 mL), NaHCO 3 (sat. aq., 10 mL) and brine (10 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. Column chromatography of the residue (30 g silica, 2:1 v/v hexanes:EtOAc) gave the product as yellow needles (0.400 g, 44%), m.p. 194-196° C.
[0184] (Found: C, 49.5; H, 3.60; N, 7.95; I, 35.15. C 15 H 13 N 2 I requires: C, 49.47, H, 3.60, N, 7.69, I, 34.85%).
[0185] δH (DMSO-d 6 , 500 MHz): 9.47 (s, b, 1H, H-6), 7.99 (d, J 7.7, 1H, H-12), 7.71 (d, J 15.4, 1H, H-8), 7.70 (d, J 8.1, 1H, H-9), 7.51 (dd, J 7.7, 7.3, 1H, H-11), 7.38 (d, J 7.5, 1H, H-5), 7.17 (dd, J 8.1, 7.3, 1H, H-10), 6.94 (dd, J 7.7, 7.3, 1H, H-3), 6.84 (d, J 15.4, 1H, H-7), 6.77 (d, J 7.7, 1H, H-2), 6.60 (dd, J 7.5, 7.3, 1H, H-4), 4.99 (s, b, 2H, H-1).
[0186] δC (DMSO-d 6 , 75 MHz): 163.2, 142.8, 142.0, 140.1, 138.0, 131.5, 129.3, 127.4, 126.3, 125.8, 125.1, 123.6, 116.6, 116.3, 102.0.
[0187] v/max (film) 3233, 1648, 1452.
[0188] m/z (EZ) (%) 365 (MH + , 100).
Intermediate 9: (2E)-N-(2-Hydroxyethyl)-3-(2-iodophenyl)acrylamide
[0189]
[0190] 2-Iodocinnamic acid (0.685 g, 2.5 mmol) and SOCl 2 (3 mL) were stirred at reflux for 2 h, and the excess SOCl 2 removed in vacuo. DCM (2×10 mL) was used to azeotrope residual traces of SOCl 2 . The solid residue was dissolved in DCM (10 mL), and ethanolamine (0.31 g, 5 mmol) and NEt 3 (1.01 g, 10 mmol) added successively, dropwise over 1 min each at 0° C. with stirring. The resulting mixture was stirred for 18 h, washed successively with HCl (1M aq., 10 mL), NaHCO 3 (sat. aq., 10 mL) and brine (10 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. The residue was triturated with hexane to give the product as colourless needles (0.44 g, 58%), m.p. 130-132° C.
[0191] (Found: C, 41.75; H, 3.80; N, 4.65; I, 40.10. C 1 H 12 INO 2 requires: C, 41.66, H, 3.81, N, 4.42, I, 40.02).
[0192] δH (CDCl 3 , 500 MHz): 8.26 (s, b, 1H, H-4), 7.94 (d, J 7.5, 1H, H-10), 7.61 (d, J 7.4, 1H, H-7), 7.56 (d, J 15.6, 1H, H-6), 7.46 (dd, J 7.5, 7.3, 1H, H-9), 7.14 (dd, J 7.4, 7.3, 1H, H-8), 6.60 (d, J 15.0, 1H, H-5), 4.78 (s, b, 1H, H-1), 3.48 (s, b, 2H, H-2), 3.27 (t, J 5.5, 2H, H-3).
[0193] δC (CDCl 3 , 75 MHz): 164.8, 141.8, 140.0, 138.1, 131.3, 129.2, 127.3, 125.7, 101.9, 79.5, 60.1.
[0194] v/max (film) 3422, 3281, 1647, 1615.
[0195] m/z (EZ) (%) 318 (MH + , 100), 145 (100).
Intermediate 10: Tert-butyl (2-{[(2E)-3-(2-iodophenyl)prop-2-enoyl]amino}ethyl)carbamate
[0196]
[0197] 2-Iodocinnamic acid (1.37 g, 5 mmol) and SOCl 2 (6 mL) were stirred at reflux for 2 h, and the excess SOCl 2 removed in vacuo. DCM (2×10 mL) was used to azeotrope residual traces of SOCl 2 . The solid residue was dissolved in DCM (10 mL), and tert-butyl (2-aminoethyl)carbamate (1.60 g, 10 mmol) and NEt 3 (2.02 g, 20 mmol) added successively, dropwise over 1 min each at 0° C. with stirring. The resulting mixture was stirred for 18 h, washed successively with HCl (1M aq., 10 mL), NaHCO 3 (sat. aq., 10 mL) and brine (10 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. Crystallisation from DCM/hexane gave the product as pale yellow needles (1.33 g, 66%).
[0198] Found: 439.0473; C 16 H 21 N 2 O 3 INa requires 439.0489.
[0199] δ H (500 MHz, CDCl 3 ): 7.89 (d, J 7.5, 1H, H-11), 7.79 (d, J 15.6, 1H, H-7), 7.49 (d, J 7.3, 1H, H-8), 7.32 (t, J 7.3, 1H, H-9), 7.01 (dd, J 7.5, 7.3, 1H, H-10), 6.53 (s, b, 1H, N—H), 6.26 (d, J 15.6, 1H, H-6), 4.99 (s, b, 1H, N—H), 3.53-3.50 (m, 2H, H-4), 3.36-3.35 (m, 2H, H-3), 1.44 (s, 9H, H-1).
[0200] δ C (75 MHz, CDCl 3 ): 166.2, 157.5, 144.5, 140.4, 138.8, 131.1, 128.8, 127.6, 124.3, 101.3, 80.3, 41.7, 40.6, 28.8.
[0201] v/max (film) 3343, 3310, 1678, 1647, 1615, 1529.
[0202] m/z (%) 439 (MNa + , 100).
Intermediate 11: (2E)-3-(3-Hydroxy-4-methoxyphenyl)-N-(2-{[(2E)-3-(2-iodophenyl)prop-2-enoyl]amino}ethyl)-2-(3,4,5-trimethoxyphenyl)acrylamide
[0203]
[0204] TFA (1 mL) was added dropwise over 1 min to a stirred solution of tert-butyl (2-{[(2E)-3-(2-iodophenyl)prop-2-enoyl]amino}ethyl)carbamate (0.582 g, 1.5 mmol) in DCM (5 mL) at room temperature. After stirring for 1 h, the mixture was concentrated in vacuo, and the residue dissolved in DMF (5 mL). K 2 CO 3 (0.276 g, 2 mmol) was added portionwise over 1 min with stirring at room temperature, and the resulting mixture was added in one portion to a solution of (2E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxy phenyl)acrylic acid (0.540 g, 1.5 mmol) and DMTMM (0.414 g, 1.5 mmol) in DMF (15 mL). The resulting mixture was stirred at room temperature for 18 h, diluted with water (50 mL) and extracted with EtOAc (3×20 mL). The combined organic phases were washed with water (20 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. Column chromatography (30 g silica, EtOAc) afforded the product as a colourless amorphous solid (0.512 g, 52%).
[0205] Found: 659.1250; C 30 H 32 N 2 O 7 I requires 659.1249.
[0206] δH (CDCl 3 , 500 MHz): 7.86 (d, J 7.8, 1H, H-4), 7.76 (d, J 15.5, 1H, H-5), 7.72 (s, 1H, H-14), 7.50 (d, J 7.6, 1H, H-1), 7.31 (dd, J 7.6, 7.4, 1H, H-2), 7.01 (dd, J 7.8, 7.3, 1H, H-3), 6.90 (s, b, 1H, N—H), 6.65-6.63 (m, 2H, H-15, H-18), 6.57 (dd, J 8.4, 1.6, 1H, H-19), 6.45 (s, 2H, H-11), 6.30 (d, J 15.5, 1H, H-6), 6.04 (s, b, 1H, N—H), 5.65 (s, 1H, H-16), 3.94 (s, 3H, H-17), 3.84 (s, 3H, H-13), 3.82 (s, 6H, H-12), 3.78-3.51 (m, 4H, H-8, H-9).
[0207] δ C (75 MHz, CDCl 3 ): 164.1, 161.1, 149.5, 142.8, 140.4, 139.0, 135.0, 133.4, 133.3, 132.5, 126.9, 126.2, 125.7, 123.5, 123.0, 122.3, 119.2, 118.4, 112.1, 105.6, 101.8, 96.1, 56.2, 51.5, 51.0, 35.9, 35.0.
[0208] v/max (film): 3314, 2938, 1660, 1581, 1512.
[0209] m/z (EZ) (%) 681 (MNa + , 85), 659 (MH + , 90), 248 (100).
Intermediate 12: 4-{[1-(Cyanomethyl)-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}benzoic acid
[0210]
[0211] Prepared by the general procedure from 2-iodocinnamonitrile (0.255 g, 1.0 mmol), 4-(aminosulfanyl)benzoic acid (0.201 g, 1.0 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (40 g silica, 2:1 v/v Et 2 O:hexanes) afforded the product as an amorphous pale yellow solid (0.195 g, 53%).
[0212] Found: 391.0717; C 19 H 16 N 2 O 4 SNa requires 391.0723.
[0213] δH (DMSO-d 6 , 500 MHz): 7.79 (d, J 8.4, 2H, H-3), 7.73 (d, J 8.4, 2H, H-2), 7.43 (d, J 7.8, 1H, H-7), 7.34 (d, J 7.7, 1H, H-10), 7.22 (dd, J 7.5, 7.4, 1H, H-9), 7.12 (dd, J 7.8, 7.4, 1H, H-8), 5.51 (s, 1H, H-6), 5.48 (dd, J 10.1, 4.4, 1H, H-11), 5.13 (s, 1H, H-5), 4.53 (d, J 16.9, 1H, H-4), 4.41 (d, J 16.9, 1H, H-4), 3.34 (dd, J 17.1, 10.1, 1H, H-12), 3.08 (dd, J 17.1, 4.4, 1H, H-12).
[0214] δC (DMSO-d 6 , 75 MHz): 166.3, 142.5, 134.6, 134.0, 132.2, 130.8, 129.7, 128.6, 128.1, 127.9, 127.7, 124.0, 118.3, 111.3, 53.5, 45.0, 24.7.
[0215] v/max (film): 3386, 1697, 1342, 1160.
[0216] m/z (%) 391 (MNa + , 100).
Intermediate 13: Tert-butyl {2-[(4-{[1-(cyanomethyl)-4-methylene-3,4-dihydroisoquino-2(1H)-yl]sulfonyl}benzoyl)amino]phenyl}carbamate
[0217]
[0218] To a stirred suspension of 4-{[1-(cyanomethyl)-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}benzoic acid (0.368 g, 1.0 mmol) and DMTMM (0.276 g, 1.0 mmol) in DMF (5 mL) was added tert-butyl (2-aminophenyl)carbamate (0.208 g, IA mmol) portionwise over 1 min. The resulting mixture was stirred at room temperature for 16 hours, diluted with H 2 O (40 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts were washed with water (10 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. Column chromatography (30 g SiO 2 , 2:1 v/v Et 2 O/petroleum ether) gave the product as colourless plates (0.340 g, 61%), m.p. 186-188° C.
[0219] (Found: C, 64.25; H, 5.45; N, 9.95; S, 5.45. C 30 H 33 N 4 O 5 S requires: C, 64.50, H, 5.41, N, 10.03, S, 5.74).
[0220] δH (CDCl 3 , 500 MHz): 9.50 (s, b, 1H, H-2), 7.85 (d, J 8.1, 2H, H-9), 7.84 (s, b, 1H, H-7), 7.73 (d, J 8.1, 2H, H-8), 7.43 (d, J 8.1, 1H, H-16), 7.30-7.11 (m, 6H, 6×Ar—H), 6.67-6.66 (m, 1H, Ar—H), 5.51 (s, 1H, H-12), 5.32 (dd, J 6.8, 6.4, 1H, H-17), 5.10 (s, 1H, H-11), 4.54 (d, J 16.7, 1H, H-10), 4.31 (d, J 16.7, 1H, H-10), 3.00 (dd, J 16.7, 6.4, 1H, H-18), 2.92 (dd, J 16.7, 6.8, 1H, H-18), 1.50 (s, 9H, H-1).
[0221] δC (CDCl 3 , 75 MHz): 164.0, 155.3, 142.0, 138.7, 134.8, 131.7, 131.6, 131.0, 129.9, 129.3, 129.2, 128.2, 127.9, 127.2, 126.7, 126.6, 126.2, 125.1, 116.9, 112.0, 82.3, 54.0, 46.2, 28.7, 26.4.
[0222] v/max (film) 2979, 1656, 1524.
[0223] m/z (EZ) (%) 581 (MNa + , 100).
Example 1
Ethyl [2-(4-{[(2-aminophenyl)amino]carbonyl}benzyl)-4-methylene-1,2,3,4-tetrahydroisoquinolin-1-yl]acetate
[0224]
[0225] Prepared by the general procedure from ethyl 3-(2-iodophenyl)acrylate (0.302 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, 3:2 v/v hexanes:EtOAc) afforded the product as a pale yellow solid. Crystallisation from DCM/hexane gave the product as pale yellow needles (0.241 g, 53%),
[0226] m.p. 111-113° C.
[0227] (Found: C, 72.80; H, 6.55; N, 9.15. C 28 H 29 N 3 O 3 .⅓H 2 O requires: C, 72.86, H, 6.48, N, 9.10).
[0228] Found: 456.2271; C 28 H 30 N 3 O 3 (MH + ) requires 456.2282.
[0229] δH (CDCl 3 , 500 MHz): 7.84 (d, J 7.9, 2H, H-7), 7.83 (s, 1H, H-6), 7.70 (d, J 7.3, 1H, H-16), 7.40 (d, J 7.9, 2H, H-8), 7.33 (d, J 7.7, 1H, Ar—H), 7.27-7.25 (m, 2H, 2×Ar—H), 7.12-7.08 (m, 2H, 2×Ar—H), 6.87-6.83 (m, 2H, 2×Ar—H), 5.70 (s, 1H, H-12), 4.94 (s, 1H, H-11), 4.31 (dd, J 10.3, 5.0, 1H, H-17), 4.29-4.11 (m, 2H, H-19), 3.92 (d, J 15.8, 1H, H-10), 3.89 (s, b, 2H, H-1), 3.75 (d, J 13.7, 1H, H-9), 3.66 (d, J 13.7, 1H, H-9), 3.24 (d, J 15.8, 1H, H-10), 2.89 (dd, J 14.6, 10.3, 1H, H-18), 2.65 (dd, J 14.6, 5.1, 1H, H-18), 1.27 (t, J 7.1, 3H, H-20).
[0230] δC (CDCl 3 , 75 MHz): 171.5, 165.7, 143.6, 140.7, 136.4, 135.0, 132.9, 132.2, 129.2, 128.4, 127.7, 127.1, 125.1, 124.6, 123.7, 119.8, 118.4, 11.0, 60.6, 60.0, 57.5, 49.4, 41.9, 14.3.
[0231] v/max (film): 3420, 3344, 3069, 2983, 1724, 1655.
[0232] m/z (EZ) (%): 456 (MH + , 100).
Example 2
N-(2-Aminophenyl)-4-{[4-methylene-1-(2-oxo-2-piperidin-1-ylethyl)-3,4-dihydroisoquinolin-2(1H)-yl]methyl}benzamide
[0233]
[0234] Prepared by the general procedure from 1-[(2E)-3-(2-iodophenyl)prop-2-enoyl]piperidine (0.341 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, 1:3 v/v hexanes:EtOAc) afforded the product as a pale yellow foam. Crystallisation from DCM/hexane gave the product as pale yellow plates (0.310 g, 63%), m.p. 89-91° C.
[0235] Found: 495.2751; C 31 H 35 N 4 O 2 (MH + ) requires 495.2755.
[0236] δH (CDCl 3 , 500 MHz): 7.84 (d, J 7.8, 2H, H-7), 7.84 (s, b, 1H, H-6), 7.68 (d. J 6.8, 1H, H-16), 7.43 (d, J 7.8, 2H, H-8), 7.34 (d, J 7.1, 1H, Ar—H), 7.28-7.25 (m, 2H, 2×Ar—H), 7.17 (t, J 6.8, 1H, H-15), 7.10 (dd, J 7.3, 6.8, 1H, Ar—H), 6.87-6.84 (m, 2H, 2×Ar—H), 5.70 (s, 1H, H-12), 4.94 (s, 1H, H-11), 4.43 (dd, J 7.7, 6.1, 1H, H-17), 3.94-3.89 (m, 1H, H-19), 3.87 (d, J 15.4, 1H, H-10), 3.77 (d, J 13.4, 1H, H-9), 3.70 (d, J 13.4, 1H, H-9), 3.54-3.50 (m, 1H, H-19), 3.38-3.34 (m, 1H, H-19), 3.28 (d, J 15.4, 1H, H-10), 3.22-3.17 (m, 1H, H-19), 2.99 (dd, J 14.5, 7.7, 1H, H-18), 2.64 (dd, J 14.5, 6.1, 1H, H-18), 1.65-1.55 (m, 4H, H-20), 0.97-0.84 (m, 2H, H-21).
[0237] (CDCl 3 , 75 MHz): 169.3, 143.7, 140.7, 136.7, 136.1, 132.0, 129.4, 128.3, 128.1, 127.2, 126.9, 124.6, 123.5, 119.8, 118.4, 109.8, 60.2, 57.7, 49.9, 47.1, 43.0, 39.2, 26.4, 25.6, 24.5.
[0238] v/max (film): 3265, 2938, 2856, 1618, 1503, 1450.
[0239] m/z (EZ) (%): 495 (MH + , 100).
Example 3
Methyl [2-(4-{[(2-aminophenyl)amino]carbonyl}benzyl)-4-methylene-1,2,3,4-tetrahydroisoquinolin-1-yl]acetate
[0240]
[0241] Prepared by the general procedure from methyl 3-(2-iodophenyl)acrylate (0.288 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, 3:2 v/v hexanes:EtOAc) afforded the product as a pale yellow foam. Crystallisation from DCM/hexane gave the product as pale yellow needles (0.302 g, 68%), m.p. 151-153° C.
[0242] (Found: C, 72.8; H, 6.10; N, 9.15. C 27 H 27 N 3 O 3 .0.25H 2 O requires: C, 72.71, H, 6.21, N, 9.42).
[0243] δH (CDCl 3 , 500 MHz): 7.85 (d, J 7.9, 2H, H-7), 7.85 (s, b, 1H, H-6), 7.70 (d, J 7.3, 1H, H-10), 7.39 (d, J 7.9, 2H, H-8), 7.34 (d, J 7.6, 1H, Ar—H), 7.27-7.25 (m, 2H, 2×Ar—H), 7.12-7.09 (m, 2H, 2×Ar—H), 6.87-6.85 (m, 2H, 2×Ar—H), 5.70 (s, 1H, H-12), 4.96 (s, 1H, H-11), 4.29 (dd, J 10.4, 5.0, 1H, H-17), 3.93 (d, J 15.7, 1H, H-10), 3.89 (s, b, 2H, H-1), 3.75 (d, J 14.0, 1H, H-9), 3.73 (s, 3H, H-19), 3.65 (d, J 14.0, 1H, H-9), 3.25 (d, J 15.7, 1H, H-10), 2.90 (dd, J 14.6, 10.5, 1H, H-18), 2.66 (dd, J 14.6, 5.0, 1H, H-18).
[0244] δC (CDCl 3 , 75 MHz): 171.9, 165.4, 143.5, 140.7, 136.3, 134.9, 133.0, 132.2, 129.3, 128.4, 127.7, 127.2, 127.1, 125.1, 124.6, 123.7, 119.8, 118.4, 110.1, 59.7, 57.5, 51.8, 49.5, 41.7.
[0245] v/max (film): 3347, 1732, 1637.
[0246] m/z (EZ) (%): 442 (MH + , 100).
Example 4
N-(2-Aminophenyl 4-{[4-methylene-1-(2-morpholin-4-yl-2-oxoethyl)-3,4-dihydroisoquinolin-2(1H)-yl]methyl}benzamide
[0247]
[0248] Prepared by the general procedure from 4-[(2E)-3-(2-iodophenyl)prop-2-enoyl]morpholine (0.343 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, 1:1 v/v hexanes:EtOAc) afforded the product as a pale yellow foam. Crystallisation from DCM/hexane gave the product as pale yellow needles (0.282 g, 57%), m.p. 99-101° C.
[0249] Found: 497.2558; C 30 H 33 N 4 O 3 (MH + ) requires 497.2547.
[0250] δH (CDCl 3 , 500 MHz): 7.88 (s, b, 1H, H-6), 7.85 (d, J 7.8, 2H, H-7), 7.70 (d, J 6.4, 1H, H-16), 7.42 (d, J 7.8, 2H, H-8), 7.35 (d, J 7.8, 1H, Ar—H), 7.28-7.24 (m, 2H, 2×Ar—H), 7.14 (d, J 6.8, 1H, Ar—H), 7.11 (dd, J 7.9, 7.4, 1H, Ar—H), 6.88-6.86 (m, 2H, 2×Ar—H), 5.71 (s, 1H, H-12), 4.97 (s, 1H, H-11), 4.40 (dd, J 6.5, 7.5, 1H, H-17), 3.91 (s, b, 2H, H-1), 3.85 (d, J 15.5, 1H, H-10), 3.77 (d, J 13.4, 1H, H-9), 3.72-3.64 (m, 5H, H-19 & 4×H-20), 3.57-3.52 (m, 1H, H-19), 3.41-3.35 (m, 2H, H-19 & H-9), 3.32 (d, J 15.5, 1H, H-10), 3.19-3.13 (m, 1H, H-19), 2.95 (dd, J 14.2, 7.5, 1H, H-18), 2.67 (dd, J 14.2, 6.5, 1H, H-18).
[0251] δC (CDCl 3 , 75 MHz): 169.8, 143.4, 140.7, 136.5, 135.7, 133.1, 132.1, 129.4, 128.4, 128.0, 127.3, 127.2, 125.2, 124.6, 123.7, 119.8, 118.4, 110.0, 66.8, 66.4, 60.4, 57.8, 50.1, 16.3, 42.1, 38.8.
[0252] v/max (film): 2967, 1623, 1503.
[0253] m/z (EZ) (%): 497 (MH + , 100).
Example 5
N-(2-Aminophenyl)-4-{[4-methylene-1-(2-oxo-2-phenylethyl)-3,4-dihydro isoquinolin-2(1H)-yl]methyl}benzamide
[0254]
[0255] Prepared by the general procedure from 3-(2-iodophenyl)-1-phenylprop-2-en-1-one (0.334 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, 2:1 v/v hexanes:EtOAc) afforded the product as an amorphous pale yellow solid (0.240 g, 49%).
[0256] Found: 488.2353; C 32 H 30 N 3 O 2 (MH + ) requires 488.2333.
[0257] δH (CDCl 3 , 500 MHz): 7.96 (d, J 7.7, 2H, H-19), 7.78 (s, b, 1H, H-6), 7.74-7.70 (m, 3H, H-13 & H-7), 7.57 (t, J 7.3, 1H, H-21), 7.46 (dd, J 7.7, 7.3, 2H, H-20), 7.32 (d, J 7.7, 1H, Ar—H), 7.28-7.21 (m, 4H, 4×Ar—H), 7.17 (dd, J 3.4, 5.1, 1H, Ar—H), 7.10 (dd, J 7.7, 6.8, 1H, Ar—H), 6.88-6.83 (m, 2H, 2×Ar—H), 5.71 (s, 1H, H-12), 4.95 (s, 1H, H-11), 4.57 (dd, J 8.6, 5.1, 1H, H-17), 3.97 (d, J 15.6, 1H, H-10), 3.87 (s, b, 2H, H-1), 3.71 (d, J 13.7, 1H, H-9), 3.64 (dd, J 15.8, 8.6, 1H, H-18), 3.62 (d, J 13.7, 1H, H-9), 3.23 (d, J 15.6, 1H, H-10), 3.17 (dd, J 15.8, 5.1, 1H, H-18). δC (CDCl 3 , 75 MHz): 143.4, 140.7, 137.7, 136.5, 135.9, 133.0, 132.8, 132.2, 129.3, 128.7, 127.8, 127.2, 127.1, 127.0, 125.1, 124.7, 123.7, 119.8, 118.4, 110.0, 59.5, 57.6, 49.8, 45.3.
[0258] v/max (film): 3411, 1649.
[0259] m/z (EZ) (%): 488 (MH + , 100).
Example 6
N-(2-Aminophenyl)-4-{[1-(cyanomethyl)-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]methyl}benzamide
[0260]
[0261] Prepared by the general procedure from 2-iodocinnamonitrile (0.255 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, 2:1 v/v hexanes:EtOAc) afforded the product as a pale yellow foam. Crystallisation from DCM/hexane gave the product as colourless prisms (0.281 g, 69%), m.p. 93-95° C.
[0262] (Found: C, 76.2; H, 5.9; N, 14.0. C 26 H 24 N 4 O requires: C, 76.45, H, 5.92, N, 13.72).
[0263] δH (CDCl 3 , 500 MHz): 7.89 (d, J 8.4, 2H, H-7), 7.87 (s, b, 1H, H-6), 7.72 (d, J 7.1, 1H, H-13), 7.54 (d, J 8.4, 2H, H-8), 7.36-7.27 (m, 3H, 3×Ar—H), 7.13-7.06 (m, 2H, 2×Ar—H), 6.88-6.84 (m, 2H, 2×Ar—H), 5.76 (s, 1H, H-12), 5.04 (s, 1H, H-11), 4.07 (dd, J 9.8, 5.2, 1H, H-17), 3.91 (d, J 15.5, 1H, H-10), 3.87 (s, b, 2H, H-1), 3.86 (d, J 14.0, 1H, H-9), 3.71 (d, J 14.0, 1H, H-9), 3.36 (d, J 15.5, 1H, H-10), 2.91 (dd, J 17.0, 9.8, 1H, H-18), 2.69 (dd, J 17.0, 5.2, 1H, H-18).
[0264] δC (CDCl 3 , 75 MHz): 165.7, 142.6, 140.7, 135.7, 133.4, 132.7, 132.3, 129.3, 128.7, 128.0, 127.8, 127.5, 127.2, 125.2, 124.7, 124.0, 119.8, 118.4, 118.2, 110.8, 58.5, 57.6, 50.0, 24.8.
[0265] v/max (film): 3434, 3322, 1639, 1524, 2252.
[0266] m/z (EZ) (%): 409 (MH + , 35), 225 (fragment C 1 -C 9 , 100)
Example 7
N-(2-Aminophenyl)-4-[(4-methylene-1-oxo-3,4-dihydroisoquino-2(1H)-yl)methyl]benzamide
[0267]
[0268] Prepared by the general procedure from methyl 2-iodobenzoate (0.131 g, 0.5 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.133 g, 0.55 mmol), Pd 2 dba 3 (0.011 g, 0.0125 mmol), TFP (0.012 g, 0.05 mmol), K 2 CO 3 (0.138 g, 1.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (25 g silica, 1:1 v/v hexanes:EtOAc) afforded the product as a pale orange solid. Crystallisation from DCM/hexane gave the product as pale orange plates (0.115 g, 60%), m.p. 202-204° C.
[0269] (Found: C, 74.55; H, 5.50; N, 10.60. C 24 H 21 N 3 O 2 .0.25H 2 O requires: C, 74.30, H, 5.59, N, 10.83).
[0270] δH (CDCl 3 , 500 MHz): 8.21 (d, J 7.8, 1H, H-16), 7.88 (d, J 7.8, 2H, H-7), 7.84 (s, b, 1H, H-6), 7.57 (d, J 7.6, 1H, Ar—H), 7.53 (dd, J 7.4, 7.7, 1H, Ar—H), 7.48-7.44 (m, 3H, 3×Ar—H), 7.33 (d, J 7.7, 1H, Ar—H), 7.10 (dd, J 6.8, 7.1, 1H, Ar—H), 6.87-6.84 (m, 2H, 2×Ar—H), 5.59 (s, 1H, H-12), 5.18 (s, 1H, H-11), 4.89 (s, 2H, H-9), 4.16 (s, 2H, H-10), 3.86 (s, b, 2H, H-1).
[0271] δC (CDCl 3 , 75 MHz): 165.5, 163.7, 141.1, 140.7, 136.3, 135.8, 133.6, 132.3, 129.0, 128.7, 128.2, 127.8, 127.5, 127.2, 125.2, 124.6, 123.2, 119.8, 118.4, 112.6, 52.0, 50.0.
[0272] v/max (film): 3400, 1632, 1530, 1501.
[0273] m/z (EZ) (%): 384 (100, MH + ), 406 (82, MNa + ), 789 (2MNa + ).
Example 7
Alternative synthesis of N-(2-Aminophenyl)-4-[(4-methylene-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)methyl]benzamide
General Materials and Methods
[0274] LCMS analyses were carried out using the following equipment and method:
Liquid handler and SFO: Alliance e2695.
UV detector: Waters 2998. The detection was done at 254 nm and using an array between 210-600 nm. The diode array trace was used to measure purity.
Mass spectrometer: Acquity SQ, detecting masses in the range of 100 and 700 g/mol.
Column: 5 micron SunFire C18, 50×4.60 mm 0
Injection volume: 10 μL.
Flow rate . 1.5 mL/min
Mobile phase A: Water+0.1% Formic acid
Mobile phase B: Acetonitrile+0.1% Formic acid.
[0000] Time/min. % Mobile Phase A % Mobile Phase B 0.00 95 5 10.00 5 95 10.50 5 95 10.60 95 5 12.00 95 5
NMR spectra were acquired on an Oxford Instruments AS400 9.4 Tesla 400 MHz magnet with either a 5 mm BBO or PH SEF 400SB F—H-D-05 probe and an AVANCE/DPX400 console. Deuterated solvents were from Sigma-Aldrich or Acros organics. Chemical shifts are in ppm. Laboratory chemicals were purchased from commercial sources and used without further purification.
Names were generated using Autonom 2000.
Step 1—Preparation of [4-(2-Amino-phenylcarbamoyl)-benzyl]-carbamic acid tert-butyl ester
[0275]
[0276] 4-(Boc-aminomethyl)benzoic acid (10.09 g, 40.154 mmol) and 4-(4,6-Dimethoxy-1,3,5-triazin2-yl)-4-methylmorpholinium chloride (11.11 g, 40.149 mmol, 1.0 equivalents) were suspended in DMF (130 ml) and stirred at ambient. To this was added 1,2 phenelynediamine (6.08 g, 56.223 mmol, 1.4 equivalents), and the addition rinsed in with 20 ml DMF. The reaction was stirred at ambient overnight, after which time LCMS analysis indicated 95% conversion to product. The reaction mixture was poured into 150 ml 1M NaOH solution and extracted with 3×200 ml ethyl acetate. The ethyl acetate layers were combined and washed with 2×200 ml water, then dried over magnesium sulphate, filtered and concentrated under reduced pressure to give crude 1, 13.88 g (101%). This crude solid was suspended in 70 ml diethyl ether and stirred at ambient temperature for 24 hours. The solid was isolated by filtration, washed through with 2×10 ml diethyl ether and dried in vacuo at ambient to give 11.99 g (87%) 1, 90% by LCMS.
[0277] 11.08 g of this was suspended in 110 ml ethyl acetate and stirred at ambient temperature for 4 hours. The solid was isolated by filtration, washed through with 2×10 ml ethyl acetate and dried in vacuo at 40-45° C. to give 1, 8.46 g (76% recovery).
[0278] LCMS: Purity >99% Retention time 5.3 minutes MI:M+1=342
[0279] NMR (d6-DMSO): 9.62 (s, 1H), 7.93 (d, J=8 Hz, 2H), 7.49 (t, J=6 Hz, 1H), 7.36 (d, J=8 Hz, 2H), 7.17 (d, J=7 Hz, 1H), 6.97 (m, 1H), 6.78 (dd, J=1 Hz, 8 Hz, 1H), 6.60 (m, 1H), 4.89 (s, 2H), 4.20 (d, J=6 Hz, 2H), 1.41 (s, 9H).
Step 2—Preparation of 4-Aminomethyl-N-(2-amino-phenyl)-benzamide
[0280]
[0281] [4-(2-Amino-phenylcarbamoyl)-benzyl]-carbamic acid tert-butyl ester (4.50 g, 13.181 mmol) was suspended in DCM (45 ml) and cooled by ice-bath. To this was added trifluoroacetic acid (23 ml) over a period of 15 minutes, at which time the reaction was removed from cooling and allowed to warm to ambient. The reaction was stirred for a further 2 hours at ambient, LCMS indicating >99% conversion. The reaction mixture was concentrated under reduced pressure and the evaporation residue dissolved in methanol (70 ml) and loaded onto a 70 g Isolute SCX-2 cartridge. This was then eluted with a further three 70 ml portions of methanol. These methanol fractions were discarded to waste. The column was then eluted with 4×70 ml 2M ammonia in methanol, the final three fractions were combined and concentrated under reduced pressure to give 2, 3.24 g (102%).
[0282] LCMS: Purity >98% Retention time 0.8 minutes MI:M+1=242
[0283] NMR (d4-MeOH, 400 MHz): 7.96 (d, J=8 Hz, 2H), 7.49 (d, J=8 Hz, 2H), 7.18 (dd, J=1 Hz, 8 Hz, 1H), 7.08 (m, 1H), 6.90 (dd, J=1 Hz, 8 Hz, 1H), 6.77 (m, 1H), 3.88 (s, 2H).
[0284] This procedure was repeated on 3.97 g (11.628 mmol) of 1, using 40 ml DCM and 18 ml trifluoroacetic acid. This gave 2.85 g (101%), analytical data as above.
Step 3—Preparation of N-(2-Amino-phenyl)-4-(4-methylene-1-oxo-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-benzamide
[0285]
[0286] DMF degassed by sparging with nitrogen for 1 hour. To a Schlenk tube was charged 2 (0.70 g, 2.901 mmol), methyl 2-iodobenzoate (0.68 g, 2.595 mmol, 0.9 equivalents), potassium carbonate (0.72 g, 5.209 mmol, 1.8 equivalents), tri(2-furyl)phosphine (0.067 g, 0.289 mmol, 10 mol %), tris(dibenzylideneacetone)dipalladium(0) (0.066 g, 0.072 mmol, 2.5 mol %) and DMF (70 ml). The Schlenk tube was sealed, then evacuated and backfilled with nitrogen twice. It was then left open to vacuum for 2 minutes. A cylinder of allene was set to 8 psi, the Schlenk tube isolated from vacuum and then opened (whilst still under vacuum) to the allene cylinder, and left open to it for 1 minute. The Schlenk tube was sealed and heated to 80° C. for 21 hours (behind a blast shield). The reaction was left to cool to ambient, then vented. LCMS analysis showed >99% conversion of the methyl 2-iodobenzoate. The Schlenk tube was evacuated and backfilled with nitrogen twice to remove residual allene. The reaction mixture was poured into 3% sodium chloride solution (300 ml) and extracted with ethyl acetate (2×100 ml). The ethyl acetate layers were combined and washed with 3% sodium chloride solution (100 ml), saturated disodium citrate solution (30 ml), 0.1M EDTA disodium salt solution (50 ml) and 3% sodium chloride solution (50 ml). The organics were dried over magnesium sulphate and filtered. To the filtrate was added activated charcoal (0.07 g) and stirred for 35 minutes. The charcoal was removed by filtration through Kieselguhr and the filtrate concentrated under reduced pressure to give crude 3, 1.10 g (99%). This was then columned using a Combiflash Rf (120 g silica column, DCM/MeOH) to give 3, 0.58 g (52%).
[0287] This procedure carried out on 4 more batches, the results are summarised in the following table.
[0000]
Input/g
Time/hours
Yield/g
0.70
21
0.64(58%)
0.60
23
0.55(58%)
0.60
25½
0.62(65%)
0.56
24
0.53(60%)
[0288] The 5 batches were combined, dissolved in a mixture of DCM and methanol and the resulting clear solution concentrated under reduced pressure to give 3, 2.87 g.
[0289] LCMS: Purity 99% Retention time 5.6 minutes MI:M+1=384
[0290] NMR (CDCl 3 ): 8.23 (m, 1H), 7.97 (s, b, 1H), 7.90 (d, J=8 Hz), 7.60-7.44 (m, 5H), 7.36 (d, J=8 Hz, 1H), 7.11 (m, 1H), 6.87 (m 2H), 5.61 (t, J=1 Hz), 5.19 (t, J=2 Hz, 1H), 4.89 (s, 2H), 4.17 (t, J=1 Hz, 2H), 3.90 (s, 2H).
[0291] NMR (d6-DMSO): 9.65 (s, 1H), 8.03 (dd, J=1 Hz, 7 Hz, 1H), 7.97 (d, J=8 Hz, 2H), 7.74 (d, J=7 Hz, 1H), 7.61 (m, 1H), 7.51 (m, 1H), 7.44 (d, J=8 Hz, 2H), 7.16 (d, J=8 Hz, 1H), 6.97 (m, 1H), 6.78 (dd, J=1 Hz, 8 Hz, 1H), 6.59 (m, 1H), 5.73 (s, 1H), 5.32 (s, 1H), 4.90 (s, 2H), 4.81 (s, 2H), 4.27 (s, 2H).
Example 8
N-(2-Aminophenyl)-4-{[1-{2-[(2-aminophenyl)amino]-2-oxoethyl}-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]methyl}benzamide
[0292]
[0293] Prepared by the general procedure from (2E)-N-(2-aminophenyl)-3-(2-iodophenyl)acrylamide (0.364 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, 1:3 v/v hexanes:EtOAc) afforded the product as a pale yellow solid. Crystallisation from DCM/hexane gave the product as pale yellow needles (0.208 g, 40%), m.p. 135-137° C.
[0294] (Found: C, 74.0; H, 6.05; N, 13.25. C 32 H 31 N 5 O 2 requires: C, 74.25, H, 6.04, N, 13.53).
[0295] δH (CDCl 3 , 500 MHz): 10.10 (s, 1H, N—H), 7.79 (s, b, 1H, N—H), 7.75-7.71 (m, 3H, 3×Ar—H), 7.37-7.29 (m, 5H, 5×Ar—H), 7.16 (d, J 6.8, 1H, Ar—H), 7.11-7.02 (m, 3H, 3×Ar—H), 6.87-6.78 (m, 4H, 4×Ar—H), 5.79 (s, 1H, H-12), 5.04 (s, 1H, H-11), 4.27 (dd, J 11.5, 2.8, 1H, H-17), 4.06 (d, J 15.4, 1H, H-10), 3.90 (s, b, 2H, H-1), 3.82 (d, J 13.0, 1H, H-9), 3.76 (d, J 13.0, 1H, H-9), 3.41 (d, J 15.4, 1H, H-10), 3.0 (dd, J 16.7, 11.5, 1H, H-18), 2.65 (dd, J 16.7, 2.8, 1H, H-18).
[0296] δC (CDCl 3 , 75 MHz): 169.9, 166.0, 141.8, 141.6, 141.2, 135.7, 134.3, 131.9, 130.3, 129.5, 128.4, 128.0, 127.9, 127.7, 127.6, 125.8, 125.7, 124.8, 124.5, 124.1, 120.2, 119.6, 118.8, 118.3, 111.6, 60.0, 57.7, 49.4, 41.9.
[0297] v/max (film): 3381, 3225, 1644, 1616, 1495, 1454.
[0298] m/z (EZ) (%): 518 (MH + , 25), 146 (100).
Example 9
[2-(4-{[(2-Aminophenyl)amino]carbonyl}benzyl)-4-methylene-1,2,3,4-tetra hydroisoquinolin-1-yl]acetic acid
[0299]
[0300] To a stirred solution of methyl [2-(4-{[(2-aminophenyl)amino]carbonyl}benzyl)-4-methylene-1,2,3,4-tetrahydroisoquinolin-1-yl]acetate (0.115 g, 0.26 mmol) in EtOH (2 mL) was added NaOH (0.5 mL, 1M aq, 0.5 mmol). The mixture was stirred at room temperature for 18 h, and the organic solvent was removed in vacuo. HCl (10 mL, 1 M aq) was added, and the mixture was extracted with DCM (3×10 mL). The combined organic phases were dried (MgSO 4 ), filtered and concentrated in vacuo to give the product as colourless plates (0.069 g, 62%), m.p. >230° C.
[0301] Found: 450.1781; C 26 H 25 N 3 O 3 Na (MNa + ) requires: 450.1788.
[0302] δ H (500 MHz, DMSO-d 6 ): 9.66 (s, b, 1H, H-19), 7.95 (d, J 7.5, 2H, H-7), 7.79 (d, J 7.1, 1H, H-13), 7.41 (d, J 7.5, 2H, H-8), 7.36-7.31 (m, 2H, 2×Ar—H), 7.21-7.16 (m, 2H, 2×ArH), 6.99 (dd, J 7.7, 6.8, 1H, H-3), 6.81 (d, J 7.7, 1H, H-2), 6.62 (dd, J 6.8, 6.4, 1H, H-3), 5.82 (s, 1H, H-12), 5.01 (s, 1H, H-11), 4.31-4.26 (m, 1H, H-17), 3.88 (d, J 15.6, 1H, H-10), 3.74-3.67 (m, 2H, H-9), 3.25 (d, J 15.6, 1H, H-10), 2.84-2.78 (m, 1H, H-18), 2.62 (dd, J 15.4, 5.5, 1H, H-18).
[0303] δC (DMSO-d 6 , 75 MHz): 172.7, 165.5, 143.5, 142.5, 136.6, 135.7, 133.8, 131.9, 128.8, 128.7, 128.1, 128.0, 127.3, 127.0, 126.8, 123.9, 123.7, 116.6, 116.5, 110.5, 60.1, 59.3, 57.0, 41.0.
[0304] v/max (film): 3412, 1641, 1502, 1451, 1315.
[0305] m/z (EZ) (%): 450 (MNa + , 100)
Example 10
N-(2-Aminophenyl)-4-{[1-{2-[(2-hydroxyethyl)amino]-2-oxoethyl}-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]methyl}-benzamide
[0306]
[0307] Prepared by the general procedure from (2E)-N-(2-hydroxyethyl)-3-(2-iodophenyl)acrylamide (0.159 g, 0.5 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.133 g, 0.55 mmol), Pd 2 dba 3 (0.011 g, 0.0125 mmol), TFP (0.012 g, 0.05 mmol), K 2 CO 3 (0.138 g, 1.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g silica, EtOAc to 99:1 v/v EtOAc:MeOH) afforded the product as an amorphous pale yellow solid (0.108 g, 46%).
[0308] Found: 471.2388; C 28 H 31 N 4 O 3 (MH + ) requires: 471.2391.
[0309] δH (CDCl 3 , 500 MHz): 8.17 (s, b, 2H, H-6, H-19), 7.90 (d, J 7.5, 2H, H-7), 7.71 (d, J 6.8, 1H, H-13), 7.42 (d, J 7.5, 2H, H-8), 7.35 (d, J 7.7, 1H, H-16), 7.31-7.28 (m, 2H, 2×Ar—H), 7.11-7.07 (m, 2H, 2×Ar—H), 6.86-6.82 (m, 2H, 2×Ar—H), 5.78 (s, 1H, H-12), 5.04 (s, 1H, H-11), 4.21 (dd, J 11.1, 3.0, 1H, H-17), 3.97 (d, J 15.2, 1H, H-10), 3.80 (d, J 12.8, 1H, H-9), 3.71 (d, J 15.2, 1H, H-10), 3.70-3.64 (m, 2H, H-21), 3.43-3.31 (m, 3H, H-20, H-9), 2.84 (dd, J 16.2, 11.1, 1H, H-18), 2.50 (dd, J 16.2, 3.0, 1H, H-18).
[0310] δ C (75 MHz, CDCl 3 ): 172.5, 165.8, 142.2, 140.7, 135.7, 134.4, 133.7, 131.6, 129.7, 128.9, 128.0, 127.7, 127.3, 125.3, 124.6, 123.6, 119.7, 118.4, 110.6, 62.4, 59.4, 57.3, 49.5, 42.5, 41.6.
[0311] v/max (film): 3300, 3067, 2932, 1641, 1530.
[0312] m/z (EZ): (%) 471 (MH + , 100).
Example 11
N-(2-Aminophenyl)-4-{[4-methylene-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-3,4-dihydroisoquinolin-2(1H)-yl]methyl}benzamide
[0313]
[0314] Prepared by the general procedure from 1-[(2E)-3-(2-iodophenyl)prop-2-enoyl]-4-methylpiperazine (0.356 g, 1.0 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.265 g, 1.1 mmol), Pd 2 dba 3 (0.022 g, 0.025 mmol), TFP (0.023 g, 0.1 mmol), K 2 CO 3 (0.276 g, 2.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (30 g basic Al 2 O 3 , EtOAc) afforded the product as an amorphous pale pink solid (0.256 g, 50%).
[0315] Found: 510.2879; C 31 H 36 N 5 O 2 (MH + ) requires 510.2864.
[0316] δH (CDCl 3 , 500 MHz): 8.05 (s, b, 1H, H-6), 7.84 (d, J 8.1, 2H, H-7), 7.68 (d, J 6.4, 1H, H-16), 7.41 (d, J 8.1, 2H, H-8), 7.32 (d, J 7.3, 1H, Ar—H), 7.26-7.23 (m, 2H, 2×Ar—H), 7.13 (d, J 6.6, 1H, Ar—H), 7.08 (t, J 7.7, 1H, Ar—H), 6.85-6.83 (m, 2H, 2×Ar—H), 5.70 (s, 1H, H-12), 4.95 (s, 1H, H-11), 4.38 (dd, J 6.0, 8.1, 1H, H-17), 3.91 (s, b, 2H, H-1), 3.87 (d, J 15.8, 1H, H-10), 3.75 (d, J 13.5, 1H, H-9), 3.77-3.74 (m, 1H, N—CH 2 ), 3.68 (d, J 13.5, 1H, H-9), 3.63-3.57 (m, 1H, N—CH 2 ), 3.42-3.37 (m, 1H, N—CH 2 ), 3.30 (d, J 15.8, 1H, H-10), 3.22-3.16 (m, 1H, N—CH 2 ), 2.96 (dd, J 14.1, 8.1, 1H, H-18), 2.67 (dd, J 14.1, 6.0, 1H, H-18). 2.41-2.33 (m, 2H, N—CH 2 ), 2.29-2.23 (m, 1H, N—CH 2 ), 2.26 (s, 3H, H-21), 2.19-2.13 (m, 1H, N—CH 2 ).
[0317] δC (CDCl 3 , 75 MHz): 169.6, 165.9, 143.5, 140.8, 136.7, 135.9, 133.1, 132.1, 129.3, 128.4, 128.0, 127.3, 127.2, 127.1, 125.3, 124.7, 123.6, 119.7, 118.3, 109.8, 60.0, 57.7, 55.0, 54.7, 50.1, 46.0, 45.9, 41.7, 39.1.
[0318] v/max (film): 3410, 1625, 1503, 1450.
[0319] m/z (EZ) (%): 497 (MH + , 100).
Example 12
N-(2-Aminophenyl)-4-{[1-{2-[(2-{[2E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)prop-2-enoyl]amino}ethyl)amino]-2-oxoethyl}-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]methyl}benzamide
[0320]
[0321] Prepared by the general procedure from (2E)-3-(3-hydroxy-4-methoxyphenyl)-N-(2-{[(2E)-3-(2-iodophenyl)prop-2-enoyl]amino}ethyl)-2-(3,4,5-trimethoxyphenyl)acrylamide (0.329 g, 0.5 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.133 g, 0.55 mmol), Pd 2 dba 3 (0.011 g, 0.0125 mmol), TFP (0.012 g, 0.05 mmol), K 2 CO 3 (0.138 g, 1.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (25 g silica, EtOAc) afforded the product as a pale yellow solid. Crystallisation from DCM/hexane gave the product as pale yellow prisms (0.192 g, 47%), m.p. >230° C.
[0322] (Found: C, 69.50; H, 6.00; N, 8.40; C 47 H 49 N 5 O 8 requires: C, 69.53; H, 6.08; N, 8.63%).
[0323] δH (CDCl 3 , 500 MHz): 8.43 (s, b, 1H, H-6), 8.11 (d, J 8.1, 2H, H-7), 7.72 (d, J 8.6, 1H, H-13), 7.51 (s, 1H, H-26), 7.39-7.33 (m, 3H, 3×Ar—H), 7.31-7.28 (m, 2H, 2×Ar—H), 7.10-7.05 (m, 2H, H-3, H-5), 6.86 (d, J 7.3, 1H, H-2), 6.75 (t, J 7.3, 1H, H-4), 6.62 (d, J 8.5, 1H, H-30), 6.43 (s, 1H, H-27), 6.40-6.35 (m, 3H, H-31, H-23), 5.92 (s, b, 1H, N—H), 5.78 (s, 1H, H-12), 5.47 (s, b, 1H, N—H), 5.11 (s, 1H, H-11), 4.17 (s, b, 1H, H-28), 4.11 (d, J 15.6, 1H, H-10), 4.02 (dd, J 11.8, 2.3, 1H, H-17), 3.92 (s, 3H, H-25), 3.85-3.77 (m, 5H, 2×H-1, 1×H-9, 2×H-21), 3.83 (s, 3H, H-29), 3.77 (s, 6H, H-24), 3.57 (d, J 12.8, 1H, H-9), 3.48 (d, J 15.6, 1H, H-10), 3.17-3.08 (m, 2H, H-20), 2.78 (dd, J 17.1, 11.8, 1H, H-18), 2.36 (dd, J 17.1, 2.3, 1H, H-18).
[0324] δC (CDCl 3 , 75 MHz): 171.6, 168.3, 166.0, 154.4, 147.4, 145.1, 142.6, 141.8, 141.3, 137.6, 135.6, 134.3, 134.1, 131.6, 131.0, 129.5, 129.0, 128.6, 128.2, 127.8, 127.4, 127.1, 125.9, 124.8, 123.6, 122.4, 119.3, 118.2, 116.5, 110.6, 110.1, 106.7, 61.1, 57.9, 57.4, 56.4, 55.8, 51.0, 41.0, 39.5, 38.2.
[0325] v/max (film): 3419, 1644, 1508.
[0326] m/z (EZ) (%): 812 (MH + , 100).
Example 13
Methyl 2-(4-{[(2-aminophenyl)amino]carbonyl}benzyl)-4-methylene-1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylate
[0327]
[0328] Prepared by the general procedure from dimethyl 2-iodoterephthalate (0.160 g, 0.5 mmol), 4-(aminomethyl)-N-(2-aminophenyl)benzamide (0.133 g, 0.55 mmol), Pd 2 dba 3 (0.011 g, 0.0125 mmol), TFP (0.012 g, 0.05 mmol), K 2 CO 3 (0.138 g, 1.0 mmol) and allene (0.5 bar) in DMF (10 mL), heated at 80° C. for 24 h. Column chromatography (25 g silica, Et 2 O) afforded the product as a pale orange solid. Crystallisation from toluene gave the product as colourless needles (0.150 g, 68%), m.p. 196-198° C.
[0329] Found: 442.1760; C 26 H 24 N 3 O 4 (MH + ) requires 442.1761.
[0330] δH (CDCl 3 , 500 MHz): 8.27 (d, J 8.2, 1H, H-16), 8.23 (d, J 1.2, 1H, H-13), 8.08 (dd, J 8.2, 1.2, 1H, H-15), 7.90-7.88 (m, 2H, H-6 & H-7), 7.44 (d, J 8.0, 2H, H-8), 7.33 (d, J 7.7, 1H, H-5), 7.11-7.08 (m, 1H, H-4), 6.86-6.84 (m, 2H, H-2 & H-3), 5.71 (s, 1H, H-12), 5.25 (s, 1H, H-11), 4.88 (s, 2H, H-9), 4.18 (s, 1H, H-10), 3.97 (s, 3H, H-14), 3.87 (s, b, 2H, H-1).
[0331] δC (CDCl 3 , 75 MHz): 166.25, 162.6, 140.8, 140.6, 135.9, 135.4, 133.7, 133.5, 130.1, 129.6, 129.1, 128.3, 127.9, 127.3, 125.1, 124.8, 124.6, 119.9, 118.5, 113.9, 52.5, 51.9, 50.2.
[0332] v/max (film): 1722, 1652, 1630, 1487, 1271.
[0333] m/z (EZ) (%): 442 (MH + , 100), 464 (MNa + , 80).
Example 14
N-(2-Aminoethyl)-2-(4-{[(2-aminophenyl)amino]carbonyl}benzyl)-4-methylene-1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxamide
[0334]
[0335] Methyl 2-(4-{[(2-aminophenyl)amino]carbonyl}benzyl)-4-methylene-1-oxo-1,2,3,4-tetra hydroisoquinoline-6-carboxylate (0.429 g, 1 mmol) was dissolved in EtOH (5 mL) and 1M aq NaOH (2.5 mL, 2.5 mmol) and stirred at room temperature for 6 h. The organic solvent was removed in vacuo, and the resulting mixture acidified to pH 4 with HCl (1M aq). The product was collected by filtration, dried in vacuo and used in the next step without further purification.
[0336] To a stirred solution of the resulting solid material (0.427 g, 1 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (0.276 g, 1 mmol) in DMF (5 mL) was added tert-butyl (2-aminoethyl)carbamate (0.224 g, 1.4 mmol) in one portion at room temperature. After stirring at room temperature for 16 h, the mixture was diluted with water (50 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with water (20 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. Flash chromatography (25 g SiO 2 , 4:1 v/v EtOAc:hexanes) gave a colourless solid (0.372 g, 65%) which was used without further purification.
[0337] To a stirred solution of the resulting solid (0.569 g, 1 mmol) in DCM (5 mL) was added TFA (0.150 g, 2 mmol) in one portion at room temperature. After stirring for 2 h, the mixture was diluted with DCM (10 mL), washed with 1M aq NaOH (2×10 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. Trituration with Et 2 O gave the product as pale yellow plates (0.415 g, 88%), m.p. 172-174° C. (dec).
[0338] Found: 470.2189; C 27 H 28 N 5 O 3 requires 470.2187.
[0339] δH (DMSO-d 6 , 500 MHz): 8.18 (s, b, 2H, H-13, H-6), 8.11 (d, J 8.1, 1H, H-15), 7.99 (d, J 8.1, 2H, H-7), 7.96 (d, J 8.1, 1, H-14), 7.44 (d, J 8.1, 2H, H-8), 7.21 (q, J 3.0, 1H, H-16), 7.17 (d, J 7.5, 1H, H-5), 6.98 (dd, J 8.1, 7.3, 1H, H-3), 6.79 (d, J 8.1, 1H, H-2), 6.61 (dd, J 7.5, 7.3, 1H, H-4), 5.83 (s, 1H, H-12), 5.41 (s, 1H, H-11), 4.92 (s, b, 2H, H-19), 4.82 (s, 2H, H-9), 4.31 (s, 2H, H-10), 3.36-3.32 (m, 2H, H-18), 2.81-2.79 (m, 2H, H-17).
[0340] δC (DMSO-d 6 , 75 MHz): 166.4, 165.4, 162.2, 143.0, 141.0, 137.7, 136.1, 136.0, 134.0, 129.6, 128.5, 128.0, 127.9, 127.0, 126.9, 123.9, 123.0, 116.9, 116.7, 115.5, 114.3, 51.7, 49.7, 37.6, 34.6.
[0341] v/max (film): 3030, 1635, 1531, 1503.
[0342] m/z (%): 470 (MH + , 100), 492 (MNa + , 10).
Example 15
N-(2-Aminophenyl)-4-{[1-(cyanomethyl-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}benzamide
[0343]
[0344] To a stirred solution of tert-butyl{2-[(4-{[1-(cyanomethyl)-4-methylene-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}benzoyl)amino]phenyl}carbamate (0.279 g, 0.5 mmol) in DCM (5 mL) was added TFA (0.11 g, 1.0 mmol) in one portion at room temperature. The resulting mixture was stirred at room temperature for 4 hours, washed with NaOH aq., 2×5 mL), dried (MgSO 4 ), filtered and concentrated in vacuo. Column chromatography (25 g SiO 2 , Et 2 O) gave the product as pale yellow prisms (0.153 g, 67%), m.p. 213-215° C.
[0345] Found: 459.1488; C 25 H 23 N 4 O 3 S requires 459.1485.
[0346] δH (CDCl 3 , 500 MHz): 9.74 (s, 1H, H-6), 7.92 (d, J 8.3, 2H, H-7), 7.78 (d, J 8.3, 2H, H-8), 7.51 (d, J 7.9, 1H, H-12), 7.39 (d, J 7.7, 1H, H-15), 7.26 (dd, J 7.9, 7.5, 1H, H-13), 7.17 (dd, J 7.7, 7.5, 1H, H-14), 7.12 (d, J 7.5, 1H, H-5), 6.98 (dd, J 7.5, 7.3, 1H, H-3), 6.78 (d, J 7.5, 1H, H-2), 6.60 (dd, J 7.5, 7.3, 1H, H-4), 5.58 (s, 1H, H-11), 5.52 (dd, J 9.8, 4.3, 1H, H-16), 5.19 (s, 1H, H-10), 4.55 (d, J 16.7, 1H, H-9), 4.41 (d, J 16.7, 1H, H-9), 3.38 (dd, J 17.3, 9.8, 1H, H-17), 3.11 (dd, J 17.3, 4.3, 1H, H-17).
[0347] δC (CDCl 3 , 75 MHz): 164.1, 143.5, 141.5, 138.5, 134.3, 132.4, 130.9, 128.6, 128.4, 128.1, 127.7, 127.5, 127.2, 124.2, 123.1, 118.4, 116.5, 116.4, 111.4, 53.2, 45.0, 24.9.
[0348] v/max (film) 2985, 1663, 1624, 1501.
[0349] m/z (EZ) (%) 459 (MH + , 55), 481 (MNa + , 100).
Example 16
In Vitro Assay for HDAC 3 and HDAC 6 Inhibitory Activity
[0350] The activity of the compounds of the invention against HDAC 3 (Class I) and HDAC 6 (Class II) can be determined using the Caliper Life Sciences HDAC inhibitor profiling assay, which utilises microfluidic mobility-shift detection.
Reagents:
[0351] Reaction buffer: 25 mM Tris/Cl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl 2 , 0.1 mg/ml BSA (fatty acid free).
Stop Buffer: 100 mM HEPES, pH 7.5, 10 mM EDTA, 0.04% Brij-35, 0.25% CR-3, and 2.5 μM Trichostatin A.
Assay Protocol:
[0352] Stopped reactions were assembled in microtiter plate wells by adding 1 μL of the inhibitor compound in DMSO, 15 μL 2× Enzyme, and 15 μL 2× peptide. The reactions were incubated for 1 hour at room temperature, stopped with the addition of 45 μL Stop Solution, and read on the LabChip EZ Reader®. The curves were fit with sigmoidal dose response algorithm using GraphPad Prism.
[0353] Although the pharmacological properties of the compounds of the formula I will vary with structural change as expected, compounds of the formula I, were found to be active in the above screens against HDAC 3 (a Class I HDAC) and relatively inactive against HDAC 6 (a Class II HDAC). In general, the activity possessed by compounds of the formula I, is represented by an IC 50 of less than 10 μM against HDAC 3. Preferred compounds of the invention have an IC 50 of less than 5 μM against HDAC 3, and the most preferred compounds of the invention have an IC 50 of less than 1 μM. With regard to HDAC 6 activity, the compounds of the invention, in general, demonstrate an IC 50 value which is greater than 10 μM.
[0354] The inhibitory activity of selected compounds of the invention against HDAC 3 and HDAC 6 is shown in Table 1 Below.
[0000]
TABLE 1
Compound/Example
IC50 (μM)
number
HDAC3
HDAC6
1
0.89
>10
2
0.51
>10
3
0.98
>10
4
0.26
>10
5
2.7
>10
6
0.31
>10
7
0.22
>10
8
0.35
>10
9
0.78
>10
10
0.67
>10
11
0.56
>10
13
0.27
>10
14
0.23
>10
15
1.4
>10
[0355] It will be understood, the IC 50 values quoted above are not absolute and further measurements of the IC 50 value for a compound may result in a different geometric mean IC 50 value.
Example 17
In Vitro Assay for Class I and Class II HDACs
[0356] The inhibitory effects of the compounds of Examples 7 and 9 above on HDAC activity were determined using a fluorescence-based assay with electrophoretic separation of substrate and product carried out using a microfluidic system followed by quantitation of fluorescence intensity in the substrate and product peaks.
[0357] The assays were performed using isolated HDAC isoforms that had been expressed as 6×His-tagged fusion proteins in a baculovirus expression system in Sf9 cells. HDACs 1, 2, 3, 6, and 8 were expressed as full length fusion proteins. For HDAC-4 and 7 only catalytic domains were expressed (HDAC-4 CAT and HDAC-7 CAT). The HDAC10 fusion protein was expressed as a carboxy-terminal deletion of 38 amino acids (residues 632-669). HDAC3 was coexpressed with a fragment of the SMRT gene (residues 395-489) to generate enzymatically active protein. Purified proteins were incubated with 1 μM carboxyfluorescein (FAM)-labeled acetylated peptide substrate and test compound for 17 h at 25° C. in HDAC assay buffer containing 100 mM HEPES (pH 7.5), 25 mM KCl, 0.1% BSA, and 0.01% Triton X-100. Reactions were terminated by the addition of buffer containing 0.078% SDS for a final SDS concentration of 0.05%. Substrate and product were separated electrophoretically using a Caliper LabChip 3000 system with blue laser excitation and green fluorescence detection (CCD2). The fluorescence intensity in the substrate and product peaks was determined using the Well Analyzer software on the Caliper system. The reactions were performed in duplicate for each sample.
[0358] IC50 values were automatically calculated using the IDBS XLFit version 4.2.1 plug-in for Microsoft Excel and the XLFit 4 Parameter Logistic Model (sigmoidal dose-response model): (A+((B−A)/1+(C/x) D )), where x is compound concentration, A is the estimated minimum, B is the estimated maximum of % inhibition, C is the inflection point, and D is the Hill slope of the sigmoidal curve. The standard errors of the IC50s were automatically calculated using the IDBS XLFit version 4.2.1 plug-in for Microsoft Excel and the formula xf4_FitResultStdError( ).
[0359] The pharmacological properties of the compounds of the formula I will vary with structural change, as expected. In general, the compounds of the formula I, were found to possess good activity in the above screen against the HDAC 2 and HDAC 3 (both of which are Class I HDACs) and were relatively less active against HDACs 1, 4, 6, 7, 8, and 10. In general activity possessed by compounds of the formula I possess an IC 50 of less than 10 μM against HDAC 2 and/or 3 in the above assay (preferred compounds have an IC 50 of less than 1 μM, more preferably less than 0.1 μM). The compounds of the invention may also exhibit an IC 50 of greater than 10 μM against HDACs 6 and 8, and greater than 5 μM against the class II HDACs 4, 7 and 10.
[0360] Particular data obtained for the compounds of Examples 7 and 9 are shown below.
[0000]
CLASS 1
CLASS 2
HDAC 1
HDAC 2
HDAC 3
HDAC 8
HDAC 4-CAT
HDAC 6
HDAC 7-CAT
HDAC 10
Compound
IC50
IC50
IC50
IC50
IC50
IC50
IC50
IC50
number
(μM)
(μM)
(μM)
(μM)
(μM)
(μM)
(μM)
(μM)
7
8.7
0.0544
0.0287
>30
9.22
>30
7.53
8.04
9
>30
2.11
0.797
>30
>30
>30
>30
>30
Example 18
Evaluation of the Activity of the Compound of Example 7 (MI-192) in MTS, CD11b and CYP26 Assays
Experimental Procedures
[0361] MTS Assays ( FIG. 2 i )
[0362] HL60 or NB4 cells were diluted in complete growth medium and plated at a density of 5000 cells per 0.1 ml in wells of a 96 well plate. Cells were then treated with various concentrations of the compound of Example 7 (MI-192) or were left untreated as a control in a total volume of 0.2 ml of complete growth medium. After 3 days, relative cell numbers were determined using the MTS assay, as described by the manufacturer (Promega, Southampton, UK). The results shown in FIG. 2( i ) are absorbance (490 nm) relative to control cells (untreated cells 100%).
[0000] CD11b ( FIG. 2 ii )
[0363] HL60 cells were cultured at 0.5×10 6 cells/ml in complete growth medium. Cells (2 ml) were then treated with ATRA (sourced commercially), the compound of Example 7 (MI-192), or left untreated as controls. After 3 days, CD11b expression was determined by flow cytometry using a PE-conjugated anti-CD11b monoclonal antibody.
[0000] CYP26 ( FIG. 2 iii )
[0364] HL60 or NB4 cells were cultured at 1.0×10 6 cells/ml in complete growth medium. Cells (10 ml) were then treated with ATRA, the compound of Example 7(MI-192), or left untreated as controls. After 1 day, the expression of CYP26 and BACT RNAs were determined using quantitative PCR (Taqman). The expression of CYP26 RNA was normalised to BACT, and expression in control cells was set to 1.0.
[0365] As can be seen from the data shown in FIG. 2 , the compound of Example 7 (MI-192) induces expression of CYP26, a gene that is repressed by HDAC3 12 . (Note that CYP26 is a specialised CYP important for retinoic acid metabolism but not a major player in drug metabolism). The compound of Example 7 also promotes growth inhibition and differentiation in AML cells ( FIG. 2 ). Interestingly, in HL60 cells the transcription modulating activity of MI-192 exceeded that of ATRA, the “gold standard” differentiation agent for AML.
REFERENCES
[0000]
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3. Zhang J, Kalkum M, Chait B T, Roeder R G. The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2. Mol. Cell. 2002; 9:611-623.
4. Guenther M G, Lane W S, Fischle W, Verdin E, Lazar M A, Shiekhattar R. A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness. Genes Dev. 2000; 14:1048-1057.
5. Petrie K, Zelent A, Waxman S. Differentiation therapy of acute myeloid leukemia: past, present and future. Curr Opin Hematol. 2009; 16:84-91.
6. Minucci S, Nervi C, Lo Coco F, Pelicci P G. Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukemias? Oncogene. 2001; 20:3110-3115.
7. Grignani F, De Matteis S, Nervi C, et al. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature. 1998; 391:815-818.
8. Lutterbach B, Hou Y, Durst K L, Hiebert S W. The inv(16) encodes an acute myeloid leukemia 1 transcriptional corepressor. Proc Natl Aced Sci USA. 1999; 96:12822-12827.
9. Lutterbach B, Westendorf J J, Linggi B, et al. ETO, a target of t(8; 21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Mol Cell Biol. 1998; 18:7176-7184.
10. Gelmetti V, Zhang J, Fanelli M, Minucci S, Pelicci P G, Lazar M A. Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Mol Cell Biol. 1998; 18:7185-7191.
11. Redner R L, Liu J M. Leukemia fusion proteins and co-repressor complexes: changing paradigms. J Cell Biochem. 2005; 94:864-869.
12. Atsumi A, Tomita A, Kiyoi H, Naoe T. Histone deacetylase 3 (HDAC3) is recruited to target promoters by PML-RARalpha as a component of the N-CoR co-repressor complex to repress transcription in vivo. Biochem Biophys Res Commun. 2006; 345:1471-1480.
13. Ozeki M, Shively J E. Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells. J Leukoc Biol. 2008; 84:769-779.
14. Cote S, Rosenauer A, Bianchini A, et al. Response to histone deacetylase inhibition of novel PML/RARalpha mutants detected in retinoic acid-resistant APL cells. Blood. 2002; 100:2586-2596.
15. Stimson L, Wood V, Khan O, Fotheringham S, La Thangue N B. HDAC inhibitor-based therapies and haematological malignancy. Ann Oncol. 2009; 20:1293-1302.
16. Hayashi A, Horiuchi A, Kikuchi N, et al. Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with down-regulation of E-cadherin. Int J. Cancer.
17. Khabele D, Son D S, Parl A K, et al. Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth: implications for therapy. Cancer Biol Ther. 2007; 6:795-801.
18. Wilson A J, Byun D S, Popova N, et al. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol. Chem. 2006; 281:13548-13558.
19. Thangaraju M, Carswell K N, Prasad P D, Ganaphthy V. Colon cancer cells maintain low levels of pyruvate to avoid cell death caused by inhibition of HDAC1/HDAC3. Biochem J. 2009; 417:379-389.
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This invention relates to the discovery of novel compounds, or pharmaceutically acceptable salts thereof, which possess HDAC inhibitory activity. In particular, the compounds of the invention demonstrate selectivity towards Class I HDAC enzymes, and are accordingly expected to be useful for their anti-proliferative activity and in methods of treatment of the human or animal body, for example in preventing or inhibiting tumour growth and metastasis in cancers. The invention also relates to processes for the manufacture of the compounds defined herein, or pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an anti-proliferative effect in a warm-blooded animal such as man.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is the U.S. national phase application of PCT International Application No. PCT/EP2007/051440, filed Feb. 14, 2007, which claims priority to German Patent Application No. DE102006008956.1, filed Feb. 23, 2006, and German Patent Application No. DE102006059949.7, filed Dec. 19, 2006, the contents of such applications being incorporated by reference herein in their entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a method of operating a motor vehicle brake system of the ‘brake-by-wire’ type, including
a) a brake booster operable both by means of an input member that is movable into a force-transmitting connection with a brake pedal and by means of an electronic control unit, with a distance being provided between the brake pedal and the brake booster which allows decoupling a force-transmitting connection between the brake pedal and the brake booster in the ‘brake-by-wire’ operating mode, b) a master brake cylinder connected downstream of the brake booster, c) means to detect the actuating travel of the brake pedal, d) a pedal travel simulator which cooperates with the brake pedal and allows simulating a resetting force that acts on the brake pedal in the ‘brake-by-wire’ operating mode independently of an actuation of the brake booster, and e) a connecting and disconnecting device connecting the pedal travel simulator in the ‘brake-by-wire’ operating mode when the force-transmitting connection between the brake pedal and the brake booster is decoupled and disconnecting it outside the ‘brake-by-wire’ operating mode.
[0009] 2. Description of the Related Art
[0010] A brake system of this type is disclosed in the applicant's German patent application DE 10 2004 011 622 A1. The above-mentioned connecting and disconnecting device in a design of the prior art brake system is provided by a hydraulic cylinder-and-piston arrangement, the pressure chamber of which is connected to a pressure fluid volume take-up element by means of a closable connection and on the pistons of which a simulator housing is supported. The connection between the pressure chamber and the pressure fluid volume take-up element that is designed as a low-pressure accumulator is closed by means of an electromagnetically operable shut-off valve which is configured as a normally open switch valve. The mentioned piston is moved when the connecting and disconnecting device is tested, and the pressure rising in the hydraulic pressure chamber is measured and the corresponding pressure signal is evaluated. The testing operation can be performed at standstill in a first application of the brake pedal after the ignition has been turned on. This state can be referred to as ‘conventional mode’. Upon termination of the testing operation a change is made into the actual ‘by-wire mode’, and the change-over is executed as soon as a fully released brake pedal is detected. The brake pedal feeling imparted to the vehicle driver in the ‘conventional mode’ differs greatly from the feeling in the ‘by-wire mode’.
[0011] In view of the above, an object of the invention is to propose appropriate measures which allow changing over from the ‘conventional mode’ into the ‘by-wire mode’ and, thus, adapting the brake pedal feeling to the respective situation.
SUMMARY OF THE INVENTION
[0012] According to aspects of the invention, the foregoing object is achieved in that the travel covered upon application of the brake pedal is determined and subsequently reduced by the operator, and in that upon reduction of the actuating travel by a predetermined value or in the event of a detected vehicle movement or a positive result of a monitoring function of the connecting and disconnecting device running in the background, the connecting and disconnecting device is activated and the brake booster is actuated by the electronic control unit.
[0013] More specifically, the connecting and disconnecting device is formed of a hydraulic cylinder-and-piston arrangement, whose piston on which a housing of the pedal travel simulator is supported delimits a pressure chamber, which can be connected to a pressure fluid volume take-up element by way of a connection which is closable by means of a shut-off valve, and in that the connecting and disconnecting device is activated by change-over of the shut-off valve into its closed switch position.
[0014] In this context, it is especially favorable when the nominal value of the hydraulic pressure that is introduced into the master brake cylinder by actuation of the brake booster is taken from a characteristic curve, which associates a pressure value with an actuating travel of the brake pedal and which, compared to a nominal characteristic curve (along the axis on which the actuating travel values are plotted), is shifted by a value which corresponds to the shortest actuating travel since the activation of the connecting and disconnecting device and the actuation of the brake booster minus a correction value.
[0015] These and other aspects of the invention are illustrated in detail by way of the embodiments and are described with respect to the embodiments in the following, making reference to the Figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Aspects of the invention will be explained in detail in the following description making reference to the accompanying drawings. In the drawings:
[0017] FIG. 1 is a representation of the brake system in which an exemplary method can be implemented, according to one aspect of the invention;
[0018] FIG. 2 is a partial cross-sectional view of a design of the brake actuation unit which is used in the brake system according to FIG. 1 ;
[0019] FIGS. 3 a, b show graphs of the time variations of the brake pedal actuating travel; and
[0020] FIG. 4 shows characteristic curves which associate values of the hydraulic pressure introduced into the master brake cylinder to defined brake pedal actuating travels.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0021] The motor vehicle brake system shown in FIG. 1 of the drawings which preferably can be operated in the ‘brake-by-wire’ operating mode, essentially consists of an actuating unit 1 , a hydraulic control and regulation unit (HCU) 17 , vehicle wheel brakes 13 , 14 , 15 , 16 connected to the hydraulic control and regulation unit (HCU) 17 , a first electronic control and regulation unit 7 associated with the actuating unit 1 as well as a second electronic control and regulation unit 12 associated with the hydraulic control and regulation unit (HCU) 17 . The actuating unit 1 , in turn, consists of a brake booster, preferably a vacuum brake booster 2 , a master brake cylinder connected downstream of the brake booster 2 , preferably a tandem master cylinder 3 , to the pressure chambers (not shown) of which the above-mentioned wheel brakes 13 , 14 , 15 , 16 are connected by the intermediary of the hydraulic control and regulation unit 17 , and a pressure fluid supply tank 4 associated with the master brake cylinder 3 . A brake pedal 5 is used for actuation of the brake booster 2 by the driver, and a pedal travel simulator 6 is provided which cooperates with the brake pedal 5 , in particular in the ‘brake-by-wire’ operating mode, and imparts the customary brake pedal feeling to the driver. A driver's deceleration request or the actuating travel of the brake pedal 5 is detected by means of at least one sensor device 21 , the signals of which are sent to the above-mentioned first electronic control unit 7 . The output signals of the first electronic control unit 7 enable, among others, actuation of an electromagnet 8 associated with the brake booster 2 which renders it possible to actuate a pneumatic control valve 9 independently of the driver's wish, the said control valve controlling the supply of air to the brake booster 2 . As will be explained in detail in the following description, the first electronic control and regulation unit 7 comprises a control circuit for controlling a characteristic quantity of the brake booster 2 , preferably the travel covered by the output member 20 of the brake booster 2 , and/or a quantity for controlling the hydraulic pressure that prevails in the system.
[0022] An axial slot or distance ‘a’ provided between the end of an input member (piston rod) 10 coupled to the brake pedal 5 and a control piston 11 of the above-mentioned control valve 9 ensures decoupling the force-transmitting connection between the brake pedal 5 and the brake booster 2 in the ‘brake-by-wire’ operating mode. A travel sensor 18 is used to detect the travel of a movable wall 19 that generates the boosting power of the brake booster 2 , or the travel of the above-mentioned output member 20 of the brake booster 2 , which transmits its output force onto a non-illustrated first piston of the master brake cylinder 3 . In addition, a pressure sensor 34 is integrated in the hydraulic control unit 17 and senses the hydraulic inlet pressure that prevails in the system.
[0023] The pedal travel simulator 6 by which, as has been mentioned above, a resetting force acting on the brake pedal 5 in the ‘brake-by-wire’ operating mode can be simulated irrespective of an actuation of the brake booster 2 , is designed in such a fashion that it can be enabled in the ‘brake-by-wire’ operating mode by means of a connecting and disconnecting device 60 illustrated in an axial cross-section in FIG. 2 when the force-transmitting connection between the brake pedal 5 and the brake booster 2 is decoupled, and can be disabled outside the ‘brake-by-wire’ operating mode.
[0024] Further, it can be taken from the drawing that the hydraulic control and regulation unit (HCU) 17 includes all hydraulic and electrohydraulic components required to perform brake pressure control operations such as ABS, TCS, ESP, etc. Among these are per brake circuit: each one separating valve 22 a, b, one electric change-over valve 23 a, b, a hydraulic pump 24 a, b, in each case two electrically actuatable pressure control valves or inlet and outlet valves 25 a, b, 26 a, b, 27 a, b, and 28 a, b for the selective adjustment of the brake pressure at the wheel brakes 13 to 16 , each one low-pressure accumulator 29 a, b as well as pressure sensors 30 , 33 associated with the wheel brakes 13 to 16 .
[0025] Document DE 10 2004 011 622 A1 described previously discloses the layout of the above-mentioned brake actuating unit 1 . Therefore, a partial cross-sectional view of FIG. 2 depicts only the control group of the vacuum brake booster 2 in detail. The pedal travel simulator 6 , which cooperates with the brake pedal 5 in particular in the ‘brake-by-wire’ operating mode imparting the usual brake pedal feeling to the driver, and which is outside the flux of forces between the brake pedal 5 and the brake booster 2 in the embodiment shown, cooperates with an electrohydraulic connecting and disconnecting device 60 that disconnects the pedal travel simulator 6 outside the ‘brake-by-wire’ operating mode. The connecting and disconnecting device 60 basically includes a piston-and-cylinder arrangement 51 and a hydraulic pressure fluid take-up element 56 . By means of an actuating rod 58 , the piston 52 of the piston-and-cylinder arrangement 51 is in a force-transmitting connection with a housing 61 of the pedal travel simulator 6 and delimits a pressure chamber 53 , which is connected to the pressure fluid take-up element 56 by means of a hydraulic connection 54 shown in dotted lines, the said take-up element being designed as a low-pressure accumulator in the illustrated example. An electromagnetically operable shut-off valve 55 is inserted into the hydraulic connection 54 and allows shutting off the mentioned connection 54 . The hydraulic pressure in the pressure chamber 53 of the piston-and-cylinder arrangement 51 can be determined by means of a pressure sensor 57 . The measured pressure value must be almost zero in the initially opened shut-off valve 55 , while an abrupt pressure rise must take place upon change-over of the shut-off valve 55 into its closing position. It is thus proven that the piston 52 has moved before the shut-off valve 55 is closed, that the shut-off valve 55 is sufficiently seal-tight and that the pressure sensor 57 is functioning.
[0026] In particular when performing a pre-drive or post-drive test, the use of a pressure sensor 57 is advantageous because the pressure sensor signal can be employed additionally as a plausibilisation of the signal that is produced by a pedal travel sensor associated with the brake pedal. The pressure sensor then makes it possible to detect certain fail conditions of the system, such as faulty detection of the brake pedal travel, thereby activating fallback modes.
[0027] As has been mentioned hereinabove, the representations according to FIGS. 3 a and 3 b show temporal variations of the brake pedal actuating travel s and the quantity s 0 , which corresponds to the shortest actuating travel since the activation of the connecting and disconnecting device 60 and the actuation of the brake booster 2 . Point A corresponds to the maximum actuating travel reached upon depression of the brake pedal 5 , while the curve portion A to A 0 corresponds to a withdrawal of the actuating force which acts on the brake pedal 5 and results in a reduction of the actuating travel S A by a predetermined value Δs to the value s 0 . The actuation is performed in the initially mentioned ‘conventional’ mode in period 0 to T 0 . At time T 0 the connecting and disconnecting device 60 of the pedal travel simulator 6 is activated and the brake booster 2 is driven by the electronic control unit 7 so that the actuating unit is subsequently operated in a mixed form of ‘conventional’ mode and the ‘by-wire mode’ in the interval T 0 to T 2 . At time T 1 lying between the points T 0 and T 2 , there is a new actuation or a continued depression of the brake pedal 5 by the operator, and a value s 01 is reached before the continued depression which is taken into consideration as the shortest actuating travel since the activation of the connecting and disconnecting device 60 and the actuation of the brake booster 2 . At time T 2 , the value s 02 corresponds to distance ‘a’ which serves for the decoupling of the force transmission between the brake pedal 5 and the brake booster 2 . The above-mentioned mixed form is terminated, and the brake system has fully adopted the ‘by-wire’ mode. At time T 3 , the brake pedal 5 is completely released and the actuation of the brake system is terminated.
[0028] FIG. 4 eventually shows the effect the measures explained above have on the characteristic curves, which represent the dependency of the nominal value P nominal of the hydraulic pressure introduced into the master brake cylinder 3 on the brake pedal actuating travel s. While the characteristic curve P nominal [T 2 ] represents the nominal characteristic curve, the characteristic curves P nominal [T 0 ] and P nominal[T 1 ] correspond to the previously explained performance of the system at times T 0 and T 1 . In this context, it can be taken from FIG. 4 that the characteristic curve which corresponds to the ‘first’ lowest actuating travel value s 0 is shifted along the abscissa by a predetermined value s Shift . Characteristic curves are obtained by fixing further actuating travel values s 0 (see characteristic curve P nominal[T 1 ]) which move in the direction of the nominal characteristic curve. The predetermined value s Shift is calculated according to the equation s Shift =s 0 −k*s corr in which s corr implies a correction value that depends on value s 0 . FIG. 5 illustrates the dependency of the correction value s corr on value s 0 . The factor k, which can adopt the values 0 or 1 in the simplest case, results from an assessment of the driving situation. A change-over from 0 to 1 is, for example, practicable when a rapid forward pedal movement above a threshold value is detected.
[0029] While preferred embodiments of the invention have been described herein, it will be understood that such embodiments are provided by way of example only. Numerous variations, changes and substitutions will occur to those skilled in the art without departing from the spirit of the invention. It is intended that the appended claims cover all such variations as fall within the spirit and scope of the invention.
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In order to impart a pleasant brake pedal feeling to the operator in the transition from a ‘conventional mode’ to a ‘brake-by-wire’ mode, it is disclosed that the travel (s) covered upon application of the brake pedal is determined and subsequently reduced by the operator, and in that upon reduction of the actuating travel (s) by a predetermined value (Δs) or in the event of a detected vehicle movement or a positive result of a monitoring function of the connecting and disconnecting device running in the background, the connecting and disconnecting device is activated and the brake booster is actuated by the electronic control unit.
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BACKGROUND OF THE INVENTION
[0001] The invention relates to humanized antibodies that bind to the amyloid beta peptide (Aβ) and to preventative and therapeutic treatment of conditions associated with the Aβ peptide, such as Alzheimer's disease, Down's syndrome, and cerebral amyloid angiopathy.
[0002] The Aβ peptide in circulating form is composed of 3943 amino acids (mostly 40 or 42 amino acids) resulting from the cleavage of a precursor protein, amyloid precursor protein (APP). Conversion of Aβ from soluble to insoluble forms with high β-sheet content and its deposition as neuritic and cerebrovascular plaques in the brain appears to be associated with a number of conditions and diseases. Among these conditions and diseases are both pre-clinical and clinical Alzheimer's disease, Down's syndrome, and pre-clinical and clinical cerebral amyloid angiopathy (CAA). Prevention and/or reversal of Aβ deposition are promising methods for treating conditions associated with the Aβ peptide.
[0003] Therapeutic agents which may prevent or reverse Aβ deposition include antibodies to Aβ peptide. WO 00/72880 and Bard, F., et al., Nature Med. (2000) 6:916-919 describe significant reduction in plaque in cortex and hippocampus in a transgenic mouse model of Alzheimer's disease when treated using N-terminal fragments of Aβ peptides and antibodies that bind to them, but not when treated with the Aβ 13-28 fragment conjugated to sheep anti-mouse IgG or with an antibody against the 13-28 fragment, antibody 266. N-terminal directed antibodies were asserted to cross the blood-brain barrier and to induce phagocytosis of amyloid plaques based on in vitro studies as well as a subsequent, ex vivo assay (Bard, F. et al., Proc. Natl. Acad. Sci. (2003) 100:2023-2028).
[0004] U.S. Pat. Nos. 5,766,846; 5,837,672; and 5,593,846 (which are incorporated herein by reference) describe the production of murine monoclonal antibodies to the central domain of the Aβ peptide. Among antibodies known to bind between amino acids 13 and 28 of Aβ are mouse antibodies 266, 4G8, and 1C2.
[0005] It had been previously been found, as described in WO 01/62801, that administration of the mouse antibody 266 (m266) almost completely restores cognition following prolonged periods of weekly administration of the 266 antibody (object memory) in 24-month old hemizygous transgenic mice (APP V717F ). It was also observed that peripheral administration of antibody 266 results in rapid efflux of relatively large quantities of Aβ peptide from the CNS into the plasma. Prolonged treatment also resulted in altered clearance of soluble Aβ, prevention of plaque formation, and improvement in cognition, even without necessarily having the features the art teaches are required for an antibody to be effective, namely, reducing Aβ amyloid plaque burden, crossing the blood brain barrier to any significant extent, decorating plaque, activating cellular mechanisms, or binding with great affinity to aggregated Aβ.
[0006] In conjunction with disclosing results with a mouse model indicating a therapeutic utility of a 266 antibody, WO 01/62801 also disclosed humanized 266 antibodies. These antibodies contain variations in framework regions surrounding complementary determining regions (CDRs) of antibody m266, as well as two amino acid substitutions at a single position in CDR1 of the m266 light chain. Additional humanized 266 antibodies are disclosed in PCT/US02/21322, in which amino acid substitutions occur at three positions in CDR2 from the heavy chain of antibody m266.
[0007] Therapeutically beneficial antibodies that bind to the epitope recognized by m266 will desirably be stable in solution, display favorable pharmacokinetics, and possess affinity toward an epitope formed by amino acids 13 and 28 of Aβ. Thus, there is a need in the art for additional antibodies possessing characteristics similar to or better than m266 which will be efficacious in humans.
SUMMARY OF THE INVENTION
[0008] This invention provides an antibody or fragment thereof that binds Aβ, in which the antibody has a light chain and a heavy chain, such that the light chain has a light chain complementary determining region (CDR) 1 that is either SEQ ID NO:7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 18, 20, 21, or 22, a light chain CDR2 that is either SEQ ID NO:23, 24, 25, 26 or 27, and a light chain CDR3 that is either SEQ ID NO:28, 29, 30, 31, 32, 33, 34, 35, or 36, and wherein the heavy chain has a heavy chain CDR1 that is either SEQ ID NO:37 or 38, a heavy chain CDR2 that is either SEQ ID NO:39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 or 68, and a heavy chain CDR3 that is either SEQ ID NO:69, 70, 71, 72, 73, 74, 75, or 76, provided that no antibody has a light chain CDR-1 of SEQ ID NO:7; a light chain CDR2 of SEQ ID NO:23, a light chain CDR3 of SEQ ID NO:28, a heavy chain CDR1 of SEQ ID NO:37, a heavy chain CDR2 of SEQ ID NO:39, and a heavy chain CDR3 of SEQ ID NO:69.
[0009] The invention also includes methods of treating, preventing, or reversing conditions and diseases associated with Aβ peptide, including both pre-clinical and clinical Alzheimer's disease, Down's syndrome, and pre-clinical and clinical cerebral amyloid angiopathy (CAA). These methods comprise administering to a subject an effective amount of an antibody described and claimed herein.
DETAILED DESCRIPTION OF THE INVENTION
[0010] The term “antibody”, as used herein, is intended to refer to immunoglobulin molecules comprised of four polypeptide chains, two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CH1, CH2 and CH3. Each light chain is comprised of a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Based on this ordering, the CDRs of the light chain may be referred to as CDR L1, CDR L2, and CDR L3, while the CDRs of the heavy chain may be referred to as CDR H1, CDR H2, and CDR H3. The assignment of amino acids to each domain is in accordance with well known conventions [Kabat “Sequences of Proteins of Immunological Interest,” National Institutes of Health, Bethesda, Md., 1987 and 1991; Chothia et al. J. Mol. Biol. (1987) 196:901-917; Chothia, et al., Nature (1989) 342:878-883]. The CDRs include residues defined by Kabat and Chothia (underlined in the m266 sequence). Light chains are classified as kappa and lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, and define the antibody's isotype as IgG, IgM, IgA, IgD and IgE, respectively. Within light and heavy chains, the variable and constant regions are joined by a “J” region of about 12 or more amino acids, with the heavy chain also including a “D” region of about 3 or more amino acids.
[0011] IgG antibodies are the most abundant immunoglobulin in serum. IgG also has the longest half-life in serum of any immunoglobulin. Unlike other immunoglobulins, IgG is efficiently recirculated following binding to FcR. There are four IgG subclasses G1, G2, G3, and G4, each of which have different effector functions. G1, G2, and G3 can bind C1q and fix complement while G4 cannot. Even though G3 is able to bind C1q more efficiently than G1, G1 is more effective at mediating complement-directed cell lysis. G2 fixes complement very inefficiently. The C1q binding site in IgG is located at the carboxy terminal region of the CH2 domain.
[0012] All IgG subclasses are capable of binding to Fc receptors (CD16, CD32, CD64) with G1 and G3 being more effective than G2 and G4. The Fc receptor binding region of IgG is formed by residues located in both the hinge and the carboxy terminal regions of the CH2 domain.
[0013] The term “fragment” of an antibody as used herein refers to one or more fragments of an antibody that retain the ability to bind to an antigen (e.g., Aβ.). It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments encompassed within the term “fragment” of an antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH 1 domains; (ii) a F(ab′) 2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, and (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which consists of a VH domain. Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and H regions pair to form monovalent molecules (known as single chain Fv (scFv); see e.g., Bird et al. (1988) Science 242:423-426: and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). Such single chain antibodies are also intended to be encompassed within the term “fragment” of an antibody. Other forms of single chain antibodies, such as diabodies are also encompassed. Diabodies are bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain, but using a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites (see e.g., Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, R. J., et al. (1994) Structure 2:1121-1123).
[0014] Still further, an antibody or fragment thereof may be part of a larger immunoadhesion molecule, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion molecules include use of the streptavidin core region to make a tetrameric scFv molecule (Kipriyanov, S. M., et al. (1995) Human Antibodies and Hybridomas 6:93-101) and use of a cysteine residue, a marker peptide and a C-terminal polyhistidine tag to make bivalent and biotinylated scFv molecules (Kipriyanov, S. M., et al. (1994) Mol. Immunol. 31:1047-1058). Antibody fragments, such as Fab and F(ab) 2 fragments, can be prepared from whole antibodies using conventional techniques, such as papain or pepsin digestion, respectively, of whole antibodies. Moreover, antibodies, antibody portions and immunoadhesion molecules can be obtained using standard recombinant DNA techniques, as are well known in the art.
[0015] The term “humanized antibody” refers to an antibody that is composed partially or fully of amino acid sequences derived from a human antibody germline or a rearranged sequence and made by altering the sequence of an antibody having non-human complementarity determining regions (CDRs). The framework regions of the variable regions are substituted by corresponding human framework regions. The human framework regions include genomic framework regions, as well as those containing one or more amino acid substitutions. In particular, such substitutions include mutations in which an amino acid at a particular position in the human framework is replaced with the amino acid from the corresponding position of the natural framework for the non-human CDR. For example, a humanized antibody having mouse CDRs may contain one or more substitutions that replace a particular human framework amino acid with the corresponding mouse framework amino acid. As discussed herein, antibody in the context of humanized antibody is not limited to a full-length antibody and can include fragments and single chain forms.
[0016] The antibodies of the present invention are monoclonal antibodies. Such antibodies, however, are monoclonal only in the sense that they may be derived from a clone of a single cell type. However, this is not meant to limit them to a particular origin. Such antibodies may be readily produced in cells that commonly do not produce antibodies, such as CHO, NSO, or COS cells. In addition, such antibodies may be produced in other types of cells, especially mammalian and even plant cells, by genetically engineering such cells to express and assemble the polypeptide light and heavy chains forming the antibody product. In addition, such chains can be chemically synthesized but, since they would be specific for a given antigenic determinant, would still constitute “monoclonal” antibodies within the spirit in which that term is used. Thus, as used herein, the term monoclonal antibody is intended to denote more the specificity and purity of the antibody molecules rather than the mere mechanism used for production of said antibodies.
[0017] The term “K D ”, as used herein, is intended to refer to the dissociation constant of a particular antibody-antigen interaction. It is calculated by the formula:
[0000] K D =k off /k on (measured in M )
[0000] The term “k on ” as used herein is intended to refer to the association rate constant, or specific reaction rate, of the forward, or complex-forming, reaction, measured in units: M −1 sec −1 . The term “k off ”, as used herein, is intended to refer to the dissociation rate constant, or specific reaction rate, for dissociation of an antibody from the antibody/antigen complex, measured in units: sec −1 .
[0018] The term “nucleic acid molecule”, as used herein, is intended to include DNA molecules and RNA molecules. A nucleic acid molecule may be single-stranded or double-stranded, but preferably is double-stranded DNA.
[0019] The term “vector”, as used herein, is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments may be ligated. Another type of vector is a viral vector, wherein additional DNA segments may be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operably linked. Such vectors are referred to herein as “recombinant expression vectors” (or simply, “expression vectors”). In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” may be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.
[0020] The term “recombinant host cell” (or simply “host cell”), as used herein, is intended to refer to a cell into which a recombinant expression vector has been introduced. It should be understood that such terms are intended to refer not only to the particular subject cell but to the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term “host cell” as used herein.
[0021] The light and heavy chains of m266 have the following sequences:
[0000] m266 light chain: (SEQ ID NO: 1) DVVMTQTPLSLPVSLGDQASISC RSSQSLIYSDGNAYLH WFLQKPGQSPK LLIY KVSNRFS GVPDRFSGSGSGTDFTLKISRVETEDLGVYFC SQSTHVP WT FGGGTKLEIK. m266 heavy chain: (SEQ ID NO: 2) EVKLVESGGGLVQPGGSLKLSCAVS GFTFSRYSMS WVRQTPEKRLELVA Q INSVGNSTYYPDTVKG RFTISRDNAEYTLSLQMSGLRSDDTATYYCAS GD Y WGQGTTLTYSS
The CDRs include residues defined by Kabat and Chothia. The underlined portions represent the sequences that have been identified as the m266 CDRs, which are listed in Table 1.
[0000]
TABLE 1
m266 CDR sequences
CDR
Sequence
SEQ ID NO:
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTHVPWT
28
H1
GFTFSRYSMS
37
H2
QINSVGNSTYYPDTVKG
39
H3
GDY
69
[0022] The antibodies of the present invention include humanized antibodies, in which CDR sequences corresponding to or derived from those of m266 are effectively grafted into a human antibody framework. An important aspect of humanizing antibodies from another species is to reduce the possibility that the antibody causes an immune response when injected into a human patient as a therapeutic. The more sequences that are employed in a humanized antibody resemble those of human antibodies, the lower the risk of immunogenicity. In addition, the injected humanized antibodies generally have a longer half-life in the circulation than injected non-human antibodies. Furthermore, if effector function is desired, because the effector portion is human, it may interact better with the other parts of the human immune system.
[0023] In principle, a framework sequence from any human antibody may serve as the template for CDR grafting. However, the framework context of CDRs influences their binding to antigen, such that variation between different frameworks may lead to some or significant loss of binding affinity to the antigen.
[0024] Preferred human framework amino acid sequences for the light chain variable region of the antibodies of the present invention include the following sequences, which for illustrative purposes are represented with the CDRs of m266 (underlined sequences) inserted:
[0000]
(SEQ ID NO: 3)
DIVMTQTPLSLSVTPGQPASISC RSSQSLIYSDGNAYLH WYLQKPGQS
PQLLIY KVSNRFS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC SQS
THVPWT FGGGTKVEIK;
(SEQ ID NO: 4)
DVVMTQSPLSLPVTLGQPASISC RSSQSLIYSDGNAYLH WFQQRPGQS
PRRLIY KVSNRFS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC SQS
THVPWT FGGGTKVEIK.
[0025] Preferred human framework amino acid sequences for the heavy chain variable region of the antibodies of the present invention include the following sequences, which for illustrative purposes are represented with the CDRs of m266 (underlined sequences) inserted:
[0000]
(SEQ ID NO: 5)
EVQLVESGGGLVKPGGSLRLSCAAS GFTFSRYSMS WVRQAPGKGLEWV
G QINSVGNSTYYPDTVKG RFTISRDDSKNTLYLQMNSLKTEDTAVYYCT
T GDY WGQGTLVTVSS;
(SEQ ID NO: 6)
EVQLLESGGGLVQPGGSLRLSCAAS GFTFSRYSMS WVRQAPGKGLEWV
S QINSVGNSTYYPDTVKG RFTISRDNSKNTLYLQMNSLRSEDTAVYYCA
K GDY WGQGTLVTVSS.
[0026] In preferred embodiments, antibodies of the present invention will have a light chain framework as shown in SEQ ID NO:3, and a heavy chain framework as shown in SEQ ID NO:5. In alternative embodiments, antibodies of the present invention will have a light chain framework as shown in SEQ ED NO:4, and a heavy chain framework as shown in SEQ ID NO:6.
[0027] Peripheral administration of m266 to a transgenic mouse model of Alzheimer's disease (APP V717F mice) results in a rapid increase in plasma Aβ, indicating that circulating m266 is able to alter the equilibrium of Aβ between CNS and plasma, yielding a net increase in Aβ efflux from CNS and a net decrease of Aβ efflux into CNS (WO 01/62801; DeMattos et al., Proc. Natl. Acad. Sci. 98:8850-8855 (2001)). Preferably, upon peripheral administration, the antibodies or fragments thereof of the present invention are capable of facilitating Aβ efflux from the central nervous system (CNS) to plasma. The antibodies disclosed herein preferably will facilitate Aβ efflux from CNS into plasma in humans in a manner that is comparable to or, more preferably, more efficient than that through which m266 facilitates Aβ efflux from CNS into plasma in mice.
[0028] The antibodies of the present invention or fragments thereof contain light chain and heavy chains having CDRs with amino acids selected from the group consisting of SEQ ID NOS:7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 18, 20, 21, and 22 for CDR L1, SEQ ID NOS:23, 24, 25, 26 and 27 for CDR L2, SEQ ID NOS:28, 29, 30, 31, 32, 33, 34, 35, and 36 for CDR L3, SEQ ID NOS:37 and 38 for CDR H1, SEQ ID NOS:39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67 and 68 for CDR H2, and SEQ ID NOS:69, 70, 71, 72, 73, 74, 75, and 76 for CDR H3, provided that no antibody has the combination of SEQ ID NO:7 for CDR L1, SEQ ID NO:23 for CDR L2, SEQ ID NO:28 for CDR L3, SEQ ID NO:37 for CDR H1, SEQ ID NO:39 for CDR H2, and SEQ ID NO:69 for CDR H3.
[0029] CDR H2 of antibody m266 is glycosylated due to its Asn-Ser-Thr sequence, as described in PCT/US02121322. This sequence is an example of an Asn-X-Ser/thr signal for N-linked glycosylation, wherein the Asn is the site of attachment of N-linked glycosyl chains. Removal of the CDR H2 glycosylation site in antibodies derived from m266 advantageously provides for more reliable antibody production and less batch-to-batch variability in glycosylation while preserving or improving affinity and specificity. In a preferred embodiment, antibodies of the present invention lacking an N-glycosylation site in CDR H2 contain a light chain and a heavy chain having CDR sequences selected from the following: SEQ ID NO:8 for CDR L1, SEQ ID NOS:23 and 24 for CDR L2, SEQ ID NO:34 for CDR L3, SEQ ID NO:38 for CDR H1, SEQ ID NOS:58, 62, 63, 64, 65, 66, 67, and 68 for CDR H2, and SEQ ID NO:71 for CDR H3.
[0030] The antibodies of the present invention contain six CDRs, three from the light chain and three from the heavy chain. A given antibody may contain 1, 2, 3, 4, or up to 5 CDRs which are identical to the corresponding CDRs from m266, with the remaining 5, 4, 3, 2, or 1 CDR(s) being derived from m266. For example, an antibody of the present invention might contain CDRs L1, L2, L3, H1, and H2 that are identical to m266 CDRs L1, L2, L3, H1 and H2, with CDR H3 being a CDR derived from m266 CDR H3 (as represented by SEQ ID NOS:70, 71, 72, 73, 74, 75, and 76).
[0031] The CDRs described herein can be used to make full-length antibodies as well as functional fragments and analogs or other proteins which incorporate the CDRs in an active structural conformation, such that the protein employing the CDRs binds Aβ.
[0032] Table 2 indicates the amino acid sequences (using standard amino acid one letter code) of the CDRs employed in the antibodies of the present invention. The CDRs are presented in the table in the context of individual antibody clones (Fab fragments). In Table 2, the locations of amino acid substitutions made relative to the corresponding m266 CDRs listed in Table 1 (i.e. locations at which CDRs differ in amino acids) are indicated in bold and underlined. Each of these clones have the respective light and heavy chain framework sequences of SEQ ID NOS:3 and 5, with the exception of clone A7, which has the respective light and heavy chain framework sequences of SEQ ID NOS:4 and 6.
[0000]
TABLE 2
CDR sequences of selected
antibodies having affinity to Aβ
Clone
CDR
Sequence
SEQ ID NO:
A7
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTHVPW A
29
H1
GFTFSRYSMS
37
H2
QI S SVGNSTYYPDTVKG
40
H3
G P Y
70
1B7
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
1E1
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L2
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD H
72
3D5
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
12
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS T GNSTYYPDTVKG
42
H3
GD F
71
2A9
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L2
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QIN A VGNSTYYPDTVKG
43
H3
GD F
71
D3
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS I GNSTYYPDTVKG
44
H3
GD W
73
1C5
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSV A NSTYYPDTVKG
45
H3
GD F
71
A3
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L2
SQSTH T PWT
31
H1
GFTFSRYSMS
37
H2
QINS S GNSTYYPDTVKG
46
H3
GD F
71
A4
L1
RSSQSLIYSDGNAYLH
7
12
KVSNRFS
23
12
SQSTH S PWT
30
111
GFTFSRYSMS
37
H2
QINS P GNSTYYPDTVKG
47
H3
GD S
74
1D4
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L2
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS Q GNSTYYPDTVKG
48
H3
GD R
75
3D12
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH A PWT
32
H1
GFTFSRYSMS
37
H2
QINS P GNSTYYPDTVKG
47
H3
GD F
71
3F9
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD V
76
5F11
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
G Y TFSRYSMS
38
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
2B2
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L2
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QIN IR GNSTYYPDTVKG
49
H3
GD F
71
1A2
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSRGN H TYYPDTVKG
50
H3
GD F
71
1B1
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSRGN N TYYPDTVKG
51
H3
GD F
71
2A11
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GN R TYYPDTVKG
52
H3
GD F
71
6F9
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSRGNSTYYPD P VKG
53
H3
GD F
71
3H1
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSVGNSTYYPD K VKG
54
H3
GD F
71
3H2
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSVGNSTYYPD A VKG
55
H3
GD F
71
6H8
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSVGNSTYYPD E VKG
56
H3
GD F
71
6F6
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINSVGNSTYYPDTV T G
57
H3
GD F
71
7E1
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
4D1
L1
L SSQSLIYSDGNAYLH
14
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
4D3
L1
R V SQSLIYSDGNAYLH
15
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTV K G
41
H3
GD F
71
4D6
L1
RS N QSLIYSDGNAYLH
16
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
4D9
L1
RSS I SLIYSDGNAYLH
17
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
4F12
L1
RSS K SLIYSDGNAYLH
18
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
4C11
L1
RSSQSLI F SDGNAYLH
19
L2
K VSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
6D4
L1
RSSQSLI YW DGNAYLH
9
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
6D3
L1
RSSQSLIYSDG I AYLH
10
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
6E11
L1
RSSQSLTYSDG S AYLH
11
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
6D7
L1
RSSQSLI YL DGNAYLH
12
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
3E2
L1
RSSQSLIYSDGN N YLH
20
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVK
41
H3
GD F
71
3E10
L1
RSSQSLIYSDGN H YLH
21
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
3F1
L1
RSSQSLIYSDGNA W LH
22
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
5C8
L1
RSSQSLIYSDGNAYLH
7
12
KVSNRF W
24
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
5A11
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNR R S
25
L3
SQSTHS P WT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
5D1
L1
RSSQSLIYSDGNAYLH
7
L2
KV Y NRFS
26
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
5B10
L1
RSSQSLIYSDGNAYLH
7
L2
R VSNRFS
27
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
6B6
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
A QSTHSPWT
33
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
6C3
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
T QSTHSFWT
34
H1
GFTFSRYSMS
37
H2
QINS R GNS T YYPDTVKG
41
H3
GD F
71
1E8
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PW S
35
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
2A6
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PW E
36
H1
GFTFSRYSMS
37
H2
QINS R GNSTYYPDTVKG
41
H3
GD F
71
1F3
L1
S SSQSLIY L DGNAYLH
13
L2
KVSNRFS
23
L3
A QSTH S PWT
33
H1
G Y TFSRYSMS
38
H2
QIN IR GN N TYYPD P VKG
58
H3
GD F
71
1A1
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR GNNTYYPDTVKG
59
H3
GD F
71
1A7
L1
S SSQSLIY L DGNAYLH
13
L2
KVSNRFS
23
12
A QSTH S PWT
33
H1
G Y TFSRYSMS
38
H2
QIN IR GNSTYYPDTVKG
49
H3
GD F
71
11F12
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
12
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR GN N TYYPDTVKG
59
H3
GD F
71
1F2
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
12
T QSTHSPWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR GNSTYYPD P VKG
60
H3
GD F
71
1A12
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRPS
23
L3
SQSTH S PWT
30
H1
GFTFSRYSMS
37
H2
QIN IR GN N TYYPDTVKG
59
H3
GD F
71
1A10
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR GN H TYYPDTVKG
61
H3
GD F
71
1B3
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
A QSTH S PWT
33
H1
G Y TFSRYSMS
38
H2
QINS R GN N TYYPDTVKG
51
H3
GD F
71
1C1
L1
S SSQSLIY L DGNAYLH
13
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
G Y TFSRYSMS
38
H2
QIN IR GN N TYYPDTVKG
59
H3
GD F
71
1D2
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
A QSTH S PWT
33
H1
G Y TFSRYSMS
38
H2
QINS R GN N TYYPDTVKG
51
H3
GD F
71
1D10
L1
RSSQSLIYSDGNAYLH
7
L2
KVSNRFS
23
L3
SQSTH S PWT
30
H1
G Y TFSRYSMS
38
H2
QIN IR GN N TYYPDTVKG
59
H3
GD F
71
7F7
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR GN N TYYPD P VKG
58
H3
GD F
71
1A1W
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRF W
24
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR GN N TYYPDTVKG
59
H3
GD F
71
1A1-KNT
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
T QSTH S PWT
34
H1
G Y l TFSRYSMS
38
H2
QIN IR G KN TYYPDTVKG
62
H3
GD F
71
1A1-SNL
L1
S SSQSLTYSDGNAYLH
8
L2
KVSNRFS
23
L3
T l QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR G KN LYYPDTVKG
63
H3
GD F
71
1A1-TNS
L1
S SSQSLIYSDQNAYLH
8
L2
KVSNRFS
23
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR G TNS YYPDTVKG
64
H3
GD F
71
1A1-LNT
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR G LNT YYPDTVKG
65
H3
GD F
71
1A1-HNT
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRFS
23
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR G HNT YYPDTVKG
66
H3
GD F
71
1A1W-KNT
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRF W
24
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR G KN TYYPDTVKG
62
H3
GD F
71
1A1W-KET
L1
S SSQSLLYSDGNAYLH
8
L2
KVSNRF W
24
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR G KE TYYPDTVKG
67
H3
GD F
71
1A1W-KST
L1
S SSQSLIYSDGNAYLH
8
L2
KVSNRF W
24
L3
T QSTH S PWT
34
H1
G Y TFSRYSMS
38
H2
QIN IR G K STYYPDTVKG
68
H3
GD F
71
[0033] Each of the clones listed in Table 2 have been demonstrated to bind to Aβ, as determined by screening assays, including a capture filter lift assay and a capture ELISA. Subsequently, several clones were further characterized for binding properties as described below in the Examples.
[0034] The antibodies of the present invention represented by the different clones listed in Table 2 differ from each other by sequence changes in at least 1 CDR, and up to as many as 6 CDRs. The differences in CDRs among the clones is indicative of the interchangeable nature of the CDRs, wherein one CDR L1 may be substituted for another CDR L1, one CDR L2 substituted for another CDR L2, and so forth. Accordingly, the various CDR combinations present in the antibodies of the present invention are anticipated to bind Aβ.
[0035] Several of the antibodies of the present invention were obtained through combination of CDR substitutions found in other antibodies. These antibodies include 1F3, 1A1, 1A7, 11F12, 1F2, 1A12, 1A1, 1B3, 1C1, 1D2, 1D10, and 7F7. For example, antibody 1A1 was obtained by combining the mutations found in antibodies 2B2 and 1B1. Theoretically, each of the amino acid substitutions indicated in Table 2 may be combined to yield additional antibodies that are likely to specifically bind to Aβ. Antibodies of the present invention therefore encompass additional CDRs derived through combination of the CDR substitutions listed in Table 2.
[0036] CDRs of antibodies of the present invention may also encompass alternative substitutions obtained by conservative amino acid substitution of the specific substitutions indicated in Table 2. “Conservative substitution” or “conservative amino acid substitution” is well known in the art and refers to replacement of one or more amino acid residue(s) in a protein or peptide with an amino acid residue that has a common side chain property. As is known in the art, groupings of amino acids based on side chain properties include, but are not limited to, hydrophobic, neutral hydrophilic, acidic, basic, and aromatic amino acids. For example, an alternative to CDR H2 of antibody 1B7 (see Table 2, clone 1B7) may be obtaining by replacing the basic arginine (R) residue of SEQ ID NO:41 with a lysine (K).
[0037] The affinity of a given antibody for Aβ is one of several properties that is likely to contribute to its utility for a particular application of the antibody. In one embodiment, antibodies of the present invention will have an affinity for Aβ equal to or, more preferably, greater than m266, as determined by K D . As described above, K D is measured by the ratio of the k on and k off constants. For example, a k of 3.1×10 7 (M −1 sec −1 ) and a k off of 0.9×10 −4 (sec −1 ) would combine to give a K D of 2.8×10 −12 M. Thus, affinity can be improved by increasing the k on or decreasing the k off . Several of the antibodies listed in Table 2 have improved affinity for Aβ, based on determination of K D or k on , as described in Examples 1 and 2.
[0038] The antibodies of the invention can be present in a relatively pure or isolated form as well as in a supernatant drawn from cells grown in wells or on plates. The antibodies of the invention can also be present in the form of a composition comprising the antibody of the invention and a pharmacologically acceptable diluent or excipient, in which the antibody is suspended. The antibodies of the invention may be present in such a composition at a concentration, or in an amount, sufficient to be of therapeutic or pharmacological value in treating or preventing diseases (for example, preventing Alzheimer's disease). The antibodies may also be present in a composition in a more dilute form.
[0039] In another aspect, the present invention also is directed to recombinant DNA encoding the antibodies and fragments of the invention. The sequence of recombinant DNA encoding an antibody or fragment of the invention can be readily determined by one of skill in the art using the genetic code. A nucleic acid having the determined sequence can be prepared and expressed in any of a wide variety of host systems using techniques that are well known in the art.
[0040] Preferably, the DNA encodes antibodies that, when expressed, comprise one to five of the light and heavy chain CDRs of m266 [SEQ ID NOS:7, 23, 28, 37, 39, 69], and one or more of the light and heavy chain CDRs of the present invention [SEQ ID NOS:8-22, 2427, 29-36, 38, 40-68, 70-76]. In addition, the DNA preferably encodes antibodies that, when expressed, comprise these CDRs in combination with a light chain framework of either SEQ ID NOS:3 or 5, and a heavy chain framework of either SEQ ID NOS:4 or 6. More preferably, the light and heavy chains will consist of either SEQ ID NOS:3 and 5 or SEQ ID NOS:4 and 6.
[0041] DNA encoding the antibodies of the present invention will typically further include an expression control polynucleotide sequence operably linked to the antibody coding sequences, including naturally-associated or heterologous promoter regions. Preferably, the expression control sequences will be eukaryotic promoter systems in vectors capable of transforming or transfecting eukaryotic host cells, but control sequences for prokaryotic hosts may also be used. Once the vector has been incorporated into the appropriate host cell line, the host cell is propagated under conditions suitable for expressing the nucleotide sequences, and, as desired, the collection and purification of the light chains, heavy chains, light/heavy chain dimers or intact antibodies, binding fragments or other immunoglobulin forms may follow.
[0042] The nucleic acid sequences of the present invention capable of ultimately expressing the desired antibodies can be formed from a variety of different polynucleotides (genomic or cDNA, RNA, synthetic oligonucleotides, etc.) and components (e.g., V, J, D, and C regions), using any of a variety of well known techniques. Joining appropriate genomic and synthetic sequences is a common method of production, but cDNA sequences may also be utilized.
[0043] Human constant region DNA sequences can be isolated in accordance with well known procedures from a variety of human cells, but preferably from immortalized B-cells. Suitable source cells for the polynucleotide sequences and host cells for immunoglobulin expression and secretion can be obtained from a number of sources well-known in the art.
[0044] As described herein, in addition to the antibodies specifically described herein, other “substantially homologous” modified antibodies can be readily designed and manufactured utilizing various recombinant DNA techniques well known to those skilled in the art. For example, the framework regions can vary from the native sequences at the primary structure level by several amino acid substitutions, terminal and intermediate additions and deletions, and the like. Moreover, a variety of different human framework regions may be used singly or in combination as a basis for the humanized immunoglobulins of the present invention. In general, modifications of the genes may be readily accomplished by a variety of well-known techniques, such as site-directed mutagenesis.
[0045] Alternatively, polypeptide fragments comprising only a portion of the primary antibody structure may be produced, which fragments possess one or more immunoglobulin activities (e.g., complement fixation activity). These polypeptide fragments may be produced by proteolytic cleavage of intact antibodies by methods well known in the art, or by inserting stop codons at the desired locations in vectors using site-directed mutagenesis, such as after CH1 to produce Fab fragments or after the hinge region to produce F(ab′) 2 fragments. Single chain antibodies may be produced by joining VL and VH with a DNA linker.
[0046] The antibodies (including immunologically reactive fragments) are administered to a subject at risk for or exhibiting Aβ-related symptoms or pathology such as clinical or pre-clinical Alzheimer's disease, Down's syndrome, or clinical or pre-clinical amyloid angiopathy, using standard administration techniques, preferably peripherally (i.e. not by administration into the central nervous system) by intravenous, intraperitoneal, subcutaneous, pulmonary, transdermal, intramuscular, intranasal, buccal, sublingual, or suppository administration. Although the antibodies may be administered directly into the ventricular system, spinal fluid, or brain parenchyma, and techniques for addressing these locations are well known in the art, it is not necessary to utilize these more difficult procedures. The antibodies of the invention are effective when administered by the more simple techniques that rely on the peripheral circulation system. The advantages of the present invention include the ability of the antibody to exert its beneficial effects even though not provided directly to the central nervous system itself. In addition, humanized antibodies used in the invention, when administered peripherally, do not need to elicit a cellular immune response in brain when bound to Aβ peptide or when freely circulating to have their beneficial effects. Further, when administered peripherally they do not need to appreciably bind aggregated Aβ peptide in the brain to have their beneficial effects. Indeed, it has been demonstrated that the amount of antibody that crosses the blood-brain barrier is <0.1% of plasma levels.
[0047] The pharmaceutical compositions for administration are designed to be appropriate for the selected mode of administration, and pharmaceutically acceptable excipients such as, buffers, surfactants, preservatives, solubilizing agents, isotonicity agents, stabilizing agents and the like are used as appropriate. Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton Pa., latest edition, incorporated herein by reference, provides a compendium of formulation techniques as are generally known to practitioners.
[0048] The concentration of the humanized antibody in formulations from as low as about 0.1% to as much as 15 or 20% by weight and will be selected primarily based on fluid volumes, viscosities, and so forth, in accordance with the particular mode of administration selected. Thus, a pharmaceutical composition for injection could be made up to contain in 1 mL of phosphate buffered saline from 1 to 100 mg of the humanized antibody of the present invention. The formulation could be sterile filtered after making the formulation, or otherwise made microbiologically acceptable. A typical composition for intravenous infusion could have a volume as much as 250 mL of fluid, such as sterile Ringer's solution, and 1-100 mg per mL, or more in antibody concentration. Therapeutic agents of the invention can be frozen or lyophilized for storage and reconstituted in a suitable sterile carrier prior to use. Lyophilization and reconstitution can lead to varying degrees of antibody activity loss (e.g. with conventional immune globulins, IgM antibodies tend to have greater activity loss than IgG antibodies). Dosages may have to be adjusted to compensate. The pH of the formulation will be selected to balance antibody stability (chemical and physical) and comfort to the patient when administered. Generally, pH between 4 and 8 is tolerated.
[0049] Although the foregoing methods appear the most convenient and most appropriate for administration of proteins such as humanized antibodies, by suitable adaptation, other techniques for administration, such as transdermal administration and oral administration may be employed provided proper formulation is designed. In addition, it may be desirable to employ controlled release formulations using biodegradable films and matrices, or osmotic mini-pumps, or delivery systems based on dextran beads, alginate, or collagen. In summary, formulations are available for administering the antibodies of the invention and are well-known in the art and may be chosen from a variety of options. Typical dosage levels can be optimized using standard clinical techniques and will be dependent on the mode of administration and the condition of the patient.
[0050] In addition to their therapeutic utility, the antibodies of the present invention are useful in diagnosing the amount of brain amyloid burden in patients either at risk for or who have been diagnosed with Alzheimer's disease. In studies with the APP V717F transgenic mouse model of Alzheimer's disease, peripheral administration of mouse m266 resulted in a rapid increase in plasma Aβ (DeMattos et al., Science 295:2264-2267 (2002)). The magnitude of this increase was found to highly correlate with amyloid burden in mouse hippocampus and cortex. Peripheral administration of m266 thereby provides a method of quantifying amyloid burden in mice. This method of diagnosing amyloid burden through peripheral administration of antibodies that recognize the same Aβ epitope of m266 may be useful for quantifying brain amyloid burden in patients. Accordingly, the antibodies of the present invention may be used to diagnose the amyloid burden of patients either at risk for or who have been diagnosed with Alzheimer's disease.
[0051] The antibodies of the present invention also have useful in vitro applications. For example, the antibodies may be used in determining the presence and levels of Aβ by ELISA, immunocytochemical assays, and the like.
[0052] The following examples are intended to illustrate but not to limit the invention.
Example 1
Binding Affinity Measurements
[0053] Affinities to Aβ of Fab fragments and/or monoclonal antibodies of m266 and preferred antibodies of the present invention were determined by KinExA™ (Sapidyne) measurements. KinExA™ is an instrument that permits the measurement of the kinetics of solution phase binding. (Glass, T. (1995), Biomedical Products 20:122-123, Ohmura, N. et al., (2001), Analytical Chemistry 73: 3392-3399.)
[0054] The Aβ antigen used in these affinity measurements was attached to sepharose beads. Specifically, 0.1 mg of biotinylated β Amyloid peptide 1-40 (Biosource) was bound to 0.5 mL of Avidin Sepharose (Sigma) for 1 hour at room temperature. The beads were then washed three times with 10 mL of phosphate buffered saline pH 7.4 with 0.01% NaN 3 (PBSA) and re-suspended in 15 mL of PBSA.
[0055] Fabs for these experiments were produced by expression in E. coli . Briefly, XL-0 cells were infected with phage harboring the Fab genes for 1 hour at 37° C. The temperature was then lowered to 25° C. and the culture shaken for 16 hours. Fab protein was then extracted form the cells using Bugbuster (Novagen) reagent and purified using nickel beads. (Qiagen).
[0056] Monoclonal antibodies used in these experiments were produced by placing DNA encoding the V regions of Fab fragments into a vector encoding the remaining portions of an IgG1 antibody, such that complete IgG1 antibodies would be expressed from the vector. Antibody proteins were expressed by transiently transfecting the IgG1 vectors into 293 EBNA cells. Antibodies were purified using protein A sepharose. Briefly, culture supernatants were loaded onto a 1 ml protein A sepharose column. The column was then washed with 20 ml of PBS and eluted using 0.1M Glycine pH 2.7 and immediately neutralized using 1M Tris pH 9. Antibody containing fractions were then dialyzed into PBS.
[0057] For the KinExA™ K D measurements, twelve two fold serial dilutions of antigen at 2× concentration were prepared in PBSA 0.2% BSA and mixed 1:1 with a 2× antibody sample prepared in the same buffer. Typical 1× concentrations were 10 μM of antibody active sites (0.75 ng/mL) and an upper antigen concentration of 100 μM (0.43 ng/mL). The samples were then allowed to equilibrate for 24-72 hours at room temperature. A KinExA™ instrument (Sapidyne) and standard K D run file were then used to determine the K D of the system. Briefly, the KinExA™ flow cell was charged with the β Amyloid peptide coated beads and washed with PBSA. For the first sample, free antibody in solution was captured by the beads washed with PBSA and detected using 1:250 Goat anti-human Cy5 (Jackson Immunochemicals) in PBSA. The flow cell was then flushed, re-charged with beads and the next sample analyzed. The process was repeated until all 12 samples were analyzed. The completed data was analyzed using the KinExA™ software entering the 1× antigen concentration in each sample to calculate the K D for the antibody-antigen reaction.
[0058] For KinExA™ k on and k off measurements, antigen and antibody were prepared as described above. Antigen and antibody samples at 2× active concentration were prepared in PBSA with 0.2% BSA. Samples were mixed 1:1 and the timing for the experiment started. Typical 1× concentrations were 1 nM antibody active site concentration (75 ng/mL) and 2 nM antigen (8.6 ng/mL). A KinExA™ instrument (Sapidyne) and a kineticsdirect run file were used to follow the reaction. Time for each measurement was determined using the manufacturer's instructions. Free antibody remaining in the reaction was captured using β amyloid coated beads packed into the flow cell washed with PBSA and detected at each time point using 1:250 Goat anti-human Cy5 (Jackson) in PBSA. The flow cell was then flushed and recharged with beads for the next measurement, the process continued until a complete decay curve obtained. The data was analyzed using the KinExA™ Inject software. 1× active concentrations of antibody and antigen and the K D measured previously were used to calculate the k on and k off for the reaction.
[0059] Kinetic parameters of Fab fragments, as determined by KinExA™ following equilibration of Fab fragments with antigen, are provided in Table 3. The kinetic parameters of monoclonal antibodies which were equilibrated with antigen prior to KinExA™ measurement are presented in Table 4. The K D determinations from another set of experiments, in which monoclonal antibodies were equilibrated with antigen for either 16 to 24 hours or 48 hours are provided in Table 5.
[0000]
TABLE 3
Binding properties of anti-Aβ Fab
fragments determined by KinExA ™
ET*
K D ×
k on ×
k off ×
Fab Samples
(hours)
10 −12 M
10 5 M −1 sec −1
10 −6 sec −1
1A1W
48
0.69
17.4
1.2
1A1-KNT*
48
1.0
14.2
1.4
1A1
24
1.9
8.3
1.6
11F12
24
2.7
8.7
2.4
1A1-SNL*
24
3.2
8.4
2.7
7F7
24
3.4
5.2
1.8
1A12
16
10.8
15.9
17.2
m266
16
137.5
3.6
49.6
*Equilibration time
[0000]
TABLE 4
Binding properties of anti-Aβ monoclonal
antibodies determined by KinExA ™
ET*
K D ×
k on ×
k off ×
Mab Samples
(hours)
10 −12 M
10 5 M −1 sec −1
10 −6 sec −1
1A1
24
1.2
8.8
1.1
6C3
16
7.9
12.8
10.1
m266
16
76.5
0.88
6.73
1B7
16
122
17.6
214.1
1C5
16
973
4.2
371.0
1D4
16
6314
1.2
740.0
*Equilibration time
[0000]
TABLE 5
Affinity for anti-Aβ monoclonal variants measured by KinExA ™
Fold increase
SAMPLE
K D (pM)
in affinity
m266
67.5
85.4
76.5
1
1A1
3.2
5.7
4.5
17
1A1-W
2.2
1.9
2.1
36
1A1-W b
1.2
64
1A1-KNT b
0.29
264
1B7
674
0.11
1D4
15100
0.005
a Numbers in bold are the averages calculated from individual experiments and were used to calculate fold increase in affinity.
b The samples were equilibrated for 48 hrs before measurements were done.
Example 2
Association Rate Measurements
[0060] The kinetics of association of m266 and preferred monoclonal antibodies of the present invention with Aβ were determined using either BIAcore™ or KinExA™ (Sapidyne) measurements.
[0061] BIAcore™ is an automated biosensor system that measures molecular interactions (Karlsson, et al. (1991) J. Immunol. Methods 145: 229-240). BIAcore™ analyses described herein were carried out at 25° C. In these experiments, antibody was immobilized at low density on a BIAcore™ CM5 or B1 chip. For the m266 antibody, goat anti-mouse Fc (Jackson Immunoresearch) immobilized on CM5 in flow cell 2 was used for measuring binding constants. Goat anti-mouse was used as control antibody in flow cell 1. For the humanized antibodies, protein A or protein A/G was immobilized via amine coupling to flow cells 1 and 2 of a B1 or CM5 sensor chip.
[0062] Antibody was then captured only to flow cell 2 at desired levels (usually a 10-60 second injection of antibody) and allowed to stabilize for 5 minutes. For these experiments, a fresh aliquot of Aβ 1-40 was thawed and then diluted 1:10 in HBS-EP running buffer. The 1:10 dilution was used to make up a 200 nM Aβ solution which was serially diluted (1:2 dilutions) to a lowest concentration of 6.25 nM. Each concentration was injected over the surface for 5 minutes at a flow rate of 50 μl/min (250 μl total). The Aβ and antibody were eluted from both flow cells with a 40s injection of glycine pH 1.5. The signal is allowed to stabilize for 2 minutes before the next cycle. The data from flow cell 1 is subtracted from flow cell 2 to account for any bulk shifts due to buffer differences or non-specific binding to the sensor chip or Protein A. The various concentrations were injected randomly and each concentration was run in duplicate. Two control runs of buffer only were used to control for any dissociation of antibody from the capture surface. The data was analyzed using the Biaevalution™ software. A 1:1 model with mass transfer and a local Rmax was used as the best fit for the data.
[0063] Association rate constants (k on ) were determined by BIAcore™ for separate preparations of antibodies. The results of these determinations are summarized in Table 6.
[0064] Association rate constants (k on ) of m266 and antibodies of the present invention with Aβ were determined by KinExA™, using methods as described above in Example 1. The results of two separate k on determinations by KinExA™, in which separate preparations of antibodies were used, are provided in Tables 7 and 8. Furthermore, separate preparations of antibodies and Aβ antigen were used for the determinations provided in Table 8.
[0000]
TABLE 6
Summary of on-rate constants for anti-Aβ monoclonal
variants using BIAcore ™
Sample
k on (M −1 sec −1 10 5 )
Fold Increase
m266
1.3
1
1A1
3.9 ± 0.3
3
1A1-W
6.1 ± 0.03
5
1B7
5.9 ± 0.3
5
1D4
4.7 ± 1
4
1A1-KNT
4.7
4
1A1-SNL
4.2
3
1A1-SNL
4.7
4
1A1-KNT
4.1
3
1A1-W
4.1 ± 0.1
3
1A1-W-KNT
4.2
3
6C3
6.1
5
1A12
4.1
3
7F7
3.5
3
[0065] Concentrations of human Aβ (1-40) from 200 nM to 1.6 nM in 2-fold serial dilution were used to obtain on-rate constant. The upper half of Table 6 represents determinations made with a first set of antibody preparations, while the lower half represents determinations made with a second set of antibody preparations
[0000]
TABLE 7
Summary of on-rate constants for anti-Aβ monoclonal
variants using KinExA ™
Fold increase
SAMPLE
k on (×10 5 M −1 sec −1 )
in k on
m266
2.1
2.4
2.3
1
1A1
5.8
5.5
3.9
5.1
2
1A1-W
14.7
20.8
17.8
8
1B7
6.3
3
1A1-KNT
14
6
1A1-SNL
11
5
a Numbers in bold are the averages calculated from individual experiments and were used to calculate fold increase in on-rate.
[0000]
TABLE 8
Summary of on-rate constants for anti-Aβ monoclonal
variants using KinExA ™
SAMPLE
k on (×10 5 M −1 sec −1 )
m266
1.29
1.27
0.88
1.86 b
2.40 b,c
1.57 c
1.54
1A1
10.55
9.54
9.12
8.83
8.51 b,c
7.62 b
9.76 c
9.13
1A1-W
18.05
1A1-KNT
32.26
1A1-WKNT
38.31
a Numbers in bold are the averages calculated from individual experiments.
b A separate preparation of antibodies was used for these experiments.
c A separate preparation of antigen was used for these experiments.
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The present invention encompasses isolated antibodies, or fragments thereof, that are humanized variants of murine antibody 266 which employ complementarily determining regions derived from murine antibody 266. The variant antibodies are useful for treatment or prevention of conditions and diseases associated with Aβ, including Alzheimer's disease. Down's syndrome, cerebral amyloid angiopathy, mild cognitive impairment, and the like.
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This application is based on U.S. Provisional Patent Application Ser. No. 62/071,868 filed Oct. 6, 2014, priority of which is claimed and which is incorporated herein by reference.
This invention relates to hand held tools and more particularly to tool handles for hand held tools which have high gripping power.
BACKGROUND OF THE INVENTION
There are many industries and situations where hand held impact tools are swung with considerable force. One handed hammers, two handed sledge hammers and axes are common examples. In some situations, circumstances are such that the user cannot grip the tool handle securely. A common example is where the user's hands or the tool handle is wet. Oil, grease, drilling mud and other similar slick materials make it difficult to grasp a tool handle and swing the tool with the requisite force without losing grip of the handle. There are obvious safety concerns to the user, to bystanders and to nearby equipment.
There have been some attempts made in manufactured tool handles to make them rougher, as with grooves, ribs of hard or soft rubber and the like. There have been improvised attempts as with string, tape or the like wound around the handle.
Disclosures of interest are found in U.S. Pat. Nos. 3,585,101; 4,825,552; 5,097,566; 5,234,740; 6,372,323; 6,610,382; 7,309,519; 7,703,179 and 8,277,922 along with U.S. Printed Patent Application; 2012/0027990 and Japan Patent 2012158091.
SUMMARY OF THE INVENTION
A tool handle includes a series of outwardly extending pegs which are sufficiently far apart to allow the user's hand to abut the tool handle. The pegs are rigid, meaning they indent the skin of the user when the tool handle is forcibly grasped. In some embodiments, the pegs are long enough and spaced far enough apart to make it overly painful to grasp and forcibly swing the tool bare handed. In some embodiments the pegs are embedded in a molded handle or formed during molding of a handle. In other embodiments, the pegs are captivated against an exterior of the handle, as by the use of shrink wrap bands.
It is an object of this invention to provide an improved tool and tool handle.
Another object of this invention is to provide an improved tool handle for impact tools which provides high gripping power.
These and other objects and advantages of this invention will become more fully apparent as this description proceeds.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view of a hand held tool incorporating a handle of this invention;
FIG. 2 is an end view of the tool handle of FIG. 1 ;
FIG. 3 is a cross-sectional view of FIG. 1 , taken substantially along line 3 - 3 thereof as viewed in the direction, indicated by the arrows;
FIG. 4 is a partial side view of another embodiment of a tool handle of this invention;
FIG. 5 is a cross-sectional view of FIG. 4 , taken substantially along line 5 - 5 thereof as viewed in the direction indicated by the arrows;
FIG. 6 is a cross-sectional view, similar to FIG. 5 , of another embodiment of a tool handle.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIGS. 1-3 , there is illustrated an impact tool 10 such as a one handed hammer having a handle 12 and an impact head 14 . The impact tool 10 may be of any suitable type such as the hammer/chisel form shown, a sledge hammer, axe, maul or the like.
The handle 10 includes a conventional shaft 16 which is typically of wood but which may be of any suitable material, such as plastic, metal, fiberglass or the like. A series of rigid pegs 18 are captivated to the shaft 16 in any suitable manner, as by the use of sections of shrink wrap tubing 20 . The pegs 18 include an enlarged head 22 which may be buttressed by a beveled or unbeveled washer 24 and a shaft 26 which protrudes through an opening in the tubing 20 . The peg shaft 26 may terminate in a flat blunt end 28 perpendicular to an axis 30 of the shaft 26 and may preferably include a tapered, beveled or chamfered edge 32 to avoid a sharp edge on the end 28 of the peg 18 .
The pegs 18 may extend outwardly from the handle 12 in a more-or-less radial fashion as shown in FIG. 2 . The pegs 18 may be symmetrically placed about the handle 12 as in FIG. 2 where the pegs 18 are spaced 45° apart or may be more randomly positioned. Similarly, each group of pegs 18 , i.e. those bound to the shaft 16 by a single length of tubing 20 , may be identically positioned to the group above or below it or may be staggered in some fashion. The number of pegs 18 bound by each of the tubing sections 20 may vary considerably but there may be 4-20 pegs 18 bound by each of the tubing sections 20 and may preferably be 6-8 pegs 18 for each tubing section 20 . There may be a series of tubing sections 20 or a single long length of tubing 20 in which the pegs 18 are held.
To apply the pegs 18 to the handle shaft 16 , the washers 24 are installed on the pegs 18 , the pegs 18 are passed through openings in the tubing 20 which are then slipped over the end of the handle shaft 16 to a desired location. A heat gun (not shown) such as a hair dryer is used to shrink the tubing 20 onto the shaft 16 and thereby captivate the pegs 18 to an exterior of the handle 12 . Some shrink wrap material includes glue on the underside and some may not. In any event, glue may be added to the underside of the tubing 20 to promote adhesion to the handle 12 .
The function of the pegs 18 is to increase the frictional forces between the user's hand and the handle 12 . By making the pegs 18 small in area, spaced widely apart and relatively long, the forces in some embodiments are so great that a user cannot hold the hammer 10 bare handed and swing in a normal forceful manner because the pain is too great. This may sound disadvantageous but, in some industries like the upstream oil and gas industry, it is counter-intuitively desirable because workers are encouraged or required to wear gloves. By making the pegs 18 so the handle 12 is painful to grasp, one accomplishes two ends, i.e. create maximum frictional force between the user's hand and the handle 12 and encourage the worker to wear gloves.
In one sense, the measurement of pain is a subjective matter but, in another sense, is subject to objective consideration. As used herein, the pain being so great that the person cannot hold onto the handle and swing it forcibly means that at least ninety percent of a random selection of adult American males cannot drive a common six penny nail completely into the short side of a 2×4 commercial grade piece of lumber in thirty seconds while gripping the handle bare handed in the gripping area between the upper and lower peg boundaries.
To promote the frictional forces between the handle 12 and the user's hand, it is desirable to make the pegs 18 of small cross-sectional size, widely dispersed and sufficiently long. The cross-sectional area of each peg shaft 26 , taken perpendicular to the axis 30 along a section of maximum diameter or value, is relatively small and may be in the range of 0.002-0.07 square inches each and may preferably be in the range of 0.008-0.02 square inches each. It may be preferred that each of the pegs 26 be identical for ease of manufacture but the pegs 18 may be of mixed cross-sectional size if desired.
The peg shaft 26 may be of complex shape but may preferably or conveniently be slightly tapered or cylindrical. The diameter of cylindrical peg shafts 26 may vary considerably but typically may be in the range of 0.05-0.3 inches and may preferably be in the range of 0.08-0.20 inches.
The cumulative cross-sectional area of the pegs 18 is very small compared to the surface area of either the shrink wrap tubing 20 or to the handle shaft 16 . The more appropriate comparison in the embodiment of FIGS. 1-3 is to the diameter of the tubing sections 20 which abuts the user's hand or glove in use. The cumulative cross-sectional area of the pegs 18 , from an upper peg boundary 34 to a lower peg boundary 36 which constitute the gripping area of the handle 16 , may be in the range of about ½-8% of the area between the boundaries 34 , 36 . The cumulative cross-sectional area of the pegs 18 , between the boundaries 28 , 30 , may preferably be in the range of 1-2.5%. The exact number of pegs in any particular embodiment depends, of course, on the cross-sectional area of each peg.
The pegs 18 do not have to be symmetrically or evenly dispersed on the handle shaft 16 as shown in the drawings but there is no adult male hand sized area on the handle shaft 16 , i.e. a distance of 3″ or greater along the axis of the shaft 16 , between the boundaries 34 , 36 that is free of pegs 18 . In some embodiments, there may preferably be at least one peg 18 in any square having an area of two square inches between the boundaries 34 , 36 .
One factor determining the rigidity of the pegs 18 is the material from which they are made. The pegs 18 may be of any suitable metal, plastic or composite of considerable hardness. The pegs may be soft metals such as copper or aluminum having a 2.5 or greater hardness on the Mohs scale. Copper alloys, aluminum alloys, iron and iron alloys are, of course, considerably harder and may be used. Hard polymers such as polycarbonates, polypropylene, polyamides and similar plastics having a Shore Durometer in excess of 70 may also be used. Plastics presumptively have a disadvantage because, when broken, they produce sharp edges. Sharp edges in fact promote frictional forces between the user's glove and the handle 16 but they wear gloves at an inordinately high rate.
Another factor determining the rigidity of the pegs 18 is the length of the pegs 18 above the surface of the sections 20 relative to their diameter. When the pegs 18 are made of suitable metals or plastics and are no longer than 0.4″ long, they remain rigid and are not flexible because of overly large aspect ratios.
The exposed length of the pegs 18 above the shrink wrap tubing sections 20 has another effect. If the pegs 18 are too short, they do not produce sufficient frictional forces. If the pegs 18 are too long, they become like spikes and are too sharp. The pegs 18 may be exposed above the shrink wrap section 20 in the range of 0.05-0.4″ and may preferably extend in the range of 0.1-0.2″ above the exterior of the shrink wrap tubing sections 20 . Although the pegs 18 shown in FIGS. 1 and 2 are of the same length above the exterior of the tubing 20 , they may be of random length and may extend at different lengths above the tubing 20 .
Referring to FIGS. 4-5 , there is illustrated another tool handle 40 which may be molded from a suitable polymer, fiberglass, composite material or the like. The handle 40 accordingly includes a shaft 42 in which are embedded a series of rigid pegs 44 . The pegs 44 may include an enlarged lower end or flange 46 promoting retention of the peg 44 . The size, spacing and distribution of the pegs 44 relative to the handle shaft 42 may be the same as the size, spacing and distribution of the pegs 18 relative to the shrink wrap sections 20 .
Referring to FIG. 6 , there is illustrated another molded tool handle 50 having a handle shaft 52 from which extend a series of rigid pegs 54 which are integral with the handle shaft 52 and are molded from the same material as the handle shaft 52 during manufacture. The size, spacing and distribution of the pegs 54 relative to the handle shaft 52 may be the same as the size, spacing and distribution of the pegs 18 relative to the shrink wrap sections 20 .
The type of work gloves which may be used with the handle 16 of this invention may vary widely. Plastic dot gloves, leather, suede and more modern work gloves, such as those made by Wells Lamont of Niles, Ill. which is a division of The Marmon Group of Chicago, Ill. or Ringers Gloves of Houston, Tex. and similar gloves may be suitable for use to swing the hammer 10 without the least discomfort. The basic reason that one can grasp the handle 16 without discomfort is that work gloves spread the effect of the blunt peg ends 28 over a greater area of the user's hand.
Although this invention has been disclosed and described in its preferred forms with a certain degree of particularity, it is understood that the present disclosure of the preferred forms is only by way of example and that numerous changes in the details of operation and in the combination and arrangement of parts may be resorted to without departing from the spirit and scope of the invention as hereinafter claimed.
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A hand held hammer includes a handle incorporating a series of outwardly extending pegs providing gripping power between the user's hands and the handle. In some embodiments, the pegs are spaced far enough part to make it overly painful to swing the hammer bare handed. In some embodiments, the cumulative surface area of the pegs occupy less than 8% of the surface area of the handle. The pegs may be embedded in a plastic handle, captivated to the exterior of a conventional handle or may comprise an integral part of a plastic handle.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority under 35 U.S.C. 119 of U.S. provisional application No. 60/133,894 filed May 12, 1999 and Danish application no. PA 1999 00611 filed May 6, 1999, the contents of which are fully incorporated herein by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing paper materials such as paper, linerboard or corrugated linerboard from unbleached and semi-bleached chemical or semichemical pulp or pulp from recycled fibers.
2. Description of the Related Art
Linerboard and corrugated medium, used for making corrugated paperboard and corrugated cartons, are commonly made from a suspension of unbleached chemical or semichemical pulp or pulp from recycled fibers.
Typically, the pulp is treated in a screening process, refined, then mixed with paper making additives in the stock preparation section before the pulp suspension is de-watered on the paper/board machine, and the drained water (so-called white water) is recycled back into the process for dilution of the screened stock.
The white water will normally contain high amounts of wood fibers/fines, sterol esters, resin acids, lignans, and lignin fragments typically in concentrations of 100-500 ppm or higher; all of this material will have phenolic or phenol-like groups.
Strength, particularly compression strength, is an important mechanical property of the unbleached board grades used to make corrugated boxes: linerboard and corrugated linerboards. Due to new governmental rules in some countries giving an alternative specification based on combined board edge crush and since combined edge crush can be tied directly to the compression strength of the board's components it is now possible to sell board on a performance per square meter basis rather than only by weight.
Clearly, the wet strength of unbleached board grades used to make corrugated boxes is also of importance.
EP 429,422 discloses reduction of energy consumption in the refining stages by use of laccase during pulp preparation between the first and second refining stage; the document indicates that some increase of paper strength is also obtained.
WO 93/23606 (EP 641 403) discloses a process for treating a mechanical pulp with a phenol-oxidizing enzyme system to increase the strength of the produced paper.
WO 95/09946 discloses a process for producing linerboard or corrugated medium having increased strength by treating pulp with a phenol-oxidizing enzyme.
WO 95/07604 discloses a process for producing fiberboard having improved mechanical properties by treating a slurry or suspension of a lignin-containing wood fiber material with a phenol-oxidizing enzyme.
U.S. Pat. No. 4,687,745 discloses a process for enhancing the strength properties and brightness stability of mechanical pulp by treating the pulp with ligninolytic enzymes. The wet strength of paper materials may be enhanced by adding wet strength resins to the pulp. However, these resins will enhance the strength of the paper material in such a way that re-use of the paper material will become difficult.
It is an object of the present invention to provide a process for producing, from unbleached or semi-bleached chemical or semichemical pulp, paper materials such as paper, linerboard or corrugated linerboard having improved wet strength.
SUMMARY OF THE INVENTION
The present inventors have now surprisingly found that the wet strength of paper materials can be increased by treating a pulp suspension with a phenol-oxidizing enzyme system prior to the paper machine. It has also been found that the wet strength can be further improved by a combined enzyme/mediator treatment. The wet strength may be even further improved by additionally applying a heat treatment.
Accordingly, in a first aspect the present invention relates to a process for producing paper materials with improved wet strength, comprising:
(a) preparing a suspension of unbleached or semi-bleached chemical or semichemical pulp or pulp from recycled fibers;
(b) treating the pulp with a phenol oxidizing enzyme and a mediator; and
(c) de-watering the treated pulp in a paper making machine to remove process water and produce the paper material.
In a preferred embodiment, the process water from step (c) is recycled, and step (a) comprises dilution of the pulp with the recycled process water. Advantageously, the enzymatic treatment of the pulp and white water suspension will to a large extent polymerize the aromatic materials present in the white water (lignans, resin acids, sterol esters, lignin-like compounds fibers and fines), so that they are retained in the paper sheet, leading to an increased yield and a decreased COD (chemical oxygen demand) load and toxicity of the effluent. This polymerization is also believed to contribute to strengthening of the linerboard or corrugated medium.
In a further preferred embodiment the paper material is heated after the completion of step (c).
In a second aspect the present invention relates to a process for making corrugated paperboard or corrugated boxes using the linerboard and/or corrugated linerboard produced by the process of the invention.
In a third aspect the present invention relates to the use of a phenol-oxidizing enzyme in combination with a mediator to produce a paper material with improved wet strength.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the wet tensile strength of the sheets produced in Example 1. Data is taken from Table 1. Vertical bars indicate the 95% confidence limit.
FIG. 2 shows the wet strength after immersion into distilled water for 24 hours of paper subjected to different treatments as described in Example 2. The following abbreviations have been used:
C: Conventional drying in condition chamber.
H: Heat drying of the wet sheet at 150° C. for 5 min.
L: Treatment of pulp with 10 LACU/g for 1 hr.
M: Addition of 50 mM PPT.
The strength of #1 was below the detection limit of 2.2 Nm/g and was a conservative estimate set to this value in FIG. 2 . Vertical bars indicate the 95% confidence limit.
DETAILED DESCRIPTION OF THE INVENTION
In the context of the present invention the term “paper material” refers to products, which can be made out of pulp, such as paper, linerboard, corrugated paperboard, corrugated container or boxes.
The term “improved wet strength” indicates that the wet strength of the paper material is increased/enhanced in comparison to the paper material which has not be treated according to the invention.
Pulp
The pulp to be used in the process of the invention is a suspension of unbleached or semi-bleached chemical or semichemical pulp or pulp from recycled fibers. Unbleached or semi-bleached pulp is characterized by containing lignin, which is used as substrate for the enzyme system. The chemical pulp may be unbleached kraft pulp, and the semichemical pulp may be NSSC (neutral sulfite semichemical) pulp. The pulp from recycled fibers may be made from a chemical pulp, such as unbleached kraft pulp. A specific example of recycled fibers made from a chemical pulp includes OCC (old corrugated containers).
The preparation of the pulp suspension may comprise beating or refining of the pulp, depending on the type of pulp.
Phenol Oxidizing Enzyme System
The enzyme system used in the invention consists of a suitable oxidase together with O 2 or a suitable peroxidase together with H 2 O 2 . Suitable enzymes are those, which oxidize and polymerize aromatic compounds such as phenols and lignin.
Examples of suitable enzymes are catechol oxidase (EC 1.10.3.1), laccase (EC 1.10.3.2), bilirubin oxidase (EC 1.3.3.5) and peroxidase (EC 1.11.1.7) and haloperoxidases. The peroxidase may be derived from a strain of Coprinus, e.g. C. cinerius or C. macrorhizus , or of Bacillus, e.g. B. pumilus , from soy bean or horse radish. It may be preferable to use two different phenol oxidizing enzymes together.
Suitable laccases may, for example, be derived from a strain of Polyporus sp., in particular a strain of Polyporus pinsitus (also called Trametes villosa ) or Polyporus versicolor , or a strain of Myceliophthora sp., e.g. M. thermophila or a strain of Rhizoctonia sp., in particular a strain of Rhizoctonia praticola or Rhizoctonia solani , or a strain of Scytalidium sp., in particular S. thermophilium , or a strain of Pyricularia sp., in particular Pyricularia oryzae , or a strain of Coprinus sp., such as a C. cinereus.
The laccase may also be derived from a fungus such as Collybia, Fomes, Lentinus, Pleurotus, Aspergillus, Neurospora, Podospora, Phlebia, e.g. P. radiata (WO 92/01046), Coriolus sp., e.g. C. hirsitus (JP 2-238885), or Botrytis.
In a preferred embodiment of the invention the laccase is derived from a strain of Polyporus sp., especially the Polyporus pinsitus laccase (in short: PpL).
The amount of peroxidase should generally be in the range 10-10,000 PODU per g of dry substance (PODU unit of peroxidase activity defined below). The amount of laccase should generally be in the range 0.001-1000 units per g of dry substance (unit of laccase activity defined below).
Molecular oxygen from the atmosphere will usually be present in sufficient quantity. Thus, contrary to prior art bleaching processes (including laccase and mediator) where a high oxygen pressure is necessary, this will usually not be necessary for the purposes described herein. Therefore, the reaction may conveniently be carried out in an open rector, i.e. at atmospheric pressure.
A suitable amount of H 2 O 2 will usually be in the range 0.01-10 mM, particularly 1-10 mM.
Mediator
According to the invention the phenol-oxidizing enzyme is used in combination with a suitable redox mediator. A so-called “redox mediator” is sometimes in literature referred to as “an enhancing agent”. In the present context the term “mediator” will be used.
A “mediator” is an agent capable of enhancing the activity of phenol-oxidizing enzymes.
The mediator may be a phenolic mediator or a non-phenolic mediator. Which mediator is preferred depends on the purpose.
Examples of mediators capable of enhancing the activity of phenol-oxidizing enzymes include the compounds described in WO 95/01426, which is hereby incorporated by reference, and described by formula I:
The definition of the R1 to R10 and A groups can be found in WO 95/010426 (see pp. 9 to 11).
Specifically contemplated compounds within the above formula I include the following: 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate (ABTS); 6-hydroxy-2-naphtoic acid; 7-methoxy-2-naphtol; 7-amino-2-naphthalene sulfonic acid; 5-amino-2-naphthalene sulfonic acid; 1,5-diaminonaphthalene; 7-hydroxy-1,2-naph-thimidazole; 10-methylphenothiazine; 10-phenothiazine-propionic acid (PPT); N-hydroxysuccinimide-1O-phenothiazine-propionate; benzidine; 3,3′-dimethylbenzidine; 3,3′-dimethoxybenzidine; 3,3′,5,5′-tetramethylbenzidine; 4′-hydroxy-4-biphenylcarboxylic acid; 4-amino-4′-methoxystilbene; 4,4′-diaminostilbene-2,2′-disulfonic acid; 4,4′-diaminodiphenylamine; 2,7-diaminofluorene; 4,4′-dihydroxy-biphenylene; triphenylamine; 10-ethyl-4-phenothiazinecarboxylic acid; 10 -ethylphenothiazine; 10-propyl-phenothiazine; 10-isopropylphenothiazine; methyl-10-phenothiazinepropionate; 10-phenylphenothiazine; 10-allyl-phenothiazine; 10-phenoxazinepropionic acid (POP); 10-(3-(4-methyl-i-piperazinyl)propyl)phenothiazine; 10-(2-pyrrolidinoethyl)phenothiazine; 10-methylphenoxazine; imino-stilbene; 2-(p-aminophenyl)-6-methylbenzothiazole-7-sulfonic acid; N-benzylidene-4-biphenylamine; 5-amino-2-naphthalenesul-fonic acid; 7-methoxy-2-naphtol; 4,4′-dihydroxybenzophenone; N-(4-(dimethylamino)benzylidene)-p-anisidine; 3-methyl-2-benzo-thiazolinone(4-(dimethylamino)benzylidene)hydrazone; 2-acethyl-10-methylphenothiazine; 10-(2-hydroxyethyl)phenothiazine; 10-(2-hydroxyethyl)phenoxazine; 10-(3-hydroxypropyl)phenothiazine; 4,4′-dimethoxy-N-methyl-diphenylamine, vanillin azine.
Other mediators contemplated include 4-hydroxybenzoic acid, L-tyrosine, syringate acids, ferulic acid, sinapic acid, chlorogenic acid, caffeic acid and esters thereof.
Still further examples include organic compounds described in WO 96/10079, which is hereby incorporated by reference, and by the following formula II:
in which A is a group such as —D, —CH═CH—D, —CH═CH—CH═CH—D, —CH═N—D, —N═N—D, or —N═CH—D, in which D is selected from the group consisting of —CO—E, —SO 2 —E, —N—XY, and —N + —XYZ, in which E may be —H, —OH, —R, or —OR, and X and Y and Z may be identical or different and selected from —H and —R; R being a C 1 -C 16 alkyl, preferably a C 1 -C 8 alkyl, which alkyl may be saturated or unsaturated, branched or unbranched and optionally substituted with a carboxy, sulfo or amino group; and B and C may be the same or different and selected from C m H 2m+1 ; 1≦m≦5.
Specific compounds covered by the above formula I are acetosyringone, syringaldehyde, methylsyringate, syringic acid, ethylsyringate, propylsyringate, butylsyringate, hexylsyringate, octylsyringate and ethyl 3-(4-hydroxy-3,5-dimethoxyphenyl).
Other suitable mediators are vanillic acid, NHA, HOBT, PPO and violoric acid.
Process Conditions
The enzyme treatment can be done at conventional consistency, e.g., 0.5-25% (particularly 0.5-10%) dry substance, at temperatures of 20-90° C. and at a pH of 4-10. Furthermore, the enzyme (and mediator) treatment may be carried out at atmospheric pressure.
The enzyme activity when using a laccase is 0.001-1000 LACU per gram of dry substance.
Determination of Peroxidase Activity (PODU)
Peroxidase activity is determined from the oxidation of 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) by hydrogen peroxide. The greenish-blue color produced is photometered at 418 nm. The analytical conditions are 0.88 mM hydrogen peroxide, 1.67 mM ABTS, 0.1 M phosphate buffer, pH 7.0, 30° C., 3 minutes reaction.
1 peroxidase unit (PODU) is the amount of enzyme that catalyzes the conversion of 1 mmol hydrogen peroxide per minute at these conditions.
Determination of Laccase Activity (LACU)
Laccase activity was determined by a similar method without addition of hydrogen peroxide. 1 laccase unit (LACU) is defined as the amount of enzyme which, under standard conditions (pH 5.5, 30° C.), oxidizes 1 mmol syringaldazine per minute.
The invention is further illustrated by the following non-limiting examples.
EXAMPLES
Example 1
A beaten and unbleached kraft pulp kappa 85 obtained from the Obbola mill in Sweden was disintegrated in a laboratory disintegrator and diluted to a consistency of 1%. A water phase was used either tap water or white water from the Obbola mill. pH was adjusted to 5.5±0.1 with 1 M sulphuric acid and this was maintained by further addition of acid. An enzyme dosage of 15 LACU/g dry pulp (laccase derived from Polyporus pinsitus ) was added and the suspension was stirred for 1 hour.
Isotropic sheets with a specific weight of 150 g/m 2 were formed on a semiautomatic papermaker of the Rapid-Konthen type. When comparing the tensile strength of sheets subjected to different treatment it is of crucial importance that the sheets have the same density. Heat drying of a sheet increases its density, and to compensate for this, sheets to be air-dried were pressed to a higher density than sheets to be heat-dried.
A trial was performed comprising the following variables: white water, laccase and heat drying.
In experiments without white water, the pulp was suspended in distilled water. Heat dried sheets were dried in an oven at 170° C. and were stacked with each sheet separated by blotting paper and placed with a weight on top to prevent shrinkage. All blotting papers were replaced after 20, 30 and 40 min. After heat drying all sheets were placed in a condition chamber at 50% RH and 23° C. overnight. Sheets not heat dried were dried conventionally in a condition chamber at 65% RH and 21° C.
Test of tensile strength was performed after SCAN-P67 with 10 test strips. Permanent wet tensile strength was tested after immersion of the test piece into distilled water for 24 hr.
For each of the eight treatments, five sheets were made. The same batch of pulp and white water was used for all treatments, and the entire experiment was carried out on the same day. Data were analyzed with the statistical software package SAS.
Results:
The obtained results are compiled in Table 1 and FIG. 1 . From Table 1 it can be seen that the density between the sheets differ somewhat, which should be borne in mind when interpreting the results.
TABLE 1
Heat drying 170° C.
Specific
Wet tensile
Exp.
White
15
Drying
weight
Density
index
No.
water
LACU/g
170° C.
(g/m 2 )
(kg/m 3 )
(kNm/kg)
1
−
−
−
154.8
710
2.56
2
+
−
−
154.7
710
2.73
3
−
+
−
155.4
713
3.13
4
+
+
−
166.2
717
3.48
5
−
−
+
154.8
704
5.30
6
+
−
+
152.8
661
5.63
7
−
+
+
153.8
660
6.04
8
+
+
+
161.6
682
6.64
Result from experiments comprising: white water, PpL laccase and heat drying at 170° C.
The main effects are shown in Table 2 with the corresponding least significant difference (LSD) values.
TABLE 2
Main effect of variables (difference between means of the variables
at high and low level). Significance at the 0.05 level is indicated by ***
based on a T-test. Least significant differences (LSD) on the 0.05 level
written in parentheses. All values are in Nm/g.
Effect
Wet tensile strength (LSD 0.33)
White water
0.36***
Enzyme (15 LACU/g)
0.77***
Heat drying at 170° C.
2.93***
The wet tensile strength was significantly affected by all variables. Heat drying had the highest impact on the wet tensile strength with almost 3 Nm/g followed by the laccase treatment with 0.8 Nm/g. The increase in wet tensile strength by adding enzyme to a pulp suspended in white water and where the sheets are heat-dried, is in the order of 20% (compare experiments Nos. 6 and 8).
Example 2
A beaten and unbleached kraft pulp kappa 85 obtained from the Obbola mill in Sweden was disintegrated in a laboratory disintegrator and diluted to a consistency of 1%. pH was kept at 5.5 using a 0.05 M sodium acetate buffer. PpL laccase and a mediator were added and the slurry stirred for 1 hour at room temperature. The enzyme dosage was 10 LACU/g dry pulp in all experiments.
Isotropic handsheets with a specific weight of 150 g/m2 were made of the modified pulp according to SCAN-P:26. In those experiments where the sheets were subjected to a heat treatment this was done to the wet sheets immediately after the second pressing step in a restrained dryer at 150° C. for 5 min, and was then conditioned at 65% RH and 23° C. All other sheets were dried in a conditioning chamber at 65% RH and 21° C. The dry- and wet tensile strength were determined according to SCAN-P:38. Before measuring the wet tensile strength, the test strip was immersed in distilled water for 1 or 24 hours.
Results:
A standard method for testing the strength of a chemical pulp was used, where the sheets were dried in a condition chamber at 65% RH and 21° C. The obtained results are compiled in FIG. 2 .
As can be seen from FIG. 2, the laccase mediator (PPT) treatment gives a significant increase in the wet tensile strength of the linerboard, both when the paper is subjected to heat treatment (experiments Nos. 3 and 6) and when not subjected to heat treatment (Nos. 1 and 2). Heat treatment of paper is known to confer wet strength, possibly through generation of covalent bonds between cellulose chains, but the treatment of the pulp with laccase and PPT increased this effect by about 50%, cf. FIG. 2 .
Addition of PPT or laccase alone (experiments Nos.4 and 5), did not change the wet tensile strength of the heat treated paper. This was also observed when the paper was not heat-treated (not shown).
Table 3 shows the wet tensile strength of paper sheets made from kraft pulp oxidized with laccase and different mediators prior to sheet formation. Although the error within an experiment was low, the day-to-day variation was rather high, and therefore the effect of a given mediator should be evaluated by comparing all values to the control sheet within the same experiment. By doing so, it becomes evident that PPT, followed by ABTS, yields the highest wet strength.
TABLE 3
Wet strength of isotropic handsheets made of a kraft pulp oxidized
with PpL (10 LACU/g) and a mediator. The wet tensile strength was tested
after immersion into distilled water for 1 hour. In some of the experiments
the control sheet did not have a measurable wet strength, and therefore this
was set to maximum <2.2, which is the lowest detection limit
Wet tensile
Concentration
index
Mediator
(mM)
(kNm/kg)
None (control)
0
2.7
Vanillic acid
60
4.1
Vanillic acid
600
4.3
4,4′-dihydroxy-
250
4.7
diphenylmethane
None (control)
0
3.1
TEMPO
40
5.0
PPT
40
Methyl
40
5.5
syringate
NHA
40
4.9
None (control)
0
<2.2
PPO
40
3.7
ABTS
40
4.7
Promethiazine
40
2.7
3,5-dimethoxy-
40
3.1
4-hydroxy-
acetophenon
None (control)
0
<2.2
PPT
40
4.4
HOBT
40
2.3
10-methylpheno-
40
3.0
thiazine
Violoric acid
40
2.3
Under the right conditions, heat treatment of paper is known to increase the wet strength up to a value of 30% of the dry strength (Stenberg, E. L., Svensk Papperstidning 8:49-54, 1978).
In this study it was tested if the effects of the laccase/ mediator treatment shown in Table 3 could be further increased by combining this with a heat treatment of the paper. It was chosen to apply the heat treatment to the paper as soon as possible after the oxidation with laccase and PPT, and was therefore given after pressing the wet sheet. From the data depicted in FIG. 2, it can be seen that the heat treatment itself more than doubles the wet strength. Adding laccase alone or PPT to the pulp before the heat treatment does not effect the wet strength, but using a combination of laccase and PPT gives an increase of 50% in wet strength of the heat-treated paper. It should be noted that all wet tensile strength in this part of the report was tested after 24 hours immersion. When a sheet made from pulp oxidized with laccase and PPT and then heat dried, was immersed for only 1 hour a wet tensile strength of 10 Nm/g could be measured (not shown).
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A process for producing paper materials having improved wet strength. This process involves (a) preparing a suspension of unbleached or semi-bleached chemical or semichemical pulp or pulp from recycled fibers; (b) treating the pulp with a phenol-oxidizing enzyme and a mediator; and (c) de-watering the treated pulp in a paper making machine to remove process water and produce the paper material. Preferably, the paper material is heated after the completion of step (c). By the process of the invention, the wet strength of paper materials can be improved without using wet strength resins which makes the product more easily re-used. Further disclosed is a process for producing corrugated paperboard or corrugated containers.
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RELATED APPLICATIONS, PATENTS AND PRIOR ART
This application is related to our own, commonly assigned patents, U.S. Pat. No. 5,224,098, entitled "Compensation for Mismatched Transport Protocols in a Data Communications Network", U.S. Pat. No. 5,361,256, entitled "Protocol Selection and Address Resolution for Programs Running in Heterogeneous Networks", and our own, commonly assigned, currently allowed application Ser. No. 08/189,816 filed Feb. 01, 1994 now U.S. Pat. No. 5,491,693 which is a continuation of application Ser. No. 08/175,985 filed on Dec. 30, 1993 entitled "General Transport Layer Gateway for Heterogeneous Networks" now abandoned. The above stated patents provide a substantial foundation to and are prior art with respect to this application. U.S. Pat. No. 4,914,571 entitled "Locating Resources in Computer Networks" also provides additional foundation in the area of SNA (Systems Network Architecture) for this application and is prior art for this application. This application is also related to our own commonly assigned, copending application Ser. No. 08/336,948 filed on Nov. 10, 1994 entitled "Method and Apparatus for Interconnecting Networks" now U.S. Pat. No. 5,586,261.
U.S. Pat. No. 5,224,098 describes a Multi-Protocol Transport Networking (MPTN) Architecture which allows an application program running at one node in a network to communicate with a second application program running at another node in the network even where the application programming interface (API) assumes a different set of transport functions than those supported by the transport provider. In particular, it relates to a method for establishing communications, either connectionless or with a connection, between the applications and compensating for transport protocol mismatches if they arise.
U.S. Pat. No. 5,361,256 relates to address resolution and protocol selection among multiple transport protocols for the applications and the nodes in the MPTN network.
Application Ser. No. 08/189,816 relates to an MPTN gateway which has no dependencies on the particular transport protocols running on the Single Protocol Transport Networks (SPTNs) being interconnected. It utilizes a common transport provider interface called a Gateway Services Protocol Boundary (GSPB) between the SPTN transport protocols and the gateway components. The MPTN gateway supports connections between end systems across multiple intermediate networks. The MPTN gateway provides automatic routing based on dynamic participation in the routing protocols of the interconnected SPTNs so that any number of gateways may be interconnected and in any topology desired. It supports both MPTN nodes and gateways and non-MPTN nodes and gateways.
U.S. Pat. No. 4,914,571 describes the implementation of the LOCATE processing for APPN. It describes the changes in APPN over sub-area SNA for location of resources and routing of information.
Application Ser. No. 08/336,948 describes the implementation of dependent logical unit server (DLUS) and dependent logical unit requester (DLUR) on an APPN (Advanced Peer-to-Peer Networking) network. It describes a method of permitting dependent Logical Unit (LUs) (LUs that can not establish sessions by themselves, they need a server) to run over an APPN network.
BACKGROUND AND PRIOR ART
As communications networks have evolved, independent suppliers of computer hardware and software have developed different, incompatible formats and protocols for transporting data through the communications networks. Examples of well-known communications protocols include Systems Network Architecture (SNA), Digital Network Architecture (DECnet), Transmission Control Protocol/Internet Protocol (TCP/IP), Network Basic Input Output System (NetBIOS) and Open Systems Interconnect (OSI). Other communications protocols also exist and are widely used.
As networks have grown, and particularly as local area networks have come into widespread use, many organizations have ended up with conglomerations of individual networks running different networking protocols. For example, a single organization may have dozens of networks running many different networking protocols. This heterogeniety complicates the network communication as distributed programs are generally written for a particular application programming interface (API) which requires a specific networking transport protocol and can, therefore, only communicate over limited parts of the complete network.
If a mismatch exists between the transport protocols required by the particular API for a company's application program, and the transport protocols actually implemented in one or more of the networks on which the company would like to transport the application data, compensation between the API and the network is required.
In addition, there are addressing problems associated with the heterogeneous networks. A program today identifies itself and finds its partners using addresses associated with a particular networking protocol. In order for the program to operate over multiple, different networking protocols, a mechanism is needed to bridge the gap between the specific address set used by the program and the address sets used by the networking protocols. In particular, program independence from specific networking protocols requires a transport-independent mechanism for finding the source and destination application programs and the corresponding available transport protocols.
Since many programs already exist using existing address formats, it is not feasible to require all programs, including those in existence, to use a single standard address format. Likewise, it is not feasible to change all existing transport protocols to support the complete list of address formats used by application programs or to use a single standard format.
One of the more complicated architectures which is addressed in this application is APPN (Advanced Peer-to-Peer Networking). Further information on APPN may be found in "Systems Network Architecture Advanced Peer-to-Peer Networking Architecture Reference", IBM Publication number SC30-3422-003.
FIELD OF THE INVENTION
Many of the noted problems have been solved in the U.S. Patents or the pending U.S. Patent applications mentioned above but a significant gap still exists in that MPTN transport gateways support the concatenation of diverse networks with partner applications running on different networks, but do not fully maintain the characteristics of a SNA/APPN network when attaching to a non-SNA network. This application relates to methods of transporting information across conglomerations of networks containing many different protocols. More specifically, this application deals with a method and apparatus for maintaining the dynamic addressability and search capabilities of APPN across a multi-protocol network as well as the ability to route traffic through a gateway to a non-SNA network, from a dependent LU server to a dependent LU requester.
SUMMARY OF THE INVENTION
This invention solves the problem of preserving the functions of fully dynamic directory and route selection and the ability to use parallel gateways when connecting a native (SNA) network to an MPTN network in addition to allowing the routing of information from a dependent LU requester through a gateway to a non-SNA network to a dependent LU server in the SNA network. In particular, it addresses connecting a native SNA/APPN network to a non-SNA network (e.g., IP, IPX or NetBIOS network) for the support of all SNA applications. In this specification, all references to a native network refer to a SNA/APPN network. The solution implements a fictitious control point (CP) name(s) for each non-native network attached through the gateway(s), indicating that the gateway(s) is functioning as an intermediate routing node(s), and utilizing standard APPN transport mechanisms to exploit the fictitious CP name to route the information across the non-native network to the gateway from which it (the gateway) can route into the non-native network with non-native protocols. In addition, a fictitious connection network name is established to allow the support of a dependent LU requester in the non-native network to communicate with a dependent LU server in the SNA network in order to establish a dependent LU session across the networks.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an example of a network in which this invention is implemented.
FIG. 2 demonstrates the logic necessary to create a connection from a non-native network to a native network.
FIG. 3 is a prior art exposition of APPN directory function.
FIG. 4 shows the connection of an APPN network to a non-native network using a fictitious control point name and implementing intermediate routing nodes.
FIG. 5 further describes the implementation of the fictitious control points when multiple non-native networks are connected to the APPN network.
FIG. 5A demonstrates the use of multiple parallel gateways between a single native network and a single non-native network.
FIG. 6 depicts the connection network used in DLUS/DLUR support for APPN as well as the established control sessions.
FIG. 7 demonstrates the logic used to process a LOCATE from an APPN network, for an LU in the non-native network.
FIG. 8 demonstrates how a border node functions to do topology and routing.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 is a sample network in which this invention is implemented. Device 010 represents any one or more pieces of computer equipment which contains at least one LU. Device 010 is connected to an SNA Network(015) which is in turn connected to a piece of computer equipment which contains a gateway(020). This gateway(020) is then connected to a Non-Native e.g. IP Network(025) which is connected to another piece of computer equipment containing at least one LU(030).
FIG. 1 also demonstrates the flow of traffic through a simplified network. Device 010 contains a node, say node1, which has an SNA application running. The SNA application produces information in a standard SNA format. This information is transmitted along the SNA network(015) to the MPTN gateway(020). Upon reaching the MPTN gateway(020), the gateway transforms the information and transports it across the non-native network(025) to the device at the other end (030) which also contains a node, say node2, running an SNA application. The application in node2 will then interpret and use the information.
FIG. 2 describes the connection setup from a non-native network to a native network. First the non-native node uses an MPTN address mapping mechanism to find the location of the requested LU (202). Next, this mechanism returns the address of the gateway to the requesting non-native node(204). The non-native node then sends a connection request for the desired LU to the gateway (206). If the LU is on the gateway (208) then the connection is established (210); otherwise the connection set-up request causes the gateway to send a LOCATE for the desired LU into the APPN network(212). The gateway waits for a reply from the APPN network indicating whether the LU is found in the network(214). If the LU is not found in the network(215), the connection is rejected(216). If the LU is found(217) in the network, a BIND is created from the information contained in the MPTN connection request, and the LOCATE response(218). The BIND is sent into the native network and the BIND response is returned to the gateway. When the BIND response is received, the MPTN connection reply is created and is returned(220) to the requesting node.
As shown in FIG. 3, the logic to locate a resource for APPN can be quite complex. A review of the standard APPN locate functions and terms is helpful at this point. APPN defines three types of nodes. For purposes of directory search, a network node (NN) is a node that fully participates in the directory search functions. An end node (EN) is a node with limited directory functions, to wit, it can initiate a search by asking a network node to locate an LU and, when asked, it can reply whether it contains the requested LU. A low entry network (LEN) node is a node that cannot participate in directory searches at all. All LEN node directory functions are handled for the LEN node by a NN. A NN and the ENs and LEN nodes it supports for searches is referred to as a domain. A NN contains a local database that contains the location of LUs: this includes all LUs residing on the NN and LEN nodes in its domain and a portion of the LUs in its ENs and in other domains. The latter LU information must always be validated before it can be used.
To initiate the locate processing, first the request to locate a resource is received by a network node (either locally generated or from an EN or LEN node)(301). A search of the local database is made for the resource (302). If the resource is not found (303), then a check is made to see if the destination LU name is a known CP name (304), if it is not (305), then a broadcast is made to the domain of the network node (306), if the resource is found (307), then a positive reply is returned to the requester (308). If the resource was not found in the broadcast (309), then a check is made for the nearest directory server (310). If a directory server is found (311), then a search is made of that directory server for the resource to be located (312). If the resource is not found by the directory server after its search process (313), which can include a broadcast to the network as in (318), a negative reply is returned to the requester (314); if the resource is found (315), a positive reply is returned to the requester (316). If, when the check was made for the nearest directory server (310), no server was found (317), then the LOCATE request is broadcast to the network (318). If the resource is found (319), a positive response is returned to the requester (320); if the resource is not found (321), a negative response is returned to the requester (322).
If, when the check is made to determine if the destination LU name is a known CP name (304), the answer is yes (323), then a positive reply is returned to the requester (332). If the reply to that directed search is negative (325), then a return is made to the path of doing a broadcast search of the local domain (306) and the path is traversed as before. If the reply to the directed search is positive (326), then a positive reply to the locate is returned to the requester (327).
If, when the search of the local database for the resource is issued (302), it is found that the resource to be located is a Local LU or on a LEN node within that domain (328), then a positive reply is returned to the requester (329). If, on the other hand, the resource was determined to be on an APPN end node within the domain (330) or in another domain (331), a directed search is sent (324) to the appropriate node and the path from (324) is traversed as before.
Some additional information on the APPN transport mechanism is helpful prior to describing the next figure. When multiple nodes are connected to a shared access facility (e.g., a local area network (LAN)), they are all in fact connected to each other. Rather than capturing the many connections thus enabled, APPN defines a virtual routing node (VRN) that represents the shared access facility. The VRN is not a true routing node but is given a control point name and is treated like any other routing node for route computations. The VRN and the shared access facility that it represents are referred to as a connection network.
In the present invention there are two models that are used by the gateway to define resources on the non-native network: the LU can appear to be on the fictitious LEN node with a fictitious CP having a link to each gateway (which appears as a NN) or it can appear to be connected to each gateway (NN) through the non-native connection network (CN). The fictitious CP name is a simpler model and is used for independent LUs (those that are able to set up connections without support from any other nodes). For dependent LUs (those that require assistance from dependent LU requesters and servers for session establishment) where DLUR-DLUS communication has knowledge of the real CP name or is cognizant of the individual nodes, this model does not suffice and the connection network model is used. The two basic aspects to this invention which utilize the above concepts are the dynamic support demonstrated in FIGS. 4 and 5 and the support for the non-native DLUR demonstrated in FIG. 6.
As shown in FIG. 4, in order to support the full dynamic directory and route selection capabilities of APPN, the MPTN gateway(403) appears as an intermediate routing network node to the rest of the APPN network(402) which includes one or more APPN nodes(401). When requests are initiated on the MPTN (non-native) side of the gateway, it appears to the rest of the APPN network as if the request was initiated at a low entry network (LEN) node behind the gateway (i.e. NN) and the normal processing procedures prevail. The gateway appears to the MPTN network(404) as an intermediate node that bridges two different networks and the network expects it to provide all networking functions on the non-MPTN portion of the network including support for dynamic directory and route selection.
When the requests are initiated on the native (APPN) side of the gateway, the requirement for supporting the full dynamic directory and route selection capabilities of APPN become more difficult. A quick review of the present APPN connection establishment technique is beneficial in understanding this situation. Within the APPN network, when an end node requires that a connection be established, it issues a LOCATE request for the desired LU to its supporting network node. A LOCATE reply is returned to the requesting network node with information about how to reach the destination beyond the topology that the network node knows. With this information, plus the known topology, a preferred route is selected.
In the present invention the shared-access transmission facility and the set of nodes(405) in the non-native network(404) having defined a connection to a common virtual routing node are said to comprise a connection network(406). The general model that is used by the gateway is that all LUs or nodes(405) in the non-native network are made to look as if they reside in a node for which the gateway(403) is the serving network node. The control point (CP) name of this node is a fictitious one. In the current implementation, when the non-native network is IP, this fictitious CP name is stored as address 127.0.0.3 in the reverse address table of the domain name server. The fictitious name for the connection network is also stored in the reverse address table at address 127.0.0.4. When reporting the location of an independent LU on the non-native network, each gateway will report that the LU is on the fictitious node and connected through the gateway. As would be evident to one skilled in the art, any unused or invalid address could be used to store these variables.
As shown in FIG. 5, when there are multiple unconnected non-native networks(501) connected through one or more gateways(502) to an APPN network(503), a unique CP name and Connection Network are defined for each non-native network(501) whether they use one or multiple gateways. In FIG. 5, CP1(520) is defined as the fictitious control point for one non-native network, CP2(521) is defined as the fictitious control point for a second non-native network, and CP3(522) is defined as the fictitious control point for the third non-native network. A default fictitious CP name of $ANYNET.$GWCP is provided. However, only one non-native network that is accessible from a SNA network is allowed to use the default. When a non-default name is to be used, it is learned by the gateway(s)(502) using MPTN address mapping functions. For example, when the non-native network is IP, and when using a domain name server for address mapping, the CP name is mapped to the IP address 127.0.0.3 in the reverse address table. This is an arbitrarily chosen invalid IP address and one skilled in the art will realize that any otherwise unused address could be chosen.
Another version of this invention is the use of multiple parallel gateways to connect a single native network to a single non-native network. This is shown in FIG. 5A. With this configuration, each of the parallel gateways (552) connecting the native network (553) to the non-native network (551) uses a single unique fictitious CP name. This is done to maintain connectivity in case one of the gateways (552) fails. As long as at least one of the gateways between the native network (553) and the non-native network (551) remains operative, the LUs will be able to be located and information will be able to flow between the networks.
There are two different methods the MPTN gateway uses to respond to a request for an LU that resides on the non-native network (which will be further described within), one for independent logical units (LUs) being on fictitious end nodes and one for dependent LUs being on fictitious connection networks. For independent LUs, when a LOCATE arrives at the gateway, it acts as a standard network node and checks with all of its end nodes for the requested LU. In this sense it treats the entire MPTN network to which it is attached as another end node. It uses the MPTN directory mechanisms to determine whether this LU is known. If it is, the gateway returns a positive LOCATE reply indicating that the LU is on a fictitious end node where all LUs on the IP network appear to reside. This provides support for the movement of LUs, also referred to as dynamic support.
MPTN also supports dependent LUs across a non-native network through the use of Dependent LU Server and Dependent LU Requester (DLUS/DLUR) which is further described in FIG. 6. In the DLUS/DLUR model, control sessions between the mainframe and the DLUR are carried on independent LU sessions. When a request for a connection to a dependent LU is received, the DLUS replies that it owns the LU.
FIG. 8 demonstrates prior art APPN route computation. In APPN, all network nodes share the topology of the network in order to compute routes. As networks grow, this topology can become too large for each network to maintain. In such a case, a border node (807) is added into the network to isolate portions of the topology (805 & 806). For routes that cross border nodes, the route must be computed in pieces, from the origin to a border node, from one border node to another or from a border node to a destination.
When the DLUS and DLUR are not separated by a border node (801 & 802), the connectivity information that is sent on the DLUR-DLUS control session is used to compute the route. When the two are separated by a border node (803 & 804), the additional connectivity information is of no use to the DLUS component as it has no knowledge of the network topology to which the DLUR is connected. In this case, when the connection is to be established, the border node will compute the route by sending out a LOCATE with the Owning CP Respond Indicator (OCR) bit set.
For dependent LUs on an MPTN network, the DLUR on a non-native network indicates that it is on the fictitious connection network. A standard APPN network node will handle this as it does any other request by computing the preferred route based on the topology of the SNA network and the additional hop through the fictitious connection network to the end node.
As shown in FIG. 6, a situation of interest for this invention is when the DLUS(601) is in the SNA (native) network(602) and the DLUR(606) is in the non-native network(607) connected via the gateway (604). At set-up time for this configuration, the dependent LUs associate themselves with the fictitious Connection Network name that is stored at location 127.0.0.4 of the reverse address table. The gateway (604) also associates itself with the fictitious connection network. When a LOCATE for a dependent LU arrives at the gateway(604) from a requesting LU in the native network with the OCR bit off, the gateway will not reply to the request, as it is not the owner. Only the DLUS will reply. The dependent LU Server has an LU 6.2 session, also called a control session(603), with the DLUR (606) in the non-native network. Information passed on this session allows the requesting LU (615), to locate the target LU(610) via the DLUS(604). Once the target LU is located, a BIND is sent from the LU in the SNA(615) to the LU in the non-native network(610) via the gateway(604) and through the fictitious connection network(608).
There is one exception to the prior paragraph, when a request comes through a border node and the OCR bit is on (This bit indicates that a route is being computed rather than ownership being sought), the gateway will return a LOCATE FOUND. Recognizing whether to respond to a LOCATE requires that the gateway recognize whether the LU is independent or dependent. This is made possible by a new address mapping function introduced with this invention. The general MPTN mapping function returns user-specific data. For LUs, this data indicates whether the LU is dependent or independent. When the non-native network is IP and domain name system (DNS) is used for address mapping between SNA and IP, each dependent LU that can be reached through an SNA over TCP/IP gateway must be mapped twice in the DNS. One entry maps the dependent LU to its IP address, and the other entry maps the dependent LU to the invalid IP address 127.0.0.2. The mapping of the destination LU to 127.0.0.2 identifies it as a dependent LU. All dependent LUs are mapped to this address. As would be evident to one skilled in the art, any invalid or otherwise unused address could be used to store this information in alternative implementations, so long as it is done consistently.
Because the DLUS is a standard APPN component, it must be provided the information of how to reach the non-native LU in standard APPN fashion. All nodes on the non-native network with DLUR, and all gateways, report that they are on the fictitious connection network(608) when the DLUS is not separated from the DLUR through a border node. Across the DLUS/DLUR control session(603), the DLUR(606) passes connectivity information that indicates that it is accessible through the fictitious connection network(608). Because the gateway has reported this connection network(608) in the topology of the APPN network, normal route computation provides the preferred route to the dependent LU. As is the case with the fictitious CP name, if there are multiple disconnected non-native networks, the fictitious connection network name must be unique for each non-native network. As with the fictitious CP name, the name of the connection network is learned from the address mapping function or, when the non-native network is IP, through the use of the reverse address table definitions of the IP domain name system. In the case of parallel gateways, the procedure as described in FIG. 7 is followed for each gateway. Multiple positive replies will be received for the same LU, but they will all report that they are on the same connection network, located on the same end node.
When the DLUS(ie. 804) and DLUR(ie. 801) are separated by a border node(807), the route computation will be made by the border node. Like the DLUS component, the border node must be provided the information of how to reach the non-native LU in the standard APPN manner. All gateways report that they are on the fictitious connection network and the LOCATE with OCR indicator on is replied to with the information that the EN is on the fictitious connection network. With this information, normal route computation provides the preferred route to the non-native dependent LU.
FIG. 7 depicts the information flow for issuing a LOCATE from an APPN network. The LOCATE is issued from an APPN node (701). When the MPTN gateway receives the LOCATE it checks with the address mapping mechanism (703) to determine if the desired LU is on the non-native network. If it is not on the non-native network, then a negative response is returned to the LOCATE (705). If the LU is located on the non-native network, next it must be determined whether the LU is a dependent LU(707) again using the MPTN addressing mapping function. If it is not, a positive response to the LOCATE is returned(709) indicating that the LU was found on the fictitious CP with connectivity to the gateway. If the LU is dependent, then the OCR bit must be checked(711) to determine whether it is on. If it is not, then a negative response is returned for the LOCATE(713). If the OCR bit is on, then a positive response is returned to the LOCATE(715) including the fictitious CP name and connection network connectivity which indicates that the LU was found on the non-native node.
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In order to more fully support the need to interconnect dissimilar networks, methods and apparatus are set forth which allow a transport gateway between a native (SNA/APPN) network and a mixed or non-native network to preserve the dynamic functions of the native network. The functions of fully dynamic directory and route selection are supported, in addition to the ability to use parallel gateways when connecting a native network to a mixed network. The ability to route information through a gateway from a dependent LU requester in a non-native network to a dependent LU server in a SNA/APPN network is also demonstrated. This allows concatenation of native and non-native networks while maintaining the addressability and accessibility of the native network.
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REFERENCE TO CO-PENDING APPLICATION(S)
The present application is a continuation of U.S. Provisional Patent Application Ser. No. 60/547,642, filed Feb. 23, 2004, the entire disclosure of which is hereby incorporated by reference.
TECHNICAL FIELD
The present invention relates to medical devices, and more particularly, a server for medical devices such as pumps.
BACKGROUND
Medical pumps are an important part of providing care to a patient. They are used for a variety of different therapies such as pain relief, nutrition, chemotherapy, and insulin. Each one of these therapies typically requires a different program for controlling operation of the pump. Additionally, each program typically requires different operating parameters for each patient depending on a variety of factors such as the substance prescribed for delivery, the prescribed dosage, and physical attributes of the patient.
Additionally, medical clinics, hospitals, or other facilities need to manage all of their medical pumps. Managing the pumps requires updating programs, loading the appropriate program into the pump depending on the prescribed therapy, loading and tracking operating parameters into the pump, and tracking performance of the pump.
All of these issues present a tremendous amount of information related to the patient and the pump that needs to be tracked, managed, and coordinated. Examples of such information includes patient records, standing orders, prescriptions, and the like. These issues also present a great deal of functionality that must be executed, managed, and coordinated. Examples include programming pumps, tracking pump inventory, downloading pump software and upgrades, monitoring and relaying alarm conditions, and tracking pump history logs.
Additionally, when an institution has a variety of different networked devices through which a caregiver would like to communicate with the pumps, each one needs to be individually programmed to communicate with the pumps. This programming drives up the cost and time required to network programmable devices and pumps. The cost and required time is even greater when the institution has a variety of different pumps and medical devices because the networked devices would require separate programming to communicate with each different make and model of medical pump or other medical device.
SUMMARY
In general terms, the present invention is directed to communicating with a medical device such as a pump.
One aspect of the present invention is a server for communicating with a medical device. The server comprises a web browser process for communicating with a remote device and a pump interface process for communicating with a medical device.
Another aspect of the present invention is a medical device. The medical device comprises memory configured to store data and a programmable circuit in electrical communication with the memory. The programmable circuit is programmed with a web server for communicating data with a remote device.
Another aspect of the invention is a server for communicating with a medical device. The server comprises memory for storing data and a programmable circuit in electrical communication with the memory. The programmable circuit programmed with an interface for communicating with a medical device.
One aspect of the invention set forth herein is a pump server that provides all communication with a set of medical devices such as a medical pump. Other networked devices that exchange information (e.g., commands, instructions, or other data) with the networked medical devices communicate that information through the pump server.
Another aspect of the invention is the use of a web server to communicate with a medical device such as a medical pump. The use of a web server in this manner may permit a remote device to communicate with a medical device such as a medical pump without the use of a pump server and without the need for a special program or other interface loaded on the remote device.
DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates a networked system that includes a medical device server and embodying the present invention.
FIG. 2 illustrates an alternative embodiment of the networked system illustrated in FIG. 1 .
FIG. 3 illustrates an alternative embodiment of the networked system illustrated in FIG. 1 .
FIG. 4 illustrates software architecture for the pump server illustrated in FIG. 1 .
FIG. 5 illustrates an alternative embodiment of the networked system illustrated in FIG. 1 .
FIG. 6 illustrates an alternative embodiment of the networked system illustrated in FIG. 1 .
FIG. 7 illustrates an alternative embodiment of the networked system illustrated in FIG. 1 .
DETAILED DESCRIPTION
Various embodiments of the present invention will be described in detail with reference to the drawings, wherein like reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the invention, which is limited only by the scope of the claims attached hereto. Additionally, any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the claimed invention. There are alternative embodiments for all of the structures and methods disclosed herein regardless of whether specific alternatives are set forth.
Referring to FIG. 1 , one possible embodiment of a pump server system 10 includes a pump server 100 , a point of care (POC) server 102 , one or more programmable devices 104 , and one or more medical pumps 106 . The pump server 100 and the POC server 102 are connected to a computer network 108 . Additionally, the pump server system 10 includes communication/output devices such as a mobile phone 110 , a pager 112 , a fax machine 114 , a printer 116 , and a modem 118 . The server 100 is called a “pump server” as an exemplary embodiment for purposes of explanation. The server 100 can be used to communicate with any type of medical device, including medical devices other than medical pumps.
The network 108 can be any appropriate network capable of transporting data from one device to another, including a wired network such as an Ethernet network, a wireless network such as an 802.11a/b/g or other wifi network. Additionally, the network 108 can be any type of data network such as an internal network, the Internet, or an Intranet.
The pump server 100 and the POC server 102 divide and coordinate tasks for managing information, executing various functions, and communicating with various devices within the pump server system 10 . The pump server 100 and the POC server 102 can be any programmable device that stores information and performs critical functions for the storage of that information. In various embodiments, the server also might be programmed to execute various functions related to the operation and monitoring of medical pumps 106 . A structure that includes a separate pump server 100 and POC server 102 has several advantages. For example, the medical pumps 106 need to be programmed and otherwise configured to interface with only one device—the pump server 100 . Another advantage for institutions that utilize medical pumps 106 from different manufactures or even different pumps from the same manufacturer is that various components of networked hardware do not need to be programmed with all of the different pumps—only the pump server 100 needs to be programmed to talk directly with the medical pumps 106 . As a result, it is simpler and more cost effective for a caregiver institution to add and remove various medical pumps 106 from its inventory of equipment.
The pump server 100 communicates directly with the pumps 106 and with the POC server 102 . The POC server then communicates with all of the other devices. In this exemplary embodiment, the POC server 102 instructs the pump server 100 to retrieve data from any selected medical pump 106 in communication with the network 108 ; instructs the pump server 100 to send data to any selected medical pump 106 in communication with the network 108 ; and requests data from the pump server 100 regarding any selected medical pump 106 regardless of whether the selected medical pump 106 is in communication with the network 108 .
Although the exemplary embodiment illustrates an architecture in which the programmable devices 104 communicate through a POC server 102 , other embodiments are possible. In various embodiments, programmable devices 104 and systems other than the POC server 102 might communicate directly with the pump server 100 . Examples, include programmable devices in a biomedical engineering (biomed) department of a caregiver institution. Such biomed programmable devices might communicate with the medical pumps 106 directly through the pump server 100 for a variety of different reasons such as tracking pump performance, running pump diagnostics, or downloading pump error logs. Other systems or other departments within an institution might communicate directly with the pump server 100 as well. Other examples include a caregiver institution's pain service, which monitors and treats patient's pain, pharmacies, and computerized physician order entry (CPOE) systems, which physicians use to enter prescriptions.
The pump server stores a variety of data, executes a variety of functions, and communicates directly with the medical pumps 106 and the POC server 102 through the network 108 . In an exemplary embodiment, the pump server 100 requests and receives information (e.g., I.D. of current program and version loaded in the medical pump 106 , history log, alarm status, battery state, and biomed status such as odometers, time until next scheduled maintenance, etc.) from the medical pumps 106 on the network 108 ; receives unsolicited messages (e.g., alarms, manual pump program changes, pre-programmed periodic updates, etc.) from the medical pumps 106 ; maintains a database of information retrieved from or sent to the medical pumps 106 ; provides a web browser interface to the medical pumps 106 , which allows a caregiver to perform a variety of tasks from networked programmable devices 104 including remotely viewing the I.D. and version of the program currently loaded on a medical pumps 106 , viewing the status of a medical pumps 106 , and in one possible embodiment, allowing a caregiver to change various programming parameters such as setup and titration; providing pump alert functionality such as sending emails, pages, or notices to client applications upon the occurrence of certain pump events (e.g., alarms, programming changes, patient tampering, ratio of dose attempts to doses given too high indicating the patient pain is not adequately controlled, and programming that exceeds soft limits programmed into the medical pump 106 ); sending messages to the display on the medical pumps 106 (e.g., when alarms are acknowledged, display message to patient stating that nurse is on the way); sending voice messages to the medical pumps 106 (e.g., when alarms are acknowledged, tell patient that nurse is on the way); sending messages (e.g., medical pump 106 needs reservoir changed at approximately 8:00 pm) to the printer 116 or the fax 114 at a nursing station; providing information (e.g., electronic copy of manuals, troubleshooting guides, patient guides, etc.) about the medical pumps 106 to a caregiver using programmable devices 104 ; verifying the software revision for programs loaded on the medical pumps 106 and downloading new or updated software to the medical pumps 106 ; and controlling pump and document results during biomed testing processes.
In another possible embodiment, the pump server 100 implements Standing Order protocols. An example of implementing Standing Order protocols is described in U.S. Provisional Patent Application Ser. No. 60/526,810, which was filed on Dec. 4, 2003 and entitled “PROGRAMMING MEDICAL PUMPS WITH ELECTRONIC STANDING ORDER TEMPLATE,” the disclosure of which is hereby incorporated by reference. In this embodiment, the pump server 100 enables the creation, storage, and management of a database of Standing Orders; processes requests from the medical pumps 106 to send it an index of standing order protocols or specific standing orders; sends Standard Orders-based protocols to the medical pumps 106 ; and sends updated library of Standing Orders-based protocols to the medical pumps 106 ;
Additionally, the pump server 100 is programmed to provide notification to a caregiver about when it is time to check on a patient. For example, the pump server 100 might generate a notification to check on a patient or check fluid levels every two hours. Notification can be through any suitable means such as a pop-up window on a programmable device, a pager, a cell phone, a printer, a fax, or the like.
In yet another possible embodiment, when a medical pump 106 is programmed, the pump server 100 disables the medical pump 106 until its programmed parameters (e.g., delivery protocol) is reviewed by a caregiver at the point of care. In one possible programming procedure as illustrated in FIG. 8 , when a medical pump 106 is programmed, the pump server 100 sends a disable signal or command to the medical pump 104 at operation 140 . Pumping operation of the medical pump is then disabled. The caregiver programs the medical pump 106 while it is disabled at operation 142 . After programming is complete, the caregiver reviews the programmed settings at operation 144 . In one possible embodiment, the medical pump 106 automatically indexes through the programmed settings. In another possible embodiment, the caregiver must press a button or activate a menu item to acknowledge that the programmed settings were reviewed and accurate. After the programmed settings are reviewed, the medical pump 106 sends a signal to the pump server 100 at operation 146 , and the pump server 100 replies to the medical pump 106 with an enable signal on command at operation 148 . The medical pump can then pump fluid as programmed.
The pump server 100 can have different locations depending on the desired embodiment. In the exemplary embodiment, the pump server 100 is located at the caregiver's facilities. In another possible embodiment, the pump server 100 is located at a third party, such as the pump manufacturer or other third-party administrator.
The medical pump 106 can be any medical pump configured for infusing a fluid into a patient. It includes a data port configured for communicating with the network 108 . Examples of possible data ports for the medical pump 106 includes a wireless data card for transmitting according to the 802.11 a/b/g, Bluetooth, or other appropriate wireless networking protocol, USB data ports, firewire data ports, RS-232 data ports, an infrared data port, a modem, or any other data port capable of communicating with the network 108 or directly with the pump server 100 . In the operation of one possible embodiment, the medical pump 106 talks directly and only to the pump server 100 via the network 108 . Accordingly, the medical pump 106 requires no knowledge or programming for interfacing with and talking to the POC server 102 or other devices in the pump server system 10 .
In one possible embodiment, the programmable devices 104 communicate with the POC server 102 via the network 108 and do not communicate directly with the pump server 100 of the medical pumps 106 . The programmable devices can include any type of computing platform capable of data input and interfacing with the network 108 . In various embodiments, the programmable devices 104 are mounted in a convenient location such as a hospital room, nurse's station, or other location convenient for the caregiver. Additionally, another embodiment includes a desk-top computer on a cart that can be conveniently rolled from one location to another. Examples of various programmable devices 104 include a pen-based computer such as a Tablet PC, a lap-top computer, a desk-top computer, or a hand-held computing platform such as a personal digital assistant (PDA). Additionally, one possible embodiment of the PDA can include a bar code reader or radio frequency ID (RFID) reader capable of scanning a barcode or RFID tag, respectively, on a medical pump 106 and then communicating this information to the POC server 102 .
FIG. 2 illustrates an alternative embodiment in which the programmable devices 104 and the communication/output devices such as a mobile phone 110 , a pager 112 , a fax machine 114 , a printer 116 , and a modem 118 communicate directly with the pump server 100 without a POC server 102 .
FIG. 3 illustrates another possible embodiment that includes additional point of care medical devices 120 such as a pulse oximeter. As with the medical pumps 106 , the other medical devices 120 communicate directly with the pump server 100 over the network 108 rather than communicating with other networked devices. In this embodiment, the pump server 100 is programmed to selectively associate various medical devices 120 and/or medical pumps 106 using a set of programmed rules that a caregiver may define. For example, the pump server 100 can be programmed to start or stop operation of a medical pump 106 based on data received from another medical device 120 (e.g., if respiration drops below a predefined limit, the pump server 100 instructs the medical pump 106 to stop pumping and generates an alarm). The pump server 100 also selectively provides a virtual connection between the various medical pumps 106 and medical devices. As a result, the medical devices 120 and medical pumps 106 do not need to be programmed to talk directly with each other. Again, because each medical device does not need to be individually programmed, this functionality makes it easier and less costly to add various devices to the inventory of equipment. As with medical pumps 106 , the pump server 100 is programmed to generate and/or communicate various alerts for the medical devices 120 via pages, e-mail, faxes, printouts, voice messages, etc.
FIG. 4 illustrates one possible embodiment of the architecture for the pump server 100 . In this embodiment, the pump server 100 includes an interface 122 for communicating with the POC server 102 and a Web server 124 , which allows other devices such as the programmable devices 104 to remotely interface with the medical pumps 106 or other medical devices 120 . The web server 124 allows the other devices to communicate with the pump server 100 using standard text files without the need of loading special software such as interfaces, communications software or other programs into the remote or other devices. A remote device includes any device that is a separate and distinct device from the medical device 120 . Examples of standard text files include files formed according to a markup language such as a hypertext markup language (HTML), standard generalized markup language (SGML), and extensible markup language (XML).
The pump server 100 is also programmed with various code and logic 126 for executing various tasks and functions described herein and an information manager 128 for storing and retrieving pump information in a database 130 . A pump interface manager 132 provides an interface for the medical pumps 106 . In various embodiments, the pump interface driver 134 for the medical pump 106 itself is programmed into the pump server 100 , or in an alternative embodiment, the pump interface driver 136 is either programmed in the medical pump 106 itself or in a programmable module attached to the medical pump 106 . Additionally, one possible embodiment allows the medical pump 106 to have a direct connection 138 to the pump server 100 .
FIG. 5 illustrates a possible embodiment in which a programmable device 104 a is programmed to function as a pump server. In this embodiment, the programmable device 104 a performs the same functions as the pump server 100 as described herein. Additionally, the programmable device 104 a can request and receive information from medical pumps 106 that are remotely located at a location such as a patient home or a medical pump 106 that is not otherwise provided with a direct network connection. The connection between the programmable device 104 a and the medical pump 106 is through a dialup connection using a modem 118 . The medical pump 106 can connect to the modem 118 through a wired or wireless connection such as a connection operating according to the Bluetooth protocol. Either the programmable device 104 a or the medical pump 106 can initiate a data connection between the two. Accordingly, the programmable device 104 a can request and receive information about any medical pump 106 or other medical device 120 that is not on the network 108 as otherwise described herein. Additionally, the medical pump 106 or other medical device 120 can transmit to the programmable device 104 a unsolicited messages such as alarms, manual pump changes, pre-programmed period updates, etc.
FIG. 6 illustrates the possible embodiment in which the programmable devices 104 communicate directly with the pump server 100 through a web server programmed in the pump server. In this embodiment, any networked programmable device 104 with a web browser can communicate with the medical pump 106 or any other medical device. An advantage of this embodiment is that a caregiver can connect to the medical pump with wireless and remote devices to check the status of the medical pump 106 or other any medical device when not physically with the patient or located at a site where there is a networked programmable device 104 . Another advantage is that the programmable devices 104 do not need to be individually programmed to communicate with the pump server 100 .
FIG. 7 illustrates another possible embodiment in which the pump 106 or other medical device 120 is itself programmed with a web server, which allows the medical device 120 to communicate with the pump server 100 or directly with other or remote devices using standard text files without the need of loading special software such as interfaces, communications software, or other programs into the other devices. Again, examples of standard text files include files formed according to a markup language such as a hypertext markup language (HTML), standard generalized markup language (SGML), and eXtensible markup language (XML).
An advantage of this embodiment is that a caregiver can connect to the medical pump with wireless and remote devices, from any distance, to check the status of the medical pump 106 or other medical device 120 when not physically with the patient or located at a site where there is a networked programmable device 104 . Additionally, two programmable devices 104 can be simultaneously connected to the same medical pump 106 or other medical device 120 for training and troubleshooting. Additionally, a medical pump 106 or other programmable device 120 can be utilized without a display and without a keyboard. Another advantage is that because the web server provides an interface using a standardized protocol to communicate information such as serving up documents, files, scripts, and other information, no further program or control application need be written for the programmable devices 104 .
The various embodiments described above are provided by way of illustration only and should not be construed to limit the invention. Those skilled in the art will readily recognize various modifications and changes that may be made to the present invention without following the example embodiments and applications illustrated and described herein, and without departing from the true spirit and scope of the present invention, which is set forth in the following claims.
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One aspect of the present invention is a server for communicating with a medical device. The server comprises a web browser process for communicating with a remote device and a pump interface process for communicating with a medical device. Another aspect of the present invention is a medical device. The medical device comprises memory configured to store data and a programmable circuit in electrical communication with the memory. The programmable circuit is programmed with a web server for communicating data with a remote device. Another aspect of the invention is a server for communicating with a medical device. The server comprises memory for storing data and a programmable circuit in electrical communication with the memory. The programmable circuit programmed with an interface for communicating with a medical device.
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FIELD OF THE INVENTION
[0001] The method, and system of our invention relate to client server systems, and especially to development tools, methods and systems that build upon functions, routines, subroutines, subroutine calls, or object oriented programming.
BACKGROUND OF THE INVENTION
[0002] Programming paradigms built upon such concepts as functions and function calls, subroutines and subroutines and subroutine calls, global variables and local variables, and object orientation are characterized by such features as “reusable code”, and “inheritance.”
[0003] In older languages, such as FORTRAN and BASIC, reusability and inheritance were obtained through crafting of functions, routines, and subroutines that were called through global variables in a main program. Subsequently, this has evolved into object oriented programming in such languages as C++ and Java and is built upon a programming paradigm foundation of objects, functions, and class data types. An “object” is a variable that has “functions” associated with it. These functions are called “member functions.” A “class” is a data type whose variable are “objects.” The object's class, that is, the type of the object, determines which member functions the object has.
[0004] In a modern, object oriented programming language, such as C++ or Java, the mechanism to create objects and member functions is a “class.” Classes can support “information hiding” which is a critical part of modern program design. In “information hiding”, one programming team may design, develop, and implement a class, function, routine, or subroutine while another programming team may use the new class, function, routine, or subroutine. It is not necessary for the programmers who use the class, function, routine, or subroutine to know how it is implemented.
[0005] To be noted is that “object oriented programming” uses the terms “public” and “private” while the older techniques use the terms “global” and “local” for the domain of variables.
[0006] One aspect of both paradigms is “code reusability,” whether implicitly by the subroutine or function calls of FORTRAN and the like or explicitly by declaring variables in C++ or JAVA.
[0007] There is an especially strong need for a development environment, including development tools, and either functions, routines, and subroutines with global and local variables, or base classes, to allow end users to develop business applications customized to their needs and derived from the supplied functions, routines, and subroutines with global and local variables, or base classes.
SUMMARY OF THE INVENTION
[0008] The method and system of our invention is an application development environment. It is designed to meet the customization needs of demanding sales, marketing, and customer service information system deployments.
[0009] One embodiment of our invention is a system for customizing an application program. The system includes a plurality of reusable modules (characterized as “base” modules in object oriented programming literature and as functions, routines and subroutines in other programming paradigms) for incorporation into end-user derived modules (characterized as “derived” in object oriented programming literature). At least one of the reusable modules has a set of variables accessible by an end-user (“public” in object oriented programming and “global” in conventional programming) and a set of variables not accessible by the end-user (“private” in object oriented programming and “local” in conventional programming). When a derived module incorporates a reusable module, the derived module inherits attributes of the reusable module.
[0010] A further aspect of our invention is the provision of a graphical editor for modifying and managing software modules, and an object visualization editor for graphically representing relationships between modules and variables within modules. A further aspect of our invention is the provision of one or more applet designer modules for doing one or more of modifying and extending lists, forms, dialogs, and chart user interfaces. The system can also include one or more view designer modules for visually modifying existing views, as well as wizard modules for creating end user created modules. In one embodiment of our invention at least one of the wizard modules provides an enumeration of required end-user entries for an end user module, this being in response to an end-user entry of the type of end-user created module to be created.
[0011] A directory or module repository manager may be provided to allow only one end-user to modify a module at one time.
[0012] Depending on the underlying source code, the system of the invention may include a compiler or translator for incremental compilation or translation of end user created modules.
[0013] In a preferred embodiment the system of our invention includes one or more interfaces for accessing data and rules from external applications.
[0014] In still another embodiment, especially useful for spreadsheet or database applications, the system includes database extension modules for extending a database and to capture data from new fields in one or more of application screens, and external sources. In a particularly preferred embodiment, the database extension modules may contain modules for triggering updates to client applications that reflect and incorporate new database extensions, and for reflecting new columns in existing end user created modules.
[0015] A further aspect of the system of our invention is the provision of modules for notification of conflicts between new end user created modules and existing modules. These modules may be incorporated in the translator or compiler, or in an index to the repository.
[0016] A further aspect of our invention is a method having for customizing an application program. This method works with the system of the invention, summarized above, and includes the steps of modifying and managing the end user created modules through a graphical editor; and graphically representing relationships between modules and variables within modules.
[0017] A further aspect of the method of our invention is doing one or more of modifying and extending lists, forms, dialogs, and chart user interfaces. Another aspect of our invention is visually modifying existing views.
[0018] Another aspect of the method of our invention is creating end user created modules using wizard modules. This may include the additional step of providing an enumeration of required end-user entries for an end user created module in response to an end-user entry of the type of end-user derived module to be created.
[0019] Yet another aspect of our invention is storing derived (that is, end user created) modules in a derived module repository manager. This is to allow only one end-user to modify a software module at one time.
[0020] A still further aspect of our invention is incrementally compiling a derived module.
[0021] Another aspect of our invention is accessing data and rules from external software applications through interfaces.
[0022] Another aspect of our invention is extending or scaling a database, that is, modifying its metadata and/or schema, to include new fields and capturing data from new fields in one or more of application screens, and external sources. A further aspect of this is triggering updates to client applications that reflect and incorporate new database extension, as well as reflecting new columns in existing end user created modules.
[0023] A further aspect of our invention is providing notification of conflicts between end user created modules and existing modules.
[0024] The software development method and system of our invention utilizes a suite of tools that serve as the bases for “reusability”, whether implicitly or explicitly. This enables developers to rapidly configure all aspects of the underlying application software, including the look-and-feel, behavior, and workflow, without modifying application source code, SQL, or base classes. The sophisticated repository management capabilities of the method and system of our invention allows teams of developers work efficiently on configuring applications.
[0025] The suite of conventional and object oriented development tools includes a business object designer; a Microsoft Visual Basic-like scripting language, a set of business object interfaces, a Database Extension Designer, and an Application Upgrader.
[0026] The application upgrader provides an automated process to upgrade the customizations to future product releases thus protecting the investment in customization. The ease, comprehensiveness, scalability, and upgradeability of the customization process help reduce the total lifecycle cost of customizing enterprise applications.
[0027] To be noted is the difference between declarative programming and procedural programming. Declarative programming allows developers to control the behavior of a class by merely setting attribute values, that is, set the property color=black, instead of writing a line of code to set the color the color to black. This may be accomplished under either paradigm.
[0028] Also to be noted is that the meta-data repository that contains configuration and customization information can serve to separate this configuration and customization data from the application source code. By this expedient, developers and end-users can configure these objects in an intuitive and easy manner that is less prone to error.
THE FIGURES
[0029] The method and system of our invention may be understood by reference to the Figures appended hereto.
[0030] [0030]FIG. 1 illustrates a screen shot of a Business Component definition.
[0031] [0031]FIG. 2 illustrates a screen shot of details of a Business Component definition.
[0032] [0032]FIG. 3 illustrates a screen shot of features of the Applet Designer.
[0033] [0033]FIG. 4 illustrates a screen shot of features of the view.
[0034] [0034]FIG. 5 illustrates a screen shot of aspects of the editor and debugger.
[0035] [0035]FIG. 6 illustrates a screen shot of the components of the application upgrader.
DETAILED DESCRIPTION OF THE INVENTION
[0036] Using the method and system of our invention, teams of developers can work together cooperatively, to rapidly customize all aspects of software applications without modifying application source code, SQL, or vendor supplied base classes (referred to herein as “business objects”). This approach to customization results in dramatically lower development and maintenance costs, and provides seamless upward compatibility with future product releases.
[0037] The components of the development tool include:
[0038] 1. A business object designer
[0039] 2. A language, such as Microsoft Visual Basic, Microsoft Visual C++, Microsoft Visual J++ or the like.
[0040] 3. Business object interfaces
[0041] 4. A Database Extension Designer
[0042] 5. An Application Upgrader
Business Object Designer
[0043] The business object designer gives developers the ability to quickly and easily customize software applications. It includes a business object explorer. This is a graphical editing tool for modifying and managing object definitions. It includes a hierarchical object explorer that allows developers to browse the various object types, an object list editor viewing and editing object definitions, and a properties window for editing object property values. The business object explorer also includes a Windows-style “Find” capability that allows developers to quickly locate objects in the repository.
Object Visualization Views
[0044] The Object Visualization Views are a set of graphical representations of the relationships between the various object definitions in the business object repository that help simplify the configuration process. A typical application configuration contains thousands of objects. Developers can use these views to understand and navigate through the object hierarchies. Then, using the editing tools, they can modify the properties of these objects. These views help assess the impact of these modifications, and track down configuration errors. The visualization views can be printed and used as a valuable reference during configuration. FIG. 1 illustrates a screen shot of a Business Component definition, 1 , with an objects field, 11 , a field indicating the source and type of components, 12 , and a field indicating the actions to be taken with respect to a component, 13 , while FIG. 2 illustrates a screen shot of the details of a Business Component definition with the account object explorer, 21 , the account external products, 22 , and the object attributes, 23 . It depicts the various Fields in the Business Component, their types, and points to their respective sources either Columns in underlying database tables, or Fields in other Business Components. A developer can further introspect the properties of an object in this view, by using the Properties window. The other Visualization Views work similarly. The Hierarchy View describes the object hierarchy as it relates to the selected object i.e. the Objects used by the selected Object and the Objects that use it. For example, the Hierarchy View for a View Object will show the Applets contained in that View, the Business Components on which each of these Applets are based, the Screens and Applications in which this View appears.
Applet Designer
[0045] The Applet Designer module is an intuitive drag-and-drop visual programming interface for modifying and extending list, form, dialog, and chart user interface objects (Applets). These objects can be populated with standard Windows controls, including buttons, combo boxes, check boxes, labels, and text fields, as well as ActiveX controls. The Applet Designer of the method and system of our invention leverages the familiarity of developers with popular graphical application development tools such as Microsoft Visual Basic. Features of the Applet Designer are illustrated in FIG. 3. These include the object explorer, 31 , and the applet being designed or modified, 32 . An account information form is being designed in block 32 .
[0046] The developer can add, delete, and modify the properties of the controls. The controls can be configured using the Properties Window. For example, a control can be associated with a Field in the underlying Business Component. This is accomplished by setting the Field attribute of the Control to one of the Fields in the Business Component. The choice of Fields is limited to those that belong to the Business Component that the Applet is based on. The behavior of controls can be scripted using the Visual Basic or other script editor. The Applet Designer also helps ensure visually accurate and correctly translated configurations by providing a design-time preview of the Applet on various screen resolutions, and under different language settings. In this mode, the Applet designer simulates the Applet being viewed under the specified settings and allows the developer to quickly detect any presentation errors such as truncation or overlapping controls. Features of the Applet Designer are illustrated in FIG. 3.
View Designer
[0047] The view designer module of the development tool method and system of our invention allows developers to visually modify existing views and construct new views by simply dragging and dropping the desired Applets onto the view canvas.
[0048] There is no additional specification or code required to define the relationships between the Applets. Most other application customization tools require developers to write significant amounts of code to achieve this same functionality. In the prior art, this code had to be replicated for each and every screen in the application. This was inefficient and error-prone. Features of the view designer 4 are illustrated in FIG. 4. To create a View based on a specific Business Object, the developer is presented with a blank canvas with eight sectors and a window 41 containing the list of Applets that can be included in the View (based on the Business Object of the View). The desired Applets can then be simply dragged from the Applets window and dropped on the View canvas in the desired sector. The Applets may be resized at this point, if necessary. The underlying Business Components, and their context within the Business Object determine the relationships between the Applets in the View. Hence, these relationships do not need to be specified again in the definition of the View. They are simply re-used.
Menu Designer
[0049] The menu designer module of the development tool method and system of our invention allows developers to customize and extend Siebel menu structures using a visual metaphor. A menu can be created by adding menu items, defining the command to be executed when the menu is clicked, and specifying an accelerator key for easy navigation.
Object Wizards
[0050] The development tool method and system of our invention provides a set of Wizards to assist developers in the creation of new objects in the underlying repository. Examples of Wizards include a Form Applet Wizard, Chart Applet Wizard, List Applet Wizard, and Business Component Wizard. The user clicks on the type of the new object he or she wants to create, and the Wizard guides them through the entry of the properties needed for that type of object.
[0051] Typically, the graphical user interface guides the user through the various steps of creating an applet, such as selecting the business component that it is based on, the dimensions of the applet, the fields to be included, the buttons that appear in the applet, and the like. Wherever possible, the list of choices are restricted to only those that are applicable—Fields in the underlying Business Component, Projects that have been locked by the developer, etc. Once the developer has gone through the various screens in a wizard, a new Object is created based on the attributes specified. A default layout is generated for the type of Object being created. For example, for a Form Applet, Text box and Check box controls are created for each Business Component Field that is to be included in the Applet, depending on the data type of Field. Labels are also created right next to the Text boxes and Check boxes. All these controls are laid out in an aesthetically pleasing columnar layout.
Business Object Repository Manager
[0052] The business object repository manager of our invention provides application developers with an efficient multi-user development environment that includes access to check-in/check-out functionality and version control. In a typical development environment, there is a server repository that contains the master application definition. Each developer on the team has a local repository that the development tools method and system of our invention connects to. The various object definitions in the business object repository are grouped into Projects. Developers lock and check out projects from the server repository onto their local repositories in order to make changes to the object definitions. If another developer tries to check out the same Project, he/she is unable to do so, and is informed that the Project is locked. This prevents other developers on the team from modifying the same project. Once the developer has made the changes and tested them, the project can be checked into the server repository. Before checking in a project, the developer can review the changes that have been made thereby minimizing check-in errors. The check-in/check-out process can be integrated with an external version control system such as Microsoft Visual SourceSafe, PVCS, or ClearCase. This allows the development team to maintain a version history of all changes to the repository.
Business Object Compiler
[0053] This tool that is part of the development tool method and system of our invention allows developers to compile the repository or projects either completely or incrementally. Incremental compilation involves a compilation of only a subset of the Projects (typically those that have been modified). The definitions of objects in these Projects are the only ones that are updated. The remainder of the repository file is left untouched. This significantly speeds the development cycle of any project. The compiler generates a repository file that is used to run the underlying application. The storage of the application definition in the repository file is optimized for high-speed access and performance. This repository file is then deployed to the end-users of the application. The application executable reads the application definition from the repository file and instantiated objects based on their definitions stored in the repository file.
Programming Platform
[0054] The development tool method and system of our invention includes a development platform. For example, a Microsoft Visual Basic or Microsoft Visual C++ programming platform for integrating enterprise applications with third-party cooperative applications and extending the base functionality of the application screens and business components. In a preferred embodiment of our invention, the Visual Basic provides a Visual Basic-compliant environment that includes an editor, debugger, and interpreter/compiler. This allows application developers to extend and further configure applications. This capability may be integrated with the Applet Designer so developers can attach scripts to user interface element controls such as buttons, fields, and ActiveX controls. Business component behavior can also be further configured using the programming platform. FIG. 5 illustrates some aspects of the editor and debugger screen 5 . It includes the object explorer 51 and the object code view, 52 .
Business Object Interfaces
[0055] Not only can application developers extend applications with the development platform, e.g., Visual Basic, they can also use COM interfaces to access data from third-party applications, provide integration with legacy systems, and automate applications from other external applications. This allows developers to extend application behavior, provide client-side integration to other applications, and enable access to data and business rules from other programs that use Microsoft Visual Basic, Powerbuilder, Java, or ActiveX. COM interfaces expose selected objects to custom routines external from the applications. Developers can access these COM interfaces using a wide variety of programming languages.
Database Extension Designer
[0056] When developers require extensions beyond built-in database extensions, the database extension designer module of the method provides a point-and-click interface to extend application tables. Developers can use these database extensions to capture data from new fields in application screens, or from external sources using enterprise integration managers.
[0057] The database extension designer is integrated with the business object repository. The developer first defines the extensions in the repository and makes use of these extensions in Business Components and Applets. These changes are then applied to the local database by clicking on the Apply button. This causes the database schema of the local database to be updated. The developer then tests these extensions in the local environment. Once the testing is complete, the changes are checked into the server repository and made available to the rest of the team.
[0058] This process allows developers to make one set of changes that automatically triggers updates to client applications that reflect and incorporate the new database extension into mobile users' databases. These changes reflect the appropriate visibility rules for database extensions. New columns are automatically reflected in the business object repository and named appropriately to ensure easy migration to, for example, future releases of applications.
[0059] The database extension designer works with client-server applications to provide seamless integration of database extensions for mobile user databases. The database extension designer automatically applies database extension instructions to the server database and these extensions are automatically routed to mobile user databases via remote software distribution applications such as Siebel Remote. Changes take effect automatically the next time mobile users synchronize. The changes are “in-place.” so mobile users do not need to refresh or reinitialize their local database.
Application Upgrader
[0060] The application upgrader module of the method and system of our invention dramatically reduces the time and cost of version upgrades by allowing customers to better determine what changes are available with each release and compare unique object customizations from the prior release with changes in the new release. The application upgrader provides systems administrators with notification of conflicts between object customizations and new releases, automatically merges differences between object definitions, and allows administrators to manually override and apply any changes. This tool obviates the need to manually migrate changes from release to release and significantly reduces the total lifecycle cost of ownership of typical business applications as compared to traditional client/server applications. FIG. 6 illustrates the components of the application upgrader 6 of the method and system of our invention. The Application Upgrader screen has two views, an “Application Upgrades” view, 61 , and an “Object Differences” view, 62 , as well as a “Merge Repositories” choice box 63 .
[0061] The Application Upgrader identifies customizations made to an Application, and applies these customizations to the newer release of that Application. Application definitions are contained in a repository. The Application upgrader compares three repositories—the Prior Standard Repository, the Customized Repository, and New Standard Repository—and generates a fourth repository (New Customized Repository) based on the new repository but containing the customizations made by the customer. Any object definitions that have been added to the Customized Repository, but not in the New Standard Repository are added to the New Customized Repository. If an object definition has been modified in the Customized Repository and also in the New Standard Repository, the upgrader compares each attribute of the two versions of object definition, and for each conflict encountered (i.e. differing attribute values), selects the value from one of the versions based on a set of predetermined rules. All conflicts and their resolutions are presented to the user who then has the option of reviewing these and overriding the default resolution adopted by the Application Upgrader.
[0062] The result of the upgrade process is an upgraded version of the Application that incorporates the features of the new release with the customizations made to the prior release.
[0063] While the invention has been described with respect to certain preferred embodiments and exemplifications, it is not intended to limit the scope of the invention thereby, but solely by the claims appended hereto.
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A software development method and system having a suite of graphical customization tools that enables developers to rapidly configure all aspects of the underlying application software, including the look-and-feel, behavior, and workflow. This is accomplished without modifying application source code, base objects, or SQL. The sophisticated repository management capabilities of the method and system of our invention allows teams of developers to work efficiently on configuring applications. The application upgrader provides an automated process to upgrade the customizations to future product releases thus protecting the investment in customization. The ease, comprehensiveness, scalability, and upgradeability of the customization process help reduce the total lifecycle cost of customizing enterprise applications.
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BACKGROUND
1. Field of the Invention
The present invention relates to a vee-shaped endless transmission belt.
2. Description of the Related Art
There are currently in existence numerous types of vee-shaped transmission belts intended to be mounted on pulleys.
One example of a vee-belt notably comprises an elastomer heart in the form of a trapezium, a transverse reinforcing layer connected to the heart to prevent it from deforming, one or more cord(s), for example made of inextensible material, embedded in the structure (notably the heart) and a coating layer of coated fabric peripherally surrounding this assembly over the entire length of the belt.
However, these solutions are not entirely satisfactory because when the cord(s) is (are) inextensible, it is difficult to produce a whole series of belts having exactly the same dimensions. Now, in certain applications, it is necessary to be able to lengthen one or more belts slightly in order to bring it or them to the same length as others, for example in a drive system involving multiple parallel belts with identical separations, or in order to compensate for a differential separation between the axes of the pulleys bearing two or more parallel belts.
It is therefore an object of the present invention to overcome the abovementioned problems using a solution that is simple to manufacture, easy to use and optimized in terms of efficiency.
SUMMARY OF THE INVENTION
The subject of the present invention is a vee-shaped endless transmission belt comprising a main core in the shape of a trapezium made of natural and/or synthetic rubber, containing at least one substantially inextensible cord extending over the entire length of said belt, at least one layer of fiber-reinforced elastomer placed in contact with the core, near the long base of the trapezium, and at least one thin external coating layer, based on fabric laterally enveloping the entirety of the core and of the reinforced layer over the entire length of the belt. The vee-shaped endless transmission belt further comprises a peripheral cushion of rubber made of an elastomeric material which is elastically softer and more deformable than that of which the core is made. The cushion of rubber surrounds the core and the layer of fiber-reinforced elastomer over the entire length of the belt and is surrounded by the coating layer.
At least one other internal, fine coating layer substantially similar to the previous coating layer surrounds the layer of fiber-reinforced elastomer and the core and is in direct contact therewith, so that the cushion is positioned between the two coating layers.
The two coating layers each may close up around the core and/or the cushion and the layer of fiber-reinforced elastomer, respectively along the long base and along the short base, or vice versa.
One coating layer may close up along the long base by an overlapping of its free ends, whereas the other coating layer may close up along the short base through an overlapping of its free ends.
Another layer of fiber-reinforced elastomer may be positioned on the opposite side from the previously described reinforced layer and closer to the long base, so that the two layers of fiber-reinforced elastomer are arranged on each side of each cord.
Each cord may be coated in a bonding layer.
The belt may comprise several parallel cords, particularly around 2 to 10 and preferably 6 to 8.
The cushion may have a constant thickness of between around 0.1 mm and 1.5 mm, for example several tenths of a mm.
The cushion may be made of an elastomer based on natural rubber and on synthetic rubber SBR and may have a Shore A hardness comprised between around 45 and 65, preferably between 54 and 58; and
Each coating layer may be made of cotton coated with a chloroprene-based rubber.
The invention will now be described in greater detail with reference to one particular embodiment given by way of illustration only and depicted in the attached FIG. 1 .
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a cross-sectional view of a vee-shaped transmission belt in accordance with one embodiment of the invention.
DETAILED DESCRIPTION
FIG. 1 depicts a transmission belt 1 intended to be mounted under tension on two pulleys, a transmission first pulley, for example connected to the input shaft of a drive motor, and a receiving second pulley to which the rotational drive force is transmitted in order to drive an output shaft.
This belt 1 has a vee-shaped cross section with a long base 2 , a short base 3 parallel to and opposite the long base, and two flanks 4 which are intended to rest against corresponding flanks of the transmission pulley and of the receiving pulley. In this regard, and in the usual manner, drive is effected through contact/grip between the flanks 4 of the belt and the flanks of the pulleys, without any contact between the bottom of the groove of the pulleys and the short base 3 of the belt 1 .
As can be seen, the belt 1 comprises several layers joined together, notably in the hot state using vulcanizing.
First of all, the belt 1 comprises a central core 10 made of elastomer consisting of a blend of natural rubber and of synthetic rubber (SBR) and having a Shore A hardness of around 70 to 80, for example 75-76.
This core 10 has, on top of it in the direction of the long base 3 , a layer 12 of reinforced elastomer containing synthetic fibers so that it has good transverse rigidity and deformation of the belt 1 is avoided. The thickness of this reinforced layer 12 may vary between around 1 and 6 mm, for example of the order of 2 to 3 mm. The Shore A hardness of the reinforced layer 12 is comprised between around 70 and 100, for example of the order of 85 to 90.
On top of this first reinforced layer 12 , still in the direction of the long base 2 , there is a bonding layer 13 of elastomer based on natural rubber having elastic memory. This bonding layer 13 has a thickness varying between around 0.2 and 3 mm, for example 0.4 to 2.4 mm, and a Shore A hardness comprised between around 50 and 70, for example of the order of 60 to 64.
Embedded in this bonding layer 13 is a series of parallel inextensible cords 20 based on aramid, for example made of Kevlar (registered trademark). These parallel cords 20 run all around the belt 1 and notably allow the rotational force to be transmitted mechanically from the transmission first pulley to the receiving second pulley.
Another layer 14 of elastomer, reinforced with synthetic fibers and identical to the previous layer 12 (in terms of material and hardness notably), is also added to the bonding layer 13 , on top of the latter in the direction of the long base 2 , so that the bonding layer 13 is sandwiched between the two reinforced layers 12 and 14 . The result of this is that the cords 20 , embedded in the bonding layer 13 , are also positioned between the two reinforced layers 12 and 14 . These two reinforcing layers 12 and 14 notably make it possible to avoid deformation of the belt 1 and, in particular, of the cords 20 (by bridging) because the tension produced by the pulleys may be particularly high and lead to high stresses. This reinforced layer 14 typically measures around 0.5 to 2 mm thick, for example 1 to 1.4 mm thick.
The assembly made up of the core 10 , the two reinforcing layers 12 and 14 , the bonding layer 13 and the cords 20 is surrounded by a coating layer 16 consisting of fabric, for example a cotton-based fabric, coated with chloroprene. This coating layer 16 extends around the entire circumference of the belt and forms a kind of first peripheral wrapper the ends 16 a and 16 b of which are folded over one on top of the other longitudinally so that they overlap so that they can be joined together. In the embodiment depicted, the coating layer 16 is closed up by joining (particularly in the hot state) at the longest base 2 of the belt 1 , for example near the middle thereof.
A layer 17 forming a deformable cushion, made of an elastomer that is softer than that of which notably the core 10 is made, surrounds all of the first coating layer 16 (and therefore the core 10 , the reinforced layers 12 and 14 , the cords 20 and the bonding layer 13 ).
This cushion 17 has elasticity that is more pronounced than that of the core 10 , of the reinforcing layers 12 and 14 and possibly of the bonding layer 13 . By way of example, the elastomer of which the cushion 17 is made may have a Shore A hardness comprised between around 45 and 65, for example of the order of 54 to 58. The cushion 17 also has a coefficient of elongation at break that is 50 to 80% higher than that of the core 10 . According to the embodiment depicted, the thickness of the cushion 17 is around 0.1 to 1.5 mm, typically of the order of a few tenths of a mm depending on the required elasticity (which is itself dependent on the material chosen and on the physico-chemical properties thereof).
Another coating layer 18 , made from the same material as the previous coating layer 16 and having the same physico-chemical properties, peripherally surrounds all of the cushion 17 over the entire length of the belt 1 . The ends 18 a and 18 b of this coating layer 18 are folded over one onto the other and overlap longitudinally to form a (hot) join running along the short base 3 of the belt 1 , substantially in the middle thereof.
Thus, the cushion 17 is completely sandwiched between the two coating layers 16 and 18 .
The choice to position the overlap of the two coating layers 16 and 18 in opposition on the two bases of the trapezium allows the belt 1 to be better balanced and avoids local additional thicknesses of fabric leading to stiffness (if the connecting overlaps of the ends 16 a , 16 b , 18 a and 18 b were to be situated in the same place).
Because this cushion 17 has good elasticity and a good coefficient of elongation, it allows the belt 1 , once stretched and placed around the transmission and receiving pulleys, to deform by squashing substantially perpendicular to the surface of the flanks 4 .
It will be recalled that the cords 20 are not extensible but that they serve to transmit the force induced by the transmission pulley. Thus, in order to be able to vary the circumference of the belt 1 (i.e. its length) slightly, it is impossible to rely on any elasticity of these cords 20 .
It is therefore necessary to rely on the elasticity of the soft materials of which the belt 1 is made and, in particular, the elasticity of a layer which is not in contact with and/or does not contain the cords 20 .
This then is the purpose of the peripheral cushion 17 which, by squashing by a few hundredths or tenths of a mm at the flanks 4 of the belt, allows the latter to become noticeably longer.
Thus, it is no longer essential to supply strictly identical belts to a customer who wishes to place several of them in parallel over pulleys with identical separations. Indeed quite often when a batch of belts is supplied for this type of application, some of the belts will be slightly shorter and others slightly longer. Because they each contain inextensible cords, it is highly probable that certain belts will be stretched more than others, and this may be to the detriment of the operation of the system. Thanks to the presence of the elastically deformable cushion 17 , a kind of compensation tolerance is created through the squashing so that the slightly shorter belts can stretch slightly to reach the length of the others. Thus, the system with multiple parallel belts can operate efficiently and there is no need to supply strictly identical (calibrated) belts.
In another application, in instances in which the user has two exactly identical belts, if two pairs of parallel pulleys do not have exactly the same separation, it is possible to compensate for this differential because the elastically deformable cushion of the belt mounted on the pulleys that are closest together will deform in such a way as to lengthen the belt.
It goes without saying that the detailed description of the subject matter of the invention, which is given solely by way of illustration, does not in any way constitute a limitation, the technical equivalents also being comprised within the scope of the present invention.
Thus, the elastomeric materials that make up the various parts may vary, as may the inextensible material of which the cords are formed.
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A vee-shaped transmission belt ( 1 ) has a main core ( 10 ) in the shape of a trapezium made of natural and/or synthetic rubber, containing at least one substantially inextensible cord ( 20 ) extending over the entire length of the belt ( 1 ). At least one layer ( 14 ) of fiber-reinforced elastomer is placed in contact with the core ( 10 ) near the long base ( 2 ) of the trapezium. At least one thin external coating layer ( 18 ) envelopes the entirety of the core ( 10 ) and the reinforced layer ( 14 ) over the entire length of the belt ( 1 ). A peripheral cushion ( 17 ) made of an elastomer that is elastically softer and more deformable than the core ( 10 ) surrounds the core ( 10 ) and the layer ( 14 ) of fiber-reinforced elastomer and is surrounded by the coating layer ( 18 ).
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This is a continuation-in-part of application Ser. No. 07/765,584 filed Sep. 25, 1991 now abandoned.
BACKGROUND OF THE INVENTION
The present invention relates to a method for cleaning clothes.
The dry cleaning technique is intended to remove soil from clothes by the use of a nonaqueous solvent, but conventional dry cleaning agents have the following three problems regarding environmental pollution. The first problem is based on the fact that all the organic solvents such as perchloroethylene, 1,1,1-trichloroethane and CFC 113 which have been widely used contain chlorine. Such chlorine containing solvents pollute the environment and destroy the ozone layer, and so, it will soon be impossible, by regulation, to use these solvents. The second problem is the waste pollution of detergents. Organic solvent can effectively remove hydrophobic soils, but the use of solvent alone cannot exert a sufficient cleaning ability. Nowadays, in order to improve the cleaning ability, a small amount of water and a soap (a surface active agent) for dry cleaning are added to the solvent. The used solvent is forcedly cleaned by a pressure filter, and at this time, the soil which has been removed from the clothes and dissolved in the solvent are removed together with powder adsorbing this soil.
The cleaned solvent is returned to the cleaning machine. Finally, the contaminated solvent is distilled, and the resulting residue is discharged. This residue is disposed of as an industrial waste, but since it contains the organic solvent and the surface active agent, its disposal is extremely difficult. The third problem is water pollution by the solvent caused by disposing water containing the solvent in the sewer system.
The present inventor has previously investigated the dry cleaning capabilities of 81 kinds of solvents [Journal of the Japan Research Association for Textile End-use, 27, 8, pp. 352-359 (1986)], but there has not been any solvent which can meet all requirements.
The solvent for dry cleaning must meet several requirements such as influence on the environment, detergency, handleability, safety, etc. Detergency is affected by the "solubility" and "dispersibility" of various types of soils, including oil-soluble soils such as skin oils, fat and oil, oil mist, etc.; water-soluble soils such as sweat, water-soluble foods, etc.; dirts such as sludge, dust, etc.; the degree of the "counter-contamination", or soils washed from clothes that migrate back from the cleaning liquid to the clothes; and the degree of surface tension of the solvent which penetrates into the clothes and between the soils. On the other hand, the "handleability" of the solvent is determined by the ease of drying the washed articles, the length of the solvent life, the pass of distillation and recovery of the solvent, suitability for machines with no corrosion of metal, its workability and management with low odor, no remaining odor in the washed articles, etc. Furthermore, the "safety" of the solvent is determined by the shape retention of the washed articles, denaturation of the washed articles including yellow discoloration, the decrease of gloss, the run-off of dye, the dissolution of auxiliary items such as buttons, cores and lames, as well as high ignition point and flash point, low toxicity, etc.
Propylene glycol monomethyl ether (hereinafter referred to as "PM") is known in the art as a detergent for home use (Japanese Unexamined Patent Publication No. 20400/1988), a detergent for floor use (Japanese Unexamined Patent Publication Nos. 112699/1988 and 168498/1988), a detergent for ink (Japanese Unexamined Patent Publication No. 73899/1990), and a letter-erasing liquid for erasing letters printed on clothes which is used together with a reducing or an oxidizing bleaching agent, but it is not yet known in the art that PM is used as a solvent for the dry cleaning of clothes.
The present invention is directed to a method which can solve all the problems of the above-mentioned conventional solvents, can completely achieve the inherent purpose of cleaning, and can prevent cleaning troubles.
SUMMARY OF THE INVENTION
The present invention is directed to a cleaning method which comprises the steps of bringing clothes to be cleaned into contact with a mixed solvent comprising 4 to 50% by volume, preferably 4 to 25% by volume, of water and PM, removing the contaminated solvent from the cleaned clothes, and then rinsing, squeezing and drying the clothes.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The cleaning method of the present invention can be carried out by substituting a mixed solvent of PM and water for a conventional solvent and utilizing a conventional dry cleaning machine. For the practice of the cleaning method of the present invention, a dry cleaning machine is used in which a closed and fixed outside drum and a rotatable double cylindrical inside drum are arranged laterally.
First, clothes are put in the inside drum, and the outside drum is then covered with a lid. A solvent is then jetted to the clothes. The clothes immersed in the solvent are churned by the rotation of the inside drum to create a mechanical cleaning function.
Cleaning time is about 20 minutes, as in the case of perchloroethylene. Since PM has a specific gravity smaller than that of perchloroethylene (the specific gravity of PM=0.92, and that of perchloroethylene=1.32), impact on the clothes is small, when the clothes containing the solvent drop within the inside drum onto the liquid surface below, so that the mechanical damage to the clothes is slight.
Furthermore, PM has less power to dissolve resins and dyes than perchloroethylene, and when PM is used, the mechanical function is also mild as described above. Therefore, such troubles as damage to auxiliary items and dyes can be inhibited.
Rinsing is carried out in a step in which the clothes are washed again with a soil-free solvent. In the rinsing step, a long period of time has heretofore been necessary to remove soap. In the present invention, however, the mixed solvent of PM and water does not require any soap, and therefore the rinsing time is about 5 minutes. This is about 1/3 the rinsing time necessary when perchloroethylene is used.
Drying is carried out for about 20 minutes by feeding hot air having an inlet temperature of about 60° C. However, the PM and water mixture has a larger specific heat and evaporation latent heat than perchloroethylene, and so it is necessary to increase the volume of the hot air (the specific heat of PM=0.58 and that of perchloroethylene=0.21; and the evaporation latent heat of PM=102.0 and that of perchloroethylene=50.1).
After completion of the drying, the clothes are taken out and finished, with which the cleaning operation is terminated.
In the cleaning process, a filter is used to remove solid soils from the solvent. This filter can be a cartridge type filter made of a glass fiber or a nonwoven fabric and can be used repeatedly by periodic washing with water.
The soils dissolved in the solvent are removed as a residue. That is, PM and water are evaporated in the last step by an evaporator, and the resulting residue is thrown away. The residue is a solution containing the soils at a high concentration. The residue is free from any soap and powder (diatomaceous earth) in contrast to the residue produced by the use of conventional solvent, and therefore, only an extremely small amount of the residue is formed. In addition, since PM does not contain any chlorine, it is easy to dispose of the residue as a waste.
As will be established by the various tests described below, the cleaning method of the present invention has excellent advantages.
TEST EXAMPLE 1 (SOLUBILITY)
Water, perchloroethylene, 1,1,1-trichloroethane, CFC 113 and PM were used as solvents. Solutes used with a distillation residue from a dry cleaning factory, which was used as an oil-soluble soil, and instant coffee powder, which was used as a water-soluble soil. The test was conducted by adding 5 ml of each solvent to 0.5 g of each solute in a test tube, allowing the mixture to stand at 30° C. for 72 hours, and then inspecting solubility with the naked eye.
TABLE 1______________________________________ Perchloro- 1,1,1-tri- CFCSolute Water ethylene chloro ethane 113 PM______________________________________Oil- x o o o osolubleWater- o x x x Δsoluble______________________________________ o: well dissolved, Δ: dissolved, and x: not dissolved.
It is apparent from the results in Table 1 that PM has both soil cleaning capabilities for both oil soluble and water soluble soils. PM is as effective on the oil-soluble soils as a conventional solvent and exhibits relatively good properties with water-soluble soils, although it is inferior to water. With a conventional chlorine-based solvent, a soap is used as an auxiliary so as to enhance dissolving performance for water-soluble soils, but PM exhibits good detergency for water-soluble soils even without soap. Furthermore, PM has a surface tension of 27.7, which is greater than those of petroleum (18-19) and CFC 113 (17.3) and which is comparable to those of perchloroethylene (32.3) and trichloroethane (25.6).
With the afore-mentioned results, it becomes apparent that conventional solvent cannot dissolve water-soluble soils such a soy sauce, coffee and the like, but PM or PM with added water can dissolve these water-soluble soils. Thus, a soap for dissolving water-soluble soils is not necessary. As a result, it is possible to save soap costs and the trouble of regulating the amount of soap to shorten rinse time, and to decrease the amount of waste. In addition, PM with added water can disperse and remove solid particles (e.g., earth, sand and dust) which cannot be removed by conventional dry cleaning.
TEST EXAMPLE 2 (COUNTER-CONTAMINATION)
A solvent which effects less counter-contamination (the phenomenon in which soils washed from clothes migrate back from the cleaning liquid to the hydrophobic surfaces of the clothes) provides a good cleaning finish and permits the washing of clothes even when the liquid contains a large amount of soils. Thus, distillation is not required so often, which is economical.
The degree of counter-contamination depends upon the combination of soils (solutes), the type of solvent and the types of clothes. In this test example, soy sauce (0.5 ml) and coffee (0.5 g) were used as water-soluble solutes, carbon black (0.04 g) was used as a dispersible solute, a waste oil (2 g) which was employed as a gear oil for a long period of time was used as an oil-soluble solute, and dry cleaning distillation residue (0.04 g) was used as a miscible solute. The test was conducted by putting a 2.5 cm×2.5 cm cloth strip in 75 ml of a solvent in which each solute is dissolved, stirring and then immersing it therein for 5 minutes. After air drying, the reflectance of each cloth strip was measured by UV-200, and a counter-contamination ratio was calculated from the following equation:
Counter-contamination ratio (%)=(A-B)/C×100
wherein
A: the reflectance of the original cloth
B: the reflectance of the cloth strip after immersion, and
C: the reflectance of the original cloth.
The results are shown in Table 2.
TABLE 2__________________________________________________________________________Solute Clothing Water Perchloroethylene 1,1,1-Trichloroethane CFC-113 PM__________________________________________________________________________Soy Sauce Cotton 2.57 * * * 8.75 Wool 5.67 0.01 6.16 0.001 4.25 Polyester 3.85 1.98 11.07 4.40 5.93Coffee Cotton 29.67 4.08 1.37 6.30 2.19 Wool 22.86 21.87 5.18 32.04 2.08 Polyester 11.95 4.56 6.39 4.29 4.87Carbon black Cotton 65.55 43.42 38.41 61.51 33.52 Wool 44.31 60.90 50.53 69.98 47.08 Polyester 53.02 42.41 42.74 50.25 64.92Waste oil Cotton 8.73 3.14 2.77 5.58 3.07 Wool * 3.29 2.38 6.94 * Polyester * 2.22 2.99 2.39 *Distillation Cotton 7.16 11.18 13.05 11.05 8.09residue Wool 5.44 12.03 13.46 12.30 9.79 Polyester 3.33 5.50 6.44 5.29 5.81__________________________________________________________________________ *article heavily soiled by solute
The results in Table 2 indicate the following facts.
Soy sauce: In the chlorine-based solvent, soy sauce precipitated and floated in a sol state. This sol was hydrophilic and therefore firmly adheres onto cotton, which has a hydrophilic surface. It did not adhere to wool and polyester, which have hydrophobic surfaces. On the other hand, since the soy sauce was completely dissolved in water and PM, neither dyeing nor counter-contamination was observed.
Coffee: In the chlorine-based solvent and PM, the solute floated in a fine solid particle state. The particles selectively adhered to wool in perchloroethylene and CFC 113. They did not adhere thereto in trichloroethane and PM. On the other hand, in water, dyeability was noticeable.
Carbon black: In every solvent, carbon black dispersed instead of dissolving, and there was not any significant difference among the solvents.
Waste oil: This was completely dissolved in the chlorine-based solvent, and no counter-contamination was present. On the other hand, in water and PM, the oil floated in a sol state, and since this sol was hydrophobic, it adhered to the wool and polyester which have hydrophobic surfaces.
Distillation residue: This was a mixture of three water-soluble, dispersible and oil-soluble solutes which, further, contained a soap for charge. Therefore, this distillation residue was considered to be close to actual dry cleaning residue. Noticeable counter-contamination on the wool and cotton was seen in the chlorine-based solvent, but little was seen in water. In PM, the behavior of the residue was between that in water and in the chlorine-based solvent.
As described above, counter-contamination which cannot be rectified by the use of conventional nonaqueous solvent can be prevented by the use of PM, and thus an excellent finish can be obtained. It is to be noted that the counter-contamination takes place when the selected solvent is hydrophobic, and hence, no counter-contamination occurs in the hydrophilic PM.
TEST EXAMPLE 3 (SHRINKABILITY)
A feature of dry cleaning is that whereas water-absorbable fibers swell during water washing, using solvent, washed articles can be prevented from shape loss or shrinking. In this test, the shrinkage ratio of clothes washed in PM was inspected.
Into a laundermeter cup in which 10 steel balls and 100 ml of solvent were placed, 12 cm×12 cm test cloths made of cotton, hemp and wool and having a 10 cm×10 cm thread mark were added one by one, and then immersed in the solvent at room temperature for 45 minutes. After being air-dried, the length between the thread marks of each cloth was measured. The results are shown in Table 3.
TABLE 3______________________________________ PM 75% + PM 50% + PM 100% Water 25% Water 50%______________________________________Cotton Warp (cm) 10.00 10.00 10.00 Weft (cm) 9.95 9.95 9.90Hemp Warp (cm) 10.00 10.00 10.00 Weft (cm) 10.00 9.95 9.95Wool Warp (cm) 10.00 10.00 10.00 Weft (cm) 9.90 9.80 9.80______________________________________
The results in Table 3 indicate that even when PM is mixed with 50% water, the shrinkage ratio of the cotton weft is as small as 1%, and when PM is mixed with 25% water, the shrinkage ratio of the cotton weft is only 0.5%. These results are due to the good hydratability of PM. With 1,1,1-trichloroethane or perchloroethylene, water in the articles to be washed transfers to the solvent, but this water is not hydrated in the solvent and causes the washed articles to shrink. In the case of PM, however, the articles do not shrink, as shown in Table 3.
A small amount of water is dissolved in conventional solvent (0.01% by weight), and water which is not dissolved therein is adsorbed by fibers. As a result, the fibers swell, which causes the shape loss of the washed articles to lose their shape. To prevent this phenomenon, the water has been heretofore separated and discharged, which causes sewage pollution. On the other hand, PM can dissolve large amounts of water. Added water is dissolved in PM, and therefore, fibers do not swell directly. Since the water does not cause the fibers to swell, it is not necessary to remove it, and so sewage pollution by the discharge of water is prevented.
TEST EXAMPLE 4 (READINESS OF DRYING)
In a dry cleaning process, if a great amount of time is required to dry washed articles, work efficiency is markedly lowered. A test was conducted by piling 4 cotton cloths having a size of 5×5 cm, dropping 0.125 g of each solvent on the cloths, and then measuring the vaporization rate of the solvent. When the vaporization rate of perchloroethylene is regarded as 1, the other solvents had vaporization rates shown in Table 4.
TABLE 4______________________________________ Perchloro- Trichloro- CFC ethylene ethane 113 PM______________________________________Use of 1 3.929 14.643 0.386Cotton ClothSolvent Alone 1 4.444 13.667 0.244______________________________________
The vaporization rate of PM is low, but the reason that PM is suitable for cleaning is that PM has the lowest boiling point (120° C.) in the glycol ether series and, so, is easy to dry. In this connection, the boiling point of PM is close to that of perchloroethylene, i.e., 121° C. When a solvent having a higher boiling point than this is used, high temperature must be maintained for a long period of time for drying, which increases cost and chemically damages fibers or auxiliary items of the clothes. For example, the boiling point of propylene glycol monomethyl ether acetate is 132° C., and that of ethylene glycol monoethyl ether is 136° C. Such compounds with the high boiling points are no longer suitable for the drying step of dry cleaning.
TEST EXAMPLE 5 (COMBUSTIBILITY)
The flash point of PM is in the range of 36° to 38° C., and PM is substantially identical with a petroleum solvent in combustion readiness. However, when 50% water was added to PM, the flash point of the resultant mixture ranged from 62° to 64° C. Thus, it is apparent that mixing the solvent with water can lead to the elevation of the flash point.
TEST EXAMPLE 6 (CORROSIVENESS)
1 cm×2 cm test pieces of iron, aluminum and stainless steel were immersed in solvent at room temperature for one week, and then removed. The test pieces were allowed to stand in air for 3 months, and the degree of oxidation was evaluated. With regard to the test pieces immersed in PM, no change was observed.
The mixed solvent of PM and water according to the present invention has the following advantages as a solvent for cleaning.
(1) Since the mixed solvent contains no chlorine, it does not have a bad influence on the emvironment.
(2) The mixed solvent is effective in washing off both oil-soluble and water-soluble soils.
(3) The mixed solvent has less counter-contamination.
(4) The mixed solvent does not require any soap.
(5) The life of the mixed solvent is long.
(6) The mixed solvent does not corrode the cleaning machine, etc.
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Disclosed is a method for cleaning clothes which comprises bringing the clothes into contact with a cleaning solvent, removing the contaminated solvent, rinsing and then drying the clothes, the improvement wherein said cleaning solvent consists of propylene glycol monomethyl ether containing 4 to 50% by volume of water.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. application Ser. No. 13/124,337, filed Apr. 14, 2011, and assigned a 371 Completion Date of Jul. 12, 2011, which is a Section 371 National Stage Application of International Application No. PCT/GB2009/051376, filed Oct. 14, 2009 and published as WO 2010/043904 A2 on Apr. 22, 2010, which claims priority from IN Patent Application No. 1746/KOL/2008, filed Oct. 15, 2008, the contents of which are incorporated herein in their entirety for all purposes.
FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of the active pharmaceutical ingredient vorinostat. In particular it relates to a process for preparing vorinostat substantially free from impurities.
BACKGROUND OF THE INVENTION
Vorinostat, represented by structural formula (I) and chemically named as N-hydroxy-N′-phenyl-octanediamide or suberoylanilide hydroxamic acid (SAHA), is a member of a larger class of compounds that inhibit histone deacetylases (HDAC). Histone deacetylase inhibitors (HDI) have a broad spectrum of epigenetic activities and vorinostat is marketed, under the brand name Zolinza®, for the treatment of a type of skin cancer called cutaneous T-cell lymphoma (CTCL). Vorinostat is approved to be used when the disease persists, gets worse, or comes back during or after treatment with other medicines. Vorinostat has also been used to treat Sézary's disease and, in addition, possesses some activity against recurrent glioblastoma multiforme.
Vorinostat was first described in U.S. Pat. No. 5,369,108, wherein four different synthetic routes for the preparation of vorinostat are disclosed (Schemes 1 to 4).
The single step process illustrated in Scheme 1 involves coupling of the diacid chloride of suberic acid with aniline and hydroxylamine hydrochloride. However, the yield of this reaction is only 15-30%.
The multistep process illustrated in Scheme 2 begins with the monomethyl ester of suberic acid, which undergoes conversion to the corresponding acid chloride. Further coupling with aniline gives the methyl ester of suberanilic acid. Hydrolysis of the ester and further coupling with benzyl protected hydroxylamine gives benzyl protected vorinostat which on deprotection gives vorinostat.
In addition to the disadvantage of being a five-step process with overall yields reported as 35-65%, this process suffers from further disadvantages such as the use of the expensive monomethyl ester of suberic acid.
The two step process illustrated in Scheme 3 involves coupling of the diacid chloride of suberic acid with aniline and O-benzyl hydroxylamine and then deprotection. However, the overall yield of this reaction is only 20-35%.
The process illustrated in Scheme 4 is similar to that illustrated in Scheme 3, with the exception that O-trimethylsilyl hydroxylamine was used instead of O-benzyl hydroxylamine. The overall yield of this reaction is reported as 20-33%.
Another process for the preparation of vorinostat has been reported in J. Med. Chem., 1995, vol. 38(8), pages 1411-1413. The reported process, illustrated in Scheme 5, begins with the conversion of suberic acid to suberanilic acid by a high temperature melt reaction. Suberanilic acid is further converted to the corresponding methyl ester using Dowex resin and the methyl ester of suberanilic acid thus formed is converted to vorinostat by treatment with hydroxylamine hydrochloride. However, this process employs high temperatures (190° C.) in the preparation of vorinostat which adds to the inefficiency and high processing costs on commercial scale. The high temperatures also increase the likelihood of impurities being formed during manufacture and safety concerns. The overall yield reported was a poor 35%.
Another process for the preparation of vorinostat has been reported in OPPI Briefs, 2001, vol. 33(4), pages 391-394. The reported process, illustrated in Scheme 6, involves conversion of suberic acid to suberic anhydride, which on treatment with aniline gives suberanilic acid. Coupling of this suberanilic acid with ethyl chloroformate gives a mixed anhydride which upon treatment with hydroxylamine gives vorinostat in an overall yield of 58%. In the first step, there is competition between the formation of suberic anhydride and the linear anhydride and consequently isolation of pure suberic anhydride from the reaction mixture is very difficult. This process step is also hindered by the formation of process impurities and competitive reactions. In the second step, there is formation of dianilide by reaction of two moles of aniline with the linear anhydride. In the third step, suberanilic acid is an inconvenient by-product as the suberanilic acid is converted to a mixed anhydride with ethyl chloroformate, which is highly unstable and is converted back into suberanilic acid. Consequently, it is very difficult to obtain pure vorinostat from the reaction mixture. Although the reported yield was claimed to be 58%, when repeated a yield of only 38% was obtained.
A further process for the preparation of vorinostat has been reported in J. Med. Chem., 2005, vol. 48(15), pages 5047-5051. The reported process, illustrated in Scheme 7, involves conversion of monomethyl suberate to monomethyl suberanilic acid, followed by coupling with hydroxylamine hydrochloride to afford vorinostat in an overall yield of 79%. However, the process uses the expensive monomethyl ester of suberic acid as starting material.
In conclusion, the major disadvantages of the processes disclosed in the prior art for the preparation of vorinostat can be summarised as follows:
The reaction schemes can involve lengthy process steps to obtain vorinostat and/or are low yielding. The reagents used in the processes can be very expensive and not cost effective for commercial manufacture. The product is obtained only after column chromatography or extensive purification steps and this reduces the overall yield and puts severe restrictions on the feasibility of the process for scale-up to commercial production. All the processes generally require isolation and/or purification of reaction intermediates.
In view of the importance acquired by vorinostat for the treatment of cancer, there is a great need for developing an alternative, relatively simple, economical and commercially feasible process for the synthesis of vorinostat with commercially acceptable yield and high purity.
The present inventors have surprisingly found that vorinostat can be prepared with very high purity employing a simple, efficient process starting with the readily available precursor suberic acid.
OBJECT OF THE INVENTION
It is therefore an object of the present invention to provide a simple, economical and commercially feasible process for the synthesis of high purity vorinostat with commercially acceptable yield.
SUMMARY OF THE INVENTION
The term “vorinostat” as used herein throughout the description and claims means vorinostat and/or any salt, solvate or polymorph thereof.
For the purposes of the present invention, a compound is “substantially pure” if it comprises less than 1% impurity by HPLC, preferably less than 0.5%, preferably less than 0.3%, preferably less than 0.2%, preferably less than 0.1%.
The present invention provides an efficient and economical synthesis of vorinostat which is high yielding and affords the product with very high purity on a commercial scale, whilst avoiding the need for cumbersome purification techniques of the final product or of any synthetic intermediates.
A first aspect of the present invention provides a process for the preparation of vorinostat comprising:
(a) reacting suberic acid with aniline, or a salt thereof, to form suberanilic acid; and
(b) reacting the suberanilic acid formed in step (a) with hydroxylamine, or a salt thereof.
Preferably, the process according to the first aspect of the present invention comprises the use of a coupling agent in step (a). Preferably, the coupling agent in step (a) is not a haloformate. Preferably, the coupling agent in step (a) is selected from a carbodiimide, a 1,1′-carbonyl compound, or a mixture thereof. Preferably, the coupling agent in step (a) is selected from 1,3-dicyclohexylcarbodiimide (DCC); 1,1′-carbonyldiimidazole (CDI); 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (water soluble carbodiimide hydrochloride, WSC.HCl); 1,3-diisopropylcarbodiimide (DIC); or a mixture thereof.
Most preferably, the coupling agent in step (a) is a mixture of 1,3-dicyclohexylcarbodiimide (DCC) and 1,1′-carbonyldiimidazole (CDI). Preferably, the mixture of CDI and DCC used in step (a) is in a molar ratio range of 0.1:10 to 10:0.1 CDI:DCC, more preferably in a molar ratio range of 1:5 to 5:1 CDI:DCC, even more preferably in a molar ratio range of 1:2 to 2:1 CDI:DCC, and most preferably in a molar ratio of about 1:1.6 CDI:DCC.
Preferably, the total amount of coupling agent used in step (a) with respect to the suberic acid is between 1 to 5 molar equivalents, more preferably between 1 to 3 molar equivalents, even more preferably between 1 to 1.5 molar equivalents, and most preferably is about 1.3 molar equivalents.
Preferably, in a process according to the first aspect of the present invention, step (a) is carried out in an organic solvent, preferably where the organic solvent is selected from dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), acetonitrile, 1,2-dichlorobenzene, ethanol or mixtures thereof. Most preferably, the organic solvent used in step (a) is THF.
Preferably, the total amount of aniline, or its salt, used in step (a) of the process of the first aspect of the present invention, with respect to the suberic acid is about 1 molar equivalent.
Preferably, in a process according to the first aspect of the present invention, step (a) is carried out at a temperature of between 10-60° C., more preferably at a temperature of between 15-40° C., and most preferably at a temperature of between 25-30° C.
Preferably, the process according to the first aspect of the present invention comprises the use of a coupling agent in step (b). Preferably, the coupling agent in step (b) is not a haloformate. Preferably, the coupling agent in step (b) is selected from a carbodiimide, a 1,1′-carbonyl compound, or a mixture thereof. Preferably, the coupling agent in step (b) is selected from 1,3-dicyclohexylcarbodiimide (DCC); 1,1′-carbonyldiimidazole (CDI); 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (water soluble carbodiimide hydrochloride, WSC.HCl); 1,3-diisopropylcarbodiimide (DIC); or a mixture thereof. Most preferably, the coupling agent in step (b) is 1,1′-carbonyldiimidazole (CDI).
Preferably, the total amount of coupling agent used in step (b) with respect to the suberanilic acid is between 1 to 5 molar equivalents, more preferably between 1 to 3 molar equivalents, and most preferably is about 2 molar equivalents.
Preferably, in a process according to the first aspect of the present invention, step (b) is carried out in an organic solvent, preferably where the organic solvent is selected from dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), acetonitrile, 1,2-dichlorobenzene, ethanol or mixtures thereof. Most preferably, the organic solvent used in step (b) is DMF.
Preferably, in a process according to the first aspect of the present invention, in step (b), hydroxylamine is used in the form of a salt, most preferably the hydrochloride salt.
Preferably, the total amount of hydroxylamine, or its salt, used in step (b) of the process of the first aspect of the present invention, with respect to the suberanilic acid is between 1 to 10 molar equivalents, more preferably between 1 to 6 molar equivalents, even more preferably between 2 to 5 molar equivalents, and most preferably is about 4 molar equivalents.
Preferably, in a process according to the first aspect of the present invention, step (b) is carried out at a temperature of between 10-60° C., more preferably between 15-40° C., and most preferably between 25-30° C.
Preferably, in a process according to the first aspect of the present invention, step (a) and step (b) are carried out in the same organic solvent; preferably selected from dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), acetonitrile, 1,2-dichlorobenzene, ethanol, or a mixture thereof; more preferably selected from THF, DMF, or a mixture thereof.
Preferably, in a process according to the first aspect of the present invention an activating agent is used in step (a) and/or step (b). Preferably, the activating agent is selected from cyanuric chloride, cyanuric fluoride, catecholborane, or a mixture thereof. The activating agent is preferably used in combination with the coupling agent.
A second aspect of the present invention provides a process for the preparation of vorinostat comprising:
(a′) reacting suberic acid with hydroxylamine, or a salt thereof, to form N-hydroxy-7-carboxy-heptanamide; and
(b′) reacting the N-hydroxy-7-carboxy-heptanamide formed in step (a′) with aniline, or a salt thereof.
Preferably, the process according to the second aspect of the present invention comprises the use of a coupling agent in step (a′). Preferably, the coupling agent in step (a′) is not a haloformate. Preferably, the coupling agent in step (a′) is selected from a carbodiimide, a 1,1′-carbonyl compound, or a mixture thereof. Preferably, the coupling agent in step (a′) is selected from 1,3-dicyclohexylcarbodiimide (DCC); 1,1′-carbonyldiimidazole (CDI); 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (water soluble carbodiimide hydrochloride, WSC.HCl); 1,3-diisopropylcarbodiimide (DIC); or a mixture thereof. Most preferably, the coupling agent in step (a′) is 1,1′-carbonyldiimidazole (CDI).
Preferably, the total amount of coupling agent used in step (a′) with respect to the suberic acid is between 1 to 5 molar equivalents, more preferably between 1 to 3 molar equivalents, even more preferably between 1 to 1.5 molar equivalents, and most preferably is about 1.3 molar equivalents.
Preferably, in a process according to the second aspect of the present invention, step (a′) is carried out in an organic solvent, preferably where the organic solvent is selected from dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), acetonitrile, 1,2-dichlorobenzene, ethanol or mixtures thereof. Most preferably, the organic solvent used in step (a′) is DMF.
Preferably, in a process according to the second aspect of the present invention, in step (a′), hydroxylamine is used in the form of a salt, most preferably the hydrochloride salt.
Preferably, the total amount of hydroxylamine, or its salt, used in step (a′) of the process of the second aspect of the present invention, with respect to the suberic acid is about 1 molar equivalent.
Preferably, in a process according to the second aspect of the present invention, step (a′) is carried out at a temperature of between 10-60° C., more preferably between 15-40° C., and most preferably between 25-30° C.
Preferably, the process according to the second aspect of the present invention comprises the use of a coupling agent in step (b′). Preferably, the coupling agent in step (b′) is not a haloformate. Preferably, the coupling agent in step (b′) is selected from a carbodiimide, a 1,1′-carbonyl compound, or a mixture thereof. Preferably, the coupling agent in step (b′) is selected from 1,3-dicyclohexylcarbodiimide (DCC); 1,1′-carbonyldiimidazole (CDI); 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (water soluble carbodiimide hydrochloride, WSC.HCl); 1,3-diisopropylcarbodiimide (DIC); or a mixture thereof.
Most preferably, the coupling agent in step (b′) is a mixture of 1,3-dicyclohexylcarbodiimide (DCC) and 1,1′-carbonyldiimidazole (CDI). Preferably, the mixture of CDI and DCC used in step (b′) is in a molar ratio range of 0.1:10 to 10:0.1 CDI:DCC, more preferably in a molar ratio range of 1:5 to 5:1 CDI:DCC, even more preferably in a molar ratio range of 1:2 to 2:1 CDI:DCC, and most preferably in a molar ratio of about 1:1.6 CDI:DCC.
Preferably, the total amount of coupling agent used in step (b′) with respect to the N-hydroxy-7-carboxy-heptanamide is between 1 to 5 molar equivalents, more preferably between 1 to 3 molar equivalents, even more preferably between 1 to 1.5 molar equivalents, and most preferably is about 1.3 molar equivalents.
Preferably, in a process according to the second aspect of the present invention, step (b′) is carried out in an organic solvent, preferably where the organic solvent is selected from dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), acetonitrile, 1,2-dichlorobenzene, ethanol or mixtures thereof. Most preferably, the organic solvent used in step (b′) is THF.
Preferably, the total amount of aniline, or its salt, used in step (b′) of the process of the second aspect of the present invention, with respect to the N-hydroxy-7-carboxy-heptanamide is between 1 to 10 molar equivalents, more preferably between 1 to 6 molar equivalents, and most preferably between 1 to 2 molar equivalents.
Preferably, in a process according to the second aspect of the present invention, step (b′) is carried out at a temperature of between 10-60° C., more preferably at a temperature of between 15-40° C., and most preferably at a temperature of between 25-30° C.
Preferably, in a process according to the second aspect of the present invention, step (a′) and step (b′) are carried out in the same organic solvent; preferably selected from dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane (DCM), acetonitrile, 1,2-dichlorobenzene, ethanol, or a mixture thereof; more preferably selected from THF, DMF, or a mixture thereof.
Preferably, in a process according to the second aspect of the present invention an activating agent is used in step (a′) and/or step (b′). Preferably, the activating agent is selected from cyanuric chloride, cyanuric fluoride, catecholborane, or a mixture thereof. The activating agent is preferably used in combination with the coupling agent.
Preferably, the process according to the first or second aspect of the present invention is carried out at a temperature of less than 170° C., preferably less than 130° C., preferably less than 100° C., more preferably less than 70° C.
Preferably, any reaction intermediates of the process according to the first or second aspect of the present invention are not purified. Preferably, the process according to the first or second aspect of the present invention is carried out without isolating any reaction intermediates.
Preferably, the process according to the first or second aspect of the present invention is carried out without the use of chromatography.
Preferably, the process according to the first or second aspect of the present invention is carried out on an industrial scale, preferably to obtain vorinostat in batches of 100 g, 500 g, 1 kg, 5 kg, 10 kg, 25 kg or more.
Preferably, the vorinostat is obtained in a yield of 30% or more, preferably 40% or more, preferably 45% or more, preferably 50% or more, from suberic acid.
Preferably, in a process according to the first or second aspect of the present invention, vorinostat is obtained with an HPLC purity of more than 99%, more preferably vorinostat is obtained with an HPLC purity of more than 99.5%, even more preferably vorinostat is obtained with an HPLC purity of more than 99.8%, and most preferably vorinostat is obtained with an HPLC purity of more than 99.9%.
In a third aspect of the present invention, there is provided vorinostat as prepared according to a process according to the first or second aspect of the present invention.
In a fourth aspect of the present invention, there is provided substantially pure vorinostat as prepared according to a process according to the first or second aspect of the present invention.
In a fifth aspect of the present invention, there is provided substantially pure vorinostat.
Preferably, the vorinostat according to the third, fourth or fifth aspects of the present invention is suitable for use in medicine, preferably for treating cancer, preferably skin cancer, more preferably cutaneous T-cell lymphoma (CTCL).
In a sixth aspect of the present invention, there is provided a pharmaceutical composition comprising the vorinostat according to the third, fourth or fifth aspects of the present invention. Preferably, the pharmaceutical composition according to the sixth aspect of the present invention is suitable for treating cancer, preferably skin cancer, more preferably cutaneous T-cell lymphoma (CTCL).
In a seventh aspect of the present invention, there is provided the use of the vorinostat according to the third, fourth or fifth aspects of the present invention and the use of the pharmaceutical composition according to the sixth aspect of the present invention, in the manufacture of a medicament for the treatment of cancer. Preferably the medicament is suitable for the treatment of skin cancer, most preferably the treatment of cutaneous T-cell lymphoma (CTCL).
In an eighth aspect of the present invention, there is provided a method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount of the vorinostat according to the third, fourth or fifth aspects of the present invention or a therapeutically effective amount of the pharmaceutical composition according to the sixth aspect of the present invention. Preferably, the method is for the treatment of skin cancer, most preferably the treatment of cutaneous T-cell lymphoma (CTCL). Preferably, the patient is a mammal, preferably a human.
DETAILED DESCRIPTION OF THE INVENTION
The present inventors have surprisingly found that vorinostat can be prepared with commercially acceptable yield and purity employing an extremely convenient process starting from suberic acid.
The present inventors explored the idea of reacting suberic acid directly and sequentially with aniline and hydroxylamine, in either order. The present inventors found that this direct reaction was possible using coupling agents for selective activation of the carboxyl functional groups in suberic acid. Surprisingly, the direct reactions were high yielding and afforded intermediates and products with very high purity.
Suberanilic acid was prepared by the direct reaction of suberic acid and aniline, very efficiently with good yields and purity, using coupling agents such as 1,3-dicyclohexylcarbodiimide (DCC); 1,1′-carbonyldiimidazole (CDI); 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (water soluble carbodiimide hydrochloride, WSC.HCl); 1,3-diisopropylcarbodiimide (DIC); or a mixture thereof.
Surprisingly, it was found that the use of 1,3-dicyclohexylcarbodiimide (DCC) and 1,1′-carbonyldiimidazole (CDI) in combination for the coupling of suberic acid and aniline controlled the formation of impurities to afford a very pure product and suberanilic acid was obtained with high yield (60-65%) and very high purity (typically greater than 99.5% as measured by HPLC).
In a second stage, initial attempts to convert suberanilic acid to vorinostat by using prior art methods such as reacting suberanilic acid with methyl chloroformate and hydroxylamine afforded poor yields and high levels of impurities. Consequently, even with repeated purification, the ICH controlled impurity profile for vorinostat could not be obtained.
However, the present inventors found that they could control impurity formation, in the conversion of suberanilic acid to vorinostat, by using coupling agents such as CDI, DCC, WSC.HCl or DIC to yield vorinostat with very high purity (typically greater than 99.5% as measured by HPLC).
Therefore, in a preferred embodiment, the present inventors have found that suberanilic acid can be reacted with commercially available hydroxylamine hydrochloride, using a coupling agent such as CDI, in a polar solvent such as DMF or THF, to afford vorinostat having a purity of greater than 99.5%.
Preferably, the vorinostat prepared by the process according to the present invention can be further purified by crystallization from a suitable solvent or mixture of solvents.
A preferred embodiment of the first aspect of the present invention is illustrated in Scheme 8.
Optionally, an activating agent can be used in step (a) and/or step (b) to afford products with high yields and purity. Preferably, the activating agent is selected from cyanuric chloride, cyanuric fluoride, catecholborane, or a mixture thereof. The activating agent is preferably used in combination with the coupling agent.
A preferred embodiment of the process according to the first aspect of the present invention comprises the following steps:
(i) taking a mixture of THF, CDI and DCC;
(ii) adding suberic acid;
(iii) adding aniline in THF to the solution from step (ii);
(iv) stirring at 25-30° C.;
(v) filtering off the solid dicyclohexyl urea formed in the reaction;
(vi) concentrating the filtrate in vacuo;
(vii) adding a solution of KOH in water;
(viii) filtering off the solid by-product;
(ix) heating the filtrate;
(x) adding aq. HCl;
(xi) isolating suberanilic acid;
(xii) mixing the suberanilic acid and CDI in DMF;
(xiii) adding hydroxylamine hydrochloride as solid to the mixture from step (xii);
(xiv) isolating vorinostat from the mixture obtained in step (xiii);
(xv) adding acetonitrile and aq. ammonia to the vorinostat from step (xiv);
(xvi) heating the mixture;
(xvii) cooling the mixture to 20-27° C.; and
(xviii) isolating pure vorinostat from the mixture obtained in step (xvii).
Preferably, by utilising the same organic solvent in steps (a) and (b), pure vorinostat can be obtained without isolation of any synthetic intermediate(s).
A preferred embodiment of the second aspect of the present invention is illustrated in Scheme 9.
The process according to the first or second aspect of the present invention is a very short, efficient process for the production of substantially pure vorinostat with no requirement for cumbersome purification techniques. Therefore the process of the present invention is extremely suitable for commercial production of substantially pure vorinostat.
The pharmaceutical composition according to the sixth aspect of the present invention can be a solution or suspension, but is preferably a solid oral dosage form. Preferred oral dosage forms in accordance with the invention include tablets, capsules and the like which, optionally, may be coated if desired. Tablets can be prepared by conventional techniques, including direct compression, wet granulation and dry granulation. Capsules are generally formed from a gelatine material and can include a conventionally prepared granulate of excipients.
The pharmaceutical composition according to the present invention typically comprises one or more conventional pharmaceutically acceptable excipient(s) selected from the group comprising a filler, a binder, a disintegrant, a lubricant and optionally further comprises at least one excipient selected from colouring agents, adsorbents, surfactants, film-formers and plasticizers.
If the solid pharmaceutical formulation is in the form of coated tablets, the coating may be prepared from at least one film-former such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose or methacrylate polymers which optionally may contain at least one plasticizer such as polyethylene glycols, dibutyl sebacate, triethyl citrate, and other pharmaceutical auxiliary substances conventional for film coatings, such as pigments, fillers and others.
The details of the invention, its objects and advantages are illustrated below in greater detail by non-limiting examples.
EXAMPLE 1
Stage 1: Conversion of Suberic Acid to Suberanilic Acid
A mixture of CDI (0.5 eq) and DCC (0.8 eq) in THF (15 vol) was stirred for 1 hour at 25-30° C. Suberic acid (1 eq) and aniline (1 eq) in THF (1 vol) was added and the mixture stirred for a further 16-20 hours. The solid by-product was removed by filtration and the filtrate was concentrated in vacuo at 50° C. The solid residue obtained was treated with a solution of KOH (2 eq) in water (10 vol) and stirred for 30 minutes at 25-30° C. and any solid by-product formed was removed by filtration. The filtrate obtained was heated at 60° C. for 3-4 hours and cooled to 20° C. before addition of an aqueous solution of HCl (17.5%, 3 vol). The mixture was stirred for 30 minutes and the solid filtered, washed with water (2×5 vol) and dried under vacuum at 60-65° C.
Molar Yield=60-65%
Purity by HPLC=99.5%
Stage 2: Conversion of Suberanilic Acid to Crude Vorinostat
The suberanilic acid (1 eq) obtained in stage 1 was dissolved in DMF (5 vol) and CDI (2 eq) was added at 25-30° C. and maintained for 30 minutes under stirring. Hydroxylamine hydrochloride (4 eq) was added and stirring continued for 30 minutes. Water (25 vol) was then added and the mixture stirred for 2 hours. The precipitated solid was filtered, washed with water (2×5 vol) and dried under vacuum at 50° C.
Molar Yield=70-75%
Purity by HPLC=99%
Stage 3: Purification of Crude Vorinostat
Aqueous ammonia (2.5 vol) was added to the crude vorinostat (1 eq) in acetonitrile (15 vol) at 25-30° C. The mixture was then maintained at 55-60° C. for 1 hour before being cooled to 20-25° C. and being stirred for a further hour. The resulting solid was filtered, washed with acetonitrile (2×0.5 vol) and dried under vacuum at 45-50° C. for 5 hours.
Molar Yield=55-60%
Purity by HPLC≧99.8%
EXAMPLE 2
Stage 1: Conversion of Suberic Acid to Crude Vorinostat
A mixture of CDI (0.5 eq) and DCC (0.8 eq) in THF (15 vol) was stirred for 1 hour at 25-30° C. Suberic acid (1 eq) and hydroxylamine (1 eq) in THF (1 vol) was added and the mixture stirred for a further 1 hour. Then CDI (0.5 eq), DCC (0.8 eq) and aniline (1 eq) were added to the mixture and the mixture was stirred for a further 16-20 hours. The solid by-product was removed by filtration and the filtrate was concentrated in vacuo at 50° C. to obtain crude vorinostat.
Molar Yield=55-60%
Purity by HPLC≧95.8%
Stage 2: Purification of Crude Vorinostat
Aqueous ammonia (2.5 vol) was added to the crude vorinostat (1 eq) in acetonitrile (15 vol) at 25-30° C. The mixture was then maintained at 55-60° C. for 1 hour before being cooled to 20-25° C. and being stirred for a further hour. The resulting solid was filtered, washed with acetonitrile (2×0.5 vol) and dried under vacuum at 45-50° C. for 5 hours.
Molar Yield=35-40%
Purity by HPLC≧99.8%
It will be understood that the present invention has been described above by way of example only. The examples are not intended to limit the scope of the invention. Various modifications and embodiments can be made without departing from the scope and spirit of the invention, which is defined by the following claims only.
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The present invention relates to an improved process for the preparation of the active pharmaceutical ingredient vorinostat. In particular it relates to a process for preparing vorinostat substantially free from impurities.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a centrifugal rpm governor, and in particular to a centrifugal rpm governor or regulator for fuel injected, internal combustion engines, especially diesel engines. Centrifugal rpm regulators of the type under consideration are provided with an adapter member (adapter sleeve) that is slidable under the influence of flyweights and in dependence on the rpm of the engine and in opposition to the force of idling and maximum rpm control springs. The adapter sleeve transmits its regulatory motions to a fuel supply quantity setting member which sets the fuel supply quantity of the fuel injection pump, this transmission taking place via at least one two-armed intermediate lever whose pivoting point is adjustable in dependence on the pivoted position of an operating lever. The excursion of the fuel quantity setting member in the direction of an increasing fuel supply quantity is limited by an adjustable stop equipped with a cam plate, which, in turn, is adjustable in dependence on engine rpm, the cam plate being adapted to determine the maximum fuel supply quantity. The stop is fastened by a stud to the regulator housing and is coupled with the adapter member via at least one control lever. The adapter member essentially comprises two mutually coaxially disposed portions, one a transmission member and the other a setting member which are held in their initial position by an intermediate spring installed between the two portions. The transmission member is coupled to the stop and the setting member is coupled to the intermediate lever. After performing an idling stroke, in opposition to the force of the idling control spring, the setting member encounters a stroke limiter which is influenced by the effective force of the top (maximum) rpm control spring. An energy storage mechanism is tensioned as soon as and as long as the intermediate lever attempts to move the fuel supply quantity setting member beyond the stop.
2. Description of the Prior art
A known centrifugal force rpm governor of the above-described construction operates as an idling rpm and maximum rpm regulator in which the position of the injection pump control rod, which serves as the fuel supply quantity setting member, is adjustable in dependence on the pivotal position of an operating lever. Further, a particular idling rpm, determined by an idling control spring, is maintained by control; and a maximum rpm, determined by a top rpm control spring, is limited. Still further, in the region between the idling rpm and the top rpm, the maximum fuel supply quantity is adapted to the full-load characteristics of the engine by an adjustable stop coupled to a transmission member of an adapter sleeve of the regulator. This process is known as a so-called "adaptation process." A cam plate disposed on the stop permits any desired process of adaptation, i.e., the fuel supply quantity of the injection pump can be altered in dependence on the rpm, both in the direction of an increasing, as well as in the direction of a decreasing, fuel supply quantity.
In this known centrifugal force rpm governor, the rpm-dependent path of the transmission member is determined by the pretension and the spring stiffness of an adaptation spring disposed between the transmission member and the setting member of the adapter sleeve. The utility of this governor is limited by the space available for installing the spring which itself is defined by the size of the adapter sleeve. Furthermore, an exchange of the adaptation spring, for example, or a change of the pretension or of the maximum path of the spring is possible only by substantial disassembly of the adapter sleeve and of other structural members of the regulator. The latter structural members include the idling and top rpm springs.
OBJECTS AND SUMMARY OF THE INVENTION
An object of the present invention is to provide a centrifugal rpm governor of the type described above in which the characteristics of the adaptation spring and the spring path can be changed independently of the structural size of the adapter sleeve and where this may occur without influencing the setting of the idling control spring and top rpm control spring and without the disassembly of important structural members of the regulator which determine the fundamental setting of the regulator.
This object and others are accomplished according to the present invention in that a stroke limitation is performed in a per se known manner by an unyielding part of a support lever which is pivotable about a fixed point in the regulator housing and which abuts against a stop, integral with the housing, under the influence of the force of the top rpm control spring. Furthermore, the idling control spring has an adjustable counterbearing which is disposed within the support lever but displaced parallel with respect to the axis of the adapter member, with the pretension force of the intermediate spring being greater than the maximum force of the idling control spring and with the pretension force and spring stiffness of the intermediate spring being smaller than the pretension force and spring stiffness of an adaptation spring which affects a yielding adaptation stop, known per se, and inserted in the support lever coaxially with the adapter member against which the transmission member abuts at the end of the idling stroke. By the combination of the previously-cited characteristics, together with those of the regulator cited at the outset that operates as an idling and top rpm regulator, the objects are achieved with surprising success.
According to one preferred embodiment of the present invention the setting member is guided within the transmission member and has a connecting member coupled to the intermediate lever and extends through at least one opening in the wall of the transmission member. An advantageous further embodiment of the present invention is achieved in that the connecting member consists of at least one lateral bolt guided in a guide slot disposed within the support lever and whose end opposite the adapter member forms the stroke limitation for the idling stroke.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a side view in elevation illustrating a longitudinal section through a centrifugal rpm governor according to the present invention; and
FIG. 2 is a cross-sectional view taken along the line II--II of FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Turning now to FIG. 1, there is shown a centrifugal rpm governor or regulator having a drive shaft 10 of an injection pump (not shown). Both the regulator and injection pump are used in conjunction with an internal combustion engine. The regulator includes a centrifugal governor 11 which is mounted on the shaft 10. The governor 11 is provided with pivotably mounted flyweights 12 with arms 13 that engage a front surface 14 of a thrust bearing 15. The thrust bearing 15 is mounted on the end 16a of a cylindrical extension of an adapter sleeve 16 serving as a control member. The thrust bearing 15 serves to transmit the adjustment forces of the flyweights 12 to the adapter sleeve 16. The adapter sleeve 16 consists essentially of two mutually coaxial portions, a transmission member 17 and a setting member 18. The setting member 18 is slidably mounted within a bore 19 of the transmission member 17 and is held in the installation position shown in FIGS. 1 and 2 by an intermediate spring 21. The intermediate spring 21 is supported on the one hand by a shoulder 22 in the bore 19 and on the other hand by one axial end surface of the setting member 18. The setting member 18 includes another axial end surface 23 which is pressed against a snap ring 24 inserted in the transmission member 17 to serve as a position limiter for the setting member 18. The setting member 18 is equipped with a transverse bolt 25 inserted transversely to its longitudinal axis. The transverse bolt 25 is fixed against rotation and includes two ends 25a and 25b which extend beyond the periphery of the adapter sleeve 16. This is made possible by openings 26 in the form of longitudinal slots machined into the wall of the transmission member 17. The openings 26 are open in the direction of the end 16b of the adapter sleeve 16, for the purpose of installing the setting member 18. These openings are long enough to enable a yielding motion, which will be described below, of the setting member 18 in opposition to the force of the intermediate spring 21.
The end 16a of the adapter sleeve 16 is slidably carried on a cylindrical guide or boss 27 of the drive shaft 10, while the guidance of the other end 16b of the adapter sleeve 16 is accomplished by the transverse bolt 25. The two ends 25a and 25b are guided in guide slots 28 of a support lever 29. The guide slots 28 are machined into mutually parallel guide arms 29a of the support lever 29, which, in turn, laterally envelop the adapter sleeve 16. The closed end 28a of the guide slots 28 serve as stroke limiters for the idling stroke of the regulator. The idling stroke is determined by the stroke of the transverse bolt 25 and is designated in FIG. 1 by a. The idling stroke a is transversed in opposition to the force of an idling control spring 31, embodied as a leaf spring, which is fastened to an extension 29b of the support lever 29 by means of a bolt 32. The support lever 29 carries an adjustable counter support bearing 33 embodied as a screw bolt which is adjustable for the purpose of changing the pretension of the idling control spring 31. The bolt 33 is screwed into the support lever 29 parallel too the axis of the adapter sleeve 16. The idling control spring 31 has an end 31a which is formed into the shape of a fork which embraces the transmission member 17 and which is engaged with the adapter sleeve 16 via the transverse bolt 25 (see especially FIG. 2). This arrangement of the idling control spring 31 has the advantage that when the idling stroke a has been traversed, it is not further moved during the remaining regulatory motions of the centrifugal rpm governor and hence is made inactive.
The support lever 29 is pivotably mounted to a housing 35 of the regulator by a bolt 34. The support lever 29 is influenced by the effect of the force of a top rpm control spring 36 supported on the one hand by the support lever 29 and on the other hand by an adjustable counterbearing 37 screwed into the regulator housing 35 and held in the adjusted position by a lock nut 38. Through the effect of the force of the top rpm control spring 36, the end 29c of the support lever 29 is pressed against a stop 39 fixed to the housing 35. The stop 39 is formed by the face of a stop screw 41 screwed into the regulator housing 35. In this way, the support lever 29 is held in its vertical normal position, as shown, until such time as a force deriving from the flyweights 12 and exerted by the adapter sleeve 16 on the support lever 29 is greater than the force of the top rpm control spring 36.
A lever 42 is connected on one end 25a of the transverse bolt 25 so that it will not rotate (FIG. 2), and together with the transverse bolt 25 forms a connecting member 43 which is mediately coupled to an intermediate lever 45 through the intermediate action of a motion regersing lever 44. The intermediate lever 45 is embodied as a slotted lever. The motion reversing lever 44 serves only and in a known manner for the reversal of motion of the intermediate lever 45 and is carried by a bolt 46 in the regulator housing 35. If this motion reversal is not desired, the transverse bolt 25 can also be coupled directly and pivotably with the intermediate lever 45. One arm of the motion reversing lever 44 has a bolt 47 which engages a guide slot 48 (FIG. 1) in the lever 42, while the other lever arm of the reversing lever 44 is pivotably connected with the intermediate lever 45 via a connecting bolt 49.
The intermediate lever 45 is embodied in a known manner as a two-armed slotted lever having a pivot stud 52 guided in a guide slot 51; the position of the stud 52 is changeable depending on the pivotal position of an operating arm 53 for changing the fuel supply quantity to be set by a control rod 54 serving as a fuel quantity adjustment member. The stud 52 extends in a known manner from a guide lever 55 which, in turn, is connected with the operating arm 53 via an adjustment shaft 56 mounted in the regulator housing 35. The control rod 54 and the intermediate lever 45 are connected with one another via a tab 58 equipped with an energy storing mechanism 57.
The energy storing mechanism 57 is equipped with a compression spring 59 and permits a further movement of the tab 58 and therefore also of the intermediate lever 45 in both of two possible directions of motion, i.e., whenever the control rod 54 is prevented from further motion, either in the direction of arrow V for controlling the maximum fuel supply quantity or in the direction of arrow S in the stop position.
Mounted on that end of the control rod 54 which extends into the regulator is a pin 61 which engages a slot 62 formed in one end of a stop lever 63. The stop lever 63, in the exemplary embodiment shown, is a two-armed lever mounted by a stud 60 to the housing 35. The stud 60 defines a pivot axis which is adjustable in the direction of the axis of the regulator. The stop lever 63 is equipped at its other end with a cam follower nose 64 which engages a cam plate 65 of a stop 66. The nose 64 engages the stop 66 during motions of the control rod 54 in the direction of maximum fuel supply (in the direction of arrow V) and in this way the stop 66 controls the maximum fuel supply quantity to be supplied which, in turn, corresponds to the curved cam surface 67 of the cam plate 65. This control of the full-load supply quantity of the injection pump is known as so-called "adaptation". The cam plate 65 is attached at points 68 to a motion transfer plate 69 of the stop 66, and the motion transfer plate 69 is rotatably mounted to the housing 35 by a stud 71. The motion transfer plate 69 includes an engaging slot 72 within which a pin 73 is received. The pin 73 is mounted to a guide lever 74 which, in turn, is pivotably mounted by a stud 75 to the housing 35. The guide lever 74 engages a stud 76 with its fork-shaped end 74, the stud 76 being fixedly connected by a tab 77 with the transmission member 17 of the adapter sleeve 16. During the motions of the transmission member 17, which serves as an adaptation sleeve in a manner further described below, the guide lever 74 and hence the stop 66 is pivoted or turned from the position shown into a position corresponding to the position of the displaced transmission member 17.
As an extension of the axis of the adapter sleeve 16, an elastically yielding adaptation stop 78 is inserted in the support lever 29. The essential structural member of the stop 78 is a stop pin 79 (see also FIG. 2) which is acted upon by an adaptation spring 81. The adaptation spring 81 is supported on the one hand against a shoulder 82 of the stop bolt 79 and on the other hand mediately against a bottom surface 83 of a bore 84, which serves for guiding the stop bolt 79. The bore 84 is machined into a threaded bushing 85. A disc 86 disposed between the adaptation spring 81 and the bottom surface 83 of the bore 84 serves for adjusting the pretension of the adaptation spring 81. The stop bolt 79 is held in its installed position by a snap ring 87 and the stroke b, controllable by the adaptation stop 78, can be adjusted by exchanging a disc 90 for another having a different thickness.
The idling stroke a of the regulator is so adjusted that it is equal to the distance of the transverse bolt 25 from the closed ends 28a (stroke limit). The face of the stop bolt 79 facing toward the adapter sleeve 16 is designated with the numeral 88 in FIG. 2. The face of the transmission member 17 lying opposite face 88 is designated 89 and the distance between the two is set for purpose of setting the idling stroke a (FIG. 1) by rotating the threaded bushing 85 of the stop 78 within the support lever 29. A removable cover 91 provides access to the adaptation stop 78 and therefore makes possible adjustment thereof or an exchange thereof without influencing other structural members. The removal of a closure screw 92 permits access to the adjustable counterbearing 33 of the idling control spring 31.
It is a prerequisite for the desired operation of the centrifugal rpm governor according to the present invention that the pretension Pz of the intermediate spring 21 is greater than the maximum force P1 max of the idling control spring 31; and that the pretension Pz and the spring stiffness Cz of the spring 21 are smaller than the pretension Pa and the spring stiffness Ca of the adaptation spring 81. The fact that the pretension Pz of the intermediate spring 21 is larger than the maximum force P1 max of the idling control spring 31 has the effect that in the region of idling regulation, during which the adapter sleeve 16 traverses the idling stroke a, the setting member 18 and the transmission member 17 act like a fixed member and, thus, the regulatory motions which are transmitted in the idling control region from the flyweights 12 via the arms 13 onto the adapter sleeve 16, are directly transmitted to the control rod 54 via the motion reversing lever 44, the intermediate lever 45 and the tab 58. For regulating the idling rpm, the operating arm 53 and the guide lever 55 connected thereto have been pivoted by a small amount in the counterclockwise sense. With the connecting bolt 49 fixed, the intermediate lever 45 is also pivoted counterclockwise and moves the control rod 54 via the tab 58 by a correspondingly small amount in the direction of arrow V. When the engine is running, the adapter sleeve 16 moves in the region of the idling stroke a and the fuel supply quantity corresponding to maintaining the idling rpm is controlled by the control rod 54 in a known manner. Because of the fact that the regulatory paths traversed by the control rod 54 during idling regulation are substantially smaller than the full-load regulatory path, the cam-follower nose 64 of the stop lever 63 does not contact the curved cam surface 67 of the stop 66 in the above-described motion of the control rod 54. Thus the control rod 54 can move freely. In the centrifugal force rpm regulator according to the present invention, which operates as an idling and top rpm regulator, all the movable parts in FIGS. 1 and 2 are shown in that position which they occupy when the engine is standing still and the operating arm 53 is in the shutoff position.
Having described the operation of the regulator during idling rpm regulation, regulator operation when maximum power, i.e., full-load power is demanded from the engine, will now be considered.
For the purpose of controlling the full-load power of the engine and the corresponding full-load fuel supply quantity, the operating arm 53 and the guide lever 55 fixedly connected thereto are either pivoted from the previously-described idling position or from the illustrated shutoff position, in the counterclockwise sense, until the operating arm 53 abuts a known full-load stop (not shown). In this process, the intermediate lever 45 is pivoted about its connecting bolt 49 in such a way that it moves the tab 58 and thus moves the control rod 54 in the direction of arrow V. This motion of the control rod 54 terminates when the cam-follower nose 64 of the stop lever 63, which is pivotable about its pivot stud 60, abuts the curved cam surface 67. If the adapter sleeve 16 is still in its illustrated position, then the energy storage mechanism is pretensed by an amount corresponding to the motion of the tab 58 caused by the intermediate lever 45 during the idling stroke a of the adapter sleeve 16.
When, during increasing rpm, the adapter sleeve 16 has traversed the idling stroke a in opposition to the force of the idling control spring 31, then the face 89 abuts the face 88 of the stop bolt 79 of the adaptation stop 78. During this process, the lever 42 connected with the setting member 18 has moved the intermediate lever 45 through the action of the motion reversal lever 44, so that the energy storage mechanism 57 is relaxed again.
Depending on the shape of the curved cam surface 67, it might be necessary that an appropriate pretension of the energy storage mechanism 57 must be present for the equalization of path differences effected by the curved surface 67.
When the rpm increases further, the forces exerted by the adapter sleeve 16, due to the centrifugal forces developed by the flyweights 12, are transmitted according to the present invention only by the transmission member 17 onto the adaptation stop 78 or its stop bolt 79. This occurs because after the idling stroke a has been traversed, the transverse bolt 25 of the setting member 18 is held fast to the end 28a of the guide slot 28 in the support lever 29. This separation between the setting member 18 and the transmission member 17 makes possible a flawless idling and top regulating characteristic of the regulator. Thus, by pivoting the operating arm 53, any desired partial load position of the control rod 54 can be set, independent of the prevailing rpm, in the region between the idling rpm and the top rpm to be limited. This is so because when the transverse bolt 25 has reached its stroke limit against the end 28a, the motion reversal lever 44 retains its position and thus the connecting bolt 49 serves as a fixed pivotal point for the intermediate lever 45.
When the idling stroke a has been traversed, and the rpm increases, and if the setting member 18 remains stationary, only the transmission member 17 moves in the direction toward the support lever 29 corresponding to the yielding movement of the stop bolt 79. During this process, the guide lever 74 turns stop 66 and the curved cam surface 67 of stop plate 65 moves past the cam-follower nose 64 of the stop lever 63 connected to the control rod 54, and, depending on the shape of the curved cam surface 67, the control rod 54 is displaced in the direction of arrow V, i.e. in the direction of an increasing fuel supply quantity, or in the direction of arrow S, i.e. in the direction of a decreasing fuel supply quantity. The shape of the curved cam surface 67 shown in FIG. 1 is such that, during the adaptation stroke b of the stop bolt 79, it causes at first a decreasing and subsequently an increasing fuel supply quantity. During this adaptation regulation and when the intermediate lever 45 is stationary, the spring storage mechanism 57 is tensed and subsequently relieved. If an opposite adaptation process is desired, then the previously pretensed spring 59 of the energy storage mechanism 57 is first relieved and then tensed again.
During the further motion of the transmission member 17, which can also be designated as an adaptation sleeve, by an amount equal to the adaptation stroke b, the intermediate spring 21 is compressed if the setting member 18 remains stationary and, at the same time, the adaptation spring 81 yields by the same amount.
It is possible that the cam plate 65 can be equipped in a known fashion with an offset (not shown) for controlling a starting excess fuel quantity and, by an appropriate shaping of the curved cam surface 67, any desired adaptation process can be realized.
If, in a partially loaded or unloaded engine, during further increasing rpm, the maximum rpm determined by pretensioning of the top rpm regulating spring 36 is exceeded, which is equivalent to a sleeve path greater than a + b, then the support lever 29 is pivoted counterclockwise about its fixed point 34 by the adapter sleeve 16 in opposition to the force of the top rpm regulating spring 36.
Since the stroke limiter end surface 28a of the transverse bolt 25 of the setting member 18 is a fixed structural member of the support lever 29, the transverse bolt 25 also moves away from the drive shaft 10 by the same amount as the transmission member 17 abutting the stop bolt 79. During this motion of transverse bolt 25, the motion reversal lever 44, pivotable about pivotal axis 46, is so pivoted by means of the lever 42 connected to the transverse bolt 25 that its connecting pin 49 rotates the intermediate lever 45 clockwise about its pivot 52 and, through tab 58, it moves the control rod 54 in the direction of arrow S into a position in which the fuel supply quantity of the injection pump is reduced until it corresponds to the power demanded from the engine and the rpm is held within the P-region or until such time as the fuel supply is entirely shut off.
Thus, by using the previously-describedd centrifugal force rpm regulator, operating as an idling and top rpm regulator, and desired adaptation process can be controlled in an advantageous manner in the speed region between the idling rpm and the top rpm in which no regulatory motions take place otherwise. The adaptation stop 78, which influences the rpm-dependent course of the adaptation stroke b, is so disposed, according to the present invention, that it can be adjusted or exchanged independently of and without influence on the setting of the idling control spring 31 and of the top rpm control spring 36 and this setting or exchange can occur in an advantageous manner without influencing the installed position of any movable part of the regulator.
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In a centrifugal rpm regulator for fuel injected internal combustion engines, a fuel quantity control rod is provided which receives the forces associated with the displacements of an adapter sleeve which, in turn, is displaceable under the influence of centrifugal flyweights and as a function of engine rpm. The regulator also includes an idling control spring, a maximum rpm control spring and an adapter stop having an adaptation spring, with the adapter sleeve comprising two mutually coaxially disposed portions and an intermediate spring therebetween. The pretension force of the intermediate spring is greater than the maximum force of the idling control spring and the pretension force and spring stiffness of the intermediate spring are smaller than the pretension force and spring stiffness of the adaptation spring.
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BACKGROUND
The present disclosure relates to a jig assembly for preparing a disk drive for inclusion in a computer.
Typically, during a hard disk drive (HDD) preparation process, side rails are attached to the edges of the HDD with 4 screws, two on each side. An example is shown in FIG. 4 , where respective side rails 10 are attached by screws 12 to the respective side edges 14 of an HDD 16 . Conventionally this is done manually using a hand-held power screwdriver. This is a time consuming process which induces shock (head slap).
SUMMARY
The object of the disclosure is to provide a jig assembly which is capable of reducing the HDD preparation process time and reducing measurable shock.
Accordingly, the present disclosure provides a jig assembly for preparing a disk drive for mounting in a computer.
A disk drive receiving bay is arranged to receive a disk drive in a first datum position and to receive a pair of side rails each in a second datum position.
At least one powered screwdriver is provided on each side of the bay, each screwdriver has a tool bit in register with a respective screw-threaded fixing device when a respective side rail is in the second datum position.
A respective actuator is provided for advancing each screwdriver towards the respective side rail such that the tool bit engages the respective screw-threaded fixing device, rotation of the tool bit causing the screw-threaded fixing device to be advanced into the screw-threaded hole in the respective edge of the disk drive whereby the side rail is retained tight against the edge of the disk drive, and for thereafter retracting the screwdriver.
BRIEF DESCRIPTION OF THE DRAWINGS
An embodiment of the present disclosure will now be described with reference to the accompanying drawings, in which:
FIG. 1 is a front view of a jig assembly according to a preferred embodiment of the present disclosure;
FIG. 2 is a front view of an embodiment of the jig assembly of FIG. 1 with a loaded disk drive and side rails;
FIG. 3 illustrates an embodiment of the act of loading the disk drive side rails into the jig assembly of FIG. 1 ;
FIG. 4 illustrates an embodiment of a prepared disk drive being withdrawn from the jig assembly of FIG. 1 ;
FIG. 5 is an embodiment of an underside view of the jig assembly of FIG. 1 ; and
FIG. 6 is a diagram of an embodiment of the pneumatic control circuit of the jig assembly of FIG. 1 .
DETAILED DESCRIPTION
Referring to the drawings, the jig assembly is designed to automatically screw two side rails 10 , FIGS. 3 and 4 , to respective opposite side edges 14 of a hard disk drive (HDD) 16 , each side rail 10 being affixed using two captive screws 12 .
The jig assembly comprises a bay 20 recessed into the front panel 22 of a rack or framework (not shown). The bay 20 is adapted to receive the HDD 16 “letterbox” style, the HDD 16 being slid in from the front of the bay on a steel base plate 23 (FIG. 5 ). This substantially reduces “head slap”. Opposite sidewalls 24 of the bay are stepped and the HDD 16 is received snugly between the more closely spaced upper parts 24 a of the sidewalls, as seen in FIG. 2 . At its rear the bay 20 has a pneumatic limit switch S 1 . The switch S 1 is closed when the HDD 16 is pushed fully home in the bay 20 —this defines the datum position of the HDD 16 in the bay 20 .
The lower parts 24 c of the stepped sidewalls 24 are displaced outwardly relative to the upper parts 24 a and are joined to the latter by horizontal transition parts 24 b. A respective side rail support member 28 is disposed below each transition part 24 b in the recess formed by the outwardly displaced parts 24 c of the sidewalls 24 . The support members 28 are elongated in the front-to-rear direction of the bay 20 and have a generally C-shaped cross-section. They are substantially parallel to one another and each has upper and lower longitudinal grooves 30 a, 30 b respectively.
Each support member 28 is mounted on a pair of guide rods 32 , FIG. 5 , for movement towards and away from the opposite side edges 14 respectively of an HDD 16 accommodated in the bay 20 , i.e. in the direction of the double-headed arrows in FIG. 1 . and is also coupled to the piston 34 of a respective single-acting pneumatic cylinder C 2 . Each support element 28 receives and retains a respective side rail 10 , the side rail 10 being slid in from the front of the bay 20 and the upper and lower edges thereof sliding in the respective grooves 30 a , 30 b . Initially, when the side rails 10 are slid in, the support members 28 are retracted against the lower sidewall parts 24 c , as seen in FIG. 1. A further pneumatic limit switch S 3 or S 4 at the rear end of each support member 28 is closed when the respective rail 10 is pushed fully home in the support member 28 which defines the datum position of each HDD side rail 10 in the bay 20 .
As stated, each side rail 10 has two captured screws 12 . When the HDD 16 and rails 10 are in their datum positions, the screws 12 are in register with corresponding screw-threaded holes (not shown) in the side edges 14 of the HDD 16 . The heads 12 a of the screws are also in register with respective holes 29 ( FIG. 1 ) in the support members 28 , so that the screw heads 12 a can be accessed from the other side of the support member 28 through the holes 29 .
On each side of the bay 20 a pair of pneumatic screwdrivers 40 are clamped in a pair of stocks 42 , FIG. 5 . The screwdrivers are of the type sold by Uryu of Japan under the model number US-LT20. Each pair of stocks 42 (and correspondingly the screwdrivers 40 clamped therein) is mounted on a pair of guide rods 44 for movement towards and away from the respective support members 28 , and is also coupled to the piston 46 of a respective double-acting pneumatic cylinder C 1 . The tool bits 48 of the screwdrivers are aligned with the respective holes 29 ( FIG. 1 ) in the support members 28 , so that the screw heads 12 a can be engaged by the tool bits 48 through the holes 29 when the screwdrivers are advanced towards the support members 28 .
In operation of the jig assembly, the HDD 16 and side rails 10 are loaded into the bay 20 as previously described, the HDD 16 being slid on the base plate 23 and the rails 10 being slid in the support members 28 . As soon as the last of the three pneumatic switches S 1 , S 3 and S 4 is closed, indicating that the HDD 16 and both side rails 10 are in their datum positions, a pneumatic control circuit ( FIG. 6 , to be described) automatically actuates the pneumatic cylinders C 1 to drive the stocks 42 , and hence the screwdrivers 40 , inwardly towards the HDD 16 (at the same time, the control circuit supplies pneumatic pressure to the screwdrivers 40 ).
At some point each tool bit 48 will engage a respective screw head 12 a and the screwdrivers react to the pressure of bearing against the screw heads 12 a and begin to turn. As the tool bits 48 turn, the screws 12 are driven into the respective screw-threaded holes (not shown) in the side edges 14 of the HDD 16 so that each rail 10 is drawn towards the HDD 16 . This in turn also draws the support members 28 within which the rails 10 are retained towards the HDD 16 . The screwdrivers 40 are set to switch off automatically at a pre-determined torque limit when the rails 10 are screwed tight against the side edges 14 of the HDD 16 . The control circuit causes the cylinders C 1 to retract the screwdrivers 40 automatically after a pre-determined time period has elapsed. This time period, which is set by a pneumatic timer T 1 , is sufficiently long to enable the screws 12 to be tightened as aforesaid.
The operator is now free to withdraw the prepared disk drive, which he does by sliding the HDD 16 with affixed side rails 10 as a unit out of the bay 20 , FIG. 4 . In doing so, a further pneumatic limit switch S 2 located towards the front of the bay 20 is de-actuated having been actuated on insertion of the rails 10 . This automatically causes the control circuit to drive the cylinders C 2 to retract the now vacant support members 28 back to their original positions ( FIG. 1 ) whereupon the HDD preparation cycle is complete.
FIG. 6 is a diagram of the pneumatic control circuit used to control the jig assembly of FIGS. 1 to 5 . In FIG. 6 , C 1 and C 2 are pneumatic cylinders, V 1 and V 2 are double pilot 5/2 valves, V 3 and V 4 are single pilot 5/2 valves, T 1 is a pneumatic timer, and S 1 to S 4 are mechanically-operated pneumatic 3/2 limit switches. P stands for pressure supply, the ground symbol is atmospheric pressure (vented), and the T symbol means a closed inlet/outlet.
When each of switches S 1 , S 3 and S 4 are closed, indicating that both the rails 10 and the HDD 16 have all been inserted in the bay 20 to their datum positions, P will be connected to the A outlet of each switch in sequence so providing pressure at the outlet A of S 4 . This causes valve V 2 to vent outlet B and so allows the cylinders C 2 to float. This enables the support members 28 to be drawn, with the rails 10 , towards the edges 14 of the HDD.
When the prepared drive is withdrawn from the jig assembly, the switches S 1 -S 4 spring open, so connecting the outlet A of S 4 to atmospheric pressure. S 2 will be the last switch to spring open and causes the pressure from valve V 3 outlet B to switch valve V 2 so that pressure from valve V 2 outlet B retracts the cylinders C 2 (this will only happen when pressure is removed from the outlet of S 4 so venting the right pilot of V 2 ).
A pneumatic timer T 1 operates by bleeding the air pressure from the A outlet of S 4 until the timer switches over after a set period. This period is the time after insertion of the disk drive into the jig when the screwdrivers will be retracted and during this period the outlet of T 1 is vented.
The valve V 4 is needed to vent the left pilot of V 1 to allow the timer T 1 to actuate the right pilot of V 1 and so cause the cylinders C 1 to retract. Thus, before T 1 switches, the top pilot for V 4 is vented and so the spring on the other pilot channels the pressure supplied from S 4 to the left pilot of V 1 to cause the screwdrivers 40 to extend as soon as pressure is supplied from S 4 on initial insertion.
Variations of the pneumatic circuitry are possible; for example, a pneumatic reset switch can be included so that, for example, if an operator inserts a drive without correctly inserting the rails, cylinders C 1 , C 2 can be retracted to their home positions.
The advantages of the above embodiment are that, save for the manual withdrawal of the complete HDD, it is fully automatic once the components are properly loaded into the jig assembly. No external controls require to be activated to initiate the assembly cycle. It will also be seen that only a pneumatic supply is required to operate the jig assembly—no electrical elements (power or controls) are required.
The jig assembly described above directly confers a 75% reduction (from 40 sec to 10 sec) in HDD preparation time and reduces shock induced by the assembly of the rails to below measurable levels (from 90G to less than 10G). This materially reduces the level of HDD failure in the field.
The disclosure is not limited to the embodiment described herein which may be modified or varied without departing from the scope of the disclosure.
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A jig assembly for preparing a disk drive for mounting in a computer comprises a bay arranged to receive a disk drive and a pair of side rails to be fixed to opposite edges of the disk drive. Each side rail has captive screws in register with a respective screw-threaded hole in the edge of the disk drive. Two powered screwdrivers on each side of the bay are in register with the screws and are mounted for movement towards and away from the respective side rail. When the disk drive and rails are loaded into the bay, pneumatic cylinders C1 automatically advance the screwdrivers towards the side rail to engage and rotate the screws to screw the side rails tight against the edge of the disk drive, and then retract the screwdrivers.
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RELATED APPLICATIONS
[0001] This application: is a divisional of U.S. patent application Ser. No. 14/600,270, filed Jan. 20, 2015; which is a continuation of U.S. patent application Ser. No. 13/676,292, filed Nov. 14, 2012, issued Feb. 10, 2016 as U.S. Pat. No. 8,950,055; which is a continuation-in-part of U.S. patent application Ser. No. 14/448,684, filed Jul. 31, 2014, issued Feb. 16, 2016 as U.S. Pat. No. 9,263,864; which is a continuation-in-part of U.S. patent application Ser. No. 13/676,292, filed Nov. 14, 2012, issued Feb. 10, 2016 as U.S. Pat. No. 8,950,055; all of which are hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] This invention relates to lightning protection systems and, more particularly, to novel systems and methods for anchoring cables and points thereof.
BACKGROUND ART
[0003] Lightning arresters are central to power systems. Typical power delivery and transmission systems involve towers or power poles holding long expanses of power-carrying cables high above the surface of the earth and across large tract of land. The power delivery systems of the public utilities create a grid across the country connecting cities, power plants, substations, generators, dams, and so forth.
[0004] Surge arresters or lightning arresters are responsible for drawing the current from lightning into conductors that will conduct the energy to ground. Accordingly, they may involve wires and air terminals above the level of the power carrier cables. Meanwhile, addition surge protection may be provided to assure that no breakdown occurs in the insulators that insulate the main power carrier lines from their towers or poles that suspend them above the earth.
[0005] Buildings have a similar problem. They stand above the earth and tend to draw lightning. Thus, lightning rods date from very early days in America. Basic lightning rod systems of yesteryear involved an air terminal or “point” that was typically fastened to extend above the highest point of a building. This air terminal or point was connected to a cable that conducted electricity from the point down to ground, literally the surface of the earth.
[0006] With modern architecture and modern buildings, the problem has become more complex in that multiple air terminals or points may be attached to a building, and a building may not have a single highest location. Often, with false fronts, parapets, and other architectural features, a rather large expanse of a building architecture may be located at the “highest” location.
[0007] Lightning protection for buildings has progressed according to certain standards. Typically, cables of a suitable size will be connected, anchored at approximately every three feet along their length, and run from point to point, where a “point” indicates an air terminal or a lightning “point” as that term is used in the art. Typically, all the points on a building will be connected to one another and to a grounding cable that carries any electrical power received from the points down to the ground.
[0008] Nevertheless, interfacing hardware with a building presents a design question. For example, buildings may be constructed of wood, masonry, concrete, steel, glass, combinations and so forth. The range of materials and their material properties vary widely. Similarly, lightning protection is not the only consideration in designing a building.
[0009] Meanwhile, lightning protection may often be provided retroactively. Buildings may already exist, and lightning protection may not have been designed into them. By the same token, even when lightning protection is contemplated during the architectural phase of a building, the attachment scheme of a lightning protection system is a consideration that must be dealt with in view of the other architectural features of the building.
[0010] At present, electrical fasteners are connected by any suitable means, which usually involves fastening to a structural portion of the building. Thus, protective covers, plates, caps, sheeting, flashing, or other mechanisms for protecting the upper reaches of a building from weather may be damaged, penetrated, breached, or otherwise compromised by the fasteners of a lightning protection system. What is needed is a less invasive lightning protection system.
BRIEF SUMMARY OF THE INVENTION
[0011] In view of the foregoing, in accordance with the invention as embodied and broadly described herein, a method and apparatus are disclosed in one embodiment of the present invention as including an anchor suitable for supporting the weight of a cable, a point, or other accessories associated with a lightning arrester system. In certain embodiments, an anchor in accordance with the invention may include a base or plate from which a stud extends. In this embodiment, the base or plate and the stud together form a mounting system to which to secure a bracket or other device designed to secure a cable, point, or the like.
[0012] For example, an adhesive pad or interface pad may be secured to the flat, back side of the plate, opposite the stud on the other side. The pad may provide differential strain and stress between a portion of the building or a location of the building where the anchor is mounted, and the material of the base.
[0013] Likewise, the material of the pad may be selected to provide shock resistance, sealing, flexibility, impact resistance, adhesion, and a reconciliation of differing coefficients of thermal expansion between the material of the building and the base of the anchor secured thereto.
[0014] In some embodiments, the stud may be threaded to receive a nut or other keeper. Similarly, ratchets, binding slides, keys, pins, and other types of fasteners may be used to secure brackets to the stud in order to anchor points, cables, or both to the anchor, which in turn secures them to the building.
[0015] In certain embodiments, a building may include a parapet, wall, or other architectural feature that acts as the extremum the maximum distance away from the ground. Accordingly, this parapet or wall may have a flashing, cap, protection, seal, coating, or the like protecting it from the elements. Accordingly, the pad may be provided with a structural adhesive that secures the pad to the flashing, seal, cover, cap, or the like of the building. Thus, the anchor need not penetrate the protection provided against weather on the building. In certain embodiments, the stud may hold a bracket of any suitable type that will secure a point, a standoff, a bracket, a clip, or other holder suitable for holding a component of the lightning protection system.
[0016] In yet another embodiment, an integrated or universal anchor may be formed from sheet metal to have arms that extend away from the base or plate a certain distance, cantilevering with respect thereto and deflecting in a response to force. The arms may extend and be bent or otherwise formed into guides, which may terminate in retainers. In certain embodiments, the cables may be pushed against the guides, which act as springs and also push against the arms, such that the guides and arms together deflect away from the cable, thus opening a gap suitable for receiving the cable against the base. In response to the cable snapping in past the guides, the arms and guides may return to their unstressed positions, capturing the cable by a retainer connected thereto. Thus, the cable may be held permanently, in a very simple system that snaps the cable into place.
[0017] In one embodiment of a process in accordance with the invention, a user may select parameters controlling the performance of an anchor, and select properties of materials and structures. Securements may be selected, after which materials meeting the parameters, properties, and structures may be selected. Stock may be cut and anchors may be assembled, fabricated or otherwise manufactured.
[0018] Providing an instruction for installation procedures and operating procedures with a packaging for the anchors, a manufacturer may distribute the anchors to installers. Installers may then analyze specifications for their installation, select sizes, materials, and processes suitable and apply the anchors to a building. Thereafter, the cables and points may be installed with other ancillary equipment, secured by the anchors.
[0019] For example, in one embodiment one may size the anchors in order to minimize the leverage, moment, or couple (engineering terms, used here as known in the engineering art) to support the weight of cables. The cables need to be supported not only against their own dead weight, but also against the weight of pulling or tensioning to which installers will subject the cables in order to minimize the sag in the cables.
[0020] Selecting a pad material may be done at the time of manufacture of an anchor, or may be done at a different time. Typically, pads will be sized, cut, and applied to anchors in a manufacturing situation. The pads will then be applied to a building as part of the anchor. An installer may remove a protective coating, such as a polymer film attached to an adhesive layer of the pad or on the pad in order to expose the pad for use. An installer may select a location on a building, and may need to clean that location.
[0021] For example, dust, debris, oxidized base material, and the like may interfere with adhesion. Therefore, a location on a building may be cleaned by solvents, scrubbing, wiping, or the like. Removing any protective layer will expose the pad such that the anchor can then be applied.
[0022] Applying a cure condition may be required for one of several reasons. For example, polymers may need time, heat, ultraviolet light, or other chemical effects in order to cure. In certain embodiments, where materials are adhesives that do not rely on the chemistry of their base material or of the location to which attached, materials may simply need time in order to fully flow, creep, or otherwise secure to an anchoring location. By whatever means required, application of a cure condition may be followed by positioning cables, including tensioning them in order to reduce sag. Thereafter, the cables may be bound to the anchors by brackets, whether integrated, bolted on, or the like.
[0023] Such a system provides many benefits. The load is distributed over a much larger area by anchors in accordance with the invention. The actual cross sectional area of material from the cover or wall protection to which an anchor may be secured is substantially larger than that of a threaded-in fastener, which penetrates and engages a small fraction of a square inch of area of building material. Moreover, there is no penetrating whatsoever of the seal, cap, flashing, or other protection materials and structures of the building. Thus, capillary action is absent to damage the building covered by the protection of the cap, seal, or the like.
[0024] Moreover, there is no caulking step to put a washer, caulk, putty, or the like around the area where a penetration has been put through a protective layer, into a wall, or both. Rather, the pad may form a seal to survive many freeze and thaw cycles. It may be selected of a material that will not harden with time, temperature extremes, or the like.
[0025] Likewise, there will be no need to set up a system of anchors limited to proceeding along horizontal surfaces at the top of a building. There need be no waiting for a period of days before they will sufficiently cure to hold. If some systems are used on vertical surfaces, they must be maintained above a minimum temperature, typically around fifty degrees Fahrenheit, and maintained for several days, typically two to three, before they are sufficiently cured to hold. Even then, they may have wide spread failures.
[0026] In accordance with the invention, non-penetrating, comparatively rapidly mounted, supports may be installed as anchors on vertical surfaces.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 is a perspective view of one embodiment of a non-penetrating anchor for a lightning arrester cable support in accordance with events;
[0028] FIG. 2 is a rear perspective view of the anchor of FIG. 1 ;
[0029] FIG. 3 is a front elevation view of the apparatus of FIG. 1 ;
[0030] FIG. 4 is a rear elevation view thereof;
[0031] FIG. 5 is a top plan view thereof;
[0032] FIG. 6 is a bottom plan view thereof;
[0033] FIG. 7 is a left elevation view thereof;
[0034] FIG. 8 is a right side elevation view thereof;
[0035] FIG. 9 is a frontal perspective view of an alternative embodiment relying on a circular base plate for the anchor of FIG. 1 ;
[0036] FIG. 10 is a rear perspective view thereof;
[0037] FIG. 11 a front elevation view thereof;
[0038] FIG. 12 is a rear elevation view thereof;
[0039] FIG. 13 is a top plan view thereof;
[0040] FIG. 14 is a bottom plan view thereof;
[0041] FIG. 15 is a left side elevation view thereof;
[0042] FIG. 16 is a right side elevation view thereof;
[0043] FIG. 17A is a frontal perspective view of an alternative embodiment relying on an oval shape for the base plate of the anchor of FIGS. 1 and 9 ;
[0044] FIG. 17B is a rear perspective view of the anchor of FIG. 17A ;
[0045] FIG. 18A is a front elevation view thereof;
[0046] FIG. 18B is a rear elevation thereof;
[0047] FIG. 18C is a top plan view thereof;
[0048] FIG. 18D is a bottom plan view thereof;
[0049] FIG. 18E is a left side elevation view thereof;
[0050] FIG. 18F is a right side elevation view thereof;
[0051] FIG. 19A is a frontal perspective view of an alternative embodiment relying on a diamond shape for the base plate of the anchor;
[0052] FIG. 19B is a rear perspective view thereof;
[0053] FIG. 19C is a front elevation view thereof;
[0054] FIG. 19D is a rear elevation view thereof;
[0055] FIG. 19E is a top plan view thereof;
[0056] FIG. 19F is a bottom plan view thereof;
[0057] FIG. 19G is a left side elevation view thereof;
[0058] FIG. 19H is a right side elevation view thereof;
[0059] FIG. 20 is an exploded view of one embodiment of an anchor in accordance with the invention, this having two studs rather than a single stud as in FIGS. 1-19 , and including an exemplary bracket with fasteners, a point, and so forth;
[0060] FIG. 21 is a partially cut away, exploded view and assembly view of two embodiments of brackets for anchoring cables with the anchors in accordance with the invention;
[0061] FIG. 22 is a frontal perspective view of an alternative embodiment of a universal anchor providing quick insertion and retention of cables in an anchor system in accordance with the invention;
[0062] FIG. 23A is a front elevation view thereof;
[0063] FIG. 23B is a rear elevation view thereof;
[0064] FIG. 23C is a top plan view thereof;
[0065] FIG. 23D is a bottom plan view thereof;
[0066] FIG. 23E is a left side elevation view thereof;
[0067] FIG. 23F is a right side elevation view thereof;
[0068] FIG. 24 is an exploded view of the anchor of FIG. 22 illustrating the presence of the securant pad behind the base plate thereof and the cable to be inserted therein;
[0069] FIG. 25 is an assembled view of the anchor of FIGS. 22-24 , secured to a covering or cap such as a flashing over a wall or parapet at the top of a building;
[0070] FIG. 26A is a frontal perspective view of an alternative embodiment of a universal anchor, this having an ability to completely cover the front of the secured cable;
[0071] FIG. 26B is a frontal perspective of the embodiment of FIG. 26 a , illustrating a cable, shown in a partially cut away view and retained therein;
[0072] FIG. 27A is a front elevation view of the embodiment of FIGS. 26A-26B ;
[0073] FIG. 27B is a rear elevation view thereof;
[0074] FIG. 27C is a top plan view thereof;
[0075] FIG. 27D is a bottom plan view thereof;
[0076] FIG. 27E is a left side elevation view thereof;
[0077] FIG. 27F is a right side elevation view thereof;
[0078] FIG. 28 is a schematic block diagram of one embodiment of a method for manufacturing and installing anchors in accordance with the invention, such as the anchors of FIGS. 1-27 ; and
[0079] FIG. 29 is a schematic block diagram of the details of one alternative embodiment of a method for using an anchor in accordance with the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0080] Referring to FIG. 1 , and generally to FIGS. 1-21 , an anchor 10 may be formed to have a base plate 12 . The base plate 12 will typically be secured to a building in order to support lightning protection cabling interconnecting several points or rods extending upward to cause a high voltage stress field around the distal end or tip thereof.
[0081] Accordingly, such points are typically formed of rod of a suitable diameter, and having a length of from about 8 to about 24 inches. Accordingly, each of these points tends to cause a stress concentration field of voltage potential about the distal end thereof. This preferentially causes each of these tips of these points or rods to be the first items struck by lightning, rather than having other structural or electrical components of the building take such a risk.
[0082] Anchors 10 in accordance with the invention may be distributed around walls, parapets, cupolas, or other extremities of a building. Typically, a ridge line, a parapet around a roof region, or the like may receive the anchors 10 . The anchors 10 will support various fasteners (a term of art in lightning protection technology), which may be thought of as mechanical brackets, or other securement mechanisms to hold cables, the points, and so forth.
[0083] The base plate 12 may be fabricated with a stud 16 , in a manufacturing process similar to that of manufacturing a bolt, a nail, or the like. In an alternative embodiment, the studs 16 may be attached to the base 12 after individual fabrication of each 12 , 16 .
[0084] The base plate 12 may be provided with a pad 14 that operates as a seal, and adhesive mechanism, a thermal expansion attenuator, a strain attenuator, and so forth. That is, between the base plate 12 and a corresponding portion of a building, a differential in coefficients of thermal expansion may exist. Similarly, temperature variations may change properties.
[0085] Likewise, freezing and thawing may intervene in capillary spaces between the base plate 12 and a building. A freeze-thaw cycle will eventually separate the base plate 12 of the anchor 10 from the building. Accordingly, the pad 14 may be, for example, a closed-cell foam of a particular type suitable for the task to form a seal. Likewise, the pad 14 may be provided with an adhesive material on the opposing surfaces faces in order to bond to a building and to the base plate 12 .
[0086] In certain embodiments, the pad 14 has been found to serve well if fabricated of an acrylic expanded foam or expanded acrylic, commonly known as a foam. Likewise, various acrylate adhesives have been found suitable for rendering the pad 14 pressure sensitive, curable or both in bonding to the base 14 .
[0087] Referring to FIGS. 1-2 , as well as FIGS. 3-19 (including 19 A- 19 C) illustrate various embodiments of an anchor 10 . In these embodiments, the stud 16 protrudes at a right angle or perpendicularly with respect to the front face 18 or surface 18 of the base plate 12 . Meanwhile, the back face 20 or surface 20 of the plate 12 receives the pad 14 . The pad 14 is mechanically adhered thereto to support the stress, strain, tension, compression, and shear that may be applied to the pad 14 by loads introduces through the studs 16 to the base 12 .
[0088] Meanwhile, the face 22 or front face 22 of the pad 14 adheres by way of an adhesive applied thereon or forming the face 22 thereof. This will bond to the back face 20 of the base plate 12 . Similarly, the rear face 24 or surface 24 of the pad 14 is also provided with an adhesive quality, whether applied as a separate material, or as an integral part of the pad 14 . The face 24 may be covered with a protective layer, not shown, in order to protect the face 24 against debris, and maintain it completely clean and operable. Removing the layer exposes the adhesive for adhering the rear face 24 to a suitable surface in a building.
[0089] The studs 16 may include a tip 26 formed as a screw or bolt. Typically, the tip 26 will be slightly tapered, in order to pilot the studs 16 into a threaded fastener or keeper, such as a nut.
[0090] At the opposite end of the studs 16 is the root 28 and or root portion 28 . The root portion 28 may or may not be threaded. That is, threads 30 near the tip 26 may receive a fastener, such as a keeper, nut, or the like. Meanwhile, if the threads 30 continue all the way to the root 28 , then very thin materials may be held snugly against the front face 18 of the plate 12 by such fasteners. Nevertheless, in some embodiments, the threads 30 need not proceed all the way to the root 28 of the studs 16 .
[0091] Referring to FIGS. 3-19 , note that trailing letters indicate drawings or figures in a set, having some relationship. Thus, herein, the text may refer to FIG. 19 , to include FIGS. 19A, 19B, 19C , and so forth. FIGS. 3-8 illustrate the orthogonal views of the apparatus of FIGS. 1 and 2 . FIG. 2 illustrates a partially cut away pad 14 in order to illustrate the back surface 20 of the plate 12 . In some embodiments illustrated herein, the pad 14 will be removed, and only the plate 12 and stud 16 of the anchor 10 will be illustrated. In other embodiments, or illustrations the pad 14 will be in place. In FIGS. 3-8 , the various orthogonal embodiments illustrate the rectangular, or square plate 12 with its associated studs 16 .
[0092] Referring to FIGS. 9-10 , a perspective view from the front and rear of an alternative embodiment is shown, relying on a circular plate 12 . One advantage of a circular plate 12 is that orientation of the plate 12 becomes less significant. For example, with a rectangular or otherwise cornered plate 12 , orientation will be obvious to the eye of a casual observer. In contrast, a circular plate 12 is point symmetric and need not be oriented in a specific manner in order to operate and yet to appear aesthetically pleasing.
[0093] Referring to FIGS. 11-16 , the various orthogonal views of the embodiment of FIGS. 9-10 look very similar to those of FIGS. 3-8 .
[0094] Referring to FIGS. 17A-17B , a frontal and rear perspective view of an oval embodiment of a base plate 12 needs to be oriented, but the precision required of straight lines may not be required. In this embodiment, the long axis of the elliptical or oval shape will typically be oriented vertically in order to provide more leverage advantage by the base plate 12 , and particularly, a pad 14 . In this way, the leverage of the studs 16 will be reduced against peeling or tipping the base plate 12 and pad 14 away from a wall to which it is attached.
[0095] Referring to FIGS. 18A-18F , the orthogonal views of the embodiment of FIGS. 17A-17B are illustrated. Again, these views appear very similar to those of FIGS. 11-16 , with a major and minor axis, rather than a single diameter.
[0096] Referring to FIGS. 19A-19B , a diamond shape may be suitable for one embodiment of a plate 12 in accordance with the invention. In this embodiment, the vertical dimension is a maximum, again providing additional leverage, compared to a square embodiment. Even if the square embodiment of FIGS. 1-2 were installed in a diamond configuration, the maximum vertical dimension of the installed plate 12 would have about 40% more length. This may provide, accordingly, more leverage, and a greater supporting “moment” as that terms is used in engineering.
[0097] Referring to FIG. 19C , a front elevation view of the embodiment of FIGS. 19A-19B illustrates that the other orthogonal views are unnecessary in order to have a clear understanding of the shape from each direction. Again, this embodiment militates in favor of a comparatively precise orientation. This is not so much for mechanical strength, which would very little with a matter of a few degrees of rotation of the plate 12 against the surface. Rather, it is valuable for aesthetics, where any orientation away from vertical would be immediately noticeable to a casual observer.
[0098] Referring to FIG. 20 , an exploded view of one embodiment of an anchor 10 in accordance with the invention illustrates the pad 14 backing the base plate 12 to which the studs 16 are secured, fabricated, attached, or integrally manufactured. In this embodiment, a keeper 32 , such as a nut 32 is used to thread onto the threads 30 of the stud 16 . This will secure a fastener 34 to the plate 12 , and thus to the mounting surface 35 of a building.
[0099] In this embodiment, the studs 16 pass through apertures 36 , thus making themselves available for receiving the keeper 32 or the nut 32 . As each nut 32 is threaded toward the root 28 , beginning at the tip 26 of the stud 16 , the fastener 34 is drawn toward the front face 18 of the base plate 12 . In the illustrated embodiment, a stand off 38 extends away from the base plate 12 , in order to support a point 40 . The point 40 is shown in engineering style with the intermediate length continuing as the portions illustrated.
[0100] In this embodiment, the point 40 may be secured by a securement 42 such as a set screw 42 threaded into a receiver 44 that mounts the point 40 to support it in a vertical orientation. As described hereinabove, the point 40 operates to draw lightning, by increasing the voltage stress field near the distal end thereof (farthest from the building).
[0101] Referring to FIG. 21 , while continuing to refer generally to FIGS. 1-29 , an installation of an anchor 10 in accordance with the invention may include attachment of an anchor 10 by a pad 14 to a surface 35 of a building. In the illustrated embodiment, the surface 35 is part of a covered wall 52 or parapet 52 . The parapet 52 or wall 52 is simply used by way of example.
[0102] In other embodiments, the surface 35 may be part of a covering on a ridge line or ridge cap from a building, a cupola, gable, eave, or other architectural feature that represents a high point in the structure of a building. Accordingly, the parapet 52 or wall 52 represents allocation that permits the point 40 to be the high point of the building by selecting a surface 35 to which the anchor 10 may be installed.
[0103] Thus, the installation 50 or assembly 50 may include, for example, an anchor 10 secured by a pad 14 against a surface 35 of a flashing 54 or cap 54 covering a portion of a wall 52 .
[0104] In the illustrated embodiment, the cap 54 or flashing 54 , may include a drip edge 55 . The drip edge 55 is instructive. Significant effort is taken to assure protection of the wall 52 against the elements, particularly rain, and the freeze-thaw cycle of winter moisture. Accordingly, the drip edge 54 proceeds away from the wall 52 , in order to assure that water striking the flashing 54 or cap 54 is conducted away therefrom. This may assure that it drips elsewhere, rather than feeding capillary spaces between the wall 52 and the flashing 54 . Likewise, the drip edge 55 militates against water dripping directly from the flashing 54 onto the wall 52 .
[0105] In the illustrated such as the one embodiments, illustrated in FIG. 21 , a cable 56 is secured by the anchor 10 to run along the wall 52 , attached to the surface 35 of the cap 54 or flashing 54 . In the far left embodiment, as illustrated, the anchor 10 includes a base plate 12 . Thus, the anchor 10 a shows an assembled configuration of the anchor 10 b also illustrated.
[0106] For example, a cable 56 is secured directly against the base plate 12 by tabs 58 that operate as extensions of the base plate 12 . Tabs 58 fold over to hold the cable 56 in place. In some embodiments, such a simple, straightforward attachment mechanism may be operable without tools.
[0107] With the tabs 58 fully open, and extending as if within the plane of the base 12 , an installer may press the pad 14 against the surface 35 of the flashing 54 . This anchoring of the base 12 and pad 14 secures them to the surface 35 and may be used to secure them to each other. After applying pressure and waiting, or otherwise curing the securement of the pad 14 to the surface 35 , an installer may then run the cable across the plate. Cable 56 may be fastened in place by bending the tabs 58 over the cable 56 and plate 12 , and specifically over the front face 18 of the plate 12 .
[0108] In the alternative embodiment of the anchor 10 c, a location 60 may be selected, as shown in the exploded view, for receiving a pad 14 after suitable cleaning. Typically, the pad 14 here may be preinstalled on the anchor 10 at a factory, being secured to the base plate 12 . Nevertheless, in some embodiments, the pad 14 may be applied in the field.
[0109] By whatever mechanism, the rear face 20 or back face 20 of the base plate 12 adheres to the pad 14 , by being fastened to the front face 22 thereof. Meanwhile, the back face 24 of the pad 14 , after a suitable cleaning of the surface 35 at the location 60 , is adhered to the surface 35 at the location 60 .
[0110] In the embodiments of the anchors 10 c, and 10 d, a stud 16 protruding from the base 12 receives a fastener 36 , which fastener 36 actually holds the cable 56 . In the illustrated embodiment, the fastener 34 is provided with an aperture 36 to receive the stud 16 therethrough. Accordingly, as illustrated in FIG. 20 , a nut 32 or other keeper 32 may secure to the stud 16 , thus capturing the fastener 34 , and the cable 56 held by the fastener 34 to the base plate 12 . Of course other embodiments of brackets may simply include loops, clamps, and the like simply supported by the stud 16 and base plate 12 .
[0111] Referring to FIG. 22 , which is detailed in FIGS. 22-25 , a universal anchor 10 may provide a clip mechanism for quickly securing a cable 56 to a building wall 52 . In the illustrated embodiment, the universal anchor 10 includes arms 62 that operate as springs, being able to deflect.
[0112] Near the center of the anchor 10 , shown here in a vertical orientation, the arms 62 support a horizontal cable captured thereby. The anchor 10 may include a guide 64 or guide portion extending from the arm 62 . Cable pushed between opposing guides 64 , will tend to deflect the guides 64 , and the arms 62 as cantilever springs. Upon opening a gap between the guides 64 , a cable pressed into the guides 64 will move the guides 64 and arms 62 outboard. Moving in an outboard direction opens up a gap to receive the cable 56 .
[0113] The retainers 66 will hold a cable 56 in place after the cable passes into the cable region 68 . That is, after passing the guides 64 , the cable no longer exerts the outboard pressure on the guides 64 . The guides 64 and arms 62 may again return to their unstressed, unstrained positions, locking the cable 56 in place 68 .
[0114] Typically, the vertex 69 tends to restrict the gap 63 , thus requiring the guides 64 to push the arms 62 as cantilevers. The arms 62 , acting as cantilever springs against the base 12 , are moved away (outboard) until the vertex 69 of each guide 64 passes over a center line or center diameter of the cable 56 . Thereafter, the retainers 66 tend to ride up on the cable 56 , once in the cable region 68 , thus drawing the cable in against the base plate 12 . This occurs as the arms 62 close back over the cable 56 to their 62 original position. Thus, the retainers 66 operate to draw the cable in, against the plate 12 by force of the spring loads presented by the arms 62 and guides 64 .
[0115] The anchor 10 may be referred to as a combined anchor and bracket 70 or a universal anchor 70 . Thus, a particular embodiment of an anchor 10 that includes both the base 12 integrated with a mechanism for bracketing, without requiring an extra piece distinct from the base 12 as a fastener 34 , may be considered a universal or integrated anchor 10 .
[0116] Referring to FIGS. 23A-23F , the various orthogonal views of the embodiment of FIG. 22 illustrate the details and approximate aspect ratios or relationships between dimensions. Meanwhile, these orthogonal views may be seen to present a universal anchor 70 or integrated anchor 70 that may be formed by simply cutting and bending a sheet of material. Thus, the material of the integrated bracket 70 or universal bracket 70 may typically be metal, although other materials may be suitable. For example, certain composite materials, polymeric materials, such as certain industrial plastics, and the like, may serve as the material for forming a universal bracket 70 as illustrated.
[0117] Referring to FIGS. 24-25 , while continuing to refer to FIGS. 22-23 , and FIGS. 1-29 generally, the integrated bracket 70 of FIG. 22 is illustrated in an exploded view with the pad 14 and cable 56 not secured. In FIG. 25 , the assembly 50 includes the universal bracket 70 of FIGS. 22-24 in place, having the cable 56 installed, and the anchor 10 or universal anchor 70 installed on the surface 35 of a cover 54 of a wall 52 . As mentioned hereinabove, the integrated anchor 70 or universal anchor 70 is a particular embodiment of an anchor 10 .
[0118] Referring to FIGS. 26A-26B , in an alternative embodiment of a universal anchor 70 , a base 12 may include arms 62 and guides 64 that are not necessarily symmetrical with one another. For example, in the illustrated embodiment, the lower arms 62 may be longer, or may be the same length as the upper arms of 62 . Meanwhile, the guides 64 are typically not symmetrical, and may be shaped differently to fulfill different purposes.
[0119] For example, the lower guides 64 operate as guides, tending to bend or deflect away from a cable 58 inserted between the guides 64 . Bending the arms 62 away from the cable 58 . The upper arms 62 , and the upper guides 64 b operate similarly. As cantilever springs, each pull away from or draws away from the center or unloaded position according to the force applied by a cable 58 being forced between the guides 64 .
[0120] However, unlike previous embodiments, the upper guide 64 terminates in a different shape than does the lower guide 64 a. Thus, the lower guide 64 a is a continuation or continues on as the retainer 66 a. Meanwhile, the lip 66 b is not so large, and simply provides a transition for the guide 64 b. Herein, throughout this text, a trailing letter behind a reference numeral simply indicates a specific instance of the item identified by that reference numeral. Thus, a guide 64 is also capable of being a guide 64 a, or guide 64 b. Put another way, a guide 64 a is a specific instance of a guide 64 generally, and all may be designated as a guide 64 . Similarly, a guide 64 b is a specific instance of a generic guide 64 . In similar fashion, the retainer 66 a provides an actual receiver 66 a to hold and to completely cover a cable 58 when placed in the cable 56 when received in the cable region 68 .
[0121] As illustrated, the cable 56 , when forced toward the base plate 12 between the guides 64 , tends to drive the guides 64 apart, acting as cantilever springs. Meanwhile, the guides 64 , in turn, drive the arms 62 apart, also operating as cantilever springs with respect to the base 12 . Once the gap 63 between the guides 64 has been traversed, the cable 56 may be drawn in by the retainers 66 as they close in together.
[0122] The spring force of the guide 64 b pushes the detent 66 toward the cable 56 . Accordingly, once the cable 56 , driven in between the guides 64 a, 64 b has sufficient clearance, then the diameter of the cable 56 tends to drive the guide 64 a upward, as the detent 66 b and the arms 62 drive the guides 64 b toward the cable 56 , and toward the arms 62 a. In this way, the upper arm 62 b tends to drive the cable 56 into the retainer 66 a.
[0123] In summary, an installer forces the cable 56 between the guides 64 a, 64 b. The guides 64 a, 64 b, acting as springs, deflect, also applying and transmitting force to their respective arms 62 a, 62 b. The combined deflection of the guides 64 and the arms 62 opens the gap 63 between the guides 64 , thus receiving the cable 56 . Upon the passage of the guide 64 a over the central diameter or maximum diameter of the cable 56 , the cable 56 is seated within the retainer 66 a. Meanwhile, the combined forces of the guide 64 b pushing the cable into the cable position 68 under the retainer 66 a, is augmented by the force of the arms 62 b driving the guides 64 b and detent 66 b against the cable 56 , until the cable 56 , is well into the retainer 66 a.
[0124] Referring to FIGS. 27A-27F , while continuing to refer to FIGS. 26A-26B , one can see that the integrated anchor 70 provides a cover 66 or a retainer 66 over the outermost surface of the cable 56 . Notwithstanding the embodiment of FIGS. 22-25 , which can easily retain the cable 56 , the embodiment of FIGS. 26A-27F provides a positive element 66 covering the outside of the cable 56 .
[0125] Referring to FIG. 28 , a process 80 of using an anchor 10 in accordance with the invention may include both a manufacturing process 82 and an installation process 84 . For example, in certain embodiments, the anchor 10 may actually be assembled onsite. In other embodiments, the anchor may be completely manufactured, assembled, and simply applied to a wall.
[0126] As discussed hereinabove, in certain embodiments brackets 34 may be selected according to a specific need. They may be used to support a cable, a point, or a specialty item in a lightning-protection circuit. In certain embodiments of an anchor 10 in accordance with the invention, brackets 34 may be conventional. They may be mounted to support cables, points, or the like on a structure of a building by an anchor 10 in accordance with the invention. In other embodiments, an integrated anchor 70 may actually include all bracketing and anchoring in a single piece, even a monolithic piece 70 of a simple homogeneous material.
[0127] By any mode, a method 80 for using anchors 10 in accordance with the invention may include manufacturing and providing 82 , followed by a process 84 of installation.
[0128] Selecting 85 may involve selecting parameters that will govern the performance of an anchor 10 in accordance with the invention. For example, in certain embodiments, the specific material properties may be significant. Thus, selecting values corresponding to material properties may be important.
[0129] In some embodiments, determining whether a material property requires a metal, a polymer, a composite, or the like may hinge on the specific performance characteristics in terms of strength, spring constant, yield values of stress, deflection, maximum working strength, stiffness, and so forth.
[0130] Based on the parameters that are selected 85 , selecting 86 the material properties may be done by specifying what values the parameters must meet. Thus, operational parameters may result in the characteristic properties, such as mass, density, maximum tensile stress, maximum strain, weight, dielectric or conduction properties, and so forth. Likewise, structural strength, coefficience of thermal expansion with temperature, resistance to corrosion, and so forth may be selected 86 as material properties that will govern construction of an anchor 10 .
[0131] Selecting 87 securement systems may involve securements at opposite extremes ends of each anchor 10 . For example, a securement mechanism to secure a base 12 to a wall 52 of a building may be one securement, while the securement by way of a fastener 34 , keeper 32 , or integrated arms 62 and guides 64 may also be considered securements. Accordingly, selecting 87 the types and numbers, as well as the operating mechanisms for various securements may determine what form of anchor 10 , and what mechanical configuration may be required.
[0132] Ultimately, selecting 88 materials for each of the components included in an anchor 10 , may result directly or indirectly the previous selections 85 , 86 , 87 . Moreover, selecting 85 , 86 , 87 , 88 may also include, and in an overall context will include, selecting the materials that will be used in the overall lightning protection system.
[0133] For example, cables may be fabricated of copper, aluminum, or other materials. Typically, the duty cycle, weight, electrical conductivity, thermal conductivity, and so forth do not require gold. Circuits exist that are fabricated using gold as the conducting material. Nevertheless, typically, aluminum tends to be lighter than copper, whereas copper tends to be a better conductor based on area, mass, and various other parameters. By the same token, aluminum is considered more economical. Thus, selecting 88 a material for a cable 56 , anchors 10 , brackets 34 , integrated anchors 70 , points 40 , and so forth may significant considerations of material properties, fabrication methods, and so forth.
[0134] Cutting 89 stock into the materials and components to be used applies to both the components of the installation, as well as the anchors 10 and their associated or corresponding parts. For example, cutting the pad 14 , that has been selected 88 , at the dimensions specified will constitute one element. By the same token, cutting 89 anchors 10 , or base plates 12 , or studs 16 , or otherwise fabricating them may be another consideration. Similarly, folding of metal sheets after cutting 89 to size, and possibly cutting 89 with separation lines for appropriate folding may also be included. Likewise, methods of making and using brackets 34 to support cables 56 , points 40 , or the like may be considered.
[0135] In one embodiment, cutting 89 integrated anchors 70 may involve stamping a blank, and cutting certain separation lines in that blank to be followed by other manufacturing processes.
[0136] Another manufacturing process 90 or step 90 may include assembly, fabrication, or both for an anchor. For example, in certain embodiments, the stud 16 may be formed as part and parcel of an anchor 10 , as a monolithic, homogeneous, integral portion of the anchor. Thus, like a nail, bolt, or the like, the anchor 10 may be formed with a base 12 and stud 16 of a single material, formed, stamped, forged, or otherwise manufactured in a single step, or single process, as a suitable manufacturing method.
[0137] By the same token, bases 12 and studs 16 may be cut from flat stock and round stock and welded, pressed, threaded, or otherwise fabricated to bond together. Likewise, the entire anchor 10 may be fabricated of a polymer material in a molding process or by other suitable approach.
[0138] Other components to be assembled 90 , fabricated 90 , or otherwise manufactured 90 may include a nut 32 or other type of keeper 32 , a fastener 34 , adapted to securely holding a point 40 or cable 56 , or the like.
[0139] In one fabrication 90 , contemplated within the scope of the present invention, a flat material bender may fold past a yield point the middle of a blank for an integrated anchor 70 . Various bends may be required in order to form all the distinct arms 62 , guides 64 , retainers 66 , detents 67 , vertices 69 , and so forth with the appropriate gaps 63 , angles, clearances, or the like. Likewise, other manufacturing processes, such as quality control, buffing, blasting, painting, heat treating, and so forth may be important to the material properties selected 86 . Some process steps may also be done with blanks, finished parts 10 , or the like.
[0140] Packaging 92 the individual anchors 10 or components for the anchor system may be adapted to the ultimate use thereof. For example, in assembling 90 an anchor 10 , the pad 14 may be manufactured, provided, cut 89 , and assembled 90 to go into a packaging step 92 as a system ready to be installed with virtually no tools. In other embodiments, the pads 14 may each be provided as a separate article or a supply to be secured to a base 12 of an anchor 10 at the time of installation.
[0141] Accordingly, providing 91 procedures to installers may include printed instructions, downloadable files, website instructions, or the like. In fact, written procedures that will be packaged 92 with the anchors 10 may be included, while online instructions may also be provided 91 as a back up.
[0142] Finally, distributing 93 the anchors 10 through secondary distribution channels, direct to users, to installers, or the like may be done in a suitable manner. Typically, packaging 92 may include warnings, which may also be part of providing 91 procedures.
[0143] A process 84 or method 84 for installing an anchor 10 in accordance with the invention may begin with accumulating or otherwise gathering specifications for the performance of a lighting-protection system. Based on distances, sizes, topography, geology, urbanization, and so forth, one may analyze 94 the specifications for a particular project. This may lead to the consequent points 40 to be supported and cables 56 to be carried by the anchors 10 .
[0144] Selecting 95 sizes, materials, and processes for assembling and installing the anchors 10 and their associated points 40 and cables 56 will appropriately follow. Sizes in certain embodiments are standardized and established by building codes. Building protection codes for arresting lightning exist in many jurisdictions, and may be determinative of selecting 95 the sizes, materials, and processes for installation. In other jurisdictions, cost, contemplated conditions, and the like may also factor into the selection 95 of materials, their sizes, and their processes for installation.
[0145] An installer may then apply the systems 96 by obtaining from distribution 93 the quantities of anchors 10 , keepers 32 , points 40 , cables 56 , other fasteners, and install them. Typically, anchors 10 will be installed near the highest extrema of a building, thereby protecting the building, it's metallic components, its structure, and so forth from the high voltages, currents, heating, and the like associated with lightning strikes.
[0146] In general, lightning protection systems will be grounded to earth. Points 40 will extend at their distal ends to increase the voltage stress or provide a stress concentration point at the distal end of a point 40 . Thereby, dielectric breakdown in the surrounding air will occur first at a point 40 , and particularly at the distal end of the point 40 . Thus, following the initial corona effect that is typical of electrically active atmospheres, the electrical breakdown by lightning will occur at the distal end of a point 40 , sending electrical current through the point 40 , its anchor 10 , and to the associated cables 56 carrying current to a grounding cable 56 that eventually is anchored in the earth.
[0147] Referring to FIG. 29 , in one embodiment of a method in accordance with the invention, an application process 100 may involve sizing 101 anchors 10 for use in an installation. Therefore, selecting 102 a material for the pad 14 may be conducted. Sizing 103 the pads 14 may include consideration of surrounding materials, clearances, thicknesses, areas, sealing, offsets, or the like. Thickness may be governed by structural (stress, strain) requirements, installation to tolerances, and relative coefficients of thermal expansion of surfaces 35 , bases 12 , and pads 14 . In certain embodiments, sizing 103 the pads may be dictated by the sizing of the base plate 12 to which each pad 14 will connect.
[0148] Cutting 104 the pads and applying 105 the pads 14 to a base plate 12 may be done at the time of installation, or may be done in a manufacturing process 100 at a factory shipping completed anchors 10 . Likewise, applying 105 the pad may involve cutting 104 a pad to size. Nevertheless, in some embodiments, applying 105 the pads 14 to the base plates 12 may occur in a factory.
[0149] Installation may then include selecting 106 a location 60 on a building. Typically, the location 60 will be near the top of the building, and therefore on a flashing 54 or cap 54 covering a parapet 52 or a wall 52 . Cleaning 107 the location 60 may involve mechanical abrasion, chemical cleaning, or simply a solvent wash. Typically, slight scrubbing with a solvent will clean off residues. In some embodiments, cleaning 107 may involve removing oxidized material having poor adhesion to the surface 35 of the base material at the location 60 .
[0150] Exposing 108 the pad 14 may involve removing a polymeric film that has low adhesion forces with respect to the adhesive pad 14 . Thus, exposing 108 the pad 14 by removing a film, for example, permits a user or installer to apply 109 the anchor 10 by pressing the anchor 10 , and the underlying pad 14 against the location 60 on the surface 35 . In this manner, the adhesive properties of the pad 14 may bond to the surface 35 as an adhesive process.
[0151] In certain embodiments, it has been found that a pressure sensitive adhesive operates well. Structural adhesives exist, and pressure sensitive adhesives exist. Accordingly, in one embodiment, the pad 14 is provided with, or as part of a pressure sensitive adhesive system having an expanded polymeric material (polymer foam) having adhesive front face 22 and rear face 24 . Upon application of pressure, the adhesive may adhere, or actually cure.
[0152] That is, for example, certain acrylates require a lack of oxygen to cure. Other materials, such as epoxies and other materials may cure by heat, light, reagents, other chemicals, or the like. Accordingly, the adhesive may be applied as multi-part, single-part, heat-curable, pressure-sensitive, or otherwise. Applying 109 an anchor 10 may provide sufficient strength in the bond between the pad 14 and the surface 35 to immediately mount the remainder of the lightning-protection system.
[0153] In certain embodiments, it may be required to apply 110 a cure condition. For example, time, heat, light, chemicals, or the like may be required to cure the adhesive of the pad 14 . Accordingly, applying 110 the condition required to effect a cure may require time, an additional step 110 , or the like. In certain embodiments, applying 110 to cure condition may be simply a matter of waiting for passage of time with or without pressure.
[0154] Finally, positioning 111 a cable 56 in the anchor 10 , or in a position to be supported by the anchor may be followed by binding 112 the cable to the anchors 10 as discussed hereinabove. Typically, binding 112 the cable 56 may involve tensioning the cables by binding 112 and end of a segment of cable 56 at one clamp, and pulling a tensile load in the cable 56 , in order to reduce sag, before binding 112 the cable 56 at the next or certain intermediate anchors 10 .
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An anchor for lightning protection systems include a base and pad that extend over a sufficient area and a sufficient bearing length to hold in shear and in tension against the weight, shear force, and moment of cables, points, and other components of a lightning protection systems. The mounting anchor is non-penetrating, and adheres to a vertical surface almost immediately without requiring damage to structures, long term support over days waiting for cure, and works in overhang situations as well. An integrated clip may be constructed with the base from sheet material. Adhesion of the base to a cover material on a wall or parapet may be promptly followed by snapping cable into clips formed monolithically with the base.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The field of invention relates to concrete finishing apparatus, and more particularly pertains to a new and improved vibratory concrete float apparatus wherein the same is arranged for the finishing of a concrete surface.
2. Description of the Prior Art
The use of vibratory energy directed to a float structure relative to a concrete finishing procedure is available in the prior art and exemplified by the U.S. Pat. No. 4,798,494 to Allen wherein a pneumatically driven vibratory device is mounted to a float structure.
The U.S. Pat. No. 4,838,730 to Owens sets forth a further example of a concrete finishing organization further utilizing pneumatic vibratory devices.
The instant invention attempts to overcome deficiencies of the prior art by employing a flexible cable drive, or alternatively the use of a handle mounted vibratory device to enhance efficiency and minimize accessory structure to unencumber an operator in use of the organization.
As such, it may be appreciated that there continues to be a need for a new and improved vibratory concrete float apparatus as set forth by the instant invention which addresses both the problems of ease of use as well as effectiveness in construction and in this respect, the present invention substantially fulfills this need.
SUMMARY OF THE INVENTION
In view of the foregoing disadvantages inherent in the known types of concrete float apparatus now present in the prior art, the present invention provides a vibratory concrete float apparatus wherein the same is arranged to impart a vibratory energy to a float structure to effect efficiency in a finishing procedure relative to a concrete float. As such, the general purpose of the present invention, which will be described subsequently in greater detail, is to provide a new and improved vibratory concrete float apparatus which has all the advantages of the prior art concrete float apparatus and none of the disadvantages.
To attain this, the present invention provides a float plate including vibratory members secured in operative relationship thereto to effect vibration of the float during a concrete finishing procedure. A modification of the invention includes the apparatus to have fluid dispersion structure to enhance ease of a finishing of an underlying concrete pad. Illumination members are optionally provided for the use of the organization during periods of limited available light.
My invention resides not in any one of these features per se, but rather in the particular combination of all of them herein disclosed and claimed and it is distinguished from the prior art in this particular combination of all of its structures for the functions specified.
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, of course, additional features of the invention that will be described hereinafter and which will form the subject matter of the claims appended hereto. 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.
Further, the purpose of the foregoing abstract is to enable the U.S. Patent and Trademark Office and the public generally, and especially the scientists, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application. The abstract is neither intended to define the invention of the application, which is measured by the claims, nor is it intended to be limiting as to the scope of the invention in any way.
It is therefore an object of the present invention to provide a new and improved vibratory concrete float apparatus which has all the advantages of the prior art concrete float apparatus and none of the disadvantages.
It is another object of the present invention to provide a new and improved vibratory concrete float apparatus which may be easily and efficiently manufactured and marketed.
It is a further object of the present invention to provide a new and improved vibratory concrete float apparatus which is of a durable and reliable construction.
An even further object of the present invention is to provide a new and improved vibratory concrete float apparatus which is susceptible of a low cost of manufacture with regard to both materials and labor, and which accordingly is then susceptible of low prices of sale to the consuming public, thereby making such vibratory concrete float apparatus economically available to the buying public.
Still yet another object of the present invention is to provide a new and improved vibratory concrete float apparatus which provides in the apparatuses and methods of the prior art some of the advantages thereof, while simultaneously overcoming some of the disadvantages normally associated therewith.
These together with other objects of the invention, along with the various features of novelty which characterize the invention, are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and the specific objects attained by its uses, reference should be had to the accompanying drawings and descriptive matter in which there is illustrated preferred embodiments of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be better understood and objects other than those set forth above will become apparent when consideration is given to the following detailed description thereof. Such description makes reference to the annexed drawings wherein:
FIG. 1 is an orthographic view, partially in section, of a prior art vibratory device, as set forth in the U.S. Pat. No. 3,918,214 relative to show structure providing direct vibratory energy to an associated tool surface.
FIG. 2 is an isometric illustration of the instant invention.
FIG. 3 is an isometric illustration of a further aspect of the invention.
FIG. 4 is an isometric illustration of a yet further aspect of the invention.
FIG. 5 is an isometric illustration of a still further construction of the instant invention.
FIG. 6 is an orthographic view, taken along the lines 6--6 of FIG. 3 in the direction indicated by the arrows.
FIG. 7 is an orthographic view, taken along the lines 7--7 of FIG. 4 in the direction indicated by the arrows.
FIG. 8 is an orthographic view, taken along the lines 8--8 of FIG. 7 in the direction indicated by the arrows.
DESCRIPTION OF THE PREFERRED EMBODIMENT
With reference now to the drawings, and in particular to FIGS. 1 to 8 thereof, a new and improved vibratory concrete float apparatus embodying the principles and concepts of the present invention and generally designated by the reference numerals 10, 10a, 10b, and 10c will be described.
More specifically, the vibratory concrete float apparatus 10 of the instant invention as illustrated in FIG. 2 substantially comprises a float plate 11 of a generally planar bottom surface, to include parallel forward and rear flanges 12 and 13 extending upwardly from the float plate relative to respective forward and rear side portions of the float plate 11. The float plate 11 further includes a plurality of spaced parallel mounting flanges 14 pivotally mounting a first handle tube 15 therebetween about a pivot axle 14a. As illustrated, a second handle tube 16 including a retractable lock pin 17 is arranged for reception within a first handle tube receiving bore 18 to provide for extension of the first and second handle tubes together. A drive motor 19 is mounted to the first handle tube and includes a guide tube 21 extending therefrom parallel to the first handle tube 15 and spaced relative to the mounting flanges 14, and includes a plurality of drive motor flexible output drive cables 20 directed therethrough, with a single drive cable 20 extending into a respective first and second vibrator 22 and 23 that are mounted fixedly to the top surface of the float plate 11 an equal distance relative to the first handle tube 15.
In this manner, vibratory energy is attained through the vibratory motors that are of conventional construction as set forth in the prior art, such as exemplified in the U.S. Pat. No. 3,918,214 incorporated herein by reference. The direct drive cables permit the drive motor to be mounted in a remote orientation for ease of manipulation of the organization in use.
The FIG. 3 illustrates the apparatus 10a to include a mounting plate 24 fixedly mounted to a top surface of the first handle tube 15, with the mounting plate 24 including a drive motor 25 and a fuel reservoir 26 directed thereto. A handle and speed control 27 extends laterally relative to the drive motor 25 orthogonally oriented relative to the first handle tube 15 for use as a throttle control and handle of a typical gasoline motor to be utilized as a drive motor 25 in association with the fuel tank 26. The guide tube 28 is mounted in a parallel relationship relative to and spaced from the first tube 15 to include first and second positioning mounts 29 and 30 mounting in a fixed relationship the guide tube 28 in the spaced parallel relationship above the first handle tube 15. A drive motor output shaft 31 rotatably directed through the guide tube 28 terminates in an eccentric member 32 mounted thereto, whereupon rotation of the eccentric member 32 by the drive motor 25 directs vibratory energy from the first handle tube 15 to the float plate 11.
The apparatus 10b includes the structure of FIG. 3, but to further include a fluid delivery conduit 33 directed into the tubular first handle tube 15 spaced above a valve organization to include a fluid valve handle 34, with the fluid valve handle 34 including a valve rod 36 orthogonally directed into the handle tube 15, with a valve plate 37 rotatably mounted within a first handle tube central conduit 35 in fluid communication with the fluid delivery conduit 33 through a conduit coupling portion 39, as illustrated in FIG. 8. The valve plate 37 is defined by a predetermined diameter substantially equal to a predetermined internal diameter defined by the first handle tube central conduit 35 to permit selective fluid flow through the first handle tube central conduit 35 that extends coaxially aligned and concentric relative to the handle tube 15 and mounted concentrically relative to the handle tube 15 by at least one, and preferably a plurality of, resilient torroidal mounts 38, of a type as illustrated in FIG. 8, to provide cushioning relative to the central conduit 35 minimizing interaction with the tube 15 in its transmission of vibratory energy from the eccentric member 32. The first handle tube central conduit 35 is in fluid communication with a respective plurality of output fluid conduits 40, wherein at least one output conduit 40 is directed into a respective first and second fluid manifold 41 and 42. The respective first and second fluid manifolds 41 and 42 include respective first and second manifold fluid ports 43 and 44 to direct water from the fluid delivery conduit 33 through the ports 43 and 44 for the watering of a concrete pad to be worked by the apparatus of the invention.
The FIG. 5 illustrates the utilization of a support collar 45 fixedly mounted in circumferential relationship forwardly of the drive motor 25 below the guide tube 28 and employing diametrically directed first and second mounting rods 46 and 47 extending laterally of the handle tube 15 on opposed sides thereof, with the first and second mounting rods 46 and 47 mounting a respective first and second illumination bulb 48 and 49, with utilization of battery power or alternatively, electrical power supply cord 50, to effect illumination of the illumination bulbs 48 and 49 for utilization of the invention during conditions of limited available light.
As to the manner of usage and operation of the instant invention, the same should be apparent from the above disclosure, and accordingly no further discussion relative to the manner of usage and operation of the instant invention shall be provided.
With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the invention, to include variations in size, materials, shape, form, function and manner of operation, assembly and use, are deemed readily apparent and obvious to one skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention.
Therefore, 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 and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.
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A float plate includes vibratory members secured in operative relationship thereto to effect vibration of the float during a concrete finishing procedure. A modification of the invention includes the apparatus to have fluid dispersion structure to enhance ease of a finishing of an underlying concrete pad. Illumination members are optionally provided for the use of the organization during periods of limited available light.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] Embodiments of the present invention relate generally to cartridges and modifications for an M16/AR15 rifle.
[0003] 2. Description of the Related Art
[0004] Domestic Law Enforcement Needs
[0005] Most domestic law enforcement agencies in the United States utilize the AR15/M16 rifle platform in the course of their daily duties, as patrol officers out on the street; it is often referred to as a “patrol carbine” and is carried by individual officers. These rifles are also used by SWAT teams for room entry or close quarter's battle (CQB) for close in shooting, and are used by some departments as short range sniper rifles. The reasons for the selection of this rifle platform are that they are readily available in many configurations and are fairly reasonably priced to Law Enforcement agencies, the AR15's weight and size are also attractive features of the AR15 as they are easily operable by large men and smaller stature women. The limiting factor is the cartridge that it fires, the 223 Remington, most commonly using a 55 grain bullet. Domestic law enforcement is not held to the military restriction of using full metal jacket projectiles and therefore can choose from a wide variety of available bullet styles and designs, which makes the 223 Remington more effective.
[0006] Even with the proper selection of ammunition, the 223 Remington is still substandard for most law enforcement applications and has a well known reputation for “over penetration” with its small-fast bullet. This can result in extremely dangerous situations for patrol officers working in a built up urban environment. The small weight or mass of the bullet makes it less effective and more prone to deflection on vehicles when engaged by police, especially when engaging thick windshield glass. Although there are a few “alternate” cartridges available that will function in the AR15 rifle, they do not offer enough of an improvement over the existing .223 Remington cartridge chambering to justify the cost in switching over to them, mainly cost and availability of ammunition and magazines. Thus the agencies are limited on their choices of cartridge choices if they maintain the AR15/M16 rifle platform as their weapon of choice.
[0007] The other choice for law enforcement agencies is the larger and more costly AR15 “style” rifle made by various companies that fire the .308 Winchester cartridge. The .308 Winchester is a powerful cartridge and offers a substantial improvement over the much smaller .223 Remington chambering. Most police sniper rifles are chambered in the .308 Winchester and are bolt action guns, which do not allow for quick follow up shots if needed.
[0008] When quick follow up shots are required the larger AR15 style rifles are sometimes used, they are heavier and have more recoil than the smaller rifles, but deliver ample firepower when needed. These heavier and larger rifles are not the preferred option for SWAT teams for use in room entry and building clearing operations because the power of the 308 Winchester is too much for inside building operations, due to muzzle blast, recoil, and over penetration.
[0009] These two calibers represent not only the two most popular calibers used in law enforcement but are the two extremes, with the 223 Remington not providing enough performance or power and the 308 Winchester providing too much or excessive power.
[0010] United States Military Needs
[0011] The existing standard cartridge or chambering for the military's M16 rifle is the .223 Remington or 5.56 mm NATO (military designation) cartridge. It fires a .224 caliber bullet weighing 62 grains in the military issue M855 ammunition. Bullets weighing as much as 77 grains are currently in use by the US military to increase the performance of the 5.56 mm NATO cartridge and have increased the terminal performance of the cartridge, but its terminal effects are still less than desirable for what is considered an adequate combat cartridge. The shortcomings in the performance of the 5.56 mm NATO cartridge are well documented in current and past military conflicts, and the cartridge's ineffectiveness is more pronounced when the enemy combatants are under the influence of drugs that affect the central nervous system.
[0012] An alternative for heavier machine guns is the .308 or 7.62 mm caliber bullet. The most common military caliber utilizing the .308 or 7.62 mm caliber bullet is the 308 Winchester or 7.62 mm NATO cartridge. The performance of the 7.62 NATO is also well documented in combat and is known for its increased stopping power. The U.S. M14 rifle fires the 7.62 mm NATO cartridge as does the U.S. M240 machinegun, as well as several aircraft mounted machineguns and the mini-gun. The AK47 also utilizes a 7.62 mm bullet.
[0013] What is needed is a cartridge that will provide improved stopping power without over penetrating, and is compatible with the standard size M16/AR15 rifle platform.
SUMMARY OF THE INVENTION
[0014] Embodiments of the present invention relate generally to cartridges and modifications for an M16/AR15 rifle. In one embodiment, a modified M16/AR15 rifle or carbine includes a bolt having a maximum outside diameter greater than that of a standard M16/AR15 bolt; and a bolt extractor pivoted to the bolt. The bolt and the bolt extractor are operable to: transport a cartridge from a magazine to a barrel, and eject a spent cartridge from the barrel. The rifle or carbine further includes a barrel extension configured to receive the bolt; a standard M16/AR15 upper receiver coupled to the barrel extension; a standard M16/AR15 lower receiver coupled to the upper receiver.
[0015] In another embodiment, a cartridge includes a bullet having a diameter greater than or equal to 0.224 inch; and a case having a case head diameter greater than or equal to 0.45 inch. A length of the cartridge is substantially equal to 2.26 inches.
[0016] In another embodiment, a firearm includes a barrel. The firearm further includes a bolt operable to transport a cartridge from a magazine to the barrel and eject the spent cartridge from the barrel. The firearm further includes a spring biasing the bolt toward the barrel and a piston system in fluid communication with the barrel. The piston system includes a body and a piston disposed in the body and operable to move the bolt away from the barrel in response to firing of the cartridge and force exhaust gas from the body and into the barrel in response to the spring returning the bolt to the barrel.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] So that the manner in which the above recited features of the present invention can be understood in detail, a more particular description of the invention, briefly summarized above, may be had by reference to embodiments, some of 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.
[0018] FIGS. 1A-1C illustrate cartridges, according to embodiments of the present invention.
[0019] FIG. 2 is an exploded assembly of a bolt, bolt extractor, and barrel extension usable with the cartridges of FIGS. 1A-1C .
[0020] FIGS. 3A-3E illustrate details of the bolt of FIG. 2 .
[0021] FIGS. 4A-4E illustrate details of the bolt extractor of FIG. 2 .
[0022] FIGS. 5A-5D illustrate details of the barrel extension of FIG. 2 .
[0023] FIGS. 6A-6G illustrate details of a magazine usable with the cartridges of FIGS. 1A-1C .
[0024] FIGS. 7A-7D illustrate details of a bolt usable with the cartridges of FIGS. 1A-1C and a modified gas piston system, according to another embodiment of the present invention.
[0025] FIG. 8 is a cross section of a gas piston system, according to another embodiment of the present invention.
[0026] FIG. 9 is an exploded assembly of a prior art M16/AR15.
DETAILED DESCRIPTION
[0027] FIGS. 1A-1C illustrate cartridges, according to embodiments of the present invention.
[0028] The 308 ERC was designed to maximize the performance of the AR15/M16 rifle, give it more stopping or incapacitation power and increase its performance in self defense, law enforcement, and military combat applications. The 308 ERC is based on the .308 Winchester or 7.62 mm NATO cartridge, utilizes the 308 caliber bullet, and is designed to operate in the existing standard issue sized AR15/M16 rifle platform.
[0029] Cartridge Details;
[0030] Case head diameter; 0.473″ inches (a 25% increase over the 223 Remington/5.56 NATO)
[0031] NL is an abbreviation for neck length. NW is an abbreviation for neck wall. COL is an abbreviation for cartridge overall length
[0032] Powder capacity; 52% increase over the 223 Remington/5.56 NATO & 18% less than the 308 Winchester
[0033] Projected design performance data;
[0034] Bullet weight: 135-140 grains
[0035] Muzzle velocity: 2650 feet per second (fps) (16″ barreled AR15/M16 carbine)
[0036] Muzzle energy: 2106 foot pounds
[0037] Muzzle energy increase: 82% (compared to military current issue M855 62 grain FMJBTWC@2900 fps fired from a 16″ barreled AR15/M16 carbine)
[0038] FIG. 2 is an exploded assembly of a bolt, bolt extractor, and barrel extension usable with the cartridges of FIGS. 1A-1C . Although the cartridge is designed to operate in the AR15/M16 platform, the following design changes were required (in addition to modification of the barrel);
[0039] 204-ERC redesigned bolt
[0040] 206-ERC redesigned bolt extractor
[0041] 202-ERC redesigned barrel extension
[0042] FIG. 6 A- 6 G-ERC redesigned magazines, 25 round capacity
[0043] Additional ERC cartridges:
[0044] Although any of these cartridges utilizing the ERC case can be used for self defense or law enforcement applications, their projected use is listed below;
[0045] 224 caliber/5.7 mm—varmint hunting, rifle competition
[0046] 243 caliber/6 mm—varmint hunting, rifle competition
[0047] 264 caliber/6.5 mm—varmint hunting, rifle competition
[0048] 270 caliber/6.8 mm—military, law enforcement, hunting
[0049] 308 caliber/7.62 mm—military, law enforcement, hunting
[0050] 338 caliber/8.6 mm—military, law enforcement, hunting
[0051] 440 KINETIC—military, law enforcement, door & wall breeching, hunting
[0052] 440 ENTRY (buckshot)—military, law enforcement, door & wall breeching, room entry (CQB), hunting. The barrel may be smooth bore or rifled for the 440 ENTRY.
[0053] The bullets may have hollow points and may have full metal jackets or be semi-jacketed (lead tip).
[0054] FIGS. 7A-7D illustrate details of a bolt usable with the cartridges of FIGS. 1A-1C and a modified gas piston system (see FIG. 8 ), according to another embodiment of the present invention. All dimensions are in inches.
[0055] FIG. 8 is a cross section of a gas piston system 800 , according to another embodiment of the present invention.
[0056] The use of gas piston systems in weapons to cycle the action is used in weapons such as the Russian AK 47 (1947), the U.S M1 Garand (1939) and the U.S. M14 (1957). There are as many as five gas piston systems currently manufactured for the AR15 rifle by various companies. They use a gas piston actuated by “tapped gas” from the fired cartridge via a small hole or “gas port” in the barrel, the expanding gas forces the piston to move. As such, the gas from a fired cartridge is utilized to cycle the action and load the next cartridge. The expanding gas from the fired cartridge, once utilized to cycle the piston, is then vented out of the gas manifold at the end of the piston operating stroke before the piston returns to the starting position.
[0057] The standard design gas system used in AR15 and M16 rifles utilizes a “direct gas impingement system” which directs expanding gas from the fired cartridge out of the barrel through a “gas port” or hole in the barrel. The expanding “tapped gas” is then directed through a “gas tube” which “directs” the gas back into the upper receiver. The gas then enters the “bolt carrier key” forcing the carrier to the rear and unlocking the bolt of the rifle, beginning the cycling process.
[0058] The gas piston system 800 may include a barrel 805 , a piston/rod assembly 810 , a gas block 815 , and a gas block cap 820 . The gas block 815 may have a bore formed therethrough, may be disposed around the barrel 805 , and secured to the barrel 805 with fasteners (not shown), such as screws or pins. The gas block 815 may have a piston chamber formed therein. A piston 810 p of the piston/rod assembly 810 may be disposed in the piston chamber. The piston 810 p may divide the chamber into an air sub-chamber and an exhaust sub-chamber. The piston 810 p may be longitudinally coupled to a rod 810 r of the piston/rod assembly 810 , such as by being formed integrally therewith or welded thereto. The piston 810 p may include an array of carbon grooves (not shown) formed around an outer surface thereof. The cap 820 may be coupled to the gas block 815 by a threaded connection. The rod 810 r may extend through a bore formed through the cap 820 . The cap may have one or more ports 820 p formed therethrough and providing air communication between air sub-chamber and the atmosphere. The gas block 815 may have a channel 815 c formed between the chamber and the bore and providing fluid communication between the exhaust sub-chamber and a port 805 p formed through a wall of the barrel 805 . The port 805 p may provide fluid communication between a bore 805 b of the barrel 805 and the channel 815 c. The bore 805 b barrel may be rifled (not shown) to impart rotation to a bullet (not shown) fired therethrough. The piston 810 p may include a recess formed therein in fluid communication with the exhaust sub-chamber. One or more ports 810 h may be formed through a wall of the piston 810 p and may provide fluid communication between the channel 815 c and the piston recess.
[0059] In operation, as the bullet passes the gas port 805 p in the barrel 805 , and before the bullet exits the barrel, the exhaust sub-chamber becomes pressurized from the expanding gas of the fired cartridge via (port 805 p, channel 815 c, and ports 810 h ). The pressurized exhaust gas forces the piston 810 p to the rear of the piston chamber or “full stroke” position. The operating rod 810 r pushes on the bolt carrier key (see FIG. 9 ), which then moves the bolt carrier to the rear, unlocking the bolt and cycling the rifles action. As the bolt carrier is forced to the rear, it compresses the rifles main operating spring (buffer spring). Air in the air sub-chamber is vented to the atmosphere via the ports 820 p.
[0060] Once the bullet has exited the muzzle or flash suppressor and the pressure in the rifle bore decreases, the piston/rod assembly 810 is pushed back to the forward or “resting position” by the expanding buffer spring. As the bolt and bolt carrier continue forward, the bolt carrier is returned all the way to the forward position, locking the bolt. The residual gas in the piston chamber is exhausted back into the barrel through the gas channel 815 c and gas port 805 p. The firing sequence is now complete, and the rifle is now ready to fire again. The gas piston system 800 keeps exhaust gas near the front end of the gun and in the barrel instead of discharging the gas into the upper receiver as the conventional M16/AR15 gas impingement system does.
[0061] Alternatively, the gas piston system may be incorporated into the front sight. Alternatively, the ports 810 h may be omitted and the channel 815 c may be in direct fluid communication with the piston recess. Alternatively, the ports 810 h may be omitted, a primary channel may be in direct fluid communication with the piston recess and an auxiliary gas channel may be in fluid communication with the exhaust sub-chamber when the piston is in the full stroke position, thereby aiding venting of the exhaust gas into the barrel and accelerating return of the piston to the at-rest position.
[0062] While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.
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Embodiments of the present invention relate generally to cartridges and modifications for an M16/AR15 rifle. In one embodiment, a modified M16/AR15 rifle or carbine includes a bolt having a maximum outside diameter greater than that of a standard M16/AR15 bolt; and a bolt extractor pivoted to the bolt. The bolt and the bolt extractor are operable to: transport a cartridge from a magazine to a barrel, and eject a spent cartridge from the barrel. The rifle or carbine further includes a barrel extension configured to receive the bolt; a standard M16/AR15 upper receiver coupled to the barrel extension; a standard M16/AR15 lower receiver coupled to the upper receiver.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to an assembly of a shoe and a retention element adapted to retain the leg of an athlete on a gliding board, and particularly the leg of a skier on a ski.
The invention likewise relates to a shoe and to a retention element of the assembly taken individually.
2. Description of Background and Material Information
In the case of alpine skiing, it is known to retain a shoe supported on the ski by means of a front retention or binding element and a rear retention or binding element which retain front and rear tips of the boot. These two binding elements comprise a jaw carried by a body. The jaw is movable in response to the biases of the boot against the return force of a spring which opposes displacement of the boot.
The rigidity of the spring is adjustable, in a manner such that the boot is freed from the binding element in response to a bias exceeding a predetermined bias threshold. This threshold beyond which the jaw lets the boot escape is normally referred to as a release threshold.
In order to be able to utilize boots with different binding or retention elements available on the market, the shape of the front and rear tips of the boot has been standardized. In the ISO standards system, the standard in effect is referred to as ISO 5355. As to the binding elements, they are adapted to be compatible with standardized zones of the boot and to assure the release of the boot at predetermined release values.
At the front, a boot is retained by a front binding element whose jaw is movable at least laterally towards the interior or exterior of the foot, which corresponds to a torsional bias on the leg of a skier.
Currently available bindings have a release threshold which is equal during movement towards both the interior and the exterior. Yet, it is known that the knee of the skier, which is biased during a torsional fall, is more fragile with respect to an interior rotation of the foot than in the case of rotation towards the exterior.
To take this into account, binding elements have been proposed which have a release threshold which varies depending on the direction in which the jaw rocks. Such elements are described, for example in French Patents 1503847, 1503848, and 1503849, and in German Patent Application No. 1807074.
The major disadvantage of this type of apparatus is that it requires a pairing between the shoes and the skis, i.e., the right and left skis must necessarily be identified and the skier must put the right ski on the right boot and the left ski with the left boot. He must certainly not reverse the skis when they are put on; otherwise, the reverse effect is obtained which can have serious consequences. Yet, according to the standards, the tips of the boot are symmetrical with respect to a vertical median plane. As a result, there would normally be no presumptive reason for distinguishing and identifying ski equipment as being right and left. However, for these particular bindings, it is thus necessary for the skier to pay attention to the manner in which he lines up his skis for putting them on. This represents a major risk of confusion and danger.
SUMMARY OF THE INVENTION
The problem posed by the invention is to improve the protection of the skier. It comprises improving this effect of the variation in release threshold as a function of direction of the torsional bias.
The invention proposes resolving this problem and obtaining this effect regardless of the manner in which the skis are put on the boots, left or right.
The problem is resolved by the assembly of a shoe and a binding element such as may be described in the claims below.
The problem is further resolved by the binding element such as is defined individually, and by the boot such as it is defined individually, and by the pair of boots such as it is defined below.
According to the invention, the retention element is provided to cooperate with a specially adapted boot which is equipped with a reference indication which is different depending on whether it is a right boot or a left boot. It is known that while it is possible to exchange right and left skis because the tips of the boots are symmetrical, it is not reasonable to expect that right and left boots can be put on the wrong feet.
The retention element has a means piloted by sensors to imbalance the release thresholds at will from one side or the other as a function of the information carried by the boot and sensed by the sensors.
The information carried by the reference indications indicates to the binding element if the boot engaged is a right boot or a left boot. These references are identified by sensors of the retention element. Depending upon the position of the sensors, the means of the retention element render the release threshold stronger or weaker on one side or the other to facilitate release of the boot in the direction of torsional bias of the leg where the knee is the weakest. In the other direction of torsion, the maintenance of the boot is assured more rigidly than in the first direction. One thus improves the protection of the skier and one diminishes ill-timed releases, because the binding element reacts in a different manner depending upon whether the foot pivots towards the exterior or the interior. According to the invention, the retention element reacts automatically, such that it is not necessary to identify the skis as being right and left, nor to pair a ski with a boot. Thus, one avoids any risk of reversing the skis.
According to a second preferred characteristic, the sensors of the retention element are adapted to have no effect on the mechanism of the jaw in the case where a boot without a reference is engaged, or the sensors act in the same fashion in the two directions of displacement of the jaw, in a manner such that the retention element remains compatible with a standard boot, by assuring a symmetrical release of the boot.
According to another preferred secondary characteristic, the boot has a reference which is adapted not to disturb the operation of a standard binding element, i.e., an element which is not equipped with an identification means nor a control means.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be better understood with reference to the description below and the annexed drawings which form an integral portion thereof, in which:
FIG. 1 shows a side view and in cross section of a retention element according to one non-limiting way of performing the invention.
FIG. 2 illustrates a top view and in partial cross section the binding element of FIG. 1.
FIG. 3 is a side view of the retention element and shows more particularly an identification sensor.
FIG. 4 is a top view in cross section which illustrates more particularly the linkage between the identification sensors and the return mechanism of the jaw.
FIG. 5 is an exploded view which shows the kinematic chain of the linkage elements between the sensors and the return mechanism of the jaw.
FIG. 5a schematically shows an alternative embodiment.
FIG. 6 is a partial top view of a front of a boot compatible with the retention element of the preceding figures.
FIGS. 7 and 8 illustrate the operation of the apparatus.
FIGS. 9 and 10 are alternative embodiments of the boot.
FIG. 11 illustrates in schematic fashion an alternative embodiment.
FIG. 12 illustrates a top view and in cross section a retention element according to an alternative embodiment of the invention.
FIG. 13 is a side view and cross section of the retention element of FIG. 12.
FIG. 14 is a perspective view of the front of a boot adapted to cooperate with the retention element of FIG. 12.
FIG. 15 is a cross sectional view at the level of the sensors.
DETAILED DESCRIPTION
The retention element illustrated in the Figures, by way of non-limiting illustration of the invention, is generally disclosed in published French Patent Application No. 2517214, the disclosure of which is hereby incorporated by reference thereto.
This element comprises a base 1 adapted to be affixed to the ski by an appropriate means, for example screws.
The base carries a pivot 2 topped by a screw 3. In a known manner, body 6 of the binding element is in a way connected on to the head of the screw, and by tightening the screw more or less in the pivot, it is possible to adjust the height of the body with respect to the ski. The vase and screw form on the rear two support lines against which body 6 of the retention element is supported. In a known manner, the support lines converge towards the head of the screw, and the body rests on the pivot through three zones or points, two identified zones 4a and 5a located in the lower portion of the pivot, and the head 3a of the screw 3. It is these three zones which form, taken two by two, the two converging lines of support.
On its front surface, the pivot 2 of the base has a transverse surface 8 against which the return spring 15 of the retention element exerts its action.
Towards the rear, the boy 6 has a retention jaw for engaging the boot. The jaw comprises two wings 10 and 11 which form with the body a monoblock assembly, or quasi monoblock assembly, if one takes into account the means allowing for the adjustment of angular opening of the wings. These means are known and are not referenced in the drawings.
Wings 10 and 11 assure the lateral retention of the boot. Because of their position, wings 10 and 11 retain the boot by what one refers to as a vamp grip. The standardized tip of the boot has in effect in a known manner a lower sole portion, topped by an upper portion which forms the base of the vamp. It is on this latter portion that wings 10 and 11 exert their action. Naturally, this is not limiting, and the other way of gripping the tip, referred to as a sole grip is likewise possible. The vertical retention is assured as to itself by the lower portion of the wings which furnish a support surface to the upper portion of the sole. This is not in any way limiting.
The jaw also comprises a central support point 13 against which the most advanced portion of the vamp of the boot is carried.
Towards the front, the binding element has an elastic return mechanism of the body into the aligned position with the vertical and longitudinal median plane defined by the longitudinal direction of the ski.
This mechanism comprises in a known manner a spring 15 seated in a longitudinal recess of the body which is closed by a threaded plug 16. One end of the spring bears on this plug whose tightening makes it possible to adjust the stiffness of the retention element, i.e., the initial compression of spring 15.
The other end of the spring acts on the surface 8 described above, by means of a piston 18, and intermediate plate 19 which will be described below. Preferably, the piston has on its support surface two lateral bevels 18a and 18b, which are slightly inclined. These bevels are visible more particularly in FIG. 5. Thus, the support surface of the piston has a central surface 18c of triangular shape and two lateral bevels 18a and 18b.
In a known manner, spring 15 maintains the body in a stable position aligned with respect to the median plane. Under the effect of a lateral bias of the boot, the jaw and the body tend to pivot around one or the other support lines of pivot 2, against the return force developed by the spring. In the case of excessive bias, the amplitude of rotation of the jaw becomes sufficient to allow for the release of the boot. The bias threshold beyond which the jaw releases the boot is referred to as the release threshold. This threshold depends directly on the nature of the spring and its initial compression.
The retention element has means to vary the release threshold of the retention element at will from one side or the other. These means act on the release thresholds to the right and to the left as a sort of rocker to vary one with respect to the other. These means will now be described.
In the embodiment shown in the Figures, these means comprise a flat plate 19 which is inserted between piston 18 and surface 8 of pivot 2. Thus, piston 18 is pushed against surface 8 of pivot 2 by means of plate 19.
Advantageously, plate 19 laterally presents two flanges 20 and 21 whose spacing is substantially equal to the width of surface 8, in a manner such that in the aligned position, the plate is freely nested on surface 8 and pressed against this surface. Plate 19 rests on one or the other flange in the case of pivoting of the plate with respect to the pivot. Furthermore, in its upper portion, the plate has a return 22 which assures the vertical maintenance of the plate by taking support against piston 18.
The support surface of plate 19 on pivot 2 is greater than the support surface of piston 18 on plate 19.
Means make it possible to guide the displacement of the plate 19, by associating it either with the pivot 2 or the body 6 of the retention element.
Thus, the plate has in its upper portion a stopper 25 which projects, and is aligned with the median plane. On each side of the stopper there is a movable latch 26 and 27 mounted on a transverse journal 28 carried by the body. Each latch is movable between a lower position where it blocks the relative displacement of the stopper on the side where the latch is located, and an upper position where it allows the relative displacement of the stopper. During a rotation of the body, if the plate is retained by a latch, it is forced to pivot with the body. If the latch in question is raised to the upper position, the plate remains pressed against the pivot.
The latches 26 and 27 are controlled by rocker arms 29 and 30 which are seated in the body. The rocker arms are shown in the form of shafts 31 and 32 which are approximately oriented along a longitudinal direction, and carried at each of its ends by body bearings.
The shaft carries flaps 33 and 34 which are engaged under the latches 26 and 27 in the manner so as to be capable to lift them by a rotation of the shaft.
Shafts 31 and 32 also carry flaps 35 and 36 which are oriented downwardly. It is these flaps which control the rotation of the shafts.
The flaps are driven by two sensors 37 and 38 which are shaped as fingers positioned under laterally opposed wings 10 and 11 and journalled around substantially vertical axes.
The sensors have in front of their journal axis a small arm through which they act on the rocker arms 29 and 30.
Preferably, one or more springs (not shown) elastically return the latches in individual fashion, the latches into the lower position where they block the stopper 25. This spring or springs act likewise directly or indirectly on the rocker arms and the sensors to elastically return these sensors to a position where they have a tendency to close towards one another.
Furthermore, preferably, flaps 35 and 36, or flaps 33 and 34, are relatively flexible.
Sensors 37 and 38 are adapted to sense the boot at the front of the sole. In the absence of the boot, they leave between them a smaller opening than the width of a standardized sole.
The boot adapted to cooperate with the retention element, which is a special boot, has a reference which identifies it as being a right boot or left boot. In the following case, this reference is active, i.e., it acts in a mechanical manner on the sensors of the binding element to inform the element whether the special boot which is engaged is the right or left.
The front part of a special boot 39 adapted to cooperate with the retention element is shown in FIG. 6. The boot has a sole front 40 of which one lateral portion 41 has been reduced with respect to the other lateral portion 42. The front portion of the sole is therefore no longer symmetrical. Taking into account the configuration of the retention element, the boot shown in FIG. 6 with a reduced lateral portion on the sole is a left boot. It is self-evident that the corresponding right boot has on the right of the sole a reduced lateral portion.
The lateral portion 41 has been reduced in a manner such that when the boot is engaged in the jaw, sensor 37 positioned on its side is not displaced. On the contrary, sensor 38 positioned on non-reduced side 42 of the sole is displaced. This displacement causes the rotation of the rocker arms 30 and the lifting of the latch 27. The latch 26 remains on the contrary lowered.
FIG. 7 illustrates the mode of operation of the retention element under the effect of a bias leading to the opening of the jaw towards the interior of the foot. This bias causes on the leg of the skier, more particularly at the level of the knee, a torsion whose direction is schematically shown by arrow 44. As a result of this torsion, the foot tends to pivot towards the exterior. It is in this direction of torsion that the knee is most resistant for a left leg.
As has been previously described, the latch 26 is lowered, such that the plate 19 is linked to the body for this direction of rotation. Body 6 drives plate 19 in rotation, the plate spaces itself angularly from the pivot, which causes the sliding of the piston 18 and the compression of spring 15. The release threshold for this direction of rotation of the body is defined by the force that the boot must overcome to cause a pivoting of the body which allows it to escape from the jaw. This force depends upon the compression of the spring, and thus on the extent that the piston must undergo until release.
FIG. 8 shows boot 39 biasing the retention element in the other direction of pivoting of the body. This direction corresponds to a torsion of the leg schematically shown by arrow 45. For a left leg, the knee is more fragile in this torsional direction than in the preceding direction.
For this direction of rotation of the body, the latch 27 has been raised because the sole of the boot has pushed sensor 38.
The plate 19 is therefore not forced to accompany the rotation of the body, and it remains pressed against surface 8 of body 2. The body laterally drives the piston which slides along the front surface of the plate 19. This causes the compression of the spring, but this compression is more moderate than in the preceding case, taking into account the dimensions of the support surface of the piston, and taking into account also the lateral bevels 18a and 18b. The extent of movement of the piston necessary to bring the jaw and the body to release the boot is thus less than in the preceding case. The release of the boot is thus easier on this side.
It must be understood that the activation of the sensors and the latches requires very low energy, such that these elements have only a very small impact on the release of the boot.
In a preferred manner, if a standard boot is engaged in the retention element which has been described, the two sensors 37 and 38 are pushed, which lifts the two latches 26 and 27. The retention element has a release threshold which is substantially identical to the two directions of bias of the boot. For the construction described, these thresholds correspond to the weakest preceding threshold. However, it could be otherwise.
Conversely, if the special boot 39 is engaged in a standard retention element operating by a vamp grip, i.e., wherein the jaw retains the tip of the sole of the boot through the vamp portion, there is no change in the linkage between the boot and its retention element. If the retention element acts through a sole grip, an adjustment in the opening of the wings of the jaw will certainly be necessary because the sole of the special boot will have been locally reduced.
To overcome this, FIG. 9 shows an alternative embodiment of the boot according to which the reduced zone of the boot which avoids the displacement of the sensor is formed by a groove 48 formed for example at mid-height of the sole, at the level of an angle. This groove does not modify the exterior general contour of the sole, so that such a boot is also compatible with the retention elements for gripping a sole.
For the boot shown in FIG. 9, the sensor will preferably be a rod positioned at the level of the groove, but of diameter smaller than its width. The rod can preferably be flexible.
FIG. 10 shows another alternative embodiment of the boot according to which the sole has in its lower portion a cutout 50. However, in its upper portion, the sole keeps a standardized contour, and thus the boot remains compatible with traditional retention elements.
The construction which has just been described is not limiting and numerous alternatives are possible.
In particular, for the preceding construction, it is possible to reverse the direction in which the latches are activated by the sensors, i.e., a sensor could control not the lifting, but the lowering of a latch.
FIG. 5a schematically illustrates such a situation. Flap 34' of rocker arm 30 acts on latch 27' in front of its transverse journal axis. At rest, latch 27' leaves the plate free. If the sensor which controls latch 27' is activated by the sole of the boot, it lowers towards the plate the active portion of the latch. The plate must then follow the movement of the body. In this case, if one engages a standard boot, the two sensors are activated. The plate displaces with the body in the two directions of rotation of the body. If a special boot is engaged, a single sensor is activated. On the side where the sensor is not activated, one lowers the release threshold of the binding element. One must reverse in this case on the two boots, the lateral edges of the sole which are reduced. An effect of this variation is that activation of a sensor causes not diminution, but the increase of one of the release threshold.
FIG. 11 schematically illustrates an alternative embodiment. In this embodiment, sensors 51 and 62 operate optically and detect in a differential manner an optical mark 53 on boot 55, for example a graphic or a color mark positioned on one side of the boot.
The sensors are connected to an electronic or electric control unit 54 which controls one or the other of two electromagnets 56 and 57 activating one and/or the other of the two latches 58 and 59.
Optical mark 53 has no effect on the mechanical linkage between the boot and the retention element, such that the special boot remains compatible with a standard retention element.
For this embodiment, the detection is carried out for example by photoelectric cells, but they could also be performed by field effect, or any other appropriate means.
Another embodiment is shown in FIG. 12. The structure of the retention elements shown is known in large measure from published French Patent Application No. 2640516, the disclosure of which is hereby incorporated by reference thereto.
The retention element has a body 61 adapted to be affixed to the ski. The body carries two wings 62 and 63 for retention of the boot, journalled to the body in an independent manner around substantially vertical axes.
The wings extend beyond their journal axis through a small arm 62a, 63a, which is supported on a piston 65 seated in a longitudinal recess 66 of the body. In a known manner, the piston carries at the top of its rear portion two shoulders against which small arms 62a and 63a of the wings are carried. A spring 67 opposes by virtue of its compression the displacement of the piston caused by an opening of one or the other of the wings.
Piston 65 is guided along housing 66 in its front portion, for example, by means of projecting nipples. To the contrary, its rear portion has a possibility of lateral back and forth movement within housing 66.
The lateral back and forth movement of piston 65 is guided by a longitudinal rail 68. The rail is journalled around a vertical axis 69 carried by the base of the body, and it is connected to the piston 65 by a vertical pin 70. For example, as is shown in the Figures, pin 70 is carried by the rail, and it moves in a longitudinal slot of piston 65, whose length corresponds approximately to the longitudinal extend of the piston.
Rail 68 can oscillate angularly in a horizontal plane around axis 69, which moves the rear end of the piston from one side or the other of the median plane. This serves to vary the length of the arm of the lever with which each of the wings biases the piston. For example, if the rear end of the piston is displaced towards the top of the FIG. 12, wing 63 will act on the piston with a longer lever arm, and wing 62 with a shorter lever arm. The boot will be more easily freed by wing 62 than by wing 63. It must be noted that according to the present embodiment, the modification of the release thresholds of the retention element is translated on the one side by a diminution, and on the other side by an increase in the release threshold.
To facilitate the lateral displacement of the rear of the piston preferably, the support of the small arms 62a and 63a of the wings occurs by means of a roller carried by the shoulders of the piston.
The oscillation of rail 68 is controlled by the sensors which are adapted to detect an asymmetry of the boot.
The embodiment illustrated shows two sensors 72 and 73 positioned slightly in front of support element 74 of the boot. Each sensor extends transversely on one side of the median plane, and it is journalled around a horizontal and longitudinal axis carried by the base of the retention element. These journal axes are situated in the vicinity of the vertical and longitudinal median plane. The rear end of the rail is engaged between the lower portion of the two sensors, and a compression spring 76 and 77, or any other compressible means, is inserted along a transverse direction between the end of the rail and each of the sensors.
Under the effect of the springs, and in the absence of a boot, the sensors 72 and 73 are raised above the horizontal. Possibly, an abutment (not shown) limits their upward movement. As a result, the rear end of the rail 68 is maintained in alignment of the median longitudinal plane. If one of the sensors if lowered, for example, sensor 73, rail 68 will be pushed in the direction of the other sensor by spring 77. This oscillation of the rail will offset the piston and produce the change of the lever arms of the wings previously described.
FIG. 14 shows the front of a boot, in this case a special boot, adapted to cooperate with the retention elements. The front of sole 80 has over substantially half of its width a cutaway 81 which diminishes locally the thickness of the sole. This cutaway has a depth which is substantially constant and opens downwardly.
When the boot is engaged in the retention element of FIGS. 12 and 13, sensor 73 positioned on the side of the cutout is not lowered. On the other hand, the other sensor 72 is lowered, from which a displacement towards the top of FIG. 12 of the rear end of piston 65 occurs as has been previously described. Wing 62 will oppose a resistance under these conditions to the release of the boot which is less than wing 73.
To obtain a better protection of the knees in the case of a rotation of the foot towards the interior, cutaway 81 is formed as shown in FIG. 14 for a left boot. It is formed on the other side of the sole for a right boot.
The retention element which has been described is nevertheless totally symmetrical, i.e., it is compatible with both the right boot as well as the left boot.
Preferably, if a standard boot is engaged in the retention element of FIGS. 12 and 13, it is the two sensors 72 and 73 which are lowered simultaneously. The two springs 76 and 77 are compressed, and the rail remains in alignment with the longitudinal median plane. Piston 65 remains liekwise aligned with this plane. There is no modification of the lever arms of the wings, and the release threshold of the retention element remains the same for the two sides for release of the boot.
If the boot of FIG. 14 is engaged in a standard retention element, there will be no significant change in the retention conditions of the boot for one or the other modes of retention of the boot, i.e., vamp grip or sole grip.
Numerous other variations are also possible as to the position of the sensors and the identification zones of the boot which they detect. Thus, the identification zones could be situated under the sole, towards the front, the middle or even the rear of the boot, the sensors being positioned accordingly. They could also be positioned on the vamp, above the standardized zone. The reference allowing for the identification of the boot could be a zone which is raised instead of a zone which is hollowed out.
Finally, the invention is applicable to different types of construction of retention elements, in particular, elements having a fixed body and independent jaw signs, elements having a fixed body and jaw wings which are connected in displacement, elements having wings or a jaw whose opening is progressive against a return force of a spring, or those whose opening is controlled by a movable latch.
The invention applies also to the retention elements of the boot which have specific means of compensation or release of the boot in the case of combined front-torsion and rear torsional falls.
The instant application is based upon French patent application 94.08942 of Jul. 13, 1994, the disclosure of which is hereby expressly incorporated by reference thereto, and the priority of which hereby claimed.
Generally speaking, although the invention has been described with reference to a particular means, materials and embodiments, the invention is not limited to those particular means, embodiments and materials which are disclosed and extends to all equivalents falling within the scope of the claims.
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An assembly of a boot and a binding for a gliding board, such as a ski, as well as the boot and binding themselves. The binding has a movable mechanical mechanism for enabling a modification of the release threshold of the binding at will. The boot has a local reference which differs according to whether the boot is for the right or left side. The binding has movable sensors and a linkage to affect the release threshold of the binding. The reference of the boot determines the side of the jaw for which the release threshold is modified.
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BACKGROUND OF THE INVENTION
This invention relates to door construction, and more particularly, to exterior french doors.
Double opening french doors have long been considered a gracious or otherwise desirable element of home construction. However, french doors have long been impractical for homes in northern climates, because of the high heat losses and drafts caused by the extensive surrounding gaps between such doors and their frames. French doors have been especially disfavored since the energy crisis of the 1970's. While outdoor living spaces such as decks and patios have been increasingly emphasized, the convention has been to provide sliding glass doors, rather than french doors, between home interiors and such exterior living spaces. Despite a recent resurgence in interest in french doors, the northern home dweller has generally faced a choice between a sliding glass door and a look-alike, single opening french door. Double opening french doors have remained an energy-consuming extravegance.
SUMMARY OF THE INVENTION
Given the background of the invention, the object of the inventors in making this invention has been to satisfy the long-standing desire for double opening french doors, with a french door assembly which is energy efficient, and also easily maintained and pleasing in appearance.
Another object has been to provide a french door assembly as described, which is highly adaptable to varying rough openings, for use in home rehabilitation; easily installed for superior operation despite possible installation errors; virtually maintenance free; and pleasing of appearance.
In a principal aspect, then, the invention is a double opening french door assembly. A door frame of the assembly includes a sill, a head and jambs. The head and jambs have wood cores and exterior aluminum cladding. A pair of door panels are each hingedly mounted on a door jamb, and each including stiles, rails and double glazing panels mounted on the stiles and rails. The stiles and rails have wood cores and exterior aluminum cladding. The double glazing panels define an insulating, glazing panel air space therebetween. The aluminum cladding is lanced with lances, and the stiles define air passages from the glazing panel air spaces to the lances.
Interior, air seal weatherstripping is on the jambs and head of the door frame, and on an astragal attached to one of the door panels between the astragal and other door panel. The weatherstripping is located to contact the aluminum cladding on the door frames interior to the lances. The assembly also includes exterior, water seal weatherstripping and exterior weatherstripping retainers. The retainers are mounted to the jambs and head of the door frame and to the astragal between the astragal and door panel. The retainers have two adjacent, alternate weatherstripping kerfs for receiving the exterior, water seal weatherstripping. The exterior, water seal weatherstripping is placed in the kerfs to the exterior of the air seal weatherstripping to contact the aluminum cladding on the door frames exterior to the lances.
The water seal and air seal weatherstripping together provide therebetween an insulating, weatherstripping air space about the jambs and head of the door frame and between the door panels. The lances and air passages provide weather protected pressure equalization to the glazing panel air spaces.
BRIEF DESCRIPTION OF THE DRAWING
The preferred embodiments of the invention are described in the following detailed description of the preferred embodiments with reference to the accompanying drawing. The drawing includes seventeen figures, as follows:
FIG. 1 is an exterior, perspective view of the preferred french door assembly of the invention, adapted for double opening doors hinged at the jambs;
FIG. 2 is a diagrammatic, exterior, elevational view of the preferred french door assembly of FIG. 1;
FIG. 3 is a diagrammatic plan view of the door assembly of FIG. 1, showing its manner of opening;
FIG. 4 is a cross-sectional view of the door assembly of FIG. 1, taken along line 4--4 of FIG. 1;
FIG. 5 is a detail view of the door assembly of FIG. 1, taken in the area of circle 5 in FIG. 4;
FIG. 6 is a detail view of the door assembly of FIG. 1, taken in the area of circle 6 in FIG. 4;
FIG. 6A is a detail view of the door panel aluminum cladding, taken in the area of circle 6A in FIG. 6;
FIG. 7 is a collapsed, cross-sectional view of the door assembly of FIG. 1, taken along line 7--7 of FIG. 3, depicting the frame width adjustability of the frame;
FIG. 8 is a second diagrammatic, elevational view of the preferred door assembly, adapted for a single opening door hinged at the jamb;
FIG. 9 is a diagrammatic plan view of the door assembly of FIG. 8, depicting the manner of operation;
FIG. 10 is a partial, cross-sectional view of the door assembly of FIG. 8, taken along line 10--10 of FIG. 8;
FIG. 11 is a diagrammatic, exterior elevational view of the preferred door assembly, adapted for a single, openable or fixed door;
FIG. 12 is a diagrammatic plan view of the door of FIG. 11, as adapted to be openable;
FIG. 13 is a diagrammatic plan view of the door of FIG. 11, adapted to be fixed;
FIG. 14 is a cross-sectional view of the foot of the door of FIG. 12;
FIG. 15 is a cross-sectional view of the foot of the door of FIG. 13; and
FIG. 16 is a collapsed, cross-sectional view similar to FIG. 7, depicting further the frame width adjustability of the preferred french door assembly, with an adjustable sill.
In the following detailed description, the directional terms "interiorly", "exteriorly", "inwardly" and "outwardly" are used. The terms "interiorly" and "exteriorly" refer to directions perpendicular to the plane of the door assemblies, as expected. In contrast, the terms "inwardly", "outwardly", and the like refer to directions in the plane of the door assemblies, toward and away from the centers of the assemblies.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIGS. 1-7, 8-10, 11-15 and 16 as groups, the preferred embodiments of the invention are a first double opening french door assembly 20 (FIGS. 1-7), a single opening french door assembly 30 (FIGS. 8-10), a single door assembly 40 (FIGS. 11-15), and a second double opening french door assembly 22 (FIG. 16). The most preferred assembly is the assembly 20.
Referring to FIG. 1, the assembly 20 includes a french door frame 24 and two swinging french door panels 26, 28. As shown in FIG. 3, the french door panels 26, 28 swing from opposite door frame jambs 27, 29, respectively, of the door frame 24. As diagrammed in FIG. 2, the panels 26, 28 are hingedly mounted to their jambs 27, 29. The panels swing to the interior, between a door frame head and sill.
The assembly 20 is mounted within a rough opening in a building exterior wall 18, as in FIG. 1. As shown best in FIGS. 4 and 7, the rough opening is defined by wall framing members such as wall studs 32, 33 and a wall header 31. Wall shims 34 are behind the door frame jambs 27, 29, at the locations of the door hinges, such as hinges 35 (three hinges are employed per door panel). These shims help support and straighten the jambs 27, 29. Fasteners such as screws 36 extend through the jambs and wall shims into the wall studs.
The frame jambs 27, 29 each include a plurality of jamb components. As shown best in FIG. 5, each jamb such as jamb 29 includes an interior jamb member 37 through which the screws 36 are driven. The members 37 are wood, and extend interiorly of the wall 18 to provide a nailing surface for door frame trim (not shown). The members 37 also provide hinge locations for the door hinges. The members 37 are not clad.
An exterior frame jamb member 38 is mounted to each interior frame jamb member, within the door opening area and exterior to the door panels. The members 38 are wood, and aluminum clad.
An extruded aluminum jamb frame cover 29 includes an exterior box trim segment 42, and a pair of jamb cover snap flanges 43, 44. The box trim segment 42 overlies the exterior face of the interior jamb member 37, to protect the face and provide decorative exterior detail to the door frame 24. A recess 45 of the segment 42 faces outwardly of the door opening and receives a leg of an aluminum cladding flange 46. The flange 46 extends outward of the segment 42 along the wall 18, providing a trim edge for aluminum siding (not shown) on the wall 18.
The jamb cover snap flanges 43, 44 extend parallel to each other, and are spaced a distance apart equal to the width of the exterior jamb member 38. The outermost flange 44 is along the inner edge of the box trim segment 42. Each snap flange includes a barb 47, and is resilient. The flanges 43, 44 are snapped upon the exterior ends of the exterior jamb members 38, with the barbs in opposed slots 48 within the exterior jamb members 38.
An aluminum jamb cladding strip 49 is also retained within the innermost slots 48 by the barb 47 of the innermost snap flange 43. The cladding strip 49 clads the inner side of the exterior jamb member 38. At the interior end of the jamb member 38, an exterior weatherstripping retainer 50 also holds the strip 49 to the jamb member 38.
The retainer 50 extends from its strip holding end 51 around the inner, interior corner of the jamb member 38. At the corner, the retainer 50 includes two adjacent, parallel kerfs 52, 53. The kerfs 52, 53 open interiorly, toward the adjacent door panel. An exterior, water seal weatherstripping 54, to be described, is received in the kerfs.
Adjacent the kerfs 52, 53, the retainer 50 further includes an interior jamb snap flange 55. The flange 55 and a spaced retainer leg 56 of the retainer 50 enter slits 57, 58 respectively, in the interior jamb member 37, to resiliently fasten the retainer 50 to the door jamb.
An interior, air seal weatherstripping 60 also enters the interiormost slit 57 of the retainer slits 57, 58. As shown in FIGS. 5, 6 and 7, the interior weatherstripping 60 extends fully about the jambs and head of the door frame 24, and between the door panels 26, 28. As shown in FIG. 7, the frame head includes interior and exterior head members, a head frame cover, a cladding strip and a weatherstripping retainer identical in cross-section to the corresponding jamb frame members. Thus, on the frame head, the interior weatherstripping 60 enters an interior retainer slit, as on the jambs. Between the door panels 26, 28, the weatherstripping 60 enters a slit on a door center post or astragal 62, as in FIG. 6.
Referring again to FIG. 5, the weatherstripping 60 is a leaf stripping, having a first or backing strip 61 and an angled, door contacting strip 63. The juncture of the strips 61, 63 faces interiorly, and the strips are flexibly movable relative to each other. As most preferred, the weatherstripping 60 is formed of polypropolene. Closure of the door panels 26, 28 flexes the strip 63 toward the strip 61, which causes the strip 63 to resiliently press against the edge of the door panels.
Referring again to FIG. 1, each door panel 26, 28 includes upright stiles 64, 65 and horizontal rails 66, 67, which are jointed to the stiles at the ends. As shown in FIG. 4, by example, the stiles and rails all have wood cores, such as stile cores 68, 69 and are clad by aluminum cladding such as stile cladding 70, 71. The cladding extends across the exterior faces of the stiles and rails and is curved about the edges of the stiles and rails. As shown best in FIG. 6A, the cladding is retained against the wood cores by cladding edge flanges snapped into slits in the stiles and rails, and by adhesive (not shown). Returning to FIG. 4, the stiles and rails provide exposed wood on their interior faces, for pleasing interior appearance.
Door panel hinge leafs 25 of the hinges 35 are screwed to the door panels 26, 28 in routed recesses. As shown in FIG. 5, the leafs are substantially flush with the door. Behind the leafs and in the recesses are hinge shims 23. The hinge shims, leafs and recesses are substantially identical in shape such that the shims and leafs are snug fit in the recesses. The shims are removable. On installation, and after periods of settling or wall warping, the positions of the door panels relative to the door frame may be adjusted by the addition or removal of one or more shims.
The door panels 26, 28 each include double glazing panels 73, 74. Glass is the preferred material of the panels 73, 74, as conventional, and the glazing panels 73, 74 provide between themselves an insulating dead air space in the door panels. The glazing panels are held on the door panels by abutment against the stiles and rails, and by wood retainer strips (not shown) fastened to the stiles and rails.
Turning to FIGS. 4, 6 and 6A, each stile and its cladding include pressure equalizing passages for the insulating space between the door glazing panels 73, 74. As shown by example in FIGS. 4 and 6, a stile 65 includes three passages, such as passage 76, which extend from the insulating air space 77. The passages terminate behind the aluminum cladding 71, where lanced openings, or lances, such as 75, provide for communication of the passages outside the door panels.
The lances are located in zones protected against moisture entrance due to weather. The lances on the stile of the door panel to which the astragal is nailed are adjacent the wood astragal core 78, and behind the aluminum astragal cladding 79. The lances elsewhere are exterior to the interior weatherstripping 60, which is located to contact the stile aluminum cladding, and interior to the exterior weatherstripping 54, in the dry, insulating, dead air space provided therebetween.
The passages 76 protect the air spaces between the glazing panels from suffering a pressure difference from the door exterior. At the same time, condensation between the glazing panels is minimized.
As implied, the exterior, water seal weatherstripping 54 extends fully about the door frame and between the door panels, exterior to the air seal weatherstripping 60. The exterior weatherstripping 54 is most preferably polyethylene-covered urethane foam. The exterior weatherstripping has, as in FIG. 7, a retained leg 80 and two resiliently scissoring strips 81, 82.
Referring to FIG. 7, a frame sill 85 completes the door frame 24. The sill 85 is aluminum extruded, and includes a wood threshold 86. Both the threshold 86 and sill 85 are supported atop a wood threshold support 87. The wood threshold 86 and threshold support 87 provide a thermal barrier between the aluminum sill 85 and the door interior.
The bottom of the door panels 26, 28 include a dual durometer vinyl weatherstrip 88. The strip 88 has two exterior flex legs 89, 90 and an interior flex bulb 91 to air seal the bottom of the door panel.
As shown partially hidden in FIG. 7 and best shown in FIG. 14, the door panel bottoms further include a rain drip guide 93 along the door panel exterior at the bottom edge. The drip guide is fitted with the weatherstrip 88 into a slot 94 in the door bottom. A projection 95 of the drip guide 93 projects outward from the exterior of the door panel, to a bead 96 remote from the door panel. The drip bead 96 aids beading of rain running down the door panel onto the guide. The drip guide thus keeps dripping water from the weaterstrip 88 and the wood threshold 86.
The preferred embodiment of the invention is now described in detail.
The remaining embodiments include the features of the preferred embodiment, with some modifications. The assembly of FIGS. 8-10 is modified in that the door panel 28 is fixed to the frame 24, and the panel 26 is hinged to the astragal. A second, exteriorly extended astragal cover 98 is attached to the cover 79. The sill is extended, as will be described in relation to FIG. 16.
The assembly 40 of FIGS. 11-15 has one door panel only. The panel may be openable, as in FIGS. 12 and 14, or fixed, as in FIGS. 13 and 15. Where the panel is to be fixed, the bottom weatherstrip 88 is replaced by an aluminum clad, wood core, door rest 99, as in FIG. 15. The sill threshold 86, rest 99 and door panel are screwed together.
The assembly of FIGS. 1-7 is intended for wall thicknesses of four and one half inches to four and three-quarter inches. The assembly of FIG. 16 is for wall thicknesses from four and one half inches to seven inches. The assembly of FIG. 16 includes an extended sill 100, a second astragal cover, and substantially widened exterior frame members. The exterior frame members are positioned relative to the interior frame members in relation to the thickness of the wall to which the door is to be attached. The exterior frame members are then fastened in proper position. For narrower wall thicknesses, the exterior frame members are ripped to fit. The extended sill 100 includes a slotted inner sill member 101 and a flanged outer sill member 102. The flanged outer sill member 102 is also ripped in relation to wall thickness and then fitted to the inner sill member 101.
The preferred embodiments and the invention are now described in such full, clear, concise and exact terms as to enable a person of ordinary skill in the art to make and use the same. As suggested above and otherwise, modifications may be made to the preferred embodiment without moving outside the scope of the invention. Therefore, to particularly point out and distinctly claim the subject matter regarded as invention, the following claims conclude this specification.
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A door assembly is provided and generally includes a door frame having a door hingedly mounted on one of the jambs of the frame. The door includes stiles and rails with double glazing panels mounted between the stiles and rails with an insulating air space between the glazing panels. First and second weatherstripping members cooperate with the door and jambs of the door frame to provide substantially air-tight and water-tight seals, respectively, when the door is closed within the frame. The first and second weatherstripping members are spaced apart so as to define a weatherstripping air space therebetween. The door includes passages for providing communication between the insulating air space and the weatherstripping air space so as to minimize condensation between the glazing panels.
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BACKGROUND OF THE INVENTION
This invention relates to a method for improving the performance of high temperature superconducting materials.
INTRODUCTION TO THE INVENTION
We are working with high temperature superconducting materials, in particular, YBCO (yttrium-barium-copper oxide) ceramic superconductors.
Indicia of improvement of performance of these materials include inter alia:
(1) enhancement of their critical current density (Jc);
(2) increases in their critical temperature (Tc);
(3) decreases in their normal state resistivity; and/or
(4) improvement in their durability and workability.
In accordance with these desiderata, it is known that the performance of YBCO ceramic superconductors can be significantly improved by the formation of a composite of the ceramic with silver or silver oxide.
Researchers have claimed that such composites can provide a substantial enhancement (up to fifteenfold) of the critical current density (see Appendix, Reference 1); a modest increase in the critical temperature (References 2, 3); a substantial decrease in normal state resistivity (References 2, 3); and, a noteworthy improvement in ductility and workability (Reference 4). Moreover, it has been claimed that such composites can comprise an addition of up to 60% silver by weight, without any significant degradation of bulk superconducting properties (Reference 3).
Some composite samples have been reported to exhibit very pronounced magnetization (M) versus applied magnetic field (H) hysteretic behavior, suggesting the presence of strong magnetic flux pinning centers in a composite (Reference 8). The existence of strong flux pinning, in turn, is thought to be an important condition for obtaining a high current density (Jc), and producing stable magnetic levitation or suspension (References 9, 10).
SUMMARY OF THE INVENTION
We restate, in brief, the above information. We suggest that the performance of high temperature superconducting materials, for example, YBCO ceramic superconductors, may be improved by the formation of a composite with silver or silver oxide. We now turn our attention, more precisely, to two extant methods for forming or preparing the composite.
In a first method, a silver/ceramic composite is typically formed or prepared by mechanically blending silver or silver oxide powder with an oxide superconductor powder, or with a mixture of superconductor precursor oxide powders, in appropriate ratios, and then thermally treating the blend at 850°-950° C., in air or oxygen, for 16 hours or more, with or without a subsequent annealing step (References 3, 4, 7, 8). A subsequent laboratory-scale mixing process typically involves mechanically grinding the powders in a roller or jar mill, or manually with a mortar and pestle. Typically, this process cycle of thermal treatment and milling must be oft repeated.
In a second method, a silver/ceramic composite may be prepared by melting elemental Y, Ba, Cu, and Ag in an arc furnace (Reference 11). A resulting ingot is cold rolled to thin foil shapes, which are then subjected to a number of heat treatments, to achieve oxidation.
We have recognized that both the first and second methods of forming the silver composite, although typical methodologies, may include pervasive deficiencies, which deficiencies can stymie or even thwart the sought for improvements and advantages of a silver composite superconductor.
These deficiencies can be summarized by the concept of chemical and microstructural "heterogeneity", wherein the cited methods may lead to an incomplete mixing, thus forming, after sintering, a heterogeneous ceramic superconductor. (We will subsequently show, in sharp contrast, that a desired method produces a homogeneous ceramic superconductor.)
We now expand upon this concept of heterogeneity, as empirical experiment permits.
A composite superconductor prepared by the methods 1, 2 supra, is such that the silver is typically located interstitially (Reference 1), in the boundaries between the ceramic superconductor grains, or as isolated particles (Reference 2), rather than as a homogeneous chemical substitution for copper in the superconductor crystal lattice (Reference 5). It is important for the retention of the superconductivity in these ceramics that the silver not replace copper in the lattice.
The addition of the silver or silver oxide by the methods 1, 2 supra may produce changes in the ceramic microstructure of sintered compacts of the superconductor powder. For example, there may be a (deleterious) decrease in porosity (References 3, 6), and/or an apparent (and deleterious) increase in the size and platelet-shape of the ceramic grains (i.e., an increased tendency for heterogeneity).
Furthermore, since the average particle size produced by the attrition process subsumed by the two methods supra, is relatively larger, the use of higher firing temperatures, as well as longer processing times, may be typically (if disadvantageously) required.
In net, the prior art methods 1, 2 supra promote segregation of the metallic silver, as well as discontinuous ceramic grain growth, thereby resulting in a non-uniform (heterogeneic) grain microstructure, in a final sintered ceramic superconductor.
We have now discovered a novel method for realizing a more uniform (homogeneous) distribution of silver around the ceramic superconductor grains in a sintered composite.
In summary, the novel method of the present invention prepares or forms a silver/ceramic composite from a precursor powder that has been obtained, in turn, by chemical coprecipitation from an aqueous solution containing silver ions, as well as the other required metal ions. This coprecipitation process can produce a finely divided precursor powder in which the metal oxides are intimately, hence homogeneously, mixed.
The novel method has an important advantage of retaining all the virtues of a process subsuming formation of a composite of a ceramic with silver, including enhanced critical current densities and increases in critical temperature, while eliminating and avoiding the problem of heterogeneity, as shown above to be an offsetting feature of the typical prior art methodologies. Other advantages of the novel method of the present invention, are disclosed below.
Accordingly, we now disclose a method for preparing a silver/superconducting ceramic composite comprising the steps of:
1) forming an aqueous solution of metal salts including silver and comprised of the metals that can constitute part of the ceramic and of pyrolyzable counter anions, said metal salts being present in a stoichiometric proportion necessary to form said composite ceramic;
2) forming an aqueous solution comprising an alkaline hydroxide and carbonate anions;
3) mixing said solutions together for yielding a coprecipitate with a cation ratio required for a final composite superconducting ceramic;
4) filtering the step 3) coprecipitate;
5) washing the step 4) coprecipitate until its filtrate pH is less than 10;
6) drying the step 5) washed coprecipitate for producing a dried composite precursor;
7) calcining the step 6) precursor for producing a silver composite ceramic; and
8) milling the calcined composite powder comprising two phases, a first silver phase and a second Y-Ba-Cu-O phase, said two phases being of uniform distribution and each phase being present in grains smaller than 20 μm.
BRIEF DESCRIPTION OF THE DRAWING
The invention is illustrated in the accompanying drawing, in which:
FIG. 1 shows a flowchart of the steps of the method of the present invention;
FIGS. 2a-c show X-ray diffraction patterns comparing an Example of the present invention to prior methodologies;
FIG. 3 shows a magnetization versus temperature plot for a sample derived from an Example of the present invention;
FIGS. 4a, b show hysteresis loops generated from samples derived from an Example of the present invention; and
FIGS. 5a, b show scanning electron microscope (SEM) micrographs of calcined powder samples generated from an Example of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The novel coprecipitated precursor method of the present invention, summarized above, may be used to prepare a composite powder comprising silver or silver oxide and Y-Ba-Cu oxide high temperature ceramic superconductor. An illustrative flowchart 10 of the overall coprecipitation process is shown in FIG. 1. We now work through the FIG. 1 flowchart 10.
The Flowchart
In FIG. 1, a step 1 (box 12) shows that an aqueous solution comprising the yttrium, barium, copper, and silver ions, in an illustrative ratio 1:2:3:2 (for 25% w/w Ag in the composite), may be prepared using hydrated or anhydrous nitrate salts. The total metal ion concentration is preferably adjusted to approximately 1 Molar.
The metal salt solution (box 14) (pH: 2-3) at room temperature is rapidly added, (step 2), with vigorous stirring (step 3, arrow 16) to a chilled (preferably 5°-10° C.) aqueous solution comprising a combination of sodium (or potassium) hydroxide and sodium (or potassium) carbonate, in amounts adequate to ensure complete precipitation of the metals, and to maintain pH 10-11 of the solution after addition is completed.
The formed precipitate (box 18) may be collected by either filtration (step 4, box 20) or centrifugation, and is preferably thoroughly washed (step 5, box 22) with deionized water to remove all the residual alkali metal ions. The pH of the filtrate is continuously monitored during washing. Washing is discontinued when the pH value is approximately 10. This is necessary in order to minimize the loss of barium, which is partially soluble at greater than 7 pH.
The washed coprecipitate is preferably oven dried (step 5) at preferably 80° C. in air (box 24).
Next, the dried coprecipitate is ground to a free-flowing powder (preferably 100 mesh), and calcinated (step 7, box 26) in a stream of dry air or oxygen for approximately 6 hours at 850°-900° C., to generate the high temperature superconductor phase.
The calcined powder is preferably allowed to cool slowly (in the furnace) to room temperature in an air or oxygen stream to ensure that the full oxygen stoichiometry is attained.
The black, friable solid product may be removed from the furnace and further ground (step 8, box 28) to give a free-flowing composite powder (box 30).
Measurements
The final composite material may be characterized using a variety of analytical techniques.
Phase purity of the ceramic superconductor may be assessed by X-ray powder diffraction analysis. This technique can be supplemented by differential thermal analysis (DTA), to identify small quantities of low melting point impurity phase(s).
Another thermal analysis technique, thermogravimetric analysis (TGA), can be used to determine the oxygen stoichiometry of the ceramic superconductor phase.
The metals analysis may be performed by either inductively coupled plasma (ICP) emission spectroscopy, or atomic absorption (AA) spectroscopy.
The specific surface area of the composite powder may be determined by the B.E.T. multipoint nitrogen adsorption technique.
The ceramic microstructure of the sintered composite can be observed by scanning electron microscopy, and the qualitative elemental composition of individual grains or small regions can be determined using energy dispersive X-ray spectroscopy (EDX).
A vibrating sample magnetometer equipped with a liquid helium cryostat may be used to determine the magnetic properties of the superconducting composite.
Magnetization may be measured as a function of temperature at a low constant applied magnetic field and the critical temperature, the critical temperature transition width, and superconductivity fraction SCF (an estimate of the fraction of the bulk sample that is superconducting) may be determined for the final composite material. Also, magnetization may be measured as a function of the applied magnetic field at a constant temperature and the resulting hysteresis loop. The area enclosed in the loop is indicative of the amount of magnetic flux pinning in the composite material. This also allows an estimate of the intragranular critical current density in the composite material.
Physical property measurements such as Knoop hardness can be measured on a polished section of a pressed pellet of the bulk sintered composite.
Example
The coprecipitated precursor for the preparation of a silver/Y-Ba-Cu oxide superconductor composite containing 25% w/w AG was prepared as follows.
The Ba (NO 3 ) 2 (39.22 g) was dissolved separately with heating and stirring in 0.5 L deionized water. The Y(NO 3 ) 3 ·6H 2 O (28.72 g), Cu(NO 3 ) 2 ·2.5H 2 O (52.33 g), and AgNO 3 (25.78 g) were dissolved in another 0.25 L deionized water.
The solution containing the Y, Cu, and Ag nitrates was added slowly to the Ba nitrate solution at room temperature. The combined metal nitrate solution was added quickly to a chilled (5°-10° C.), rapidly stirred solution containing Na 2 CO 3 ·H 2 O(62.00 g) and NaOH(27.00 g) in 1 L deionized water.
An instantaneous precipitation took place, and the resulting olive-green slurry was stirred for an additional 15 minutes to ensure completeness of the precipitation process.
The dark green solid was collected by filtration and washed with 2 L aliquots of deionized water, until the filtrate pH was approximately 10.0.
The filtercake was placed in a drying oven at 80° C. The resulting dark gray product (81.8 g) was ground to a gray-green powder with a mortar and pestle.
Metals analysis by ICP was performed on a sample of the dried coprecipitate: %Ba=24.8; %Cu=16/8; %Ag=19.6 (w/w); Y:Ba:Cu:Ag=1.03:2.00:2.92:2.01 (Target=1:2:3:2).
A 10.6 g sample of the above dried coprecipitate was placed in an alumina (99.8%) combustion boat, calcined in static air at 850° C. for 6 hours, and allowed to cool slowly to room temperature in the furnace. 8.5 g (80% yield) of a lightly sintered black powder was obtained.
The X-ray powder diffraction pattern of the calcined product was measured, and the major peaks characteristic of silver oxide, as well as several weaker peaks corresponding to those expected for BaY 2 Cu 3 O 7-x , were observed. A comparison of the X-ray diffraction patterns is shown in FIG. 2. The specific surface area of the powder was determined to be 0.2 M 2 /g. Metals analysis by ICP was performed on a sample of the composite powder: %Ba=31.5; %Y=10.6; %Cu=21.5; %Ag=24.2 (w/w); Y:Ba:Cu:Ag=1.04:2.00:2.95:1.96.
Another 10.0 g sample of the dried coprecipitate was calcined at 900° C. for 6 hours in flowing oxygen. The analytical results were very similar to those for the sample calcined in air.
A small quantity of the calcined powder was pressed at room temperature to form 1/2" diameter and less than 1/16" thick pellets, at about 6000 psi total pressure. The pellet was sintered in a surface for 3 hours at 900° C. in flowing oxygen, and allowed to cool in the furnace to room temperature. Samples in typical size 6 mm×3 mm×1.5 mm were cut from these sintered pellets and were used for superconducting and magnetic properties characterization. The magnetization vs. temperature plot for such a sample is shown in FIG. 3. The Tc for this sample was approximately 92° K. and the transition width was approximately 3.3°. This is very similar to the values generally seen for pure YBCO samples.
We also measured the hysteresis loops at two different temperatures (77K, B.P. of liquid nitrogen and 5K, near the B.P. of liquid helium). Typical hysteresis loops are shown in FIG. 4. The area of the loops indicate the flux pinning in the sample. As expected, the amount of flux pinning is much larger at 5K than at 77K.
Two scanning electron microscope (SEM) micrographs of the calcined powder samples are shown in FIG. 5. In FIG. 5a, micrograph of a 25% w/w Ag20+YBCO prepared by our chemical coprecipitation technique is shown under a magnification of 510 X. In FIG. 5b, micrograph of a 30% w/w Ag20+YBCO prepared by the conventional mixing and thermal treatment process is shown under the same magnification. It is evident from these figures that the composite sample prepared by our chemical coprecipitation method is much more homogeneous, even at such finer scale as indicated in the micrographs, than a conventionally prepared composite.
Purview of Method
In addition to the silver/Y-Ba-Cu oxide ceramic superconductor composites, the present coprecipitation method can be used to prepare silver composites with Bi-Sr-Ca-Cu oxide and analogous thallium oxide-based families of higher temperature ceramic superconductors as well. The preparation of lead-stabilized Bi-Sr-Ca-Cu oxide superconductor powders is also possible using this coprecipitation method. The technique has been demonstrated for several Bi-Sr-Ca-Cu oxide superconductor powders (without lead). It is expected that this coprecipitation technique is generally useful for preparing other types of metal or metal oxide/ceramic composites which require careful control of both chemical homogeneity and ceramic microstructure.
APPENDIX
Background references for the method of the present invention are now set forth. The disclosures of each of these references are incorporated by reference herein.
1. Lue J. T., Kung, J. H., Yen H. H., Chen. Y. C., Wu P. T., Mod. Phys. Lett., B, 2(2), 589-95 (1988).
2. Sherwood R. C., Jin S., Tiefel T. H., VanDover R. B., Fastnacht R. A., Yan M. F., Rhodes W. W., Mat. Res. Soc. Symp. Proc. Vol. 99, 503-6 (1988).
3. Plechacek V., Landa V., Blazek Z., Sneidr J., Trejbalova Z., Cermak M., Physica C 153-5, 878-9 (1988).
4. R. Prasad, Soni N. C., Mohan A., Khera S. K., Nair K. U., Gupta C. K., Tomy C. V., Malik S. K. et al., Mater. Lett., 7(1,2), 9-12 (1988).
5. Cohen D., Schwartz M., Reich S., Felner I., Inorg. Chem., 26, 3653-5 (1987).
6. Peterson G. G., Weinberger B. R., Lynds L., Krasinski H. A., J. Mater. Res., 3(4), 605-9 (1988).
7. J. H. Kung., Yen H. H., Chen Y. C., Wang C. M., Wu P. T., Mat. Res. Soc. Symp. Proc., Vol. 99, 785-8 (1988).
8. Huang C. Y., Shapira Y., McNiff E. J., Peters P. N., Schwartz B. B., Wu M. K., Shull R. K., Chiang C. K., Mod. Phys. Lett. B, 2(7), 869-74 (1988).
9. Brandt E. H., Science, Vol. 243, 349-355 (1989).
10. Peters P. N., Sisk R. C., Urban E. W., Huang C. Y., Wu M. K., Appl. Phys. Lett., 52(24), 2066-7 (1988).
11. Early E. A., Seaman C. L., Maple M. B., Simnad M. T., Physica C 153-5, 1161-2 (1988).
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A novel method for forming homogeneous silver high temperature superconductor (HTS) composites. The novel method comprises a chemical coprecipitation of silver, barium, yttrium, and copper salts solutions, followed by calcination and milling processes. The novel method has an advantage of retaining all the virtues immanent in a composite HTS, for example, increased critical current density (Jc), and improved mechanical properties, while bypassing extant and deficient methodologies for forming a composite, the deficient composites characterized by heterogeneity.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of Korean Application No. 2001-68632, filed Nov. 5, 2001, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to an ink cartridge used with an ink jet printer, and more particularly, to an ink cartridge used to maintain the inside of an ink reservoir under a proper negative pressure.
[0004] 2. Description of the Related Art
[0005] An ink cartridge used with an ink jet printer generally reserves ink to discharge ink droplets through a print head so that a colored image is printed on a sheet.
[0006] The ink cartridge requires a device to maintain the inside of an ink reservoir under a negative pressure in order to prevent an excessive amount of ink from leaking through the print head in a printing state, or a wetting occurrence at the print head in an idle state.
[0007] [0007]FIG. 1 illustrates an ink cartridge disclosed in U.S. Pat. No. 5,541,632. Referring to FIG. 1, the ink cartridge includes a housing and an ink reservoir arranged in the housing to reserve ink, while having a negative pressure maintenance unit 30 . The housing includes a frame 10 , and side plates 12 and 14 to seal both sides of the frame 10 . The ink reservoir is sealed by flexible walls 22 and 24 , which may be transformed while maintaining the inside of the ink reservoir in a sealed state. The negative pressure maintenance unit 30 maintains the inside of the ink reservoir under a proper negative pressure. Thus, ink is prevented from dripping through a print head 13 when discharging the ink from the ink reservoir through the print head 13 by passing through a filter 18 or when reserving the ink in the ink reservoir. In this case, the negative pressure maintenance unit 30 has a bow spring 31 and plates 32 and 34 to support the bow spring 31 .
[0008] In the ink cartridge of the above configuration, since the bow spring 31 directly contacts the ink reserved in the ink reservoir, the bow spring 31 may corrode by chemical reaction with the ink.
[0009] Accordingly, preventing the bow spring 31 from corroding is required. However, forming the bow spring 31 by using a material which does not react with inks limits the range of materials for the bow spring 31 and increases the price of the selected material. An alternative plan for changing the main element and additives of the ink also limits the selecting range for ink and increases the price of the ink.
SUMMARY OF THE INVENTION
[0010] Accordingly, it is an objective of the present invention to provide an ink cartridge used with an ink jet printer, which prevents a negative pressure maintenance unit from corroding and improves the filling efficiency of ink.
[0011] Additional objects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice.
[0012] The foregoing and other objects of the present invention are achieved by providing an ink cartridge used with an ink jet printer having an ink reservoir to reserve ink, a housing to cover the ink reservoir, and a negative pressure maintenance unit to maintain the inner pressure of the ink reservoir under a negative pressure. The reservoir includes a base plate, a cover plate separated from the base plate, and flexible walls interposed between the base plate and the cover plate to form a sealed space to reserve ink. Here, the negative pressure maintenance unit includes at least one elastic member to be interposed between the housing and the cover plate.
[0013] In an aspect of the invention, the elastic member is a leaf spring to maintain the inner pressure of the ink reservoir under the negative pressure by applying an elastic restoring force in a pulling direction of the cover plate.
[0014] The leaf spring has a housing fixing portion fixed to the housing, plate fixing portions fixed to the cover plate, and connecting portions to integrally connect the housing fixing portion and plate fixing portion.
[0015] In another aspect of the invention, the housing is formed by fixing first and second body portions that are facing each other or by fixing a wall body having a through hole and a cover to seal one side of the wall body, so that the housing is coupled with the base plate to cover the ink reservoir. In another aspect of the invention, the housing is formed of one selected from a sheet metal and structural polymer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] These and other objects and advantages of the invention will become apparent and more readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
[0017] [0017]FIG. 1 is a separate perspective view illustrating a conventional ink cartridge;
[0018] [0018]FIG. 2 is a sectional view illustrating an ink cartridge according to an embodiment of the present invention;
[0019] [0019]FIG. 3 is a sectional view illustrating the ink cartridge according to the embodiment of FIG. 2 along the cutting plane line II-II of FIG. 2;
[0020] [0020]FIGS. 4A through 4C illustrate an aspect of a leaf spring used in the ink cartridge according to the embodiment of FIG. 2, in particular, an initial state, and before and after the operation of the leaf spring;
[0021] [0021]FIGS. 5A through 5C illustrate the leaf spring used in the ink cartridge according to another aspect of the present invention, in particular, an initial state, and before and after the operation of the leaf spring, respectively;
[0022] [0022]FIGS. 6A through 6C illustrate another aspect of the leaf spring used in the ink cartridge according to the embodiment of FIG. 2, in particular, an initial state, and before and after the operation of the leaf spring, respectively;
[0023] [0023]FIG. 7 illustrates a housing used in the ink cartridge according to another embodiment of the present invention; and
[0024] [0024]FIG. 8 illustrates a housing used in the ink cartridge according to yet another embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0025] Reference will now be made in detail to the embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like reference numerals refer to like elements throughout. The embodiments are described below in order to explain the present invention by referring to the figures.
[0026] [0026]FIG. 2 is a sectional view illustrating an ink cartridge according to an embodiment of the present invention, and FIG. 3 is a sectional view illustrating the ink cartridge along the cutting plane line II-II of FIG. 2. Referring to FIGS. 2 and 3, the ink cartridge includes an ink reservoir 120 , a housing 110 , and a leaf spring 130 as a negative pressure maintenance unit.
[0027] The ink reservoir 120 contains a base plate 100 , a cover plate 102 , and flexible walls 104 to seal a space between the plates 100 and 102 . In this case, the cover plate 102 moves vertically according to the amount of ink in the ink reservoir 120 . The flexible walls 104 formed of a flexible material are attached to the edges of the base plate 100 and the cover plate 102 that face each other, so that a sealed space is formed.
[0028] The housing 110 has an opening in the area of which the housing 110 is coupled with the base plate 100 by welding, i.e., a thermal or ultrasonic welding, or by using a combining unit, i.e., a screw or hook, so that the housing 110 with the base plate 100 covers the ink reservoir 120 .
[0029] The housing 110 and the cover plate 102 of the ink reservoir 120 are arranged with the leaf spring 130 therebetween . The initial state and before and after operation states of the leaf spring 130 are illustrated in FIGS. 4A through 4C. Referring to FIGS. 4A through 4C, the leaf spring 130 includes a housing fixing portion 130 a fixed to the housing 110 , plate fixing portions 130 b fixed to the cover plate 102 , and connecting portions 130 c to connect the fixing portions 130 a and 130 b . In this case, the housing and plate fixing portions 130 a and 130 b are fixed to the housing 110 and the cover plate 102 by a welding method or by using a combining unit like a screw or hook, respectively. The leaf spring 130 is flat in the initial state. When installing the leaf spring 130 in the ink cartridge, the leaf spring 130 is transformed toward an operation direction by a small amount, as illustrated in FIG. 4B. Since strain energy accumulates in the leaf spring 130 due to the transformation, the strain energy generates an elastic restoring force to pull the cover plate 102 of the ink reservoir 120 . Consequently, a negative pressure, under an external atmospheric pressure, is formed in the ink reservoir 120 . As the ink is discharged through a print head 114 and the amount of ink in the ink reservoir 120 decreases, the flexible walls 104 contract toward an inner direction, as illustrated by dotted lines in FIGS. 2 and 3. Accordingly, the cover plate 102 moves toward the base plate 100 . In this case, the transformation of the leaf spring 130 increases to move the cover plate 102 , so that the negative pressure in the ink reservoir 120 is maintained within a predetermined range. FIG. 4C illustrates the final state of the leaf spring 130 .
[0030] [0030]FIGS. 5A through 5C illustrate another aspect of a leaf spring used in the ink cartridge according to an embodiment of the present invention, in particular, an initial, uninstalled state of the leaf spring, and states of the leaf spring before and after operation, respectively. Prior to installation, the leaf spring 140 is transformed by a small amount in an opposite direction from the operation direction in, as illustrated in FIG. 5A. When installing the leaf spring 140 in the ink cartridge, the leaf spring 140 is transformed toward an operation direction, as illustrated in FIG. 5B. Accordingly, a stronger restoring force than that of the leaf spring 130 shown in FIG. 4B is generated to pull the cover plate 102 . FIG. 5C illustrates the final state of the leaf spring 140 .
[0031] [0031]FIGS. 6A through 6C illustrate another aspect of a leaf spring used in the ink cartridge according to an embodiment of the present invention. The leaf spring is formed by overlapping two identical leaf springs 150 and 160 inversely facing each other. The leaf springs 150 and 160 are overlapped in the state illustrated in FIG. 6B so that a restoring force is applied to pull the cover plate 102 . FIG. 6C illustrates the final state of the leaf springs 150 and 160 .
[0032] Although a few types of leaf springs used in the ink cartridge are described above, various types of leaf springs may be used without departing from the scope of the present invention.
[0033] In addition, another housing, other than an integral type housing, may be formed by coupling corresponding portions of the housing, as illustrated in FIGS. 7 and 8. FIG. 7 illustrates the housing formed by coupling first and second body portions 110 a and 110 b that are facing each other, to cover the ink reservoir 120 in FIG. 2. The first body portion 110 a has an opened side and an upper surface with an opened portion. The second body portion 110 b is formed in a shape to seal the opened side and the opened portion of the upper surface of the first body portion 110 a . The first and second body portions 110 a and 110 b are coupled to form the housing having an opened lower surface. The first and second body portions 110 a and 110 b are coupled by a welding method, such as thermal welding or ultrasonic welding, or by a mechanical coupling method using a screw or hook. In this case, the housing is formed of a processed sheet metal or structural polymer. In FIG. 8, a housing is formed by coupling a wall body 110 c having a through hole and a cover 110 d to seal the upper portion of the wall body 110 c. In this case, the material and coupling method for the wall body 110 c and the cover 110 d are the same as those for the housing illustrated in FIG. 7. Although a few types of housings used in the ink cartridge according to the present invention are described above, various types of housings may be formed without departing from the range of the present invention.
[0034] Since the ink is filled only in the ink reservoir of the ink cartridge according to the present invention, changes in the physical property of the ink by vaporization of the ink are prevented. Since the inner pressure of the ink reservoir does not vary while storing the ink cartridge for a long time or at a high or low temperature, it is unlikely that the ink drips. Moreover, the leaf spring is located outside of the ink reservoir, so that the leaf spring does not corrode while having the possibility to freely select the ink and the material for the leaf spring. The leaf spring occupies a small space between the housing and ink reservoir, so that the filling efficiency of ink improves.
[0035] Although a few embodiments of the present invention have been shown and described, it would be appreciated by those skilled in the art that changes may be made in this embodiment without departing from the principles and spirit of the invention, the scope of which is defined in the claims and their equivalents.
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An ink cartridge used with an ink jet printer. The ink cartridge has an ink reservoir and a housing to cover the ink reservoir with a negative pressure maintenance unit therebetween to maintain the inner pressure of the ink reservoir under a negative pressure. Since the negative pressure maintenance unit does not contact ink in the ink reservoir, the negative pressure maintenance unit does not corrode. In addition, the negative pressure maintenance unit is installed between the housing and the ink reservoir while occupying a small space, and thus improving the filling efficiency of ink in the ink reservoir.
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CROSS-REFERENCE TO A RELATED APPLICATION
This is a continuation-in-part of application Ser. No. 07/539,730 filed Jun. 18, 1990, now abandoned.
COPYRIGHT NOTICE
A portion of the disclosure of this patent document contains material which is subject to copyright protection. The 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.
TECHNICAL FIELD OF THE INVENTION
This invention relates generally to the process of controlling a large-scale software system and, more particularly, to a methodology for tuning a large-scale system to effectively utilize system resources such as a central processing unit and its associated database files and database servers.
BACKGROUND OF THE INVENTION
Effectuating efficient processing in the day-to-day operation of a large-scale software system has conventionally required staff personnel with expertise to interpret manifestations of system performance, and has consumed a significant amount of staff time and financial resources to identify actual and potential problem areas.
System performance is generally gauged by two very different measures, known respectively as system response time and system throughput. The former measure relates to the speed of responding to a single system command, whereas the latter means the efficiency of processing large amounts of data. Balancing these measures is the domain of the system expert, and overall efficiency depends on carefully arranging both the hardware and software that does the processing as well as the information that is stored in the system's databases. The procedure of allocating resources so that system processing is shared by the resources on a balanced basis is called "tuning."
Tuning of this type, namely, allocation of resources by a human system expert, is still carried out despite the advent of computerized, autonomous resource managers designed to optimize performance. These computerized managers are typically part of the operating system software and are designed to service general work loads, that as a rule are not backlogged. Representative of such computerized managers of the non-backlogged type is the subject matter of the disclosure of Watanabe et al. U.S. Pat. No. 4,890,227. For the non-back-logged case, it is possible to optimize both response time and throughput. For the backlogged case, improvements in response time come at the expense of throughput, with the converse also being true. However, these managers operate under the handicap that the current allocation of files to disks is outside the scope of their optimization. Also, of necessity, these managers lack application-specific knowledge. This limitation precludes them from including in their optimizations other, non-performance related concerns. A prime example of one such concern is allocating files to disks to minimize the impact on the system as a whole in the event that a particular disk fails. This concern is referred to here as developing a damage limitation policy and its implementation has a direct bearing on system availability. Finally, these managers do not attempt to regulate the flow rate of transactions into the system. Consequently, their optimization is a local, not a global optimization.
To place the response time and system throughput measures and their ramifications in a practical setting, reference is made to an illustrative example of a large-scale software system, designated the FACS system, which finds widespread use in the telecommunications environment. The FACS system assigns and inventories telephone outside plant equipment (e.g. cable pairs) and central office facilities (e.g. cable appearances on a main distribution frame). Currently, the FACS system is embodied in approximately 1 million lines of source code. It runs on a mainframe or host computer composed of a CPU complex with 2-4 processors, an I/O system containing 6-8 dual disk controllers, and 60-80 600 million byte disks. Because of the complexity and size of the FACS system as well as its sophisticated execution environment, operating the FACS system with acceptable response time while maintaining high system throughput is an on-going challenge which requires tuning skills of an expert to achieve a high level of system performance.
Formulating a thorough diagnosis and just one possible remedy for performance problems in such a large system typically takes expert analysts several days. Starting with performance symptoms, analysts manually tuning a FACS system first deduce which of several kinds of data they need to analyze the problems. Then they apply formulas and guidelines based on their own experience to arrive at a basic understanding of the problem areas--for instance, occasionally transactions stack up in queues leading to inefficient use of central-processing resources. Next, the analysts cull the data, searching for specific explanations for the degradation of performance. The final step, identifying solutions, again calls for using so much knowledge and data that short cuts based on past experience are a practical necessity. Of course, once changes are made, another cycle of analysis must be undertaken to verify that problems are corrected. Because the analysis is so time consuming and difficult, performance issues are often addressed only after system performance has degraded.
When systems of this size go awry, there are typically many symptoms to analyze. It is difficult to isolate those that are truly performance affecting from those that merely appear to affect performance. To cull the important symptoms, and then synthesize assessments of the current state of the system requires an understanding of how a symptom (such as a large number of concurrently active processes) affects the users' perception of the responsiveness of the system as a whole. Developing this view requires deep analysis, facilitated by the mathematics of queueing theory. The analysis techniques themselves are difficult to understand and to properly interpret the results obtained from them requires insight into the dynamics of the underlying system.
SUMMARY OF THE INVENTION
These deficiencies as well as other limitations and shortcoming of these and other techniques are obviated, in accordance with the present invention, by an expert system implemented by computer software that utilizes measured data and deploys a search technique which references a knowledge base, including a set of rules derived from domain experts, to tune the large-scale system.
In the preferred embodiment of the present invention, the host system that is to be monitored for tuning is linked to a workstation which implements expert system software. The host system is sized to insure concurrent transaction backlog during peak hour, and includes disks, disk control units, and files on the disks controlled by the disk control units; the host also has measurable central processing unit (CPU) and input/output (I/O) service times. A set of operational principles relating to the operation of the host system is defined by capturing operational and descriptive information supplied by a host system expert who acts as a mentor for the expert system. The operational principles are transformed into an executable knowledge base and then stored in a memory of the workstation. The CPU and I/O service times are measured on the host, as controlled by the expert system. The I/O service times are stored in the memory, and the CPU service times are processed by the expert system before storage in the memory. The stored CPU and I/O service times are then processed to generate system state data. In one aspect of the present invention, sequencing through the set of operational principles with the system state data is effected to obtain CPU-response time information with is used to modify the concurrency of the host system as determined from the CPU-response time information. In another aspect of the present invention, the expert system is loaded with the current I/O configuration arrangement of the host system, and sequencing through the set of operational principles with both the I/O service times and the I/O configuration information is effected. The result is I/O modification information which is used to reallocate the current allocation of files to disks. When tuning is recommended, program code in a form executable by the host is automatically generated by workstation software. The code may be uploaded to the host for execution to thereby implement the recommended changes.
Accordingly, the subject matter of the present invention is composed of a methodology that enhances the performance and availability of a dedicated, application specific host or main frame computer, sized to insure a transaction back-log during peak hour, where the number of concurrent transactions, the allocation of files to disks and across disk control units, are the parameters to be optimized. The subject matter of this invention not only explicitly addresses the response time-throughput trade off, but also explicitly considers a file allocation policy during system optimization, tempered by damage limitation considerations.
The ART system (ART is a trademark of the Inference Corporation) and the Lisp language are the implementation vehicles for the heuristic aspects of the file allocation optimization in this invention. A key component of this functionality involves the use of an Assumption-based Truth Maintenance System to determine file relocation solutions to I/O subsystem tuning problems. The process involved is a heuristic search through plausible file relocation solutions, considering application and system level factors. The ART system and Lisp give no guidance or structure for performing or controlling this search. The structure and control of the search are part of this invention. The role of the ART system is to provide generic truth maintenance utilities to ease the implementation task.
In performing such a search using the ART system, it is not simply the case that the ART system is missing the knowledge (data) itself which is then supplied. With the present invention, the search algorithm is devised independently of the ART system or the knowledge for which the ART system is designed to work.
The organization and operation of this invention will be understood from a consideration of the detailed description of the illustrative embodiment, which follows, when taken in conjunction with the accompanying drawing.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 depicts a logical view of a portion of the I/O system of the large-scale system to be tuned;
FIG. 2 depicts the large-scale system to be tuned in block diagram form as well as the workstation which implements the expert system (ES) analysis;
FIG. 3 is illustrative of the CPU Performance Analysis Presentation output display from the expert system;
FIGS. 4A and 4B depict the I/O System Diagram output display from the expert system.
FIG. 5 presents the repair recommendation for the particular FACS system under evaluation; and
FIG. 6 illustrates frames with I/O subsystem data.
DETAILED DESCRIPTION
To place in perspective the detailed description of the present invention, it is instructive to gain a basic understanding of the manual technique for tuning a large-scale software system. Accordingly, the first part of this detailed description discusses the conventional methodology as it is applied to the FACS system. This approach also has the additional advantage of introducing notation and terminology which will aid in elucidating the various aspects of the present invention.
The next part of the description then focuses on a discussion of the functionality of the expert system (ES) as well as the processing effected by the software modules comprising ES. After this, the actual code for ES is presented.
Conventional Tuning
A human analyst begins by first identifying which area of the tuning spectrum should receive intensive analysis. The analyst does this by determining the magnitude and source of the queueing delays present in the response time of the average FACS transaction. The source of delay may be, for example, the CPU complex or the I/O system. Once quantified, the analyst them judges where to concentrate. For illustrative purposes to introduce the notions of tuning, it is supposed that the I/O system was selected. With reference to FIG. 1, a "logical" view (in contrast to a block diagram or schematic view) of one subsystem of the FACS system, namely, FACS I/O system 100, is depicted. Elements 101,102, . . . are dual disk controllers (typically there are 6-8 disk controllers), with controller 101 being composed of single controllers 1011 (A1) and 1012 (A2), respectively, and so forth. Elements 111-114 (D11,D12,D13,D14), 121-124 (D21,D22,D23,D24), . . . are disk packs (typically there are 60-80 600 million byte packs); disk 111 is shown as being comprised of files 1111-1114 (D11F1,D11F2,D11F3,D11F4), respectively. Files typically are of specific types such as a library or database. Disks 111,121, . . . are controlled by controller 1011, disks 112,122 . . . are controlled by controller 1012, and so forth.
The types of problems that can occur in system 100 include: Disk D11 is "hot," that is, is heavily used because of the types of files stored by the disk pack; file D11F1, which is a database, and file D11F4, which is a library, are on the same disk pack which has the potential for causing an access time problem; or the average "utilization" of controller 101 exceeds a prescribed threshold.
To identify "hot" control units or disks, experienced performance analysts check a high-level report, referred to as the Controller and Disk Activity Report, by comparing the measured control unit utilization and disk utilization with their respective threshold values. To further pinpoint the possible causes of equipment being hot, expert analysts consult a report called the I/O Trace Summary Report which details I/O statistics at file level by device. Performance analysts manually calculate the utilization of each file on the hot equipment using the statistics reported on the I/O Trace Summary Report and single out the ones that have the highest utilization because their removal will most significantly relieve the workload on the hot equipment. In addition, performance analysts must also verify if file placement guidelines are carefully followed across the I/O system. The characteristics of the FACS system and the capability of computing hardware prohibit multiple, heavily used files to be placed on the same pack to avoid contention, and require certain system and application files to be duplexed, that is, the creation of an identical version of a given file, for the purpose of recovery. In the given I/O system, performance analysts examine the I/O Trace Summary Report looking for offending files located on a hot disk, say D11. This pack contains D11F1, D11F2, D11F3, D11F4, and other files. Assisted by their familiarity with their system's file numbering schemes (e.g., which number stands for which file) and their knowledge of the file naming convention, and a detailed File Placement Report, performance analysts identify that a data base file (D11F1) and a library file (D11F4) coexist on the same disk. Since both are heavily used files and placing them together on the same pack may cause the disk to be overly utilized, performance analysts compare the file utilization of both files and relocate the most heavily used one, e.g. the library file, to a less busy pack. Other than moving files around, performance analysts may take different action (e.g. duplex the offending file to reduce traffic) depending on the nature of the problem and the type (e.g., database or library file) of offending file.
Manually finding a best offload location for a file move is a complex task. Ideally, analysts must first identify all available offload equipment having the same physical characteristics but which are not as busy as the current equipment by going through the File Placement Report and the Controller and Disk Activity Report. They then need to manually adjust the performance statistics on the currently located pack and each possible offload pack to reflect the shifted load, based on the statistics reported on the Controller and Disk Activity Report and the I/O Trace Summary Report. To verify that no new performance problems are introduced, they must apply the file placement guidelines used originally to detect problems to the reorganized I/O system. Finally, performance analysts select the one with the lowest utilization and fewest potential problems. Because of the complexity of the task, performance analysts do not always follow the procedure described above. There is a tendency to stop the searching process when they find the first location that fits the problem file. To verify if existing problems are resolved and no new problems are created, performance analysts must collect and analyze another data sample.
Overview of the Present Invention
With reference to FIG. 2, pictorial diagram 200 depicts an arrangement of the computerized expert system in accordance with the present invention, namely, ES 210 operating in conjunction with modeling system 220, shown as analyzing and providing corrective performance adjustment information, via feedback paths 211 and 212, to improve the responsiveness of FACS production host 250. Typically host 250 is configured, for purposes of discussing an illustrative embodiment of the present invention, to include: arrival queue 251; host concurrency control 252; CPU queue 253; CPU 254; I/O complex 255; and measurement complex 256. ES 210 is implemented by computer software resident within workstation 205. Typically, modeling system 220 is also implemented with software resident within workstation 205. The adjustment information is of the type that provides: (a) parameter information for setting the maximum permissible concurrently active transactions (lead 211); and (b) executable code that effectuates file moves on production host 250 (lead 212). The adjustment information may also be observed by a responsible user of system 250, via display panels 240 and 245; this user is responsible for insuring that production host 250 provides acceptable service to its community of end users. The responsible user oversees the interaction between ES 210 and production host 250 and can monitor changes to production host 250 as guided by the adjustment information. As alluded to, the adjustment information is specific to two areas. The first is the response time-throughput trade off, and the second is file placement. In each case, the implementation of the adjustment information results in changes to production host 250. The effect of implementing the response time-throughput adjustment information is to modify the number of transactions permitted to process concurrently. The effect of implementing the file placement adjustment information is to move or modify the configuration of files to eliminate over utilized disks and control units or minimize the impact on production host 250 in the event that a disk or control unit fails. When a file is moved or modified for this reason, it enhances the availability of production host 250. File moves or configuration changes triggered by this reason are referred to as damage limitation modifications.
Response Time-Throughput Adjustment Information
(Reference is made to the Glossary for the complete definitions of terms and symbols contained in the remainder of this specification). To gain additional insight into the nature of the response time-throughput adjustment information identified in panel 240 of FIG. 2, an understanding of the nature of the response time-throughput time trade off, the subject of the adjustment information, must be elucidated. There exists a direct relationship between the number of transactions, T hreads , concurrently active in host 250 the rate at which they are served, λ. Although this relationship can be developed for any system, it is particularly important for systems designed to operate at high processor utilization, a condition present in back-logged systems, i.e. system where transactions are waiting to begin processing, as indicated by the state of arrival queue 251 on production host 250.
For any finite system, as the number of transactions concurrently admitted to service increases, the service rate asymptotically approaches an upper bound, λ max . This bound is governed by the physical characteristics of the host system, i.e., the number and speed of the system's physical devices, CPUs, disks and control units, and the host system resource cost, the CPU and disk service time, necessary to satisfy each transaction's demand for service. When a host system operates in the neighborhood of the bound λ max , admitting additional transactions only increases the wait-time experienced by each transaction. This effect manifests itself as an elongated transaction existence time, T. Balancing the admission of additional transactions which results in higher contention, induced wait-time against the increase in throughput obtained from the higher concurrency is known as the response time-throughput trade off. In alternate terms, the trade off consists of striking a balance between quick response for an individual transaction and the rate at which large numbers of transactions are processed by production host 250.
There are many ways to depict this trade off. The method chosen for illustrative purposes of the present invention is to display the rate of service, i.e., the transaction throughput, λ M , as a function of the amount of CPU queueing, B CPU , while explicitly stating the number of transactions concurrently active in the system. This relationship is portrayed by the curve in display panel 240 of FIG. 2. Note the asymptotic behavior--as additional transactions are admitted the throughput approaches λ max .
Once this relationship is developed, the final step in producing adjustment information is to quantify as well as to make known to the responsible user the implications of choosing one realization of the response time-throughput time trade off over another, as well as supplying for the contemplated realization, the
(1) maximum allowable concurrency that should be set in host 250 to effect the realization, T hreads .sbsb.M
(2) the expected processing rate, λ M
(3) expected CPU queuing time, B CPU
(4) the expected existence time, T M , and
(5) the expected CPU utilization, ρCPU M .
Elucidating these implications is accomplished by a set of operational principles, which also provide the operating point information stated above. The elucidation is in the form of statements that quantify changes from the current CPU queuing time and system throughput. The elucidation plus the vector (T hreads .sbsb., λ M , B CPU , T M , ρCPU M ) at the contemplated realization makes up the "Response Time-Throughput Adjustment Information", namely, panel 240 in FIG. 2. The complete set of principles that generate this adjustment information is stated in Appendix A.
Since the observer of the adjustment information is the responsible user, the form of the adjustment information, as distinguished from its content, is also important. The illustrative embodiment of ES 210 offers this adjustment information using both a graphical and textual presentation, as exemplified in FIG. 3. The default display 310 of FIG. 3 is the pictorial interpretation of the busy hour model, as traced by curve 311. The X-axis shows the amount of time each transaction waits for service by the CPU complex while the Y axis shows the throughput, given that the user is willing to tolerate the selected wait time which is an input parameter. The current wait time in the FACS system is shown by vertical straight line 312. A responsible user may investigate the tradeoff between the wait time and system throughput by moving arrow 313 toward the origin (reducing the wait time) or away from the origin (increasing the wait time.) Table 314 reports the actual measurements (average processing rate, CPU queueing, total existence time, concurrency, and CPU utilization) and the forecasted results based on the proposed wait time specified by the user. This computation module of ES 210 also allows the user to explore other hours available on menu 315. Display 310 is redrawn each time the responsible user chooses a different hour and table 314 reflects the statistics of the selected hour.
File Placement Adjustment Information
It is recalled that the objective of producing the file placement adjustment information is to move or modify the configuration of files to eliminate over-utilized disks and control units, or minimize the impact on production host 250 in the event that a disk or control unit fails.
The rationale for the decision to move or modify the configuration of files is that high device utilizations cause unnecessarily long I/O existence times, resulting in unacceptable performance. The central issue here is "What constitutes unacceptable performance"? ES 210 bases decisions on non-transitory, abnormally high device utilizations. Non-transitory is important. In practice, just as a human analyst does not react to floating hot spots, busy components caused by high, but short lived traffic to a particular file, neither does ES 210. Transitory I/O traffic can be induced by variations in the transaction workload. To avoid recommending moves one day only to discover that the move was unnecessary later, ES 210 will not generate code to move files for a-priori designated files whose traffic is known to be transitory. The responsible user identifies this type of file to ES 210.
To quantify high device utilizations, analyses determined the correlation between a hardware component's utilization and the queueing delays experienced by an average transaction. These analyses, specific for the FACS application, culminated in utilization thresholds, that if consistently exceeded, lead to the conclusion that a disk or control unit has unacceptable performance. These thresholds are supplied as defaults in ES 210, and can be modified by the responsible user.
Similarly, system availability improvements can be achieved if steps are taken to minimize the impact on production processing, if a hardware component fails, i.e. if a damage limitation policy is implemented. In the illustrative embodiment, ES 210 implements a FACS-specific damage limitation policy by consolidating files containing key application data bases on the same disk, or when appropriate, duplexing files. Duplexing files means that two live copies of a file can exist, with either copy capable of servicing an application. In the event that a disk containing one of the two copies fails, processing continues without interruption. If a file is duplexed both copies should not be placed on the same disk, or if one is conservative, on the same string.
ES 210 produces file placement adjustment information by implementing the following reasoning process. First, ES 210 detects high utilization control units and disks by comparing measured utilizations with the thresholds identified above. Next, ES 210 determines which files are causing the problem by identifying high traffic files. ES 210 will also examine how the files are allocated across packs and disk strings looking for files that violate the damage limitation policy. The hardware performance of individual disks is checked against the manufacturer's performance specification. Finally, file placements, known to have caused problems in the past, perhaps on other FACS systems, are identified. This phase of the analysis process culminates in a list of problem files.
Given the problem list, ES 210 then develops the file placement adjustment information, including file moves, duplexing, or main memory caching recommendations. This adjustment information is composed of not only moving high traffic files to less heavily utilized disks, but also preferentially taking advantage of operating system file duplexing and main memory caching capabilities to reduce the traffic to files identified as problems.
This is the most demanding portion of the process. In the case of file moves, there are potentially many candidate locations. Using a search technique, ES 210 finds the "best" new location for each offending file, as measured by minimum post-move disk and controller utilization, and smallest spare slot, large enough to accommodate the offending file, usually on the same disk. Most importantly, ES 210 does this without creating new problems. The search culminates in a list of new locations for the problem files. The current and new locations are used by ES 210 to generate code, which when executed on production host 250, effectuates the file moves.
In the illustrative embodiment of the invention shown in FIG. 2, the "File Placement Adjustment Information" of panel 245 includes the following types of recommendations, which may or may not all be present depending upon the condition of the I/O subsystem.
(1) file moves, expressed in the form of executable code, plus a pictorial representation of the effect of implementing the moves,
(2) file duplexing recommendations,
(3) main memory file caching recommendations.
Appendix B lists the operational principles that produce the file placement adjustment information.
As was the case for the response time-throughput adjustment information, in order to keep the responsible user fully informed of the curative measures ES 210 deems necessary, the illustrative embodiment presents its adjustment information in an easily understood format. The human-readable interface presents a compact, coherent, graphical representation of the I/O complex, depicting the connectivity of its control units, and disks, and the location of problem files, and animates the file moves, showing their migration from the current, problematic locations to the new locations specified in the file placement adjustment information. Other curative measures contained in the placement adjustment information, i.e. duplexing and caching recommendations, are presented in textual form. FIG. 4 is an example of this I/O display, and panel 504 of FIG. 5 is an example of the high level code which effectuates file moves when executed. Appendix C shows actual source code deployed to generate FACS-compatible code. In particular, regarding FIG. 4, so as to visualize I/O system performance problems, a compact graphical display of the I/O system may be called into view on workstation 205; the result of this activity is shown as overlay panel 401 in FIG. 4. Background panel 402 is used to summarize detailed diagnoses in textual format. Overlay panel 401 shows in graphical form the large complex comprising the disk control units (e.g., unit 411), the disks controlled (e.g., disk 420), and the files (e.g., files 421,422) stored by the disks; a partial view of overlay panel 401 was depicted in FIG. 1.
Defining a Set of Operational Principles
An operational principle is a succinct statement of a possible contingency, which, if it occurs, triggers a conclusion that obviates the contingency. A knowledge base is a set of related operational principles, whose contingencies and conclusions encompass the outcomes expected from some process under observation. Here the process being observed is the operation of a main frame computer, the contingencies are the various symptoms indicative of problematic performance or availability that might occur, where the symptoms are embedded in measurement data. The conclusions are specific actions designed to obviate problematic performance or improve system availability. Thus, a knowledge base, in its totality, is a representation of how a human expert reasons about a problem domain.
In constructing the operational principles that make up a knowledge base, it is first necessary to understand the problem domain. In this embodiment, the problem domain consists of both the response time-throughput trade off, and the factors that affect the performance and availability of an I/O complex supporting the host application. Understanding the problem domain includes knowing how the I/O components should be connected, the expected performance of each type of disk and control unit, and how files should be allocated across the I/O complex. Given this understanding, a human expert augments it with first conceptualizing contingencies that, should they occur, are performance or availability affecting, then postulates and confirms conclusions that when implemented, obviate the contingencies. Note that this conceptualization is the essence of defining the operational principles that make up a knowledge base and is independent of the computer language, or expert system knowledge encoding facility used to eventually represent the knowledge.
Part of the conceptualization process is recognizing which contingencies can be detected when observing a system and which cannot. This is a measurement issue. The robustness of the measurement instrumentation on production host 250 shown in FIG. 2 constrains the operational principle set to those principles whose contingencies will be triggered by particular values in the data. For if an event is not measurable, it is by definition not observable, and hence cannot be included in the knowledge base. In the illustrative embodiment, the complete set of data used by ES 210 is provided in Appendix D.
Transforming the Operational Principles into an Executable Knowledge Base
The transformation of operational principles into an executable knowledge base occurs through the creation of two primary types of structures in the knowledge base: frames and forward chaining rules implemented in the ART system language. These structures are broadly defined as follows:
frame--A collection of information about a stereotypical object, act, or event, and the relationship of the object to other objects. For example, with reference to FIG. 6, stereotypical disk pack 630 in FACS has expected performance information as well as descriptive attributes, and actual FACS disk pack object 640, which is connected through the instance-of(HAS INSTANCE) relationship, has actual performance information plus information inherited from stereotypical disk 630. Actual disk pack object 640 controls files 650 and 660. Similarly, stereotypical control unit object 610 has expected performance information which is inherited by actual FACS control unit object 620.
forward chaining rule--A segment of computer code which designates that
IF a particular situation is described by the program's data
THEN the program should take a particular action
Forward chaining rules are executed by a general interpreter, which for the illustrative embodiment is provided by the ART system language, that matches rules with data, and executes rules whenever their IF conditions are satisfied. This data-driven type of computer program is contrasted with traditional procedural computer programs, where ordering of the program instructions determine how the program is executed. Appendix G gives specific examples, in ART code, of forward chaining rules.
Frames give an internal representation of the external view of the FACS system. For the I/O subsystem, frames represent physical objects (disk controllers, disks) and computer software objects (files). Hand-crafted, stereotypical, frames contain expected performance (I/O existence time) of specific models of disk controllers and disks, as shown in FIG. 6. This information is inherited by instances of those objects which represent actual instances in the FAGS computer configuration, defined by the data obtained via the Reduction and Formatting software 260 identified in FIG. 2. These instances of disk controllers, disks, and files now have actual I/O existence time data, which can be compared to expected data values. Similarly, the system state space, which provides data on tradeoffs between response time and throughput as the number of customers vary, is represented as frames.
Heuristics (rules of thumb), implemented as forward chaining rules, constitute the second type of structure in the executable knowledge base. For I/O subsystem processing, these heuristics compare expected to actual service times along with relative comparisons of actual service times to pinpoint bottlenecks in the I/O subsystem. For CPU processing, rules interpret the state space relative to the amount of queueing (wait time) a user is willing to tolerate.
Lisp language computer programs provide a support structure which makes possible specialized processing, such as that needed to obtain I/O modification information as described in the Section to follow.
Obtaining the Expert System Inputs
FIG. 2 shows information labeled "RAW DATA" on lead 259, flowing between Measurement Complex 256 and Reduction, Formatting and Modeling Software 260. This data is made up of detailed information contained in the System Log File, the I/O Trace file, the SIP File and the Master File Directory, and is produced by host supplied software. The purpose of Reduction, Formatting and Modeling Software 260 is to condense and transform this detail into a form readily used by ES 210 to support the operational principles that generate the response time-throughput and file placement adjustment information.
In FIG. 2, two flows are shown emanating from Reduction and Formatting Software 260, namely information of leads 261 and 262, with both terminating in ES 210 and under control of control information provided over lead 263 from ES 210. The right hand flow over lead 261 is direct and provides the information necessary to drive the File Placement operational principles. This flow consists of the Control Unit, Disk, and File I/O service times, an inventory of the files that support the FACS application, with an accounting of the disk space these files require, the available free disk space, and an accounting of the free locations, and the connectivity of control units and disk drives, also known as I/O configuration information.
The left hand flow over lead 262 initially consists of CPU and disk service times. It first traverses Modeling System 220, where it is transformed into System State Data appearing on lead 221 before arriving at ES 210. The System State Data supports the response time-throughput operational principles, and a portion of this data eventually becomes part of the response time-throughput adjustment information.
For the complete specification of each of the individual data items that make up the generic information categories emanating from Reduction, Formatting, and Modeling Software 260, reference is made to Appendix D. Also, see this same Appendix for a list of the individual software components that make up Reduction, Formatting and Modeling Software 260.
Producing the System State Space
The state space is a compact representation of key parameters of the system derived under different conditions of transaction concurrencies. More formally, the system state space consists of an array whose rows consist of the five elements, (T hreads .sbsb.M, λ M , B CPU , T M , ρCPU M ). Each row corresponds to a particular number of transactions concurrently active in the system, i.e. The first row corresponds to one transaction, the second row, to two transactions, etc.
Note that a major portion of the response time-throughput adjustment information described earlier is a row of the system state space array, developed under the guidance supplied by the response time-throughput operational principles.
The state space array may be generated by any one of several techniques, a discrete event simulation, or modeling the system as a product form network then solving the model using a convolution or mean value analysis algorithm. All of these techniques require the service times as their inputs, and use an algorithm of choice to transform service times into the system state data.
In the current embodiment, the model is solved using Buzen's (see, for example, Allen, A. O., "Probability, Statistics, and Queueing Theory", Academic Press, 1978) recursive solution, a convolution algorithm, for a single work load class, non-priority, central server model that includes the CPU complex and all active disk devices. The model is self-calibrating in that iterative solutions attempt to match the measured transaction existence time at the measured transaction volume, and transaction concurrency, by adjusting the service time of internal software locks whose occurrences are measurable, but whose durations are not. After achieving a satisfactory match, the final model is solved to produce the system state array for all feasible transaction concurrencies. Appendix E is a listing of the code which implements the model solution above.
Obtaining I/O Modification Information
Diagnosing I/O Subsystem Problems
Forward chaining rules reason over the data described above to identify problem-causing files in the I/O subsystem. There are two categories of problem-causing files:
(1) Hot (highly utilized) files which impact the utilization of a control unit or disk, and therefore are labeled primary move candidates.
(2) Poorly placed files, which because of their placement relative to the locations of certain other files have the potential for causing performance or recovery problems. This type of file has secondary move priority.
The structure of the domain modeled above, such as control of disks by a certain control unit, or storage of file fragments by a certain disk, is used by the diagnosis heuristics to identify hot files. An example of this type of heuristic is:
IF the transfer rate of a hot file explains a hot control unit
THEN designate this hot file as a primary move candidate
The analysis heuristics make use of performance evaluation formulas, such as this formula for the heuristic above: ##EQU1## That is, the contribution of a hot file to the utilization of a dual control unit is equal to the transfer rate of that hot file times the I/O rate in requests per second, divided by two.
A heuristic which may identify other problem files (secondary move candidates) is:
IF a database spans multiple disks, and the database fits on one disk
THEN consolidate the database on one disk
Various heuristics also identify, for example, sub-par performance of I/O subsystem hardware. Heuristics and formulas thus identify files which should be moved to help balance the load across the I/O subsystem, and other heuristics identify and advise the end-user of isolated problems.
Repairing Problems in the I/O Subsystem
After finishing its I/O problem diagnosis stage, ES 210 attempts to repair the I/O subsystem problems identified. ES 210 arrives at its recommendations by simulating sequences of file moves, and choosing the sequence that solves the most problems (without creating any major new ones). These sequences of simulated moves are represented internally in ES 210 as paths in a search tree, where the root of the tree represents the initial (actual) system state, and each node represents a hypothetical system state resulting from an experimental file relocation. An Assumptive Truth Maintenance System (ATMS), provided by the ART system Viewpoint mechanism, handles the details of maintaining the distinction between ES 210's real and hypothetical system states. The search strategy devised as part of the inventive aspects of the present invention, described in the following paragraph, makes use of this Viewpoint mechanism to simplify the implementation of the search for I/O problem repairs.
For each file that it tries to relocate, ES 210 ascertains the set of disks that have enough spare space and utilization (including controller utilization) to accommodate that file. Heuristics set forth in Appendix B aid in the selection of potential new locations for a problem file. These heuristics, which represent system attributes and various FACS application characteristics that can affect performance, include the following examples:
IF reference files are being relocated
THEN place no more than two reference files on a disk
and
IF a disk has more than one space large enough for the file
THEN use a best-fit algorithm to choose one.
Now that it has a set of candidate new locations, ES 210 expands its search tree by creating a new node for each of the hypothetical new locations found for the file under consideration. ES 210 can then temporarily believe as fact the hypothetical assumptions (i.e. The file movements) that formed the new node, and reason independently about the system state embodied in each of these nodes. With the relocated file occupying the previously free space, and the disk and control unit utilizations adjusted to reflect the shifted load, ES 210 calls upon the same rules that it used for problem diagnosis in the original system state. This time, however, ES 210 does not report the diagnoses to the end user; rather, it uses them to judge the merit of the file move being considered. If any new problems are severe enough, the search tree node representing the experimental file placement is removed. This immediate pruning helps to control the size of the search tree.
Some of the problems that may be detected at a file's new location are not absolute constraints against moving the file there. ES 210 again uses heuristics to gauge the severity of the new problems and the original reasons for moving the file.
After it has considered new locations for all of the problem files, ES 210 examines the search tree and chooses the path that relieved hot spots most successfully while satisfying the greatest number of file placement heuristics. ES 210 extracts the set of file moves that compose this path and passes these recommended moves to host concurrency control 252 of FIG. 2; also, the responsible human is notified of these moves via display panel 240.
Many search techniques could be considered for this task, but those not used would fail. Alternatives to ATMS for belief revision in this repair task would not support the required reasoning to find the best solution. Brute force generate and test of consistent assignments would quickly lead to a combinatorial explosion of nodes in the search tree. Chronological backtracking would explore futile branches which were previously discovered to involve contradictory file assignments, and would re-expand various nodes of the search tree, again leading to efficiency problems. Dependency-directed backtracking (see, for example, Stallman, R., and Sussman, G., "Forward Reasoning and Dependency-Directed Backtracking in a System for Computer-Aided Circuit Analysis," Artificial Intelligence 9, pp. 135-196, 1977) as used in truth maintenance systems (see, for example, Doyle, J., "A Truth Maintenance System," Artificial Intelligence, Vol. 12, 1979) could find a solution to the file assignment problem, but would not easily find the best solution to this problem because search would stop at nodes where contradictions occur, and comparison of alternative file assignments would be almost impossible since only one alternative would be available in the database at any given time (see, for example, Williams, C., "Managing Search in a Knowledge-based System," Inference Corporation Technical Report). Therefore, the system is likely not to find the most desirable file assignments. Thus, ATMS, which allows the exploration and comparison of hypothetical file assignments, is used to handle belief revision and the search strategy entailed in the file assignment problem in ES 210.
Appendix F lists the source code to obtain the response time-throughput adjustment information for the CPU system.
Appendix G lists the source code for the rules to find the optimum placement for the files in the I/O subsystem according to what is known about those files and the disks and controllers they reside on.
Appendix H lists the source code for the frame definitions and rules the knowledge base uses to analyze the I/O subsystem, and the rules by which this analysis is accomplished. After these rules fire, ES 210 knows what problems exist in the I/O subsystem.
It is to be understood that the above-described embodiment is simply illustrative of the application of the principles in accordance with the present invention. Other embodiments may be readily devised by those skilled in the art which may embody the principles in spirit and scope. Thus, it is to be further understood that the methodology described herein is not limited to the specific forms shown by way of illustration, but may assume other embodiments limited only by the scope of the appended claims. ##SPC1##
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An expert system methodology for operating a computer system is disclosed to facilitate tuning, that is, resource balancing of the various resources comprising a large-scale software system. The computer system is adapted to store a knowledge base derived from experts who manually tune the large-scale system. The system also stores site-specific information and specifications on components configuring the large-scale system. Performance measurements collected from the large-scale system on a time consistent basis are merged, utilizing the knowledge base, with reference data derived from the site-specific information and the specifications. As a result of the merger, the status of the large-scale system is classified as to its operability. If the status is in a predefined class requiring tuning, the computer system is arranged to generate programming code which will effectuate the required changes in the resources to thereby reconfigure the large-scale system.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of and priority to U.S. Provisional Patent Application Ser. No. 61/704,630, entitled “Casing Drilling Bore Hole Assembly With A Wireless Power and Data Connection,” and filed on Sep. 24, 2012, U.S. Provisional Patent Application Ser. No. 61/704,805, entitled “System And Method For Wireless Power And Data Transmission In A Mud Motor,” and filed on Sep. 24, 2012, and U.S. Provisional Patent Application Ser. No. 61/704,758, entitled “Positive Displacement Motor Rotary Steerable System And Apparatus,” and filed on Sep. 24, 2012, the disclosures of which are hereby incorporated by reference in their entireties.
DESCRIPTION OF THE RELATED ART
During conventional measuring while drilling (MWD) or logging while drilling (LWD) operations, signals are passed between a surface unit and the BHA to transmit, for example commands and information. Typical telemetry systems involve mud-pulse telemetry that uses the drill pipe as an acoustic conduit for mud pulse telemetry. With mud pulse telemetry, mud is passed from a surface mud pit and through the pipes to the bit. The mud exits the bit and is used to contain formation pressure, cool the bit, and lift drill cuttings from the borehole. This same mud flow is selectively altered to create pressure pulses at a frequency detectable at the surface and downhole. Typically, the operating frequency is in the order 1-3 bits/sec, but can fall within the range of 0.5 to 6 bits/sec.
In conventional drilling, a well is drilled to a selected depth with drill pipe, and then the wellbore is typically lined with a larger-diameter pipe, usually called casing. Casing typically includes casing sections connected end-to-end, similar to the way drill pipe is connected. To accomplish this, the drill string and the drill bit are removed from the borehole in a process called “tripping.” Once the drill string and bit are removed, the casing is lowered into the well and cemented in place. The casing protects the well from collapse and isolates the subterranean formations from each other. After the casing is in place, drilling may continue or the well may be completed depending on the situation.
Conventional drilling typically includes a series of drilling, tripping, casing and cementing, and then drilling again to deepen the borehole. This process is very time consuming and costly. Additionally, other problems are often encountered when tripping the drill string. For example, the drill string may get caught up in the borehole while it is being removed. These problems require additional time and expense to correct.
The term “casing drilling” refers to the use of a casing string in place of a drill string which uses drill pipe. Like the drill string, a chain of casing sections are connected end-to-end to form a casing string. The BHA and the drill bit are connected to the lower end of a casing string, and the well is drilled using the casing string to transmit drilling fluid, as well as axial and rotational forces, to the drill bit. Upon completion of drilling, the casing string may then be cemented in place to form the casing for the wellbore. Casing drilling enables the well to be simultaneously drilled and cased.
Existing casing drilling systems that employ directional MWD and/or LWD assemblies have several drawbacks. A downhole drilling motor is typically used due to rotational limitations of the casing and provides power for rotation of the BHA, including the bit to drill the pilot hole and the under-reamer to enlarge the hole for the casing to pass. The downhole drilling motor typically includes a positive displacement mud motor (PDM) or turbodrill. In a directional/logging BHA for casing drilling, high speed mud pulse telemetry is seriously degraded and attenuated due to the operation of the drilling motor. Accordingly, there remains a need in the art for improved bottom hole assemblies (BHAs) for casing drilling systems.
SUMMARY OF THE DISCLOSURE
A casing drilling bottom hole assembly (BHA) may include a modulator and turbine power generation system, a wireless power and data connection, and a rotary steerable system (RSS). The modulator and turbine power generation system is coupled to a casing. The wireless power and data connection is coupled to a downhole end of the high speed modulator and turbine power generation system for providing power and data connectivity between the high speed modulator and turbine power generation system and a drilling motor. The RSS is coupled to the drilling motor for receiving power from and communicating with the high speed modulator and turbine power generation system via the wireless power and data connection and the drilling motor.
This summary is provided to introduce a selection of concepts that are further described below in the detailed description. This summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used as an aid in limiting the scope of the claimed subject matter.
BRIEF DESCRIPTION OF THE DRAWINGS
In the Figures, like reference numerals refer to like parts throughout the various views unless otherwise indicated. For reference numerals with letter character designations such as “ 102 A” or “ 102 B”, the letter character designations may differentiate two like parts or elements present in the same figure. Letter character designations for reference numerals may be omitted when it is intended that a reference numeral to encompass parts having the same reference numeral in figures.
FIG. 1A is a diagram of a system for wireless drilling and mining extenders in a drilling operation;
FIG. 1B is a diagram of a wellsite drilling system that forms part of the system illustrated in FIG. 1A ;
FIG. 1C is a diagram of an embodiment of a casing drilling system that includes a BHA for enabling wireless power and data transfer between components in the BHA;
FIG. 2 is a schematic drawing depicting a primary or transmitting circuit and a secondary or receiving circuit;
FIG. 3 is a schematic drawing depicting a primary or transmitting circuit and a secondary or receiving circuit with transformers having turn ratios N S :1 and N L :1 that may used to match impedances;
FIG. 4 is a schematic drawing depicting an alternative circuit to that which is depicted in FIG. 3 and having parallel capacitors that are used to resonate the coils' self-inductances;
FIGS. 5A-5B illustrate an embodiment of a receiving coil inside a transmitting coil;
FIGS. 6-7 are graphs illustrating the variation in k versus axial displacement of the receiving coil when x=0 is small and the transverse displacement when z=0 produces very small changes in k of given embodiments, respectively;
FIGS. 8-9 are graphs illustrating that power efficiency may also be calculated for displacements from the center in the z direction and in the x direction, respectively, of given embodiments;
FIG. 10 is a graph illustrating that the sensitivity of the power efficiency to frequency drifts may be relatively small in some embodiments;
FIG. 11 is a graph illustrating that drifts in the components values of some embodiments do not have a large effect on the power efficiency of the embodiment;
FIG. 12 depicts a particular embodiment configured to convert input DC power to a high frequency AC signal, f 0 , via a DC/AC convertor;
FIG. 13 depicts a particular embodiment configured to pass AC power through the coils;
FIG. 14 depicts a particular embodiment that includes additional secondary coils configured to transmit and receive data;
FIG. 15 is a diagram illustrating an embodiment of a casing drilling BHA that includes a wireless power and data connection for enabling wireless power and data transfer between components in the BHA;
FIG. 16 is a diagram illustrating a more detailed view of the wireless power and data connection in FIG. 15 ;
FIG. 17 is a diagram illustrating another embodiment of casing drilling BHA;
FIG. 18 is a diagram illustrating an embodiment of the modulator and turbine power system of FIG. 15 that includes a rotary pressure pulse generator or modulator;
FIG. 19 is an equation for comparatively modeling signal strengths in a casing versus drilling operation;
FIG. 20 shows an embodiment of a graphical output of the signal strength model of FIG. 19 ; and
FIG. 21 shows another embodiment of a graphical output of the signal strength model of FIG. 19 .
DETAILED DESCRIPTION
The system described below mentions how power and/or communications may flow from an Measurement While Drilling (MWD) power system through a positive displacement motor to a rotary steerable system (“RSS”) and/or Logging While Drilling systems. One of ordinary skill in the art recognizes that communications may easily flow in the other direction—from the RSS and/or LWD equipment to the MWD system.
Referring initially to FIG. 1A , this figure is a diagram of a system 102 for controlling and monitoring a drilling operation. The system 102 includes a control module 101 that is part of a controller 106 . The system 102 also includes a drilling system 104 , which has a logging and control module 95 , a bottom hole assembly (“BHA”) 100 , and wireless power and data connections 402 . The wireless power and data connections 402 may exist between several elements of the BHA 100 as will be explained below.
The controller 106 further includes a display 147 for conveying alerts 110 A and status information 115 A that are produced by an alerts module 110 B and a status module 115 B. The controller 106 in some instances may communicate directly with the drilling system 104 as indicated by dashed line 99 or the controller 106 may communicate indirectly with the drilling system 104 using the communications network 142
The controller 106 and the drilling system 104 may be coupled to the communications network 142 via communication links 103 . Many of the system elements illustrated in FIG. 1A are coupled via communications links 103 to the communications network 142 .
FIG. 1B illustrates a wellsite drilling system 104 that forms part of the system 102 illustrated in FIG. 1A . The wellsite can be onshore or offshore. In this system 104 , a borehole 11 is formed in subsurface formations by rotary drilling in a manner that is known to one of ordinary skill in the art. Embodiments of the system 104 can also use directional drilling, as will be described hereinafter. The drilling system 104 includes the logging and control module 95 as discussed above in connection with FIG. 1A .
A drill string 12 is suspended within the borehole 11 and has a bottom hole assembly (“BHA”) 100 which includes a drill bit 105 at its lower end. The surface system includes platform and derrick assembly 10 positioned over the borehole 11 , the assembly 10 including a rotary table 16 , kelly 17 , hook 18 and rotary swivel 19 . The drill string 12 is rotated by the rotary table 16 , energized by means not shown, which engages the kelly 17 at the upper end of the drill string. The drill string 12 is suspended from a hook 18 , attached to a traveling block (also not shown), through the kelly 17 and a rotary swivel 19 which permits rotation of the drill string 12 relative to the hook 18 . As is known to one of ordinary skill in the art, a top drive system could alternatively be used instead of the kelly 17 and rotary table 16 to rotate the drill string 12 from the surface. The drill string 12 may be assembled from a plurality of segments 125 of pipe and/or collars threadedly joined end to end.
In the embodiment of FIG. 1B , the surface system further includes drilling fluid or mud 26 stored in a pit 27 formed at the well site. A pump 29 delivers the drilling fluid 26 to the interior of the drill string 12 via a port in the swivel 19 , causing the drilling fluid to flow downwardly through the drill string 12 as indicated by the directional arrow 8 . The drilling fluid exits the drill string 12 via ports in the drill bit 105 , and then circulates upwardly through the annulus region between the outside of the drill string 12 and the wall of the borehole 11 , as indicated by the directional arrows 9 . In this system as understood by one of ordinary skill in the art, the drilling fluid 26 lubricates the drill bit 105 and carries formation cuttings up to the surface as it is returned to the pit 27 for cleaning and recirculation.
The BHA 100 of the illustrated embodiment may include a logging-while-drilling (“LWD”) module 120 , a measuring-while-drilling (“MWD”) module 130 , a roto-steerable system (“RSS”) and motor 150 (also illustrated as 280 in FIG. 15 described below), and drill bit 105 .
The LWD module 120 is housed in a special type of drill collar, as is known to one of ordinary skill in the art, and can contain one or a plurality of known types of logging tools. It will also be understood that more than one LWD 120 and/or MWD module 130 can be employed, e.g. as represented at 120 A. (References, throughout, to a module at the position of 120 A can alternatively mean a module at the position of 120 B as well.) The LWD module 120 includes capabilities for measuring, processing, and storing information, as well as for communicating with the surface equipment. In the present embodiment, the LWD module 120 includes a directional resistivity measuring device.
The MWD module 130 is also housed in a special type of drill collar, as is known to one of ordinary skill in the art, and can contain one or more devices for measuring characteristics of the drill string 12 and drill bit 105 . The MWD module 130 may further include an apparatus (not shown) for generating electrical power to the BHA 100 .
This apparatus may include a mud turbine generator powered by the flow of the drilling fluid 26 , it being understood by one of ordinary skill in the art that other power and/or battery systems may be employed. In the embodiment, the MWD module 130 includes one or more of the following types of measuring devices: a weight-on-bit measuring device, a torque measuring device, a vibration measuring device, a shock measuring device, a stick slip measuring device, a direction measuring device, and an inclination measuring device.
The foregoing examples of wireline and drill string conveyance of a well logging instrument are not to be construed as a limitation on the types of conveyance that may be used for the well logging instrument. Any other conveyance known to one of ordinary skill in the art may be used, including without limitation, slickline (solid wire cable), coiled tubing, well tractor and production tubing.
FIG. 1C illustrates an embodiment of the drilling system 104 that includes a casing drilling system 200 . The casing drilling system 200 may have several parts which are similar to those illustrated in the standard drillpipe drilling system 104 as illustrated in FIG. 1B . Therefore, only the differences between the two systems 104 , 200 will be described below.
The casing drilling system 200 may include casing 404 that couples with a BHA 100 via a drilling latch assembly (“DLA”) 406 . The DLA 406 may coupled with an under-reamer 412 that is also attached to a drill bit 105 . The under-reamer 412 may form the reamed hole 418 which has a diameter which is greater than the diameter of the pilot hole 416 for by the drill bit 105 .
The casing drilling system 200 may further include conductor pipe 491 which may surround and protect the casing 404 near the Earth's surface. The casing drilling system 200 may further include casing slips 444 , a casing drive head/assembly 441 , draw works 442 , and a guide rail and top drive/block dolly 443 as understood by one of ordinary skill the art. Further details of a modified BHA 100 having wireless power and data connections 402 for the casing drilling system 200 will be described below in connection with FIGS. 15-18 .
FIG. 2 is a schematic drawing depicting a primary or transmitting circuit 210 and a secondary or receiving circuit 220 . In this description, the time dependence is assumed to be exp(jωt) where ω=2πf and f is the frequency in Hertz. Returning to the FIG. 2 illustration, the transmitting coil is represented as an inductance L 1 and the receiving coil as L 2 . In the primary circuit 210 , a voltage generator with constant output voltage V S and source resistance R S drives a current I 1 through a tuning capacitor C 1 and primary coil having self-inductance L 1 and series resistance R 1 . The secondary circuit 220 has self-inductance L 2 and series resistance R 2 . The resistances, R 1 and R 2 , may be due to the coils' wires, to losses in the coils magnetic cores (if present), and to conductive materials or mediums surrounding the coils. The Emf (electromotive force) generated in the receiving coil is V 2 , which drives current I 2 through the load resistance R L and tuning capacitor C 2 . The mutual inductance between the two coils is M, and the coupling coefficient k is defined as:
k=M /√{square root over ( L 1 L 2 )} (1)
While a conventional inductive coupler has k≈1, weakly coupled coils may have a value for k less than 1 such as, for example, less than or equal to about 0.9. To compensate for weak coupling, the primary and secondary coils in the various embodiments are resonated at the same frequency. The resonance frequency is calculated as:
ω
0
=
1
L
1
C
1
=
1
L
2
C
2
(
2
)
At resonance, the reactance due to L 1 is cancelled by the reactance due to C 1 . Similarly, the reactance due to L 2 is cancelled by the reactance due to C 2 . Efficient power transfer may occur at the resonance frequency, f 0 =ω 0 /2π. In addition, both coils may be associated with high quality factors, defined as:
Q
1
=
ω
L
1
R
1
and
Q
2
=
ω
L
2
R
2
.
(
3
)
The quality factors, Q, may be greater than or equal to about 10 and in some embodiments greater than or equal to about 100. As is understood by one of ordinary skill in the art, the quality factor of a coil is a dimensionless parameter that characterizes the coil's bandwidth relative to its center frequency and, as such, a higher Q value may thus indicate a lower rate of energy loss as compared to coils with lower Q values.
If the coils are loosely coupled such that k<1, then efficient power transfer may be achieved provided the figure of merit, U, is larger than one such as, for example, greater than or equal to about 3:
U=k √{square root over ( Q 1 Q 2 )}>>1. (4)
The primary and secondary circuits are coupled together via:
V 1 =jωL 1 I 1 +jωMI 2 and V 2 =jωL 2 I 2 +jωMI 1 , (5)
where V 1 is the voltage across the transmitting coil. Note that the current is defined as clockwise in the primary circuit and counterclockwise in the secondary circuit. The power delivered to the load resistance is:
P L = 1 2 R L I 2 2 , ( 6 )
while the maximum theoretical power output from the fixed voltage source V S into a load is:
P
MAX
=
V
S
2
8
R
S
.
(
7
)
The power efficiency is defined as the power delivered to the load divided by the maximum possible power output from the source,
η
≡
P
L
P
MAX
.
(
8
)
In order to optimize the power efficiency, η, the source resistance may be matched to the impedance of the rest of the circuitry. Referring to FIG. 2 , Z 1 is the impedance looking from the source toward the load and is given by:
Z
1
=
R
1
-
j
/
(
ω
C
1
)
+
jω
L
1
+
ω
2
M
2
R
2
+
R
L
+
jω
L
2
-
j
/
(
ω
C
2
)
(
9
)
When ω=ω 0 , Z 1 is purely resistive and may equal R S for maximum efficiency.
Z
1
=
R
1
+
ω
2
M
2
R
2
+
R
L
≡
R
S
.
(
10
)
Similarly, the impedance seen by the load looking back toward the source is
Z
2
=
R
2
-
j
/
(
ω
C
2
)
+
jω
L
2
+
ω
2
M
2
R
1
+
R
S
+
jω
L
1
-
j
/
(
ω
C
1
)
(
11
)
When ω=ω 0 , Z 2 is purely resistive and R L should equal Z 2 for maximum efficiency
Z
2
=
R
2
+
ω
2
M
2
R
1
+
R
S
≡
R
L
.
(
12
)
The power delivered to the load is then:
P L = 1 2 R L ω 0 2 M 2 V S 2 [ ( R S + R 1 ) ( R 2 + R L ) + ω 0 2 M 2 ] 2 , ( 13 )
and the power efficiency is the power delivered to the load divided by the maximum possible power output,
η
≡
P
L
P
MAX
=
4
R
S
R
L
ω
0
2
M
2
[
(
R
S
+
R
1
)
(
R
2
+
R
L
)
+
ω
0
2
M
2
]
2
.
(
14
)
The optimum values for R L and R L may be obtained by simultaneously solving
R S = R 1 + ω 2 M 2 R 2 + R L and R L = R 2 + ω 2 M 2 R 1 + R S , ( 15 )
with the result that:
R S =R 1 √{square root over (1+ k 2 Q 1 Q 2 )} and R L =R 2 √{square root over (1+ k 2 Q 1 Q 2 )}. (16)
If the source and load resistances do not satisfy equations (16), then it is envisioned that standard methods may be used to transform the impedances. For example, as shown in the FIG. 3 illustration, transformers with turn ratios N S :1 and N L :1 may be used to match impedances as per equations (16). Alternatively, the circuit illustrated in FIG. 4 may be used. In such an embodiment in FIG. 4 , parallel capacitors are used to resonate the coils' self-inductances according to equation (2). As before, Z 1 is defined as the impedance seen by the source looking toward the load, while Z 2 is defined as the impedance seen by the load looking toward the source. In addition, there are two matching impedances, Z S and Z T which may be used to cancel any reactance that would otherwise be seen by the source or load. Hence Z 1 and Z 2 are purely resistive with the proper choices of Z S and Z T . Notably, the source resistance R S may equal Z 1 , and the load resistance R L may equal Z 2 . The procedures for optimizing efficiency with series capacitance or with parallel capacitance may be the same, and both approaches may provide high efficiencies.
Turning now to FIGS. 5A and 5B , a cross sectional view of two coils 232 , 234 is illustrated in FIG. 5A and a side view of the two coils 232 , 234 is illustrated in FIG. 5B . In these two figures, a receiving coil 232 inside a transmitting coil 234 of a particular embodiment 230 is depicted. The receiving coil 232 includes a ferrite rod core 235 that, in some embodiments, may be about 12.5 mm (about 0.49 inch) in diameter and about 96 mm (about 3.78 inches) long with about thirty-two turns of wire 237 . Notably, although specific dimensions and/or quantities of various components may be offered in this description, it will be understood by one of ordinary skill in the art that the embodiments are not limited to the specific dimensions and/or quantities described herein.
Returning to FIG. 5 , the transmitting coil 234 may include an insulating housing 236 , about twenty-five turns of wire 239 , and an outer shell of ferrite 238 . The wall thickness of the ferrite shell 238 in the FIG. 5 embodiment may be about 1.3 mm (about 0.05 inch). In certain embodiments, the overall size of the transmitting coil 234 may be about 90 mm (about 3.54 inch) in diameter by about 150 mm (about 5.90 inches) long. The receiving coil 232 may reside inside the transmitting coil 234 , which is annular.
The receiving coil 232 may be free to move in the axial (z) direction or in the transverse direction (x) with respect to the transmitting coil 234 . In addition, the receiving coil 232 may be able to rotate on axis with respect to the transmitting coil 234 . The region between the two coils 232 , 234 may be filled with air, fresh water, salt water, oil, natural gas, drilling fluid (known as “mud”), or any other liquid or gas. The transmitting coil 234 may also be mounted inside a metal tube, with minimal affect on the power efficiency because the magnetic flux may be captured by, and returned through, the ferrite shell 238 of the transmitting coil 234 .
The operating frequency for these coils 232 , 234 may vary according to the particular embodiment, but, for the FIG. 5 example 230 , a resonant frequency f=100 kHz may be assumed. At this frequency, the transmitting coil 234 properties are: L 1 =6.76·10 −5 Henries and R 1 =0.053 ohms, and the receiving coil 232 properties are L 2 =7.55·10 −5 Henries and R 2 =0.040 ohms. The tuning capacitors are C 1 =3.75·10 −8 Farads and C 2 =3.36·10 −8 Farads. Notably, the coupling coefficient k value depends on the position of the receiving coil 232 inside the transmitting coil 234 . The receiving coil 232 is centered when x=0 and z=0 and there is k=0.64.
The variation in k versus axial displacement of the receiving coil 232 when x=0 may be relatively small, as illustrated by the graph 250 in FIG. 6 . The transverse displacement when z=0 may produce very small changes in k, as illustrated by the graph 252 in FIG. 7 . The receiving coil 232 may rotate about the z-axis without affecting k because the coils are azimuthally symmetric. According to equations (16), an optimum value for the source resistance may be R S =32 ohms, and for the load resistance may be R L =24 ohms when the receiving coil 232 is centered at x=0 and z=0. The power efficiency may thus be η=99.5%.
The power efficiency may also be calculated for displacements from the center in the z direction in mm (as illustrated by the graph 254 in FIG. 8 ) and in the x direction in mm (as illustrated by the graph 256 in FIG. 9 ). It is envisioned that the efficiency may be greater than about 99% for axial displacements up to about 20.0 mm (about 0.79 inch) in certain embodiments, and greater than about 95% for axial displacements up to about 35.0 mm (about 1.38 inches). It is further envisioned that the efficiency may be greater than 98% for transverse displacements up to 20.0 mm (about 0.79 inch) in some embodiments. Hence, the position of the receiving coil 232 inside the transmitting coil 234 may vary in some embodiments without reducing the ability of the two coils 232 , 234 to efficiently transfer power.
Referring now to FIG. 10 , it can be seen in the illustrative graph 258 where the Y-axis denotes efficiency in percentage and the X-axis denotes frequency in Hz that the sensitivity of the power efficiency to frequency drifts may be relatively small. A ±10% variation in frequency may produce minor effects, while the coil parameters may be held fixed. The power efficiency at 90,000 Hz is better than about 95%, and the power efficiency at 110,000 Hz is still greater than about 99%. Similarly, drifts in the component values may not have a large effect on the power efficiency. For example, both tuning capacitors C 1 and C 2 are allowed to increase by about 10% and by about 20% as illustrated in the graph 260 of FIG. 11 . Notably, the other parameters are held fixed, except for the coupling coefficient k. The impact of the power efficiency is negligible. As such, the system described herein would be understood by one of ordinary skill in the art to be robust.
It is also envisioned that power may be transmitted from the inner coil to the outer coil of particular embodiments, interchanging the roles of transmitter and receiver. It is envisioned that the same power efficiency would be realized in both cases.
Referring to FIG. 12 , an electronic configuration 262 is illustrated for converting input DC power to a high frequency AC signal, f 0 , via a DC/AC convertor. The transmitter circuit in the configuration 262 excites the transmitting coil at resonant frequency f 0 . The receiving circuit drives an AC/DC convertor, which provides DC power output for subsequent electronics. This system 262 is appropriate for efficient passing DC power across the coils.
Turning to FIG. 13 , AC power can be passed through the coils. Input AC power at frequency f 1 is converted to resonant frequency f 0 by a frequency convertor. Normally this would be a step up convertor with f 0 >>f 1 . The receiver circuit outputs power at frequency f 0 , which is converted back to AC power at frequency f 1 . Alternatively, as one of ordinary skill in the art recognizes, the FIG. 13 embodiment 264 could be modified to accept DC power in and produce AC power out, and vice versa.
In lieu of, or in addition to, passing power, data signals may be transferred from one coil to the other in certain embodiments by a variety of means. In the above example, power is transferred using an about 100.0 kHz oscillating magnetic field. It is envisioned that this oscillating signal may also be used as a carrier frequency with amplitude modulation, phase modulation, or frequency modulation used to transfer data from the transmitting coil to the receiving coil. Such would provide a one-way data transfer.
An alternative embodiment includes additional secondary coils to transmit and receive data in parallel with any power transmissions occurring between the other coils described above, as illustrated in FIG. 14 . Such an arrangement may provide two-way data communication in some embodiments. The secondary data coils 266 , 268 may be associated with relatively low power efficiencies of less than about 10%. It is envisioned that in some embodiments the data transfer may be accomplished with a good signal to noise ratio, for example, about 6.0 dB or better. The secondary data coils 266 , 268 may have fewer turns than the power transmitting 234 and receiving coils 232 .
The secondary data coils 266 , 268 may be orthogonal to the power coils 232 , 234 , as illustrated in FIG. 14 . For example, the magnetic flux from the power transmitting coils 232 , 234 may be orthogonal to a first data coil 266 , so that it does not induce a signal in the first data coil 266 . A second data coil 268 may be wrapped as shown in FIG. 14 such that magnetic flux from the power transmitters does not pass through it, but magnetic flux from first data coil 266 does. Notably, the configuration depicted in FIG. 14 is offered for illustrative purposes only and is not meant to suggest that it is the only configuration that may reduce or eliminate the possibility that a signal will be induced in one or more of the data coils by the magnetic flux of the power transmitting coils. Other data coil configurations that may minimize the magnetic flux from the power transmitter exciting the data coils will occur to those with ordinary skill in the art.
Moreover, it is envisioned that the data coils 266 , 268 may be wound on a non-magnetic dielectric material in some embodiments. Using a magnetic core for the data coils 266 , 268 might result in the data coils' cores being saturated by the strong magnetic fields used for power transmission. Also, the data coils 266 , 268 may be configured to operate at a substantially different frequency than the power transmission frequency. For example, if the power is transmitted at about 100.0 kHz in a certain embodiment, then the data may be transmitted at a frequency of about 1.0 MHz or higher. In such an embodiment, high pass filters on the data coils 266 , 268 may prevent the about 100.0 kHz signal from corrupting the data signal. In still other embodiments, the data coils 266 , 268 may simply be located away from the power coils 232 , 234 to minimize any interference from the power transmission. It is further envisioned that some embodiments may use any combination of these methods to mitigate or eliminate adverse effects on the data coils 266 , 268 from the power transmission of the power coils 232 , 234 .
FIG. 15 illustrates an embodiment of a casing drilling BHA 100 for providing wireless power and data connectivity/communications 402 between components. It should be appreciated that various BHA components may be used and various configurations may be implemented for arranging the BHA components. These and other configurations may provide wireless power and data transfer to components above and/or below a downhole drilling motor 410 and, thereby, advantageously enable real-time measurement and control of various drilling conditions for optimizing drilling performance and/or reducing drilling costs.
The BHA 100 includes drilling latch assembly (“DLA”) 406 for coupling the BHA 100 to a casing 404 . The BHA 100 further includes a casing drilling modulator and turbine power system 408 , a wireless power and data connection 402 , a drilling motor 410 , an under-reamer 412 , an RSS/MWD/LWD assembly 414 (see also LWD 120 and MWD 130 of FIG. 1B ), and a drill bit 105 . The under-reamer 412 enlarges the borehole to form the reamed hole 418 relative to the pilot hole 416 formed by the drill assembly 105 . Specifically, the under-reamer 412 enlarges the borehole to form the reamed hole 418 such that it has a second diameter which is larger than the pilot hole 416 having a first diameter formed by the drill bit 105 .
The casing drilling modulator and turbine power system 408 is located below the drilling latch assembly (“DLA”) 406 with a downhole end connected to the drilling motor 410 . As understood by one of ordinary skill the art, the DLA 406 allows the turbine power system 408 and remaining equipment downward through the drill bit 105 to be retrieved and withdrawn through the casing 404 when the appropriate depth has been reached. Specifically, the diameter of the drill bit 105 is smaller than the inner diameter of the casing 404 . In this way, the casing 404 generally remains in place after drilling operations have ceased such that equipment from the turbine power system 408 may be retrieved upward and through the casing 404 . The DLA 406 also forms a fluid tight seal between the turbine power system 408 and the casing 404 so that fluid, such as mud, does not leak between the casing 404 in the turbine power system 408 .
Power and data pass through the wireless power and data connection 402 between the modulator and turbine power system 408 and the drilling motor 410 . The under-reamer 412 , the RSS/MWD/LWD assembly 414 , and the drill assembly 105 may be located below the drilling motor 410 . As understood by one of ordinary skill in the art, positioning units requiring power and/or communications below a drilling motor 410 has not been possible previously because of the need for power generation with these units, such as the MWD module 130 and LWD module 120 .
The under-reamer 412 may include a wired, collapsible under-reamer. The RSS/MWD/LWD assembly 414 generally includes a rotary steerable system (RSS) 150 , the MWD module 130 , and the LWD module 120 . The wireless power and data connection 402 may include a wireless, tuned-inductive coupler mechanism for passing both power and data communications to downhole components of the BHA 100 . It should be appreciated that separate coils may be used for power and communication transmissions. The wireless power and data connection 402 may allow the RSS module 414 to receive power from the turbine power system 408 . Meanwhile, in conventional BHA assemblies, RSS modules 414 may have their own internal power source. The RSS modules 414 of the BHA 100 of this disclosure may have their own power source but also have the option of being powered by the turbine power system 408 through the wireless power and data connection 402 .
The wireless power and data connection 402 allows relative motion between the modulator and turbine power system 408 (which is coupled to an external housing of the drilling motor 410 ) and a rotor of the drilling motor 410 (which is wired and coupled to the under-reamer 412 , the RSS/MWD/LWD assembly 414 , and the drill bit assembly 105 ), allowing power and data transfer throughout the entire BHA 100 .
FIG. 16 illustrates in more detail the modulator and turbine power system 408 and the drilling motor 410 with the wireless power and data connection 402 in between. The drilling motor 410 is also known as a mud motor or a positive displacement motor as understood by one of ordinary skill in the art.
Power and data wiring exits the downhole end of the modulator and turbine power system 408 and is coupled to a stationary coil 502 of the wireless power and data connection 402 located in the drilling motor 410 external housing. Power and data is transmitted between the stationary coil 502 and a rotating coil 504 via tuned-inductive methods, as described above and illustrated in FIGS. 2-14 . Wiring is coupled to the rotating coil 504 and passes through an interior sealed channel in the center of a wired rotor 506 of the drilling motor 410 . The modulator and turbine power system 408 are coupled to the casing 404 illustrated in FIG. 15 . And the stationary coil 502 is coupled to the modulator and turbine power system 408 .
The power system 408 and stationary coil 502 track whatever movement may exist with the casing 404 . In some instances, the casing 404 may have some slight rotation at low revolutions per minute (“RPM”) relative to the borehole and therefore, the stationary coil 502 may follow this rotational movement of the casing 404 . Meanwhile, the rotating coil 404 rotates with the drilling motor 410 , and specifically the wired rotor 506 , which rotates at significantly higher RPMs in order to rotate the drill assembly 105 as understood by one of ordinary skill in the art.
At the bottom of the rotor 506 , the wire is terminated at a connection 508 to the rotating BHA. The connection may include a threaded rotary shouldered joint and a sealed electrical connector mechanically and electrically coupling the rotating mechanism of the drilling motor 410 to the downhole components of the rotating BHA 100 (e.g., under-reamer 412 , RSS 150 , LWD module 120 , MWD module 130 , drill bit 105 ).
FIG. 17 illustrates another embodiment of the BHA 100 in which the MWD module is integrated with the modulator and turbine power system 408 . In this embodiment, the MWD module may include a direction & inclination (D&I) sensor package 477 . One of ordinary skill in the art will appreciate that this configuration may provide several desirable benefits. For example, when a D&I sensor package 477 is located below the drilling motor 410 (rather than above, as illustrated in FIG. 17 ), the pumps 29 must be disabled to prevent rotation of the D&I sensor package 477 .
Furthermore, turbine power is not available when pumps are off, so a battery would be used to power the D&I sensor package 477 along with logic using other parts of the system to detect when pumps are turned off. The embodiment illustrated in FIG. 17 may eliminate the need for battery power in an MWD module 130 (since the D&I sensor package may be powered by the modulator and turbine power system 408 ) and it also may reduce the need for stationary surveys of the borehole with pumps 29 turned off.
The power system 408 may also include a battery 488 that utilizes the wireless power and data connection 402 . The battery 488 may be used in conjunction with a modulator and turbine power system. Alternatively, the battery 488 may include the sole or primary power source for the power system 408 .
In an embodiment, as illustrated in FIG. 18 , the modulator and turbine power system 408 may include a high-speed rotary “siren” pressure-pulse generator. It should be appreciated that the rotary modulator and turbine power system 408 may be capable of high speed operation, which can generate high frequencies and data rates. Unlike conventional “poppet” type or reciprocating pulsers, the use of the rotary modulator 408 is not inherently limited in speed of operation due to limits of acceleration/deceleration and motion reversal with associated problems of wear, flow-erosion, fatigue, power limitations, etc.
The power and telemetry system 408 may include a stator 483 , a rotor 487 , and a turbine 485 . Stator 483 and rotor 487 are the modulator for producing the telemetry. Stator 483 is static (non-moving) while rotor 487 rotates to create modulation for the telemetry using mudflow.
Mudflow through the power system 408 rotates these elements in order to produce power and the telemetry signals. As noted previously, the power system 408 may include a battery 488 which could be used as a substitute for the turbine 485 . Alternate combinations of power generation (i.e. mechanical or electrical/chemical, etc.) for the power system 408 are included within the scope of this disclosure as understood by one of ordinary skill the art. This power and telemetry system 408 may generate negative mud pulse signals as well as positive mud pulse signals. EM telemetry pulse signals from coils (using the data coils 266 , 268 of FIG. 14 if the main power coils 237 and 234 cannot pass data) may be produced for internal communications within the BHA as understood by one of ordinary skill the art. As noted above, the D&I sensor package 477 may be powered by the turbine 485 of the modulator and power system 408 .
Referring now to FIGS. 19-21 , it should be further appreciated that the speed/bandwidth advantages of the rotary modulator and power system 408 and the low rate of attenuation due to the large diameter of the acoustic conduit of casing 404 may result in, for example, approximately a one order of magnitude increase in data rate, when using mud pulse signaling telemetry, as compared to conventional drill pipe conveyed operations when the rotary modulator and power system 408 is located above the drilling motor 410 so high speed telemetry is not degraded. The rotary modulator and power system 408 located above the downhole drilling motor 410 provides for the transmission of large amounts of data for casing drilling.
The equation illustrated in table 1900 of FIG. 19 shows the general effect of various parameters of the mud pulse signal strength and the rate of attenuation in the BHA 100 for casing drilling. In casing drilling applications, the effect of the larger inside diameter (d) within the casing 404 relative to conventional drill pipe BHAs 100 makes higher carrier frequencies (and hence data rate) possible since the rate of attenuation is much less for casing drilling as compared to a conventional drill pipe.
This lower rate of attenuation with the intrinsically high data rate of a rotary mud pulse telemetry system, enable greater bandwidth of real-time data than has been possible with existing directional practice and drill-pipe conveyed MWD systems. The viscosity and bulk modulus of the mud are strongly dependent on type of mud, temperature and pressure and will therefore be functions of total depth, vertical depth, water depth, geographical area, etc.
The equation in graph 1900 of FIG. 19 also demonstrates that more accurate MWD measurements may be made when the D&I sensor package 477 is incorporated in the modulator and turbine power system 408 above the motor 410 as illustrated in FIG. 17 . As noted previously, mudflow and mud pulse signaling may be continued even while the D&I sensor package 477 is operating since the sensor package 477 is above the drilling motor 410 and is therefore not rotating with the drill assembly 105 . The D&I sensor package 477 may be powered by the turbine 485 of the modulator and power system 408 as described above, so a battery or another external powering system outside of the turbine power system 408 to power the D&I sensor package 477 is not required.
The positive impact of the larger diameter (such as 7.0 inch or 17.8 cm diameter) in casing drilling compared to standard drill pipe drilling (such as 5.0 inch or 12.7 cm diameter) is very apparent in the graph 2005 illustrated in FIG. 20 . Graph 2005 is derived from signal strength modeling and prediction software, which takes all of mud pulse signaling parameters into account for a typical deepwater application using synthetic oil based mud.
Graph 2005 shows that with a larger internal diameter of casing (see line with point 2015 ), telemetry rates in the range of about 12 bit/sec may be possible to depths of approximately 20,000.0 feet or 6.01 km (point 2015 ) as compared to a smaller drill pipe diameter of about 5.0 inches or 12.7 cm (see line with point 2010 ) where about a 12 bit/sec data rate is limited to approximately 13,000 feet or 3.96 km. Line 2020 defines a minimum threshold of about 1.0 psi for detecting a signal using mud pulse signaling/modulation.
Further benefits and advantages of the BHA 100 are shown with reference to graph 2105 of FIG. 21 . This modeling comparison shows that telemetry with mud pulse signaling using drill pipe having a diameter of about 5.0 inches or 12.7 cm may be limited to approximately 1 bit/sec data rates (see line with point 2110 ). Hence, there may be a one order of magnitude higher data rate possible under these conditions with casing drilling having a diameter of about 7.0 inches or 17.8 cm (see line with point 2115 ) compared to the drill pipe scenario (see point 2110 ).
There may also be an approximately four-fold increase in signal amplitude with casing drilling as compared to standard drill-pipe drilling for about a 1 Hz telemetry in mud pulse signaling. Based on the data in graph 2105 , the maximum depth at which a signal may still be detected using casing drilling with 1 Hz telemetry may fall within the range of between about 40,000 to about 50,000 feet (about 12.19 km to about 15.24 km).
It should be appreciated that the above-described configurations for the casing drilling BHA 100 may be integrated with accompanying computer programs for configuring, operating, or otherwise interacting with the real-time measurement and control functionalities enabled by the corresponding BHA configurations. The computer programs may be implemented in control module(s) 101 and/or alert module(s) 110 , which include logic for instructing CPU(s) in the controller 106 to execute corresponding methods.
With the system described above, power and/or communications may be efficiently passed from a tool located above the mud motor to the rotor via two coils. One coil may be annular and located in the ID of the drill collar. The other coil is attached to the rotor and is located within the first coil. The coils are high Q and resonated at the same frequency. The impedance of the power source is matched to the impedance looking toward the transmitting coil. The impedance of the load is matched to the impedance looking back toward the source.
Advantages of the inventive method and system include, but are not limited to, the second coil of the two coils being able to rotate and to move in the axial and radial directions without loss of efficiency. According to the inventive method and system, room exists for mud to flow through the two coils. Further, power may be transmitted from the tool above the motor to the bit by passing the wires through the rotor.
Various sensors of the inventive system and method may be located at the bit, powered by the tool located above the mud motor. Measurements at the bit may include, but are not limited to, resistivity, gamma-ray, borehole pressure, bit RPM, temperature, shock, vibration, weight on bit, or torque on bit.
Another advantage of the inventive method and system is that two way communications may be made through the mud motor by adding a second set of coils. Additionally, resistivity measurements at the bit may be made by using two coils as receivers, as powered by this inventive system and method.
The inventive method and system may provide for efficient power transfer. According to one aspect, power may be transmitted between two coils where the two coils do not have to be in close proximity (see equation 1 discussed above) in which k may be less than (<1) or equal to one. Another potential distinguishing aspect of the inventive method and system includes resonating the power transmitting coil with a high quality factor (see equation 3 discussed above) in which Q may be greater than (>) or equal to about 10. Another distinguishing aspect of the system and method may include resonating the power transmitting coil with series capacitance (see equation 2 listed above).
Other unique aspects of the inventive method and system may include resonating the power transmitting coil with parallel capacitance and resonating the power receiving coil with a high quality factor Q (see equation 3) in which Q is greater than (>) or equal to 10. Other unique features of the inventive method and system may include resonating the power receiving coil with series capacitance (see equation 2 discussed above) as well as resonating the power receiving coil with parallel capacitance.
Another unique feature of the inventive method and system may include resonating the transmitting coil and the receiving coil at similar frequencies (see equation 2 described above) as well as matching the impedance of the power supply to the impedance looking toward the transmitting coil (see equation 10 described above). Another distinguishing feature of the inventive method and system may include matching the impedance of the load to the impedance looking back toward the receiving coil (see equation 12 described above).
An additional distinguishing aspect of the inventive method and system may include using magnetic material to increase the coupling efficiency between the transmitting and the receiving coils. Further, the inventive method and system may include a power receiving coil that includes wire wrapped around a ferrite core (for example, see FIG. 14 ). Meanwhile, the power transmitting coil may include a wire located inside a ferrite core (see FIG. 14 ). According to another aspect, the power receiving coil may be located inside the power transmitting coil (see FIG. 14 ).
Although a few embodiments have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the embodiments without materially departing from this disclosure. Accordingly, such modifications are intended to be included within the scope of this disclosure as defined in the following claims. In the above discussion of the casing drilling BHA 100 , both LWD and RSS equipment are located below the downhole drilling motor 410 . However, the RSS could run without the LWD equipment, or the LWD equipment could be run without the RSS. In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents, but also equivalent structures. Thus, although a nail and a screw may not be structural equivalents in that a nail employs a cylindrical surface to secure wooden parts together, whereas a screw employs a helical surface, in the environment of fastening wooden parts, a nail and a screw may be equivalent structures. It is the express intention of the applicant not to invoke 35 U.S.C. §112, sixth paragraph for any limitations of any of the claims herein, except for those in which the claim expressly uses the words ‘means for’ together with an associated function.
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Various embodiments of methods and systems for wireless power and/or data communications transmissions to a sensor subassembly above a mud motor in a bottom hole assembly are disclosed. Power and/or data are supplied by rotary modulator and power generation system positioned above the mud motor. Wires may connect to an annular coil. Power and/or communications are transmitted through the annular coil to an inductively coupled second, mandrel coil that is attached to the rotor. By leveraging resonantly tuned circuits and impedance matching techniques for the coils, power and/or data can be transmitted efficiently from one coil to the other despite relative movement and misalignment of the two coils.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The invention relates generally to design of handicap accessible buildings and more particularly to the design of buildings permitting handicap barrier-free access to multiple building levels without the use of mechanical lifting devices.
[0003] 2. Background Art
[0004] Barrier-free access to building environments especially to living environments is an absolute essential for persons having limited mobility. The degree of limited mobility depends, of course, on the nature of an individual's handicap. However, the single most commonly faced problem by handicapped individuals is the requirement to negotiate stairs which interconnect the living environments in their residence. For some the barrier of the stairs is a minor impediment, but for others stairs present a significant, if not overwhelmingly impossible, barrier to overcome. Significantly, the construction cost, both for new construction and for retrofit construction, for providing barrier-free access is very expensive well exceeding the standard costs for non barrier-free construction.
[0005] Before the instant invention, the design of barrier-free handicap accessible living environments was accomplished in one of three principle ways: (1) Single level design; (2) mechanical lifting devices; or (3) ramps connecting full-height living levels. In the case of single level design, the entire building environment must be built on one level (“ranch” style design). This design option requires a building foot-print that is of a size equal to the total building environment. In comparison to multi-level designs, the ranch design uses the most land, and therefore will not fit on many building lots where multi-level designs will fit. A ranch design, in comparison to a multi-level design, requires the greatest amount of excavation, foundation, exterior walls, concrete floor slab and roof in proportion to the total livable space. As a consequence of this inherent inefficiency, ranch designs cost more than multi-level building designs to build for the same area of livable space. The ranch design eliminates the need for mechanical lifting devices because there are no multiple levels but at a higher construction cost and restriction on the building lot size availability.
[0006] Mechanical devices can be used to provide access between multiple levels. For example multiple building levels can be interconnected and thereby accessed by means of mechanical devices that lift an individual or a wheel-chair from one level to another. A lifting device such as an elevator, wheel-chair lift, stair-climbing chair, moving stairway, etc. can be incorporated into the design. Mechanical devices such as these permit the designer to enjoy the cost and land saving benefits that derive from multi-level building design. However, all mechanical designs require significant initial costs for: (1) structural improvements required to accommodate the devices; (2) the devices themselves; and (3) installation of the devices. Additionally, mechanical designs are subject to on-going expenses, risks and inherent design limitations related to inspection, maintenance, repair, replacement, and limited lifting capacity and the limited area that moves between the multiple building levels.
[0007] For example, at the time of initial construction, a person may require a small elevator suitable only for one person to stand. Subsequently, increased disability may require the use of a wheelchair that requires a larger sized and increased weight-lifting capacity elevator. Also mechanical devices require electricity and have wearing parts and can, therefore, become inoperative because of power failure or mechanical breakdown. Handicapped individuals may become stranded or trapped in life-threatening circumstances in the event of power failure or mechanical breakdown.
[0008] Ramps are the third design option that permits barrier-free access to building environments. Ramps are sometimes used to interconnect multiple building levels for both commercial and residential uses. However, to be accessible for both able and disabled individuals, ramps can not exceed certain design limitations regarding their slope. For example, there are physical limits on how steep a slope can be for comfortable use by an able-bodied individual as well as partially disabled individuals. There are also physical limits on how steep a slope can be, in combination with the spacing of intermediate landings, for practical and comfortable use by individuals who propel themselves by hand-power in a wheel chair. There are also safety limits on how steep a slope can be used by persons in either hand-powered or motorized wheel chairs. This safety issue arises because there is a risk that a wheel chair may topple forward or backward or sideways because such chairs have a relatively high and therefore inherently unstable center of gravity.
[0009] In this connection, the American Disabilities Act Accessibility Guidelines (“ADAAG”) as amended in 1998 contains specifications for publically accessible new construction that are widely accepted throughout the United States of America for ramp design. The ADAAG defines a ramp as “walking surface which has a slope in the direction of travel that is greater than 1:20” (5% grade) (reference ADAAG 3.5). ADAAG section 4.8.2. specifies ramp design as follows:
[0010] 4.8.2* Slope and Rise. The least possible slope shall be used for any ramp. The maximum slope of a ramp in new construction shall be 1:12. The maximum rise for any run shall be 30 in (760 mm).
[0011] Additionally, the ADAAG requires a level maneuvering space that is at least five feet long at the bottom and top of every ramp. These design parameters result in a significantly long ramp where the total rise from one living level to another is nine feet (or one hundred eight inches).
[0012] Because the maximum rise per run may be no more than thirty inches, a one hundred eight inch rise requires four ramp segments, each connected to the other by a sixty inch level landing. The total run of ramps also requires an additional sixty-inch level maneuvering area at the top and bottom of the highest and lowest ramps in the run of ramps. Five landings are therefore required, for a total of three hundred inches of level run for all landings. Additionally, the four ramps comprise a total horizontal run of one thousand, two hundred, ninety-six inches (108″×12=1,296″). The total required run of ramps and landings is therefore one thousand, five hundred, ninety-six inches, or a total horizontal run of one hundred thirty-three feet.
[0013] Typically ramps designed to the full ADAAG standard become so long that it is impractical to fit them into most allowable housing footprints or residential building lots. In some cases, although the ramp may fit within the allowable footprint, the cost of the ramp in proportion to the other costs of the building's usable space becomes prohibitive. In residential construction, shorter length ramps with greater slope may be used depending on the nature and extent of the person's disability. What is required therefore is a way to incorporate relatively shallow ramps in residential construction at reasonable cost to provide access to multi-level dwellings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] [0014]FIG. 1 shows a split-level ramp-well, isometric schematic view, depicting how the ramps are built side-by-side and are stacked one above the other, thereby providing access to building environments that are off-set at half-story increments.
[0015] [0015]FIG. 2 shows a split-level ramp-well, schematic side view, depicting how the ramps are stacked one above the other, thereby providing access to building environments that are off-set at half-story increments.
[0016] [0016]FIG. 3A and FIG. 3B show a split-level ramp-well, plan view, depicting how the ramps are built side-by-side, thereby providing access to building environments that are off-set at half-story increments. Additionally, FIG. 3B depicts how the split-level ramp-well does not have to be in one straight orientation, but rather can have any desired angle that interrupts the direction of travel along the ramp-well.
[0017] [0017]FIG. 4 shows a plan view of a single-family residential building design that incorporates this invention, depicting levels A and B and indicating the location within this design of sectional views that are themselves depicted in FIGS. 6, 7 and 8 .
[0018] [0018]FIG. 5 shows a plan view of a single-family residential building design that incorporates this invention, depicting levels C and D and indicating the location within this design of sectional views that are themselves depicted in FIGS. 6, 7 and 8 .
[0019] [0019]FIG. 6 shows a sectional view of a single-family residential building design that incorporates this invention, depicting levels A, B, C and D, and also depicting how the split-level ramp-well provides access to building environments that are off-set at half-story increments. FIG. 6 depicts ramps AB and CD, which are stacked above one-another. FIG. 6 does not depict ramp BC which is built beside ramps AB and CD and therefore is out of the plane that is depicted by FIG. 6.
[0020] [0020]FIG. 7 shows a sectional view of a single-family residential building design that incorporates this invention, depicting levels A, B, C and D, and also depicting how the split-level ramp-well provides access to building environments that are off-set at half-story increments. FIG. 7 depicts ramp BC. FIG. 7 does not depict ramps AB and CD which are built beside ramp BC and therefore are out of the plane that is depicted by FIG. 7.
[0021] [0021]FIG. 8 shows a sectional view of a single-family residential building design that incorporates this invention, depicting levels A, B, C and D, and also depicting how the split-level ramp-well provides access to building environments that are off-set at half-story increments. FIG. 8 depicts ramps AB, BC and CD. FIG. 8 depicts how levels A and C are stacked above one-another, while levels B and D are also stacked above one-another. FIG. 8 additionally depicts how these two groups of stacked levels are offset from one-another by half-story increments.
[0022] [0022]FIG. 9 shows an exterior front elevation of a single-family residential building design showing all four building levels that incorporates this invention, as depicted in FIGS. 4, 5, 6 , 7 and 8 .
[0023] [0023]FIG. 10 shows an exterior rear elevation of a single-family residential building design showing all four building levels that incorporates this invention, as depicted in FIGS. 4, 5, 6 , 7 and 8 .
[0024] [0024]FIG. 11 shows an exterior left elevation of a single-family residential building design showing all four building levels that incorporates this invention, as depicted in FIGS. 4, 5, 6 , 7 and 8 .
[0025] [0025]FIG. 12 shows an exterior right elevation of a single-family residential building design showing all four building levels that incorporates this invention, as depicted in FIGS. 4, 5, 6 , 7 and 8 .
DESCRIPTION OF THE INVENTION
[0026] The present invention uses similarly sloped vertically stacked ramps to connect multiple building levels with oppositely sloped vertically stacked ramps that connect the intermediate levels, each building level being separated from each other by one-half story as shown schematically in FIG. 1. The total horizontal run of ramps required to provide access from one building level to another is thereby reduced by fifty percent. This means that the total run of ramps and level maneuvering spaces required to meet the maximum ADAAG design guidelines for access to different living levels reduces from one hundred thirty-three feet to sixty-six and one half feet. This reduced requirement for building lot length and the cost to construct is so significant that using ramps as a way to interconnect multiple building levels becomes a practical option instead of an impractical or impossible goal.
[0027] Few building designs can accommodate a ramp run of one hundred thirty-three feet because of the size of building lots and the extra cost required for foundations, roof and the construction of such a long ramp system. By reducing the size and cost requirements by fifty percent, this invention makes the use of ramps as a means of connecting building levels both more affordable and also more practical because of building lot sizes. As shown in FIG. 1 and FIG. 2, this invention off-sets, successive building levels by half-story increments of four and one half feet rather than the nine feet typically found in multiple story residential construction. In this respect, a residence built according to this invention resembles a split-level house. As noted, if a building were built to ADAAG standards using this invention, the total run would only be sixty-six and one half feet long. Also, as noted, shorter ramps with a greater slope may be used in residential construction depending on the nature and extent of the person's disability.
[0028] For instance, a steeper slope of 16.07% is practical for walking purposes. Furthermore, this slope can be negotiated easily by a motorized wheelchair. Furthermore, a 16.07% slope does not pose a risk for off-balance tipping for users of motorized wheel chairs. When a 16.07% slope is used, a total rise of four and a half feet requires only a 28 foot ramp. Incorporating a recommended level landing half way divides the ramp into two 14 foot sections. In addition to the preferred intermediate landing, a preferred design requires two level maneuvering spaces of 5 feet each (1 bottom and 1 top) at either end of the ramp. These spaces are part of each residential level which should be kept clear of obstacles. All totaled, the three spaces (intermediate landing, top and bottom maneuvering spaces) add an additional 15 feet to the total run of the ramp system. Thus, using a 16.07% slope, the total horizontal run of the ramps and required landings is forty-three feet. Of course, a shorter total distance is possible if the landing size and maneuvering spaces are reduced and if a greater slope is used.
[0029] In the design of the present invention shown schematically in FIG. 1, ramps connecting the half levels are constructed in a ramp well much as stairs are constructed in stair wells in typical multiple story construction. However, ramps joining each successive level are offset from one another in a side-by side configuration as shown in FIG. 4 and FIG. 5. (In some houses an intermediate landing for steps is used with a switch-back layout which reverses the direction of the stairs midway and also places the steps in a side by side arrangement.) The side by side ramp design therefore occupies twice the width of standard stairway wells, but the same amount of width as switch-back stairs. However, as a consequence of this design, it is important to note that for each ramp there is a full standard height of approximately 8 feet between the ramp surface and the ceiling above the ramp surface formed by the bottom of the ramp starting two levels above. This can be clearly seen in the schematic of FIG. 1. Thus, even though the ramps span just a half level each, full height above each ramp is preserved.
[0030] The building that is depicted in FIG. 4 through FIG. 12 uses a 16.07% slope. This present design for incorporating ramps that are both affordable and of reasonable length into residential multi-level building construction has heretofore not been known. Very little additional construction costs over that of a standard multiple story dwelling are encountered with the design of the present invention. Additionally, smaller and more affordable buildings can be designed using this method, providing safe and comfortable non-mechanical access between multiple building levels. From a functional point of view, the ramp-well either can be located between or can cut across the various levels. Because of the striking visual effect when the ramps are in the middle of the house, this is the preferred design.
[0031] For those cases for people requiring the shallowest slopes, thereby increasing the length of the ramps that are required, in order not excessively extend the side-to-side or front-to-back dimensions of the house, the ramps can be built with a 90 degree angle (or with other angles A as shown in FIG. 3B as desired) at the intermediate landing. However, multiple turns within the ramp-well (approximating spirals and other configurations found in buildings such as in parking garages) so increase the construction complexity, the building footprint, and the total building costs that such designs involving multiple turns within the ramp-well are impractical for most residential designs.
[0032] A barrier-free residential house having four floors would be designed and constructed according to the following schematic procedure:
[0033] 1. Create two or more full-ceiling-height building levels that are stacked one above the other in a group;
[0034] 2. Create two or more :such vertically stacked groups;
[0035] 3. Off-set the two groups of such vertically stacked full-ceiling-height groups of building levels in such a way that the relative building levels of each such vertically stacked group is one-half of a level of height higher (or lower) than the other vertically stacked group;
[0036] 4. Create one or more sets of stacked half-height ramps that are similar in lay-out to what is depicted in FIGS. 1, 2 and 3 to form a split-level ramp-well.
[0037] 5. Connect these off-set groups of building levels by using half-level-high ramps (with or without intermediate landings within the ramps) which ramps are themselves built side-by-side as well as above one-another, thereby minimizing the footprint of the ramp-well within the entire building.
[0038] Clearly, it can be seen that this procedure can be extended to accommodate anywhere from 3 or more building levels. In general there are two different and cost-effective ways to position the groups of stacked full-ceiling-height building levels in relationship to one-another and in relationship to the split-level ramp-wells. Specifically, the groups of building levels can be positioned side-by side with the connecting split-level ramp well positioned perpendicular to the axis that separates the two off-set groups of building levels; or, in the alternative, the groups of stacked building levels can be positioned on either side of (i.e. parallel to) the split-level ramp-well as is the case in the building example that is depicted in FIG. 4 through FIG. 12.
[0039] The design of the present invention constructively combines split-level building design with stacked ramps to minimize the length and area used by ramps, thereby providing the lowest-cost solution to non-mechanical barrier-free access to multi-level building environments for both handicapped and non-handicapped individuals. The design of the present invention can also be used to minimize development costs for buildings that are situated on steeply sloped building sites by orienting the split-level ramp-well(s) so they are parallel to the slope of the ground, thereby reducing excavation and related infrastructure effort and expense. The design of the present invention can also be used to connect off-set levels of existing split-level design buildings by adding an addition containing the split-level ramp-well onto the existing building. Such additions would enable individuals with impaired mobility to continue living in their present homes without relying on mechanical devices (i.e. elevators, wheel-chair lifts, stair-climbing chairs, etc.). For some people, the availability of adding the ramp-wells of this invention to their present split level homes will mean the difference between being able to remain in their existing home rather than having to move into an assisted-care or nursing facility.
[0040] The ramp wells of the present invention may also be used to provide a non-mechanical fail-safe and fire-safe means to enter and to exit buildings (both public and private), a feature that is particularly needed for individuals with impaired mobility.
[0041] The present invention can also be applied to the internal lay-out and design of multi-level town-houses, apartments and condominiums to provide non-mechanically assisted access both within individual living units, and between individual living units and to spaces outside of the larger building units.
[0042] Various modifications and alterations can be made by those skilled in the art to the present invention to accommodate different requirements. All such modifications which incorporate barrier-free access by ramps between half height building levels are considered to fall within the scope of this disclosure and appended claims.
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Barrier-free multiple level residential housing can be constructed by employing ramps between adjacent housing levels where the housing levels are offset by one half the normal full story height found in multiple story houses. The ramps are constructed in a stacked and side-by-side manner so that the full standard height between housing levels is maintained between the ramps that are stacked one above the other.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to cooking utensils. More particularly, the present invention relates to frying pan cooking utensils for preparing fried foods. Even more particularly, the present invention pertains to frying pans for the preparation of fried foods having means for preventing the splattering of grease.
2. Prior Art
As is known to those skilled in the art, the preparation of fried foods necessitates the use of extremely hot cooking oils and fats. Furthermore, as is known, the hot cooking oils and fats splatter around and out of the utensil in which they are placed. This creates an undue hazard to the utensil user as well as surrounding environs. The problems of grease fires in kitchens as well as severe burns to the user of the utensil, as a result of splattering hot cooking oils and fats, are well documented. Thus, a major safety hazard would be eliminated by providing a cooking utensil for the preparation of fried foods which obviates the problem of splattering cooking oils and greases. Heretofore, there has been a dearth of prior art directed to solving this very real and unnecessary hazard. However, there does exist some relevant prior art.
For example, U.S. Pat. No. 3,141,568 teaches a utensil cover adapted to enshroud most cooking vessels. The cover comprises a box having a vent and a lateral or side slit for inserting a food turner. However, because the cover is substantially a universal cover, it does not engage the cooking vessel in any manner, thereby rendering the device, in many instances, too cumbersome.
U.S. Pat. No. 871,287 teaches a frying pan for use with chimneys wherein apertures are provided in the pan for circulating air therethrough to force the smoke from the pan into the flue of the chimney.
U.S. Pat. No. 2,002,237 teaches a frying pan cover having a plurality of apertures formed therein for permitting moisture to escape from the interior of the pan.
Other relevant prior art is found in U.S. Pat. Nos. 2,299,995; 2,428,839; 832,274; 2,686,608 and 23,429.
It is to be noted, however, that the prior art fails to provide a cooking utensil which provides for the atmospheric cooling of the hot greases while concommitantly providing escapement means for hot gasses.
SUMMARY OF THE INVENTION
In accordance with the present invention there is provided a cooking utensil which obviates the problem of splattering cooking oils and greases. The cooking utensil or frying pan comprises a base member and a lid.
The base member comprises a bottom plate or member and an upstanding side wall integrally formed therewith which cooperate to define an open top base member. The side wall has a plurality of apertures formed therethrough which circulate air into the pan to cool the cooking oils.
A lid or cover member is adapted to seat on the base member. The lid is provided with a vent or opening to permit the escapement of hot air from within the frying pan. The lid, also, includes a lateral opening for inserting therethrough a spatula, spoon or the like to facilitate the turning of frying foodstuffs.
The present invention further contemplates the inclusion of a heating coil into the bottom plate and a rheostatic switch such that an electric frying pan is provided hereby.
For a more complete understanding of the present invention reference is made to the following detailed description and accompanying drawing. In the drawing like reference characters refer to like parts throughout the several views in which:
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a perspective view of a cooking utensil in accordance with the present invention,
FIG. 2 is a cross-sectional view of the utensil hereof taken along the line 2--2 of FIG. 1, and
FIG. 3 is a broken perspective view of the bottom member of the utensil hereof.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Now with reference to the drawing there is depicted therein a cooking utensil such as a frying pan generally indicated at 10, in accordance with the present invention.
The utensil 10 hereof comprises a base or bottom member 12 and a lid or dome 14. The base member 12 comprises a bottom plate 16 which seats atop a burner, grate or the like of a stove or other heat source for cooking foodstuffs.
An upstanding side wall 18 is integrally formed with the bottom plate 16 at the outer terminus thereof. The side wall 18 terminates at a free edge 20, as shown.
As clearly shown in FIG. 2, the upstanding side wall 18 has a reduced cross-section proximate the free edge 20. The reduced cross-section defines an inner peripheral ridge of seat or shoulder 22. As explained subsequently, the lid 14 seats on the seat 22.
In accordance herewith at least one aperture 24, and, preferably, a plurality of apertures 24 are circumferentially disposed about the bottom member 12. The aperture 24 permits the introduction of air into the interior space 26 defined by the enclosure between the bottom member 12 and the lid 24. The air entering thereinto is at a lower temperature than that of the interior space 26. Thus, the entering air functions to cool down the cooking oils and greases.
As shown in FIG. 3 the aperture 24 is formed such that it extends from the free edge 20 of the side wall 18 through the ridge 22 and partially into the side wall 18. Thus, the aperture extends downwardly and is inclined toward the center of the bottom member 12. Preferably, the plurality of apertures 24 are similarly configured and are equidistantly spaced about the periphery of the bottom member 12, as shown.
Because of the disposition of the apertures, which open to the atmosphere exteriorly of the bottom edge of the lid 14, as air enters through the apertures into the interior space 26, it flows past the bottom edge of the lid, thereby cooling same. Thus, the apertures function to cool the interior space, the hot cooking oils and the lid.
In order to facilitate handling of the bottom member 12, grasping means or handle 28 is secured thereto. The handle is secured to the side wall 18 and extends laterally away therefrom. The handle is secured to the side wall 18 by any suitable means such as threaded fasteners or the like (not shown) or can be integrally formed therewith.
The present invention, as noted, also, includes a dome of lid 14. The lid 14 is adapted to removably seat on the interior ridge 22 formed in the side wall 18. Thus, the lid 14 is dimensioned such that its free edge 30 seats on the ridge 22.
The lid 14 is provided with a central or apical vent 32. The vent 32 defines means for escapement of the hot gasses or atmosphere contained within the interior space 26. The lid 14 also includes a lateral opening 34 for inserting thereinto a food turner or stirrer, such as spatula 36.
By providing the lateral opening 34 the user of the utensil 10 is maintained away from the interior space 26, thereby obviating the possibility of grease burns and the like.
To facilitate removability of the lid 14 a grasping means or handle 38 is integrally formed therewith and extends laterally away therefrom.
In practicing the present invention it is preferred that the lid 14 be arcuate in nature, as depicted in the drawing, to provide a substantial surface for condensation of the hot moisture emanating from the bottom member.
It should further be noted that in practicing the present invention, although not shown, a heating coil and rheostatic control could be incorporated herein, in a conventional manner, to provide an electric frying pan.
The utensil hereof can be fabricated from any suitable materials such as heavy gauge aluminum, steel, unbreakable glass compositions and the like. However, it is preferred that the lid be fabricated of glass to permit visual observation of the contents within the utensil.
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A cooking utensil, such as a frying pan for reducing splattering comprises an open top base member having a bottom and an upstanding sidewall integrally formed therewith. The sidewall is provided with a plurality of apertures disposed therearound. A lid which seatingly engages the base member is provided with a central vent.
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REFERENCE TO RELATED APPLICATION
[0001] The present application is a utility application based upon Provisional application Ser. No. 60/188,506, filed Mar. 10, 2000.
TECHNICAL FIELD OF THE INVENTION
[0002] The present invention relates generally to a method for forming high-alumina bodies, and, more particularly, to a method for sintering high alumina bodies having superior properties and at reduced temperatures.
BACKGROUND OF THE INVENTION
[0003] Alumina (also known as Al 2 O 3 or corundum) is a useful and ubiquitous ceramic material. Alumina is a very hard crystalline material. It has a structure that may be described as a hexagonal close-pack array of oxygen atoms with metal atoms in two-thirds of the octahedrally coordinated interstices. Each metal atom is thus coordinated by six oxygen atoms, each of which has four metal neighbors (6:4 coordination). Alumina products include abrasives, insulators, structural members, refractory bricks, electronic substrates, and tools. Alumina is stable, hard, lightweight, and wear resistant, making it attractive for such applications as seal rings, air bearings, electrical insulators, valves, thread guides, and the like, as well as the ceramic reinforcing component in metal matrix composites.
[0004] Alumina is produced on an industrial scale using the Bayer Process to separate ferric oxide, silica and aluminum oxides. Bauxite ore is ground finely then treated with sodium hydroxide (NaOH) in an iron autoclave at an elevated temperature. The alumina dissolves as sodium aluminate via the equation:
Al 2 O 3+ 2NaOH→2NaAlO 2 +H 2 0
[0005] The silica dissolves to form sodium silicate but the ferric oxide, being insoluble, is filtered off. Carbon dioxide is then passed through the solution, decomposing the sodium aluminate (NaAlO 2 ) to form aluminum hydroxide and sodium carbonate:
2NaAlO 2 +CO 2 →Na 2 CO 3 +↓2Al(OH) 3
[0006] The aluminum hydroxide is separated by filtration and calcined at 1000° C. or higher, when it loses its water of constitution, yielding alumina:
2Al(OH) 3 →Al 2O 3+ 3 H 2 O
[0007] Pure crystalline alumina is a very inert substance and resists most aqueous acids and alkalis. It is more practical to use either alkaline (NaOH) or acidic (KHSO 4 , KHF 2 , etc) melts. Concentrated boiling sulfuric acid also can be used as an etchant.
[0008] In order to produce useful bodies, alumina must be densified or sintered. Sintering is the process in which a compact of a crystalline powder is heat treated to form a single coherent solid. The driving force for sintering is the reduction in the free surface energy of the system. This is accomplished by a combination of two processes, the conversion of small particles into fewer larger ones (particle and grain growth) and coarsening, or the replacement of the gas/solid interface by a lower energy solid/solid interface (densification). This process is modeled in three stages:
[0009] Initial - the individual particles are bonded together by the growth of necks between the particles and a grain boundary forms at the junction of the two particles.
[0010] Intermediate - characterized by interconnected networks of particles and pores.
[0011] Final - the structure consists of space-filling polyhedra and isolated pores.
[0012] The kinetics of sintering tend to be temperature sensitive, such that an increase in sintering temperature generally substantially accelerates the sintering process. In industrial applications, while an increase in sintering temperature decreases sintering time and increases throughput, the economic gains therefrom are offset by increased fuel costs and decreased furnace life (since higher firing temperatures result in more rapid degradation of both the furnace refractory structure and heating elements.) Therefore, an economically optimum sintering temperature is one that best balances gains from throughput with losses from fuel and furnace wear and tear.
[0013] The sintering of alumina at temperatures above 1600 ° C. is required to achieve a high density, and alumina is commonly sintered in the temperature range of 1700-1800° C., since higher temperatures promote more rapid sintering. Sintered alumina bodies reflect the properties of the constituent alumina crystallites or grains, such that they are hard, tough, substantially inert, and resistant to chemical attack. Mechanical and/or chemical failure of sintered alumina bodies usually occurs as a grain boundary phenomenon. Since the grain boundaries usually contain porosity and a glassy phase, a sintered alumina body is not as hard, tough, inert, and/or chemically resistant as a comparable single crystal alumina body.
[0014] There is therefore a need for a technique for decreasing the sintering temperature of alumina without sacrificing throughput (increasing the sintering time) or quality. There is also a need for producing sintered alumina bodies having bulk physical characteristics closer to those of single-crystal alumina. The present invention addresses these needs.
SUMMARY OF THE INVENTION
[0015] One form of the present invention relates to a process for the low-temperature sintering of high-alumina bodies. The high-alumina bodies so produced have a substantial resistance to dissolution in molten aluminum. The effective sintering temperature for a given sintering time required to achieve substantially full densification were decreased through the addition of quantities a of magnesia-titania mixture to the alumina precursor powders. The resulting substantially fully dense high-alumina bodies exhibited superior resistance to chemical attack over a broad range of pH and temperature conditions.
[0016] One object of the present invention is to provide a method for producing substantially dense high-alumina bodies at lower sintering temperatures when sintered for comparable times. Related objects and advantages will become apparent from the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] [0017]FIG. 1 is a flow chart schematically representing the processing steps of the present invention.
[0018] [0018]FIG. 2 is a table illustrating some of the physical properties of high-alumina material made by the process of FIG. 1.
[0019] [0019]FIG. 3 is a table presenting the results of exposure of the high-alumina material made by the process of FIG. 1 to various hostile chemical environments.
[0020] [0020]FIG. 4 is a table presenting some properties of thermal spray coatings of the high-alumina material of FIG. 1.
[0021] [0021]FIG. 5 is a table presenting some properties of metal matrix composites made from the low-fired high-alumina material of FIG. 1
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0022] For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations and further modifications in the illustrated device, and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to one skilled in the art to which the invention relates.
KNOWN METHODS OF DECREASING THE FIRING TEMPERATURE OF ALUMINA
[0023] To promote the rapid densification of Al 2 O 3 , additives such as CaO, MgO and TiO 2 , as well as titanates of baria and strontia, have frequently been used. The effect of these additives is sensitive to certain experimental or production procedures, including the fabrication history of the Al 2 O 3 powder, the amount of additives (especially MgO), the sintering temperature, type and concentration of impurities, and so on. The effectiveness of known methods of densification is also a function of the purity alumina and additives. Densification generally increases as a function of purity.
[0024] MgO is known in the art to act to retard grain growth or, more precisely, to restrict the mobility of grain boundaries. Two categories of grain boundaries can be distinguished: those that intersect pores and are therefore active in densification (type A) and those that are entirely connected to other grain boundaries (type B). The existence of type B boundaries is due to inhomogeneties in the original powder compaction of the green body. Densely packed regions of the green compact undergo local densification, leading to the development of dense, pore-free regions upon firing in an otherwise porous microstructure. These dense regions will be better able to support grain growth because of the drag exerted by porosity is absent.
[0025] The effect of MgO is limited to the increase in the grain boundary area. MgO alone has no effect on the pore surface area. The raising of the grain boundary area can be interpreted as being due to the inhibition of grain growth in the densified regions, i.e. the grains remain small. The function of the additive is to restrain grain growth in the densely packed regions until the less densely packed regions have an opportunity to densify. MgO can be thought of as acting as a homogenizer of the microstructure, in that MgO smoothes out the consequences of inhomogeneity.
[0026] The mechanism by which MgO aids in densification has been a source of contention in the known art. Generally, two mechanisms have been considered: pore mobility and grain boundary mobility. The contention arises from (including but not limited to) the nature and amount of impurities, experimental regimen and sintering atmosphere. One possible densification mechanism is that MgO increases the surface diffusion kinetics and thus increases pore mobility. The resultant high pore mobility keeps pores on the migrating grain boundaries during the final stages of sintering. Other mechanisms such as solute segregation at the grain boundaries and second phase pinning of grain boundaries may have been proven untenable, but the data may not be conclusive and they are being mentioned because they describe interesting sintering phenomenon.
[0027] Another sintering aid known to be effective in the densification of alumina is TiO 2 . Additions of TiO 2 to alumina have resulted in more rapid sintering relative to pure alumina. For additions of titania as the only sintering additive, the rate of initial sintering generally increases approximately exponentially with titania concentration up to a percentage beyond which the rate of sintering remained constant or decreased slightly. The concentration, which produces the maximum rate of sintering, is thought to be the solubility of TiO 2 in Al 2 0 3 . For alumina particles larger than 2 μm in initial stage sintering experiments with temperatures of 1520° C. and 1582° C., the kinetic process was mainly grain boundary diffusion. For smaller particles (less than 1 μm) in initial stage sintering experiments with temperatures ranging from 1150° C. to above 1400° C., volume diffusion dominated. For particles with sizes between the two, sintering occurred by a combination of the two kinetic mechanisms. It should be noted that the above details are for initial stage sintering wherein a maximum density of about 85% was achieved.
[0028] Fine-grained alumina bodies of about 95% theoretical density were achieved by sintering green alumina bodies with 2 wt. % additions of low melting point additives at 1400° C. Silicate additions were used because they form a liquid phase during the firing cycle. Silicate fluxes were prepared using MgO and CaO and in long firing regimens (15-17 hours) under an argon atmosphere with temperatures ranging from 1320° C. to 1430° C., theoretical densities of 93-96% were achieved with the MgO flux.
FORMING DENSE HIGH-ALUMINA BODIES
[0029] The present invention relates to a method for producing dense bodies having a high-alumina content from powder alumina precursors. More particularly, the present invention relates to a technique for the sintering of high-alumina bodies at lower temperatures to form dense high-alumina bodies having superior physical properties, as shown schematically in FIG. 1. In general, the first step in the low-temperature production of high-alumina bodies is to blend a high-alumina green powder. The high-alumina green powder is blended from calcined alumina powder, with additions of about 1-10 wt. magnesia (or a magnesia-former standardized to about 1-10 wt. % magnesia) and about 1-10 wt. % titania. The magnesia addition may be conveniently achieved through the addition of a magnesia-former, such as MgCO 3 , the firing of which readily forms magnesia upon heating according to the relation:
MgCO 3 ·MgO+CO 2
[0030] For the convenience of the reader, “magnesia” hereinbelow will be taken to refer to both MgO and any MgO forming material standardized to produce MgO. Likewise, “titania” will refer to TiO 2 and any TiO 2 forming material standardized to produce TiO 2 . Preferably, about 4 wt. % additive mixture is added to the calcined alumina powder to constitute the green precursor. Also preferably, the ratio of magnesia to titania in the additive portion is about 50:50, and more preferably the ratio is about 42:58. The precursor powders are preferably mixed by wet ball milling with alumina media, although any convenient ceramic powder mixing technique may be chosen. Also, binder phase such as carboxymethylcellulose (CMC), may be added to the green powder, depending upon the requirements of the pressing and firing parameters necessary to produce the desired high-alumina body.
[0031] The dried green powder is then sieved and formed into a green body having the desired shape. The green body is then baked to remove excess moisture and the binder phase (if any) and then fired. Preferably, the alumina body is fired in air to about cone 13 to achieve full sintering and densification. It should be noted that the cone system of measurement combines firing time and temperature to achieve what is essentially a measure of a system's energy state, i.e. the energy at which a cone of a specific composition softens and deforms. Cone 13 is roughly analogous to firing to about 1250° C. for about 2 hours. The baking and firing phases may be performed separately, or as part of one continuous process.
[0032] One alternative to the firing step is passing the green particles through a heat source, such as a flame or laser. If the green particles are rapidly passed through a sufficiently intense hot zone, rapid sintering may be induced. Moreover, if the green particles are passed through the hot zone under weightless or quasi-weightless conditions (such as aspiration), surface tension effects from the molten binder phase will cause the heated particles to take on a substantially spherical shape as they sinter.
[0033] Preferentially, CMC in a 3% aqueous solution is used as the binder. In other contemplated embodiments, other convenient organic binders may be used. Likewise, while the preferred concentration of CMC is 3% in aqueous solution, any convenient concentration of CMC capable of producing a crushable solid residue may be chosen.
[0034] The purity of the green powder precursor materials are not critical to the present invention, although if the production of a highly pure high-alumina body is desired, the use of high purity green powder precursor materials may likewise be desirable. If the purity of the resultant high-alumina bodies is not a consideration, green powder precursors of any desired purity level may be selected.
[0035] In the preferred embodiment, the calcined alumina precursors were chosen from powders having a particle size of about 1 micron or less, but precursor particles of any convenient size may be selected. The low-temperature high-alumina sintering process of the present invention is not especially sensitive to precursor particle size, with the size of the precursor particles primarily influencing slurry mixing conditions and green body pressing/forming parameters. However, it is generally preferable for the mean particle size of the additives to be about equal to or smaller than that of the calcined alumina.
PROPERTIES OF LOW-FIRED HIGH-ALUMINA BODIES
[0036] [0036]FIG. 2 is a table illustrating the basic physical properties of low-fired high-alumina material made by the above process, while FIG. 3 is a table showing the effects of various hostile chemical environments of the same low-fired high-alumina material. In addition, high-alumina bodies produced by the above process have a number of interesting properties, including: substantially full density; increased resistance to chemical attack over a very broad pH range; the substantial absence of a secondary glassy phase (i.e., they are non-vitreous); substantially uniform and linear thermal expansion; optical translucence; high-temperature corrosion resistance; and substantially uniform grain size.
[0037] Of particular interest is the pH range over which the low-fired high-alumina material is resistant to chemical attack, as illustrated in FIG. 3. Bodies made of the low-fired high-alumina material have been subjected to pH conditions ranging from extremely alkaline (concentrated hot NaOH) to extremely acidic (hot concentrated HF, H 2 SO 4 and hot H 2 gas) with minimal corrosive effects. The high-alumina bodies are even resistant to dissolution and/or corrosion from prolonged immersion in molten aluminum.
[0038] Moreover, the above process produces high-alumina pieces having a very low rate of defect, allowing net shape formability through conventional green body forming and firing means. Further, the high-alumina pieces formed by the above process consistently exhibit a superior surface finish of about 8 rms. The savings (both in energy costs and increased furnace life), the uniform and linear thermal expansion, substantially uniform grain size, low defect rate, and superior surface finish make the formation of low-fired high-alumina material by the above process very attractive from a manufacturing standpoint. Low-fired high-alumina bodies of the do not require kiln furniture or spacers for separation and may be stacked directly in contact with one another for firing without risking fusing or other firing defects.
LOW-FIRE HIGH-ALUMINA SPRAY COATINGS
[0039] Low-fired high-alumina material made by the above process may also be applied as a thermal spray material coating via techniques such as subsonic plasma coating or high velocity oxygenated fuel (HVOF) means. Thermal spray coatings of a low-fired high-alumina material of the present invention provide a tough ceramic wear resistant and corrosion resistant coating layer suitable for mechanical or electronic applications without sensitivity to the application technique. FIG. 4 tabulates some of the properties of low-fired high-alumina thermal spray coatings.
METAL MATRIX COMPOSITES CONTAINING LOW-FIRE HIGH-ALUMINA MATERIALS
[0040] [0040]FIG. 5 presents some properties of metal matrix composite (MMC) materials made using the low-fired high-alumina material of the present invention (in spherical form) as a reinforcement phase. In this embodiment, the metal matrix was aluminum, although any convenient metal matrix may be reinforced using the present low-fired high-alumina material. The high resistance to dissolution in molten aluminum exhibited by the present low-fired high-alumina material allows MMCs made therefrom to be made by a casting process instead of the more expensive cold pressed powder metallurgical process. In addition, MMCs made with the present low-fired high-alumina material enjoy the advantages of enhanced welded joint integrity, an expanded heat treatment range and a higher manufacturing throughput.
[0041] While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes and modifications that come within the spirit of the invention are to be desired to be protected.
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The present invention includes a method for producing high-alumina bodies with superior chemical properties at reduced sintering temperatures. One form of the method includes the steps of providing an alumina powder precursor, adding about 2 wt. % magnesia powder precursor and about 2 wt. % titania powder precursor, mixing the resultant green powder precursor, pressing a green body from the green powder precursor, removing residual moisture and organic material from the green body, and firing the green body to about cone 13.
The resulting high-alumina body has a substantially uniformly sized grain structure, is resistant to dissolution in molten aluminum, and has superior resistance to chemical attack over substantially the entire pH range.
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FIELD OF THE INVENTION
The present invention relates to a metering and dispensing device for the packing of liquid products, such as for example food products, in pots or similar containers, comprising metering means equipped with a piston movable inside a cylindrical metering chamber connected, via a closing valve, to a source of product, dispensing means equipped with downwardly facing tubular nozzle, and having an inlet orifice and an ejection orifice, movable longitudinally, and comprising a dispensing chamber which communicates, on the one hand, with the metering chamber and, on the other hand, with the outside through the tubular nozzle and a closing member operationally coupled to said nozzle, and actuating means for actuating the piston and the nozzle in such a way as to lower the latter before filling each container with liquid introduced therein via said nozzle under the delivery action of the piston.
BACKGROUND OF THE INVENTION
In devices of this type, already known for example from French Pat. No. 2,067,983, the tubular nozzle forms part of a dispensing head which is vertically movable so as to introduce the nozzle into a container, as far as the bottom thereof, and to bring it out therefrom. When the containers are filled inside a sterile enclosure, such as a tunnel, through the top of which the movable dispensing head penetrates into a sort of gasproof lock chamber, sterilization of the elements of the dispensing means which are in contact with the liquid product to be paceked, is difficult, and, particularly sterilization of the container-filling nozzle which is fixed under the movable dispensing head, partly in the open and partly inside the tunnel, and which is imparted with a vertical reciprocating movement. In order to make sterilization of the elements of the dispensing means in contact with the liquid product to be packed easier, it has been proposed to immobilize the dispensing head by fixing it on the tunnel and to introduce into the sterile tunnel, nozzle end parts of very small length. However, the sterilization of such nozzle ends always raises a problem and also, this type of short nozzle does not permit the dispensing of foaming products such as milk. Moreover, the accumulation in the metering chamber of the gaseous fractions contained in any liquid product, progressively alters the metered quantity of liquid introduced each time in said chamber, so that the quantity of liquid prepared for filling the packing containers reduces progressively.
SUMMARY OF THE INVENTION
It is the object of the present invention to propose a solution to these problems with a metering device in which the metered quantities remain substantially constant and which is easily sterilizable.
The device according to the invention is characterized first of all by the fact that the metering chamber and the dispensing chamber are re-grouped inside the same enclosure, that the transit channel of the tubular nozzle is permanently closed, at least at the lower end of the nozzle by a transversal plug, that at least one lower nozzle-ejection orifice issues onto the side face of said nozzle just above said transversal plug, that the wall which surrounds, inside the same enclosure, the metering and dispensing chambers is provided at the bottom with a guiding neck adjusted to the tubular nozzle which is mounted therein in tight manner in such a way as to be slidable therein between, on the one hand, a high position in which the ejection orifice is contained inside the guiding neck and is isolated from the outside, and the inlet orifice neck and is isolated from the outside, and the inlet orifice of the nozzle is situated at the upper part of the dispensing chamber which then receives the whole of the nozzle tube with the exception of the lower end part thereof and, on the other hand, a low position in which most of the nozzle projects downwardly from the guiding neck with the exception of its upper end part, of which the inlet orifice is then situated near the bottom of the dispensing chamber, and that the inlet orifice of the tubular nozzle is topped with and surrounded by a gas bubble trap in the form of an overturned bowl which is fast with the upper end of the tubular nozzle and has a smaller contour than the dispensing chamber in order to prevent any really substantial pumping effect.
With this disposition which closely re-groups the metering and dispensing means, the structure of the device according to the invention remains simple and compact. The enclosure of the metering means can be mounted outside the tunnel so that only one endpart of the guiding neck traverses tightly the upper wall of the tunnel and penetrates therein. Thus, a perfect and thorough sterilization of the metering means and in particular of the nozzle becomes possible; to this effect, it is enough to introduce into the chamber, while the nozzle is retracted therein in high position, overheated water or steam at a suitable temperature. According to this particular design, the tubular nozzle can go down through the tunnel to the bottom of a container and fill that container in a sterile atmosphere with a foaming product.
Beneath the lower ejection orifice provided in the side wall of the nozzle at the level of the transversal plug closing off the inner transit conduit or channel thereof, said nozzle is equipped with a sealing ring which applies against the guiding neck when the nozzle reaches its high position; so that the outflow of liquid through the nozzle is then interrupted. Thus, the lower end of the nozzle acts as a valve, operationally coupled to the guiding neck, and can close off the dispensing chamber and the metering chamber during a new filling phase of the latter;
The disposition according to the invention further permits the simple and straightforward elimination of the gases contained in the liquid which, heretofore, had a tendency to accumulate in the metering chamber. The gas bubbles generally form during the rising stroke of the nozzle and piston, and rise into the dispensing chamber preferably along the tubular nozzle, and they are stopped on their rising path and regrouped under the bubble trap for subsequent removal with the liquid during the filling of the next container. As a result, all the containers are ensured to receive exactly the wanted quantity of product.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be more readily understood on reading the following description with reference to the accompanying drawings, in which:
FIG. 1 is an elevational view of a vertical section across a first embodiment of the metering and dispensing device according to the invention;
FIG. 2 is a cross-sectional view of one detail, taken along line II--II of FIG. 1;
FIG. 3 is an elevational partly cross-sectional view of the tubular nozzle, shown on a larger scale;
FIG. 4 diagrammatically shows an axial section of a second embodiment of the device after the filling of the metering chamber;
FIG. 5 diagrammatically shows an axial section of the second embodiment at the start of the filling of a container;
FIG. 6 diagrammatically shows an axial section of the second embodiment at the end of the filling operation; and
FIG. 7 diagrammatically shows an axial section of the second embodiment at the start of the filling of the metering chamber.
DETAILED DESCRIPTION OF THE INVENTION
The metering and dispensing device illustrated in the drawings comprises a metering pump constituted by a cylindrical metering chamber 1 of circular cross-section and vertical axis 20 inside which a piston 2 moves according to a reciprocating movement, said chamber being connected to a reservoir 21 containing a liquid food product P to be packed in containers such as pot 3, through a conduit 4 via an admission valve such as a slide valve 5. At its upper part, piston 2 is connected, via a control rod 6, with actuating means 23 which causes it to move over a specific path between a high position (FIGS. 1, 4 and 5) situated at the top of the metering chamber 1, and a low position (FIGS. 1, in dotted line, 6 and 7) situated at the bottom part of the chamber 1, at the outlet part of conduit 4. The metering and dispensing device further comprises a dispensing chamber 24 which, according to a first embodiment, is situated next to metering chamber 1, inside the same enclosure 25 as said metering chamber 1, and communicates with said metering chamber 1 via an opening 26 provided in the lower part of a partition wall 27 provided between the two chambers 1 and 24. The two metering and dispensing chambers are, in this particular case, juxtaposed, and their axes 20 and 28 are parallel. The reservoir 21 containing the liquid P to be packed is placed directly above metering chamber 1 and dispensing chamber 24 so that its bottom 21a also constitutes the upper wall of dispensing chamber 24. The volume of reservoir 21 is in direct communication with the upper face of piston 2 and with the part of meterering chamber 1 situated above piston 2. As a result, the rod 6 of piston 2 goes through reservoir 21 and the inner face of the side wall of the metering chamber 1 is always kept very wet, i.e. very lubricated, by the liquid product P contained in reservoir 21.
Dispensing chamber 24 comprises a tubular nozzle 7 of vertical axis coinciding with the axis 28 of chamber 24. The bottom of dispensing chamber 24 is provided with a guiding neck 9 adjusted to the tubular nozzle 7 which is connected at its upper end with a coaxial massive rod 8 traversing in tight manner the bottom wall 21a of reservoir 21 which, according to FIG. 1, also constitutes the upper wall of dispensing chamber 24. Tubular nozzle 7 is provided at its upper end with an inlet orifice 11 and at its lower end with at least one ejection orifice, and preferably, two side ejection orifices 12 which are diametrically opposite and made in the side wall of said tubular nozzle 7, above a sealing ring 10 mounted on the lower end of said nozzle where its transit channel 13 is axially permanently obturated by a transversal plug 15.
The upper end of the tubular nozzle 7 is connected to its coaxial control rod 8 by means of an overturned bowl or rigid cap 14 of which the top part is fast with said rod 8 and the concave face surrounds and remotely covers over the inlet orifice 11, the said concave face being fixed to the upper end of nozzle 7 by means of a plurality of radial spacing fingers 16. It should be noted that said overturned bowl 14 acts as a bubble trap and has a maximum outer contour which is substantially smaller than the inner contour of the dispensing chamber 24, this in order to avoid any substantial pumping effect during the displacement of nozzle 7.
Said nozzle 7 moves inside dispensing chamber 24 between, on the one hand, a high position (FIGS. 1, 3, 4 and 7) where it is entirely or almost entirely retracted inside chamber 24 and where it does not allow the flow of liquid out therefrom, its lower end being then closed off by the transversal plug 15 and its side ejection orifice 12 being inside the guiding neck 9, against the lower end of which presses the sealing ring or closing member 10 provided on nozzle 7 below ejection orifice 12, and on the other hand, a low position (FIGS. 5,6) where it emerges from the dispensing chamber 24, its upper inlet orifice 11 then being slightly above the bottom of chamber 24 which is equipped with guiding neck 9. Said upper orifice 11 is, on the other hand, situated just above piston 2 when said piston is in low position (FIG. 1, in broken lines) and nozzle 7 in low position (FIG. 1, in broken lines).
According to the embodiment illustrated in FIGS. 1 and 2, the admission valve 5 provided between reservoir 21 and the metering and dispensing device, and to be more precise, between the dispensing chamber 24 and reservoir 21, is a slide valve comprising a cylindrical body of circular cross-section 29 resting without play on a cradle 30 of appropriate shape, such as a semi-cylindrical shape, also with circular cross-section. The superposed bottoms of cradle 30 and of reservoir 21 are provided with an outlet orifice 31 joining with the upper end of conduit 4 connecting reservoir 1 with the metering and dispensing device. The cylindrical body 29 has an axial length which is at least equal to three times the diameter of outlet orifice 31 and which is provided in its median part with a cylindrical annular notch 32, the axial width of which is at the most equal to the diameter of outlet orifice 31. One of the ends of cylindrical body 29 is equipped with a coaxial control rod 29 which traverses in tight manner the side wall 22 of reservoir 21. Thus, admission valve 5 works as a slide valve which is open, when its annular notch 32 covers the outlet orifice 31, as shown in FIG. 2 and closed, when said orifice 31 is closed off by an adjacent part of the cylindrical body 29 when the control rod 29' is pulled to the right as suggested by the double arrow (FIG. 2).
In the case of the embodiment illustrated in FIGS. 1 and 2, the lower face 2a of piston 2 is slightly inclined upwardly so that in low position, i.e. in the delivery position of piston 2, the highest side of inclined lower face 2a is situated about half-height of the opening 26, and the lower part of said surface 2a is situated close to the bottom of metering chamber 1. Thus, if gas bubbles accumulate under the piston 2, said bubbles can easily be transferred to the dispensing chamber 24 and in particular towards the bubble trap 14 wherefrom they will be removed through tubular nozzle 7. In order to prevent gas bubbles from accumulating in the top part of dispensing chamber 24, above the bowl 14, it is possible to give a concave or truncated conical shape to the lower face of the upper wall 33 of said dispensing chamber 24, said concave shape perfectly adopting the shape of the upper face of said bubble trap 14, so that the bubbles are expelled downwardly under said trap 14, when the latter reaches the high position.
According to the second embodiment illustrated in FIGS. 4 to 7, metering chamber 1 and dispensing chamber 24 are superposed inside the same enclosure 25 which, in this case, is cylindrical with vertical axis 20 and circular cross-section. Also in this embodiment, the lower part of the metering chamber is situated directly above the upper part of dispensing chamber 24 and there is no partition between the two chambers 1 and 24. Conduit 4 connecting reservoir 21 with the metering and dispensing device issues at its lower end into the top part of dispensing chamber 24 or into the joining zone between metering chamber 1 and dispensing chamber 24.
As illustrated in FIGS. 3 to 7, the upper end of tubular nozzle 7 can be directly connected with the lower end of control rod 8 which is massive or closed off at its lower end. Bubble trap 14, in this case, is constituted by an overturned bowl or by a sort of truncated cap which surrounds the side inlet orifice or orifices 11 into transit channel 13 of the nozzle and is fixed, by its upper end, to the lower end of rod 8. Because of the superposed position of chambers 1 and 24, the cylindrical enclosure 25 has an axial height which is at least equal to the sum of the maximum strokes of piston 2 and of nozzle 7, said piston 2 being annular-shaped and provided with a central opening adjusted in such a way that said piston 2 surrounds the control rod 8, and slides in tight manner thereon, and control rod 6 of piston 2 being tubular shaped, surrounding part of control rod 8 and being slidable in tight manner thereon.
It is possible to provide on the lower face of piston 2, a downwardly truncated conical cavity 34, centered on axis 20 and entirely situated under the inner sealing ring of piston 2. Nozzle 7 is equipped, at its upper part, i.e. immediately level with and above its inlet orifice 11, with an overturned bowl 14 of truncated shape having a truncated conical upper face complementing that of the cavity 34. Said bowl 14, which also includes a truncated lower face and acts as a bubble trap, resembles a small umbrella, and is less wide than chambers 1 and 24, so as not to act as a piston therein and so that the liquid can easily flow around it when piston 2 and/or said bowl move.
The metering and dispensing device ends at its lower end in a guiding neck 9 via which it can be fixed on a tunnel 17 and can penetrate inside said tunnel 17. The tunnel 17 is, for example, sterile and forms part of a packing installation of the type which thermo-forms, fills, seals and cuts the containers 3 and in which the bottom of tunnel 17, supplied with a slightly pressurized sterile gas, is closed, in non-tight manner, by a thermoplastic strip 18 in which the containers 3 are shaped with their inner face turned towards the tunnel 17 made sterile for the packing operations. The sterile gas then escaping between the lower edges of the tunnel and the strips or band 18. Said band 18 moves stepwise under the action of clamps 19 of lateral driving chains. Moreover, when the reservoir 21 which is situated above the metering chamber 1 contains a sterile product P, means should be provided so that the parts of rods 6 and 8 which go through the reservoir 1 or penetrate therein, remain sterile.
To this effect, reservoir 21 is closed off and partly filled with a sterile liquid product P from a suitable source and through a valve 35, the opening of which is controlled by a first level sensor 36 indicating the minimum level of the liquid product P in reservoir 21, the closure of which is controlled by a second level sensor 37 which indicates the maximum level of product P. The free space 38 at the top of reservoir 21 above product P is filled and permanently supplied with slightly pressurized sterile air through an orifice 39. The upper ends of the tubular piston rod 6 and of control rod 8 move inside upper free space 38 and are separately connected to two actuating rods 40, 41 the lower ends of which move vertically in stroke lengths which correspond respectively to the strokes of piston 2 and of tubular nozzle 7. Said actuating rods 40, 41 of vertical parallel axes, also go through a sterile lock chamber 42 provided above reservoir 21, while being guided in tight manner through the horizontal partition wall 43 between lock chamber 42 and reservoir 21, and through the upper horizontal wall 44 of said chamber 42. The chamber 42 permanently supplied with slightly pressurized sterilized air, flowing into said chamber through an upper orifice 45, and out of it through a lower orifice 46. The height of lock chamber 42 is at least equal to the maximum stroke of piston 2 or of tubular nozzle 7, and the sterile air pressure inside said lock chamber 42 is less than the sterile air pressure inside reservoir 21. Thus the risks of pollution inside reservoir 21 are kept to a minimum.
The metering and dispensing device according to the invention works as follows:
When the superposed chambers 1 and 24 have been filled with the liquid to be packed (FIG. 4), valve 5 is closed, piston 2 is then in high position and nozzle 7 goes down from its high position in which the bubble trap is slightly above the mouth of conduit 4, to take up its low position in which its side ejection orifice 12 comes near to the bottom of container 3 to be filled (FIG. 5). Filling of container 3 is achieved by the downstroke of piston 2 which forces the liquid, along with entrapped bubbles, into nozzle 7 through its upper inlet orifice 11, and out of said nozzle via its internal flowing channel 13 through its lower ejection orifice 12, which latter is preferably always kept above the bottom of container 3 during the filling operation.
At the end of the filling operation (FIG. 6), nozzle 7 is raised up so that its sealing ring 10 presses tightly against the guiding neck 9, valve 5 is opened (FIG. 7) and finally, piston 2 is raised up from its low position above the mouth or outlet of conduit 4 (FIG. 6) so as to admit another metered quantity of liquid into chamber 1 as soon as the space inside the latter is closed at the level of guiding neck 9, by the raising of nozzle 7 to the high position (FIG. 7), in which sealing ring 10 presses tightly against guiding neck 9.
A plurality of devices such as described hereinabove may be grouped in range manner to allow the simultaneous filling of a plurality of containers 3 placed side by side.
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The invention relates to the packing of liquid products. A piston, moving inside a cylindrical metering chamber, introduces successive quantities of liquid in pots via a tubular nozzle vertically movable, which can be entirely retracted inside the dispensing chamber and which is equipped with a truncated bubble trap for eliminating the gases issued from the liquid.
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RELATED U.S. APPLICATION DATA
This application is a continuation-in-part of U.S. application, Ser. No. 09/823,644, filed Nov. 27, 2000, now abandoned.
BACKGROUND OF THE INVENTION
This invention relates to a blind rivet and, more particularly, to a closed-end blind rivet with a crimped shank and method of manufacture thereof.
Blind rivets are well-known and generally comprise a mandrel having a pulling stem with a radially enlarged head attached at one end and a tubular shell having a generally cylindrical shaped shank having a radial flange formed at one end of the shank for engaging a face of the workpiece. An axial bore is formed through the flange and passes a substantial way into the shank. The radially enlarged head of the mandrel is located within the shank towards the end remote from the flange adjacent an end of the bore. The enlarged head has a circumference which is greater than that of the bore. The pulling stem extends from the enlarged head through the length of the bore and extends away from the body of the rivet. A breakneck is formed on part of the stem and which is located within the shank. When the rivet is set, the flange is held stationary whilst the exposed part of the pulling stem is pulled axially away from the flange, the enlarged head being forced to pass through at least part of the bore. Because the diameter of the pulling head is larger than the bore, it causes the shank to collapse, thus forming an annular bulge or fold which projects radially outwardly. The radial outward bulge forms a blind head and engages the blind side surface of the workpiece which is the opposite side of workpiece to that of the flange. Once the pulling force on the stem exceeds a predetermined amount, the breakneck breaks leaving the rivet set. The rest of the stem can then be removed and discarded.
One type of blind rivet comprises a shank having circumferential grooves spaced at intervals along the length of the shank. When such rivets are set, the grooves collapse in an axial direction, the sections of the rivet body between the grooves expanding radially to form the characteristic “cottage loaf” setting. The depth of the grooves is critical in certain extreme conditions for example when the rivet is set in an oversized hole whilst needing to provide an air and water tight fixing. This is particularly difficult when the rivet bodies are made of intractable material such as stainless steel, carbon steel or the like. If the grooves are too deep the rivet body will crack and if they are too shallow, the grooves will not provide sufficient resistance to prevent the mandrel head from pulling into or even through the rivet body.
This can result in two problems. Firstly, during setting in softer materials, the grooves are required to be deeper to prevent the mandrel head from pulling through the rivet body. However, this can cause fracture of the body. If the grooves are not at an optimum depth, the mandrel pulls through the body causing radial expansion of the rivet body between the grooves which can result in the splitting of the workpiece material if the expansion takes place within the bore formed in the workpiece, in which the rivet is located.
Secondly, if the grooves are less than optimum, during the setting of a rivet, the mandrel head can pull through the rivet body since there is insufficient resistance from the soft workpiece materials to help provide resistance to the head of the mandrel pulling into the rivet body. This can result in part of the stem attached to the head of the mandrel protruding from the flange giving a potentially hazardous condition.
The grooves or recesses can be formed by rolling, embossing or crimping. While the prior art patents have favored rolling or embossing, the present invention uses crimping to form the recesses or radial impressions that result in a positive leakproof setting of the blind rivet that is produced over an increased range of manufacturing tolerances than was possible in the prior art.
SUMMARY OF THE PRESENT INVENTION
Accordingly, in one aspect of the invention, there is provided a blind rivet comprising:
1. a body having a generally cylindrical shank, a radial flange formed at one end of the shank and a bore which extends axially through the flange and through at least part of the length of the shank; and 2. a mandrel comprising a mandrel head located adjacent an end of the bore remote from the flange, a stem attached to the mandrel head which passes through the length of the bore and extends beyond the flange and which comprises a breakneck located along the length of the stem; characterised in that there is provided a plurality of series of radial impressions which are crimped into the shank of the rivet at pre-set distances from the flange.
In one particular construction there is provided two series of radial impressions. Though there can be any number of radial impressions, in a preferred embodiment, there are four radial impressions in each series.
A first method of forming the radial impressions is by crimping. Angled flanks can be formed between adjacent radial impressions in each series. The shank will bulge outwardly between the series of radial impressions to form a gap between the stem and the wall of the bore in the body of the rivet between the series of radial impressions.
Though the body of the rivet can be made of many different types of material, preferably it is made from stainless steel.
According to a second aspect of the present invention there is provided a method of manufacturing a blind rivet comprising the steps of mounting the rivet body onto the mandrel so that the mandrel head is located within the shank, the stem extending from the head through the bore and flange and away from the body of the rivet, and then crimping a number of series of radial impressions onto the outer circumference of the shank at pre-set distances from the rivet body head.
According to a third aspect of the present invention, there is provided a method of setting a blind rivet in a workpiece comprising the step of selecting a rivet such that the series of radial impressions nearest the flange are located at a distance from the flange which is the same as the thickness of the workpiece so that when the rivet is located within the workpiece, the series of radial impressions nearest the flange coincides with the surface of the blind side of the workpiece.
Accordingly, it is an object of the present invention to provide a blind rivet with a crimped shank and method of manufacture thereof which overcomes the disadvantages of the prior art and provides for greater manufacturing tolerances and ease of production.
It is another object of the invention to provide a blind rivet and method of manufacture thereof which is relatively inexpensive, simple to produce and reliable in use in that its failure rate is de minimus and the product produced is leakproof.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
Additional advantages and features of the present invention will become apparent from the subsequent description, taken in conjunction with the accompanying drawings wherein:
FIG. 1 shows a side view of a rivet according to the present invention;
FIG. 2 shows a vertical cross-section of the rivet indicated by X—X in FIG. 1 ;
FIG. 3 shows a vertical cross-section of the rivet at the point indicated by Z—Z in FIG. 1 ;
FIG. 4 shows the rivet after it has been set;
FIG. 5 shows a side view of the rivet, partly in section, according to the present invention to illustrate the axial spacing between the flange and the radial impressions (“A”), the two sets of radial impressions (“B”) and the cap distance (“C”);
FIG. 6 shows the rivet of FIG. 5 in a partially set condition; and
FIG. 7 shows the rivet of FIG. 5 when set.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
With reference to the accompanying drawings, FIG. 1 shows a blind rivet having a mandrel ( 2 ) and a rivet body ( 4 ). The mandrel ( 2 ) has a mandrel head ( 6 ) attached to one end of a stem ( 8 ). The stem ( 8 ) comprises a breakneck ( 10 ) located adjacent the mandrel head ( 6 ). The diameter of the stem ( 8 ) is substantially uniform along the length of the stem ( 8 ).
The rivet body ( 4 ) has a tubular shank ( 12 ) having a flange ( 16 ) formed at one end of the shank ( 12 ). A bore ( 14 ), shown in FIG. 2 , extends through the flange ( 16 ) and through a substantial part of the length of the shank ( 12 ). The head ( 6 ) of the mandrel ( 2 ) is located within the shank ( 12 ), the outer diameter of the head ( 6 ) being larger than the bore ( 14 ). The stem ( 8 ) of the mandrel ( 2 ) extends from the head ( 6 ) through the bore ( 14 ) and extends from the body ( 4 ) of the rivet away from the flange ( 16 ). Ridges ( 18 ), shown only in FIG. 1 , are formed on part of the exposed end of the stem ( 8 ) to assist the rivet setting tool in gripping the stem in order to set the rivet. When the rivet is being manufactured, the shank ( 12 ) of the rivet initially has a substantially uniform diameter along its length. The bore ( 14 ) of the body ( 4 ) of the rivet has an internal diameter which is substantially equal to, or slightly larger than, that of the stem ( 8 ).
Two series of radial impressions ( 20 ) have been crimped onto the rivet body ( 4 ) at pre-set axial distances from the flange ( 16 ), as described in greater detail hereinafter. In FIG. 5 , the radial impression ( 20 ) is indicated by reference R and is best shown in FIG. 3 . By crimping in this manner, the depth of the crimp is pre-set and the tolerances are controlled to produce a better and more dependable product that is both strong and leakproof. There are four radial impressions ( 20 ) in each of the upper and lower serieses. The crimping results in angled flanks ( 22 ) at either side of each radial impression ( 20 ) as shown best in FIG. 1 and FIG. 5 . The radial impression ( 20 ) forces the shank ( 12 ) into a tight assembly with the mandrel at four positions ( 24 ) around the stem ( 8 ) at the same time inducing local work hardening of the rivet body ( 4 ) at these points.
During the crimping operation, some material is displaced inwardly to touch the mandrel but most is displaced longitudinally. The longitudinal displacement between the series of radial impressions results in an initial bulge ( 11 ) or a slight increase in diameter of the shank ( 12 ) between the series of radial impressions resulting in a gap ( 26 ) appearing between the stem ( 8 ) and the inside of the bore ( 14 ). This outward movement encourages the shank ( 12 ) to bend at the mid-point between the radial impressions ( 20 ) to cause the initial bulge ( 11 ).
FIG. 5 shows the relative axial distances A, B, C and D of the rivet body ( 4 ), in which:
“A” is the axial distance from the upper surface ( 13 ) of the flange ( 16 ) to the lower side of the lower series of radial impressions ( 20 ); “B” is the axial distance from the lower side of the lower series of radial impressions ( 20 ) to the upper side of the upper series of radial impressions ( 20 ); “C” is the axial distance from the upper side of the upper series of radial impressions ( 20 ) to the top of the head ( 6 ) which engages the under side of the closed end of the tubular shank ( 12 ); and “D” is the total axial distance from the top surface ( 13 ) of the flange ( 16 ) to the top of the head ( 6 ) or the total of A plus B plus C.
Interposed in the horizontal plane between each of the adjacent radial impressions ( 20 ) are four areas, best shown in FIGS. 1 and 3 , that are formed at both the upper series and the lower series of radial impressions ( 20 ), that define reinforcing ribs ( 15 ) that influence the collapse performance of the rivet body ( 4 ) or setting. The setting will occur, as shown in FIGS. 6 and 7 , when the mandrel ( 2 ) is pulled to force the head ( 6 ) toward the workpiece ( 30 ). This places a load upon the cylindrical portion of the rivet body ( 4 ) and is supported by each series of the four crimped sections ( 20 ) and the four interposed reinforcing ribs ( 15 ). Though these members collapse, the collapse will be gradual because the ribs ( 15 ) act as struts. Furthermore, greater stability of the rivet body ( 4 ) collapse will occur since the setting load is being supported also by the four reinforcing ribs ( 15 ) that are at a greater distance from the axis of the rivet body.
In other words, in order to set the rivet, the shank ( 12 ) is placed into and through a bore ( 28 ) formed through a workpiece ( 30 ) so that the end of the shank ( 12 ) remote from the flange ( 16 ) protrudes from one side ( 36 ) of the workpiece (the blind side) and the flange ( 16 ) abuts against the other side ( 34 ) (the visible side). The series of radial impressions ( 20 ) and the ribs ( 15 ) nearest the flange ( 16 ) are located the same distance from the flange ( 16 ) as the thickness of the workpiece ( 30 ) so that, when the rivet body ( 4 ) is located within the workpiece, they are each aligned with the surface of the blind side ( 36 ). (See FIGS. 4 and 7 .)
A rivet setting tool (not shown) of known design is used to set the rivet in the normal manner. The jaws of the rivet setting tool grip the part of the stem ( 8 ) which comprises ridges ( 18 ). The nose of the rivet setting tool abuts against the flange ( 16 ). As the rivet setting tool is operated to set the rivet, the stem ( 8 ) is axially pulled away from the flange ( 16 ) whilst the flange is held stationary to set the rivet.
In the initial stage of setting, the mandrel head ( 6 ) enters the rivet body ( 4 ) causing greater swelling in the region between the two series of radial impressions ( 20 ). As the shank ( 12 ) continues to collapse along the rivet body axis until, as shown in FIG. 6 , an intermediate bulge ( 17 ) is formed. The work hardened ribs ( 15 ) adjacent the radial impressions ( 20 ) controls the collapse of the material in the bulge ( 11 or 17 ). The bulge ( 17 ) flattens out to form a final bulge ( 19 ), shown in FIGS. 4 and 7 , while continuing to expand radially until the series of radial impressions ( 20 ) furthest from the flange ( 16 ) has completely collapsed. At this stage, the lower part of the rivet body expands and by so doing fills the bore ( 28 ) of the workpiece ( 30 ). The amount of linear collapse is controlled by the position of the series of radial impressions ( 20 ) nearest the flange ( 16 ). The position of the radial impressions ( 20 ) nearest the flange ( 16 ) determines the minimum thickness of the workpiece ( 30 ) which can be fastened using the rivet ( 1 ).
FIGS. 4 and 7 show the rivet ( 1 ) after it has been fully set. At this point, both series of radial impressions ( 20 ) and the ribs ( 15 ) have collapsed totally and thus effectively stopped any further linear collapse of a rivet body ( 4 ). The mandrel breaks at the breakneck ( 10 ) (not shown), while the mandrel head ( 6 ) is retained within the rivet body ( 4 ).
FIG. 6 illustrates the intermediate bulge ( 17 ) of the rivet body ( 4 ), wherein B′ is substantially equal to one-half (½) of B; A′ will be substantially equal to A; and C′ will be substantially equal to C. Therefore, D′ equals A′ plus B′ plus C′ or A plus one-half (½) of B plus C.
Likewise, FIG. 7 illustrates the final bulge ( 19 ) of the rivet body ( 4 ), wherein B″ is substantially equal to one-third (⅓) of B; A″ will be substantially equal to A; and C″ will be substantially equal to C. Therefore, D″ equals A″ plus B″ plus C″ or A plus one-third (⅓) of B plus C.
Some prior art patents reduce the diameter of the rivet shank so that insertion of the rivet into a multiple sheet workpiece could result in the rivet body being located in a crimped gap. The result would be to make further insertion in the workpiece hole difficult. In the present invention, the ribs ( 15 ) prevent sheet material from the workpiece from entering the crimped areas, thus insertion is always easier to achieve and reliable.
Also, the reinforcing ribs ( 15 ) greatly enhance the present invention in filling oversize holes, because the shank is and remains at its designed diameter or slightly larger so that upon collapse there is a corresponding increase in diameter that is deemed excellent in filling even oversize holes.
In general, the above-identified embodiments are not to be construed as limiting the breadth of the present invention. It is understood that other modifications or other alternative constructions will be apparent which are within the scope of the invention as defined in the appended claims.
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A blind rivet having a mandrel with a predetermined breakable stem disposed within a body with a bored shank. A radial flange is formed on one end of the shank to engage a workpiece and at the other end of the shank there is disposed within the shank an enlarged head of the stem the diameter of which is greater than the diameter of the bore of the shank. The breakneck of the stem formed with at least two series of radial impressions formed around the circumference of the shank at predetermined distances from the flange. Ribs are formed alternately between the radial impressions in the same horizontal series therewith.
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BACKGROUND
[0001] 1. Field
[0002] The present disclosure relates generally to testing electronic packages, and more particularly, package on package (POP) devices, which generally have a package mounted on top of another package.
[0003] 2. Background
[0004] POP devices generally have a package mounted on top of another package. The two packages are electrically connected through any suitable connection. In the past, traditional sockets and failure analysis (FA) lids have been used to test POPs. This testing poses a problem when an optical diagnostic tool is used during failure analysis testing. In order for the optical diagnostic tool to fully analyze the bottom package under test it must come into physical contact with the bottom die in order to “see” the nano structures. These nano structures include devices such as transistors, resistors, and capacitors.
[0005] During testing the POP should be electrically connected, which is difficult as the top package blocks access to the bottom package. In addition, the conventional FA lid opening does not provide adequate space for the optical diagnostic tool to access the bottom die, as the optical diagnostic tool is too large to pass through the FA lid opening.
[0006] There is a need in the art for a flat-top socket and wing board to facilitate testing of POP devices. This assembly removes the top package and mounts it on a wing board that provides electrical connectivity while allowing access to the bottom die for the optical diagnostic tool testing.
SUMMARY
[0007] Embodiments disclosed herein provide a method and apparatus for facilitating testing of a package-on-package device. The apparatus comprises a wing board having a pattern of pads for electrically connecting a top package to the pads of a bottom package as well as bond fingers for electrically connecting the package-on-package devices and a flat top socket with electrical contacts for electrically connecting wing board to a load board.
[0008] A further embodiment provides a method of testing a package-on-package device. The method includes the steps of: affixing a top package onto a wing board; affixing a bottom package onto the wing board; connecting the top side solderballs of the digital package to the bond fingers of the wing board. The wing board is then mounted onto a flat top socket. Once the mounting has been completed, the testing begins, and may use a solid immersion lens. The configuration of the flat top socket and wing board allows the optical diagnostic tool full access to the package on package device for the testing process and failure analysis.
[0009] Yet a further embodiment provides an apparatus for testing a package-on-package device. The apparatus comprises: means for affixing a top package onto a wing board; means for affixing a bottom package onto a wing board; means for connecting the top side solderballs of the bottom package to the bond fingers of the wing board; means for mounting the wing board onto a flat top socket; and means for testing the package-on-package device.
[0010] A still further embodiment provides a non-transitory computer readable medium containing instructions, which when executed by a processor, cause the processor to perform the steps of: activating an optical diagnostic tool; positioning the optical diagnostic tool over a package-on-package device reflowed onto a wing board and electrically connected to a flat top socket that in turn is connected to both the wing board and the load board; and accessing the package-on-package device with the optical diagnostic tool for testing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 illustrates the problem of testing POP assemblies using a conventional testing FA lid and an optical diagnostic device.
[0012] FIG. 2 illustrates the flat-top socket and wing board according to an embodiment of the invention.
DETAILED DESCRIPTION
[0013] Various aspects are now described with reference to the drawings. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of one or more aspects. It may be evident, however, that such aspect(s) may be practiced without these specific details.
[0014] As used in this application, the terms “component,” “module,” “system” and the like are intended to include a computer-related entity, such as, but not limited to hardware, firmware, a combination of hardware and software, software, or software in execution. For example, a component may be, but is not limited to being, a process running on a processor, a processor, an object, an executable, a thread of execution, a program and/or a computer. By way of illustration, both an application running on a computing device and the computing device can be a component. One or more components can reside within a process and/or thread of execution and a component may be localized on one computer and/or distributed between two or more computers. In addition, these components can execute from various computer readable media having various data structures stored thereon. The components may communicate by way of local and/or remote processes such as in accordance with a signal having one or more data packets, such as data from one component interacting with another component in a local system, distributed system, and/or across a network such as the Internet with other systems by way of the signal.
[0015] Moreover, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or.” That is, unless specified otherwise, or clear from the context, the phrase “X employs A or B” is intended to mean any of the natural inclusive permutations. That is, the phrase “X employs A or B” is satisfied by any of the following instances: X employs A; X employs B; or X employs both A and B. In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from the context to be directed to a singular form.
[0016] POP devices typically have a memory package mounted on top of the digital package. The two packages are electrically connected through solder balls, just as the digital package connects with the socket. In the past, traditional FA lids have been used to test POPs. This has posed a problem when a solid immersion lens (SIL) or other optical diagnostic tool is used for failure analysis of the digital die because the optical diagnostic tool must come into contact with the die to “see” the nano structures such as transistors, resistors, capacitors, and other structures. The POP should be electrically connected during optical diagnostic testing, which poses a problem as the memory package blocks access to the bottom package. In addition, the typical FA lid does not provide sufficient space for the optical diagnostic tool to access the digital die because the optical diagnostic tool is too large to pass through the FA lid opening.
[0017] FIG. 1 illustrates the problem with using a conventional FA lid in conjunction with an optical diagnostic tool to test a POP. The test set up 100 , shows a optical diagnostic tool 102 in relation to a conventional FA lid 104 . The lid is placed on top of POP 108 , which is in turn placed in conventional socket 106 . Load board 110 is also used during testing.
[0018] Embodiments described herein provide a method and apparatus that overcomes the disadvantages of conventional testing methods and apparatus. Embodiments move the memory or top package to one side and allow the optical diagnostic tool access to the bottom digital die. The memory or top package is removed from the POP and mounted on a wing board. The wing board provides electrical connections with the digital package. The assembly does not require the conventional FA lid and permits the optical diagnostic tool to contact the digital die for testing.
[0019] FIG. 2 illustrates the flat-top socket and wing board assembly 200 as viewed from the side during testing. The flat-top socket 208 replaces the conventional automated test equipment (ATE) socket. Flat-top socket 208 has a flat surface on top and does not provide a recess or pocket as an ATE socket provides. The digital die or package 204 is connected electrically to wing board 206 . Memory package 210 is mounted to the underside, or second surface of wing board 206 . Both digital die 204 and memory package 210 are electrically connected through solder balls to traces on wing board 206 . Wing board 206 has pads for both the bottom digital package 204 and the top memory package 210 . Digital package 204 and memory package 210 are reflowed or suitably affixed onto wing board 206 using conventional reflow solder techniques, however, any suitable technique may be used. The top side solder balls of the digital package 204 are bonded to wing board 206 bond fingers. Wing board 206 includes internal traces that connect the board fingers to the top or memory package 210 fingers to memory package 210 pads to provide an electrical connection. The wing board 206 is then mounted on flat top socket 208 using any suitable mounting method Because there is no FA lid to interfere, optical diagnostic tool 202 may make direct contact with the digital die 204 . Flat-top socket 208 is in electrical contact with load board 212 .
[0020] Wing board 206 has pads for digital package 204 and pads for memory package 210 . The digital package 204 and memory package 210 are reflowed or affixed onto the wing board 206 . The toe side solder balls of the digital package 204 are wire bonded or electrically connected to the fingers on wing board 206 . The wing board 206 includes internal traces that connect the board's fingers to the memory package 210 pads to form an electrical connection.
[0021] An alternative embodiment provides that the top memory package 210 may be mounted to one side on wing board 206 , instead of on the underside, as depicted in FIG. 2 .
[0022] The interface between wing board 206 and ATE load board 212 may be accomplished by several methods, including flat-top socket, flip-chip socket, elastomer, or other suitable method.
[0023] The embodiment described above provides numerous advantages over conventional techniques. No direct pressure is applied to the thinned package, which has had the protective lid removed, thus preventing die cracking. In addition, there is no FA lid to apply pressure and obstruct SIL access to the digital device under test as the memory package has been moved to the wing board. The original load board and socket may be used without modification, allowing for cost saving and avoiding duplication of dedicated failure analysis boards.
[0024] It is understood that the specific order or hierarchy of steps in the processes disclosed is an illustration of exemplary approaches. Based upon design preferences, it is understood that the specific order or hierarchy of steps in the processes may be rearranged. The accompanying method claims present elements of the various steps in a sample order, and are not meant to be limited to the specific order or hierarchy presented.
[0025] The previous description is provided to enable any person skilled in the art to practice the various aspects described herein. Various modifications to these aspects will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other aspects. Thus, the claims are not intended to be limited to the aspects shown herein, but is to be accorded the full scope consistent with the language claims, wherein reference to an element in the singular is not intended to mean “one and only one” unless specifically so stated, but rather “one or more.” Unless specifically stated otherwise, the term “some” refers to one or more. All structural and functional equivalents to the elements of the various aspects described throughout this disclosure that are known or later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the claims. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. No claim element is to be construed as a means plus function unless the element is expressly recited using the phrase “means for.”
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A method and apparatus for testing a package-on-package digital device is provided. The method includes the steps of: affixing a top device onto a wing board; affixing a bottom device onto the wing board; connecting the top side solderballs of the bottom package to the bond fingers of the wing board. The wing board is then mounted onto a flat top socket. Once the mounting has been completed, the testing begins, and may use a solid immersion lens or optical diagnostic tool. The configuration of the flat top socket and wing board allows the optical diagnostic tool full access to the bottom device for the testing process and failure analysis.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process and apparatus for preparing crystalline powders of alphaaluminum orthophosphate and alpha-gallium orthophosphate.
2. Description of the Prior Art
Alpha-aluminum orthophosphate (berlinite) and alpha-gallium orthophosphate (GaPO 4 ) are among several alpha-quartz isomorphs that have for decades been synthesized for research purposes. An attempt to grow large single crystals of berlinite began after World War II, in an effort to find new piezoelectric crystals for frequency control applications. The project ended a few years later, because success was achieved in quartz crystal growth and because quartz was considered superior for the piezoelectric devices known then. Specifically, it was concluded that berlinite had a lower Q and lower coupling coefficient than quartz. Furthermore, tests on both X and Y cuts of berlinite plates, showing a negative frequency drift with increasing temperature, indicated that there was little chance of finding a zero temperature cut similar to the AT cut of quartz.
Interest in berlinite was renewed in 1976, when Barsch and Chang found that berlinite does have temperature-compensated cuts, and that the coupling coefficient for surface acoustic wave (SAW) devices can be four times greater than for quartz.
Several processes for preparing berlinite have been reported in the technical literature (A. F. Huttenlocker, Z. Krist. 90, 508 (1935); W. Jahn et al., Chem. Erde 16, 75 (1953); and E. D. Kolb et al., J. Crystal Growth 43, 313 (1978)). Three processes for preparing GaPO 4 were described by Perloff (J. Amer. Cer. Soc. 39, 83 (1956)).
Recently, Drafall and Belt, of the Rome Air Development Center, described procedures for seeded hydrothermal growth of single crystals of berlinite for SAW applications. (RADC-TR-80-73, Final Technical Report, March, 1980). Among the three approaches to nutrient preparation described in their report, the best results were achieved by reacting Al(OH) 3 with excess H 3 PO 4 according to the reaction:
Al(OH).sub.3 +H.sub.3 PO.sub.4 →AlPO.sub.4 +3H.sub.2 O
The amount of acid was adjusted so that the final solution was 6 M in H 3 PO 4 . The reactants were heated in a sealed silver-lined autoclave under a gradient of 20°-30° C., with temperature increasing from 120°-250° C. at a fixed rate of about 5° C./day, Euhedral crystals in the 1-4 mm range was produced.
SUMMARY OF THE INVENTION
In accordance with the present invention, an apparatus is provided for preparing powders of alphaaluminum orthophosphate or alpha-gallium orthophosphate. The apparatus comprises, in combination, a substantially cylindrical fluoropolymer-lined pressure vessel, means for supporting the vessel with its cylinder axis in a substantially horizontal orientation, means for rotating the vessel about its cylinder axis, and means for controlling temperatures in the vessel.
In operation, the present invention provides a process for preparing crystalline powders of alpha-aluminum orthophosphate or alpha-gallium orthophosphate. The process comprises the steps of:
(a) heating a sealed pressure vessel containing a mixture comprising a compound selected from the group consisting of aluminum hydroxide, aluminum oxide, and gallium sesquioxide and an excess of concentrated phosphoric acid to a first temperature between about 180° C. and about 235° C.,
(b) cooling the vessel to a second temperature between about 125° C. and about 150° C.,
(c) repeating steps (a) and (b) at least one more time,
(d) rapidly cooling the vessel from the first temperature to near ambient temperature, and
(e) recovering the resultant crystalline powder.
Preferably, the pressure vessel is held in a horizontal position and rotated about a longitudinal axis during the reaction.
The present invention provides several advantages over the prior art. The apparatus is simpler, lighter, easier to use, and less expensive to build than that of the prior art. The resultant high-purity powder, consisting of uniform size, crystalline grains, is useful as nutrient material in the growth of single crystals of alpha-quartz isomorphs for SAW device applications.
BRIEF DESCRIPTION OF THE DRAWING
The FIGURE shows a sectional view of an apparatus of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
This invention provides an apparatus for preparing crystalline powders that are isomorphs of alpha-quartz.The apparatus includes a substantially cylindrical pressure vessel supported with its long dimension in a horizontal orientation, means for rotating the vessel about a longitudinal axis, and means for controlling temperatures in the vessel.
The pressure vessel, or autoclave, has a fluoropolymer lining to inhibit acid corrosion of the walls. Any fluoropolymer that can withstand the conditions of temperature and pressure in the corrosive environment of the autoclave without softening substantially is suitable as a liner material. Among these, poly(tetrafluoroethylene) and PFA (copolymer of perfluorinated ethylene and perfluorinated alkylvinylether) are particularly suitable; chlorotrifluoroethylene and polyvinylidene fluoride are not, because they soften at the high temperature. In principle, the fluoropolymer could be sprayed on the autoclave walls; in practice, however, sprayed coatings contained micropores that permitted autoclave wall corrosion.
Conventional autoclaves, fabricated from high-strength materials, are suitable. A Morey-type autoclave is convenient to use and is adequate to tolerate the required pressures (˜50 000 kPa). If an autoclave having a demountable seal at one end is used, the fluoropolymer lining may be machined from a solid cylinder. A tubular autoclave, having demountable seals at each end, is preferred for two reasons. First, it permits the fluoropolymer liner to be fabricated from extruded tubular stock, without machining. In addition, it makes loading and unloading of material from the autoclave, as well as cleaning the autoclave, simpler. Since the force required to seal the ends of the autoclave at a given pressure is essentially proportional to the cross-sectional area of the cylinder, a small cross section is advantageous. However, the cross section is preferably large enough to accommodate the desired volume of reactants without causing the collapsing strength of the liner to be exceeded during cooling. Autoclave dimensions, while not critical, involve a compromise among these competing factors.
The autoclave is supported with its cylinder axis horizontal to promote uniform distribution of the material. The support includes means for rotating the autoclave to promote uniform temperature and growth (without clumping) and to reduce the tendency for material to adhere to the liner. The rotation rate is not critical. The range from about 5 to 60 rpm is suitable, with 10 to 30 rpm preferred. If the rate is too low, the purposes of rotation, discussed above, are not achieved; if too high, there is a tendency for the tumbling of the particles against one another to have an undesirable grinding effect.
Surrounding the autoclave is a cylindrical furnace for heating the autoclave to about 235° C. The exterior temperature of the autoclave is monitored in a conventional manner, for example using thermocouples. Although not measured directly, the interior temperature is believed to be generally within about 5° C. of the measured temperature during heating and cooling cycles, closer at the temperature extremes. Interior temperatures are uniform to within about ±1° C.
In one embodiment, preparing powders of berlinite by the process of the present invention comprises first mixing chemical grade aluminum hydroxide fine powder with an excess of concentrated phosphoric acid. Electronic grade 85% H 3 PO 4 is commercially available and is suitable. Heating the mixture in an autoclave then causes the following reaction to take place:
Al(OH).sub.3 +H.sub.3 PO.sub.4 →AlPO.sub.4 +3H.sub.2 O.
Alternatively, chemical grade aluminum oxide (Al 2 O 3 ) powder may be used in place of Al(OH) 3 , to cause the reaction:
Al.sub.2 O.sub.3 +2H.sub.3 PO.sub.4 →2AlPO.sub.4 +3H.sub.2 O
An advantage of using Al 2 O 3 is that the berlinite yield is greater for a given autoclave volume, since only half as much water is generated. A disadvantage is the sluggish reaction rate. Furthermore, the reaction does not go to completion if the Al 2 O 3 powder is too coarse (maximum particle size>1 μm). Just a very small quantity of Al 2 O 3 (<0.1% of the original amount) remaining in the system can cause serious problems in subsequent single crystal growth. If the required fine powder were available at a reasonable cost, the Al 2 O 3 process would be preferred.
The reactions require that the vessel temperature be at least about 125° C.; otherwise, the product is AlPO 4 .2H 2 O. As the reaction proceeds, the temperature is cycled, preferably between about 130° and 200° C. Berlinite shows retrograde solubility. Thus, at temperatures above about 235° C., its solubility is so low that very little material precipitates.
Preferably, a temperature cycle is completed in less than about seven days, more preferably in about one day. Of course, the first cycle, beginning at ambient temperature, takes longer than later cycles. If the rate of temperature increase is too high, there is excessive nucleation of particles, and the desirably coarse grains do not result.
The amounts of reactant are chosen to meet two goals. The first is to yield a liquid product whose acid molarity is between 5 and 8, 7.3 being particularly suitable. A ratio of about 1.5-2 mL of 85% H 3 PO 4 per g of Al(OH) 3 generally yields such a product; 1.8 mL/g is preferred. If Al 2 O 3 is used instead of Al(OH) 3 , about 2.0-2.5 mL/g is suitable, with about 2.3 preferred.
The second goal is to maximize the yield of crystalline powder in a limited autoclave volume. If too much of the autoclave volume (i.e. >90%) is filled by the reactants, a single (liquid) phase fills the entire volume at 200° C. and excessive pressures may develop. Within this volume constraint, in a preferred procedure, a quantity of fine crystalline berlinite (<100 mesh), the residue (after sieving) of previous syntheses, is also added to the system as seeding material. The amount of fine berlinite is a determining factor of the number of particles in the product.
Preferably, the autoclave is held with its long dimension substantially horizontal and more preferably it is also rotated about a longitudinal axis as the reaction takes place. The horizontal position provides a uniform temperature; and rotation provides agitation, which increases the reaction rate, reduces undesirable coagulation, and yields a product in loose powder form having uniform grain size. Rotation also contributes to uniform temperature in the autoclave.
Although the reaction is complete within about two days, particle size at that time is undesirably small. To produce coarser grains, the temperature is cycled repeatedly. Small grains go into solution preferentially as the temperature is reduced, and crystallites grow as the temperature is increased. Typically, the particles grow to an acceptable size in about three weeks. Because of berlinite's retrograde solubility, the reaction mass must be cooled rapidly and removed from the system to avoid dissolution of the berlinite product into the acid after the desired particle size has been achieved. To accomplish this, the autoclave is removed from the furnace and sprayed with water. Cooling to near room temperature takes about 10 to 15 minutes. More rapid cooling, while possible, would increase the stress on the liner and thus reduce its lifetime. After being cooled, the solution is filtered and the crystalline berlinite powder is washed, dried, and sieved. Particles of size less than 100 mesh are used as seeding material in later syntheses. The coarse granular berlinite powder is used in growth of single crystals. No material is wasted.
For subsequent growth of large single crystals, optimum particle size is in the range from about 20-100 mesh, with 20-50 mesh preferred (all mesh sizes quoted herein are U.S. sieve). Smaller particles tend to go into suspension, which is deleterious to the growth of large single crystals; larger particles go into solution too slowly. A narrow particle size distribution is desirable, because it provides a uniform dissolution rate and thus permits nearly all the nutrient to be used during the single crystal growth operation. For this reason, particles of size >10 mesh are less desirable; however, since the present process generally yields no particles that large, there is no problem. By the present process, a greater fraction of the product powder has particle size in the preferred range than is achieved by prior art processes. For example, a typical reaction yields 40 percent of the crystalline berlinite granules greater than 50 mesh, 50 percent between 50-90 mesh, and 10 percent less than 90 mesh.
Starting with chemical grade Al(OH) 3 and electronic grade H 3 PO 4 , emission spectroscopic analysis of the crystalline powder product shows the following impurities: Si:20 ppm, B:20 ppm, Ga:70 ppm, transition metals: <100 ppm, alkaline earths: <30 ppm, and alkalies: <20 ppm.
Similar to the process and apparatus described above for preparing berlinite are those for preparing GaPO 4 . The latter merely involves substituting high purity (99.99%) Ga 2 O 3 for Al(OH) 3 or Al 2 O 3 and preferably cycling the temperature between about 140° C. and about 225° C., instead of the lower temperatures used in berlinite preparation. The reaction involving gallium is:
Ga.sub.2 O.sub.3 +2H.sub.3 PO.sub.4 →2GaPO.sub.4 +3H.sub.2 O
The Figure depicts a sectional view of an apparatus of the present invention. The pressure vessel comprises a tubular element 10 having flanges 11 at each end for sealing two demountable caps 12. The vessel is protected from corrosion by fluoropolymer liner 13 and cap liners 14. Optionally, an O-ring may be placed at each end between fluoropolymer elements 13 and 14 to ensure sealing, particularly when a vessel of large cross section is used. The vessel is attached at one end to a demountable coupling 15 that permits the vessel to be rotated about an axial shaft 16 driven by a motor (not shown). Preferably, coupling 15 is thermally insulating to avoid heating the motor by conduction along shaft 16. At its opposite end, the vessel is attached to a shaft 17, supported in a bearing (not shown). The vessel is enclosed in split furnace 18, with split pipe 19 filling the gap that results from the flanges. A thermocouple (not shown) fitted into a hole 20 in the pipe measures the temperature. A conventional plunger seal, or other seal not requiring the flanged structure, would obviate the need for the split pipe.
The following examples are presented in order to provide a more complete understanding of the invention. The specific techniques, conditions, materials, and reported data set forth to illustrate the principles and practice of the invention are exemplary and should not be construed as limiting the scope of the invention.
EXAMPLE 1
A 3.2 L autoclave oriented with its cylinder axis horizontal was loaded with a mixture of 1300 g Al(OH) 3 , 2.3 L of concentrated (85 wt.%) H 3 PO 4 , and 300 g AlPO 4 (size <100 mesh). The temperature of the autoclave was cycled between 130° C. and 200° C. for three weeks while the autoclave was rotated about its axis at 20 rpm. The temperature cycle period was one day. The reaction yielded 1.8 kg of berlinite having the following particle size distribution:
______________________________________ 20-45 mesh - 283 g (15.8%) 45-60 mesh - 868 g (48.6%) 60-70 mesh - 232 g (13.1%) 70-100 mesh - 250 g (14.1%) <100 mesh - 151 g (8.45%)______________________________________
EXAMPLE 2
The autoclave of Example 1 was loaded with 1200 g Al 2 O 3 and 2.7 L of 85 wt.% H 3 PO 4 (no AlPO 4 was added). The autoclave temperature was cycled daily between 140° C. and 185° C., while the autoclave was rotated about its axis at 20 rpm. After 25 days, 2.1 kg of berlinite had been produced having the following particle size distribution:
______________________________________ 20-45 mesh - 106 g (5.0%) 45-100 mesh - 1860 g (87.1%) <100 mesh - 168 g (7.9%)______________________________________
EXAMPLE 3
The autoclave of Example 1 was loaded with a mixture of 960 g Ga 2 O 3 , 2.5 L of 85 wt.% H 3 PO 4 , and 880 g α-GaPO 4 (size <90 mesh). The autoclave temperature was cycled between 150° C. and 210° C. for 30 days while the autoclave was rotated about its axis at 10 rpm. The temperature cycle period was one day. The reaction yielded 2080 g of α-GaPO 4 having the following particle size distribution:
______________________________________ 20-50 mesh - 345 g (16.6%) 50-90 mesh - 1282 g (61.6%) <90 mesh - 453 g (21.8%)______________________________________
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Berlinite crystalline powder of uniform particle size and high purity is prepared by repeated thermal cycling to react a mixture of aluminum hydroxide or aluminum oxide and an excess of concentrated phosphoric acid in a sealed pressure vessel. The vessel is preferably held in a horizontal orientation and rotated about a longitudinal axis during the reaction. The product powder is useful in growing large single crystals that have surface acoustic wave applications. Crystalline powder of alpha-gallium orthophosphate may be prepared using the same apparatus and a similar procedure.
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